methimazole and Graves-Disease

Thionamide antithyroid drugs (ATD) are the treatment of choice for Graves' hyperthyroidism. The major drawback of ATD treatment for 1-2 years is the relapse of hyperthyroidism in about 50% of patients. Recently, it has been shown that ATD treatment for more than five years is accompanied by long-term remission in majority of patients without additional major side effects in both adults and children. Compared to radioactive iodine therapy, long-term ATD results in more favorable outcomes. This review summarizes the evidence on long-term ATD therapy regarding the remission rate of hyperthyroidism, efficacy and safety, indications and mode of therapy in patients with hyperthyroidism.

Topics: Adult; Antithyroid Agents; Child; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Neoplasm Recurrence, Local; Thyroid Neoplasms; Treatment Outcome

The efficacy of anti-thyroid drugs in conjunction with radioactive iodine therapy in the management of Graves' disease is still controversial.. To compare the efficacy of pretreatment with methimazole before the administration of radioactive iodine for the treatment of Graves' disease.. A systematic review and meta-analysis was conducted at a teaching/tertiary hospital in Ibadan, Nigeria.. A systematic search of the PubMed, Embase, Cochrane Library, and Web of Science databases was performed from inception to December, 2021.. Five studies with 297 participants were included. There was no difference in the risk of persistent hyperthyroidism when radioactive iodine was used in conjunction with methimazole compared with when radioactive iodine was used alone (relative risk: 1.02, 95% confidence interval, CI: 0.62-1.66; P = 0.95, I2 = 0%). Subgroup analysis based on the duration between discontinuation of methimazole and the administration of radioactive iodine showed a lower risk of persistent hyperthyroidism when methimazole was discontinued within 7 days before radioactive iodine use, although this did not reach statistical significance (risk ratio: 0.85, CI: 0.28-2.58).. The use of methimazole before radioactive iodine administration was not associated with an increased risk of persistent hyperthyroidism. Concerns about medication toxicity and adverse effects should be considered when clinicians make decisions on combination therapies for the treatment of Graves' disease.. CRD42020150013, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=150013.

Topics: Antithyroid Agents; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Nigeria; Thyroid Neoplasms

The thionamide anti-thyroid drugs namely carbimazole, methimazole, and propylthiouracil, have been the predominant therapy modality for Graves' hyperthyroidism for over 60 years. Although these agents have proven efficacy and favorable side-effect profiles, non-thionamide alternatives are occasionally indicated in patients who are intolerant or unresponsive to thionamides alone. This review examines the available non-thionamide drug options for the control of Graves' hyperthyroidism and summarizes their clinical utility, efficacy, and limitations.. We reviewed existing literature on mechanisms, therapeutic utility, and side-effect profiles of non-thionamide anti-thyroid drugs. Established non-thionamide agents act on various phases of the synthesis, release, and metabolism of thyroid hormones and comprise historical agents such as iodine compounds and potassium perchlorate as well as drug repurposing candidates like lithium, glucocorticoids, beta-blockers, and cholestyramine. Novel experimental agents in development target key players in Graves' disease pathogenesis including B-cell depletors (Rituximab), CD40 blockers (Iscalimab), TSH-receptor antagonists, blocking antibodies, and immune-modifying peptides.. Non-thionamide anti-thyroid drugs are useful alternatives in Graves' hyperthyroidism and more clinical trials are needed to establish their safety and long-term efficacy in hyperthyroidism control. Ultimately, the promise for a cure will lie in novel approaches that target the well-established immunopathogenesis of Graves' disease.

Topics: Antithyroid Agents; Graves Disease; Humans; Hyperthyroidism; Methimazole; Propylthiouracil

Following the conventional 12-18 month antithyroid drug (ATD) treatment in Graves' disease (GD), 50% of patients experience relapse of hyperthyroidism.. The aim of this systematic scoping review was critical appraisal of duration of ATD therapy in the last 80 years.. Articles were identified through the search of PubMed from January 1, 1941 to April 30, 2021. All study types were included. Articles were eligible if they reported data on the length of ATD treatment, particularly thyroid hormones and TSH receptor antibodies (TRAb) concentrations and specifically those with data on the remission and/or relapse rates.. We described major progress regarding the duration of ATD therapy and related outcomes at every 20 years. Articles of 1941-1960 were mainly concerned with determination of favorable treatment, minimal effective dose, side effects and rate of remission after < 12-month ATD therapy. Studies with larger number of patients and longer follow-ups appeared in 1961-1980; higher remission rate after 18-24 months versus 6 months of ATD therapy was reported. Articles of 1981-2000 focused on identification of factors associated with high relapse rates after discontinuation of ATD. In 2001-2021, ATD became the first choice of treatment in many countries. However, 12-18 months of ATD therapy was arbitrarily chosen as the appropriate option. According to recent studies, persistent normalization of TRAb occurs after 5 years of methimazole therapy and ATD treatment of > 60 months could offer a 4-year remission rate of 85%.. Long-term ATD treatment for more than 60 months is safe and effective, has the highest remission rate and cures most patients with GD; hence, it should be considered as the most appropriate duration for ATD therapy in these patients.

Topics: Antithyroid Agents; Graves Disease; Humans; Methimazole; Recurrence; Thyroid Hormones

Typical symptoms which should lead to suspicion of hyperthyroidism are unintentional weight loss, tachycardia, and palpitations, heat intolerance, and hyperactivity. It is diagnosed by suppressed thyroid-stimulating hormone (TSH) with elevated thyroid hormone (TH) levels. Graves' disease (GD) due to antibodies stimulating the TSH receptor is the leading cause, and first-line treatment is with methimazole (MMI). Emerging data suggest MMI treatment, up to 8 years is effective and safe in improving the rate of remission. Radioactive iodine (RAI) and thyroidectomy offer definitive treatment and induce permanent hypothyroidism. Thyroid storm is a life-threatening condition with systemic decompensation and hyperpyrexia. Neonates of mothers with current or past GD are at risk for neonatal hyperthyroidism (NH). Appropriate identification and follow-up of at-risk neonates will reduce complications.

Topics: Child; Graves Disease; Humans; Hyperthyroidism; Infant, Newborn; Iodine Radioisotopes; Methimazole; Thyroid Neoplasms

Rash and cholestatic liver injury caused by methimazole (MMI) in patients with Turner syndrome (TS) and Graves's disease (GD) are rarely reported, and there is a paucity of reports on the management of this condition. It is not clear whether propylthiouracil (PTU) can be used as a safe alternative in this case.. A 37-year-old woman was admitted to our hospital with rash, severe pruritus and a change in urine colour after 2 months of GD treatment with MMI. Physical examination showed rash scattered over the limbs and torso, mild jaundice of the sclera and skin, short stature, facial moles, immature external genitals and diffuse thyroid gland enlargement. Liver function tests indicated an increase in total bilirubin, direct bilirubin, total bile acid, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase and alkaline phosphatase. The level of sex hormones suggested female hypergonadotropic hypogonadism. The karyotype of peripheral blood was 46, X, i(X)(q10)/45, X. After excluding biliary obstruction and other common causes of liver injury, combined with rash and abnormal liver function following oral administration of MMI, the patient was diagnosed as having TS with GD and rash and cholestatic liver injury caused by MMI. MMI was immediately discontinued, and eleven days after treatment with antihistamine and hepatoprotective agents was initiated, the rash subsided, and liver function returned to nearly normal. Because the patient did not consent to administration of. While patients with TS and GD are undergoing treatment with MMI, their clinical manifestations, liver functions, and other routine blood test results should be closely monitored. When patients with TS and GD manifest adverse reactions to MMI such as rash and cholestatic liver injury, it is necessary to discontinue MMI and treat with antihistamine and hepatoprotective agents. After the rash subsides and liver function returns to nearly normal, PTU can effectively control hyperthyroidism without adverse drug reactions.

Topics: Adult; Antithyroid Agents; Chemical and Drug Induced Liver Injury; Cholestasis; Exanthema; Female; Graves Disease; Humans; Methimazole; Prognosis; Turner Syndrome

The diagnosis of Graves' disease is mainly based on ultrasonography and laboratory diagnostics. This includes the determination of the TSH value and the peripheral thyroid hormones. TSH receptor antibody (TRAb) measurement is highly sensitive and specific for the detection of Graves' disease (GD) and helps to distinguish from autoimmune thyroiditis (AIT). However, as recent studies show, some may AIT patients may also reveal TRAb.. Current guidelines recommend primarily the use of thiamazol/carbimazole in GD. Due to the comparatively higher hepatotoxicity, propylthiouracil is not recommended as first line therapy. In case of relapse during 12 up to 18 months of antithyroid drug therapy or after a frustrating attempt at cessation, definitive therapy should be considered. Alternatively, in accordance with the current recommendations of the European Thyroid Association, drug therapy may be continued for up to 12 months after initial diagnosis.. The treatment of active GD during pregnancy is problematic due to diaplacental crossing of peripheral thyroid hormones, TSH receptor stimulating antibodies and antithyroid drugs. According to current guidelines, PTU is recommended during the first 16 weeks of pregnancy, whereas for the 2nd and 3 rd trimester no special recommendations are given. After that, you can choose which antithyroid drug might be used. The aim of antithyroid drug therapy during pregnancy is to achieve a suppressed TSH value together with normal or slightly increased fT4 while using lowest effective dose of antithyroid drug.. The most common endocrine side effect with this therapy is thyroid dysfunction. Hyperthyroidism; occur most frequently in combination therapy (CTLA-4 / anti-PD-1 therapy) ICI mainly causes destructive thyroiditis with lymphocytic infiltration; GD is absolutely rare in this context and only few cases are described.

Topics: Antithyroid Agents; Carbimazole; Causality; COVID-19; Diagnosis, Differential; Female; Graves Disease; Humans; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Hormones; Thyrotropin; Ultrasonography

Occurrence of pancytopenia in patients with untreated hyperthyroidism is extremely rare. To the best of our knowledge, only 30 cases have been reported in the English literature. Accurate diagnosis and appropriate tailored therapy are challenging due to the variegated causes of pancytopenia and the potential hematological toxicity of antithyroid drugs (ATDs).. We present a 51-year-old Caucasian man with newly diagnosed Graves' disease showing pancytopenia and liver dysfunction. Although in this context the use of ATDs is still under debate, low-dose methimazole therapy was able to induce resolution of both pancytopenia and liver dysfunction, along with euthyroidism restoration.. Searching in the English literature for previous studies, we identified only 30 cases worldwide to form our database. A demographic as well as clinical, laboratory, and histopathological analysis was performed. In most cases, the recovery of biochemical euthyroidism through the use of ATDs induced the resolution of pancytopenia (at laboratory and histological levels). Our review provides clinical, laboratory, and histopathological features of Graves's hyperthyroidism-related pancytopenia with a view to improving the knowledge of this rare hematological complication and assisting in the decision-making process regarding therapeutic options.

Topics: Antithyroid Agents; Graves Disease; Humans; Male; Methimazole; Middle Aged; Pancytopenia

A 29-year-old woman was diagnosed with Graves' disease because of her symptoms of thyrotoxicosis. After a 15-day treatment with methimazole, she began to suffer from a repeated fever, rash, and polyarticular migratory arthralgias. The clinical examination on admission showed that her white blood cell count, neutrophil count, and erythrocyte sedimentation rate (ESR) were within normal limits, while the concentration of C-creative protein (CRP) was 26.14 mg/L (ref. 0 - 10) and anti-nuclear immune body (ANA) and anti-neutrophil cytoplasmic antibody (ANCA) were both negative. Upon stopping the drug treatment, the patient's symptoms promptly disappeared. Antithyroid arthritis syndrome is poorly characterized, and the findings from our literature review indicate that this syndrome exhibits serological features that are distinct from those of antithyroid agent-induced vasculitis syndrome. Furthermore, physician's awareness of this syndrome is essential for its diagnosis in clinical practice.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Arthritis; Female; Graves Disease; Humans; Methimazole

Methimazole (MMI) is used to treat hyperthyroidism in Graves' disease. It is rare to encounter patients in whom hyperthyroidism cannot be controlled using high doses of MMI.Case presentation: A 21-year-old woman was referred to our hospital because of MMI-resistant Graves' disease. Although her MMI dose had been increased to 120 mg/day, her serum thyroid hormone concentration was too high to be measured. Additional therapy with lithium carbonate, and then with dexamethasone and inorganic iodine, was initiated. After 14 days, the patient's serum thyroid hormone concentration normalized, while she was taking 150 mg/day MMI, 800 mg/day lithium carbonate, 6 mg/day dexamethasone and 306 mg/day inorganic iodine, and total thyroidectomy was then performed. The patient was discharged 8 days after the thyroidectomy and experienced no major complications.. We have presented a rare case of Graves' disease that was resistant to high-dose MMI. Combination therapy of MMI with lithium carbonate, dexamethasone and inorganic iodine may represent a therapeutic option for the preoperative preparation of patients with MMI-resistant Graves' disease.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Methimazole; Thyroid Hormones; Thyroxine; Young Adult

Comparison of studies on remission rates in pediatric Graves' disease is complicated by lack of uniformity in treatment protocols, remission definition, and follow-up duration. We performed a systematic review on remission rates in pediatric Graves' disease and attempted to create uniformity by recalculating remission rates based on an intention-to-treat analysis.. PubMed and Embase were searched in August 2020 for studies on patients with Graves' disease: (i) 2 to 18 years of age, (ii) initially treated with methimazole or carbimazole for at least 18 months, (iii) with a follow-up duration of at least 1 year after cessation of methimazole or carbimazole. All reported remission rates were recalculated using an intention-to-treat analysis.. Of 1890 articles, 29 articles consisting of 24 patient cohorts were included with a total of 3057 patients (82.6% female). Methimazole or carbimazole was initially prescribed in 2864 patients (93.7%). Recalculation based on intention-to-treat analysis resulted in an overall remission rate of 28.8% (829/2880). Pooled remission rates based on treatment duration were 23.7, 31.0, 43.7, and 75% respectively after 1.5-2.5 years, 2.5-5 years, 5-6 years (two studies), and 9 years (single study) treatment duration. The occurrence of adverse events was 419 in 2377 patients (17.6%), with major side effects in 25 patients (1.1%).. Using a standardized calculation, the overall remission rate in methimazole-treated pediatric GD is 28.8%. A few small studies indicate that longer treatment increases the remission rate. However, evidence is limited and further research is necessary to investigate the efficacy of longer treatment durations.

Topics: Adolescent; Antithyroid Agents; Child; Graves Disease; Humans; Methimazole; Remission Induction; Treatment Outcome

Graves' disease affects 3% of women and 0.5% of men in the general population. The first line treatment of Graves' hyperthyroidism is based on the administration of antithyroid drugs (ATD), propylthiouracil (PTU), methimazole (MMI) and carbimazole. A recent warning from the Italian Drug Agency (Agenzia Italiana del Farmaco AIFA) reported the risk of MMI-induced acute pancreatitis. In addition, AIFA highlighted the possible association of MMI treatment during the first trimester of pregnancy with congenital malformations, thus recommending the use of effective contraceptive methods in women of childbearing age treated with MMI.. Revision of literature reported less than ten cases of the alleged MMI pancreatitis, allowing the inclusion of MMI in class III drug regarding the relative risk for drug-induced pancreatitis. Data available on the effect of hyperthyroidism per se on the risk of fetal malformations, although scanty, are sufficient to recommend treatment with ATD of the hyperthyroid pregnant woman. Case reports and population studies either suggesting or not suggesting MMI-induced fetal malformations do not allow unquestionable conclusions on this matter.. This consensus by experts from Italian Endocrine and Gynecologic Scientific Societies has edited recommendations derived form the available data and published guidelines of International Scientific Societies.

Topics: Antithyroid Agents; Consensus; Female; Graves Disease; Humans; Hyperthyroidism; Italy; Methimazole; Pancreatitis; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications

Myalgia and elevated creatine kinase (CK) have been reported during the treatment of hyperthyroid patients. The causes of these symptoms are usually considered to be treatments of antithyroid drugs (ATDs), thyroidectomy or radio-iodine (131-I). However, the underlying cause may be the rapid correction of thyrotoxicosis (or relative hypothyroidism), which was usually neglected in clinical practice.. This report describes a case of a 25-year-old female with typical symptoms and laboratory test results of Grave hyperthyroidism. The patient complained about fatigue and myalgia 7 weeks after receiving methimazole (MMI) treatment. Blood tests showed dramatically elevated serum CK level, although free triiodothyronine (FT3) and free thyroxine (FT4) level had returned to the normal reference range. MMI was; therefore, discontinued and the patient's muscular symptoms disappeared quickly with the normalization of CK level and the relapse of hyperthyroidism. Later she received 131-I treatment and suffered similar muscular symptoms when FT3 and FT4 decreased to the normal range. This time, her symptoms were quickly relieved by levothyroxine (L-T4) replacement treatment.. Myopathy induced by rapid correction of hyperthyroidism (or relative hypothyroidism).. MMI was discontinued after the patient's first episode of muscular symptoms. And for her second episode of muscular injury after 131-I treatment, we initiated L-T4 supplementation.. For the 2 episodes of muscular injury after ATDs or 131-I treatment, both of the interventions mentioned above brought a rapid relief of symptoms accompanied with normalization of CK level and restoration of thyroid hormone level.. Myopathy can be caused by a rapid reduction of thyroid hormone during the treatment of hyperthyroidism. This relative hypothyroidism syndrome should be considered if patients make complaints about fatigue and myalgia, even when thyroid hormone level is within the normal range during the antithyroid treatments. Serum CK level and thyroid function should be closely monitored post antithyroid treatments. Reduction of ATD dosage or replacement of thyroid hormone is suggested to relieve muscular symptoms.

Topics: Adult; Antithyroid Agents; Creatine Kinase; Female; Graves Disease; Humans; Methimazole; Myalgia; Recurrence; Thyroxine

Topics: Adolescent; Adult; Affect; Antibodies; Antithyroid Agents; Child; Cognition; Graves Disease; Heart; Humans; Hyperthyroidism; Immune System; Iodine Radioisotopes; Lipids; Methimazole; Recurrence; Research Design; Risk Factors; Thyroid Gland; Thyrotropin; Young Adult

Invited update on the management of systemic autoimmune Graves disease (GD) and associated Graves orbitopathy (GO).. Guidelines, pertinent original articles, systemic reviews, and meta-analyses.. Thyrotropin receptor antibodies (TSH-R-Abs), foremost the stimulatory TSH-R-Abs, are a specific biomarker for GD. Their measurement assists in the differential diagnosis of hyperthyroidism and offers accurate and rapid diagnosis of GD. Thyroid ultrasound is a sensitive imaging tool for GD. Worldwide, thionamides are the favored treatment (12-18 months) of newly diagnosed GD, with methimazole (MMI) as the preferred drug. Patients with persistently high TSH-R-Abs and/or persistent hyperthyroidism at 18 months, or with a relapse after completing a course of MMI, can opt for a definitive therapy with radioactive iodine (RAI) or total thyroidectomy (TX). Continued long-term, low-dose MMI administration is a valuable and safe alternative. Patient choice, both at initial presentation of GD and at recurrence, should be emphasized. Propylthiouracil is preferred to MMI during the first trimester of pregnancy. TX is best performed by a high-volume thyroid surgeon. RAI should be avoided in GD patients with active GO, especially in smokers. Recently, a promising therapy with an anti-insulin-like growth factor-1 monoclonal antibody for patients with active/severe GO was approved by the Food and Drug Administration. COVID-19 infection is a risk factor for poorly controlled hyperthyroidism, which contributes to the infection-related mortality risk. If GO is not severe, systemic steroid treatment should be postponed during COVID-19 while local treatment and preventive measures are offered.. A clear trend towards serological diagnosis and medical treatment of GD has emerged.

Topics: Antithyroid Agents; Biomarkers; Diagnosis, Differential; Disease Management; Female; Graves Disease; Graves Ophthalmopathy; Humans; Hyperthyroidism; Immunoglobulins, Thyroid-Stimulating; Iodine Radioisotopes; Male; Methimazole; Pregnancy; Pregnancy Complications; Receptors, Thyrotropin; Thyroid Gland; Thyroidectomy; Ultrasonography

Topics: Acute Disease; Antithyroid Agents; Carbimazole; Drug Hypersensitivity; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Pancreatitis

Neonatal thyrotoxicosis (hyperthyroidism) is less prevalent than congenital hypothyroidism; however, it can lead to significant morbidity and mortality if not promptly recognized and adequately treated. Most cases are transient, secondary to maternal autoimmune hyperthyroidism (Graves disease [GD]). This article summarizes recommendations for screening and management of hyperthyroidism in both the fetal and neonatal periods, with a focus on neonatal thyrotoxicosis secondary to maternal GD. Early monitoring and treatment are crucial for optimizing short-term and long-term patient outcomes.

Topics: Adrenergic beta-Antagonists; Antithyroid Agents; Female; Fetal Diseases; Graves Disease; Humans; Hyperthyroidism; Immunoglobulins, Thyroid-Stimulating; Infant, Newborn; Infant, Newborn, Diseases; Maternal-Fetal Exchange; Methimazole; Pregnancy; Pregnancy Complications; Propranolol; Thyroiditis, Autoimmune; Thyrotoxicosis

Several studies have reported inconsistent findings on the advantages and disadvantages of long-term treatment with antithyroid drugs (ATD). A systematic review and meta-analysis was undertaken to clarify the numerous aspects of long-term treatment with ATD.. Medline and the Cochrane Library for trials published between 1950 and May 2016 were systematically searched. Studies containing data for long-term (>24 months) ATD treatment were included. Summary estimates of pooled prevalence, odds ratio, and weighted mean difference were calculated with a random effects model.. Of 587 related articles found, six fulfilled the inclusion criteria. Long-term ATD treatment induced a remission rate of 57% [confidence interval (CI) 45-68%], a rate that was higher in adults than in non-adults (61% vs. 53%). The rate of complications was 19.1% [CI 9.6-30.9%], of which only 1.5% were major complications. The annual remission rate for each year of treatment was 16% [CI 10-27%], which was higher in adults than non-adults (19% vs. 14%). However, it should be noted that this is not a true linear correlation, but a positive relationship can be suggested between time and remission rate. Meta-regression revealed that smoking had a significant lowering effect on remission rate.. Long-term ATD treatment is effective and safe, especially in adults, indicating that it should be considered as an alternative treatment for Graves' disease.

Topics: Antithyroid Agents; Drug Administration Schedule; Graves Disease; Humans; Methimazole; Propylthiouracil; Remission Induction; Time Factors; Treatment Outcome

Insulin autoimmune syndrome (IAS) is an uncommon disorder characterized by hyperinsulinemic hypoglycemia related to insulin-binding autoantibodies. To the best of our knowledge, we report the first case of a pregnant female with IAS.. The 26-year-old patient with Graves disease and 10 weeks pregnant developed IAS after approximately 6 months treatment with methimazole. The patient exhibited recurrent spontaneous hypoglycemia.. On evaluation, laboratory findings detected both high fasting insulin (>1000 mIU/L) and insulin autoantibodies. An oral glucose tolerance test showed elevated insulin concentrations with disproportionately elevated C-peptide levels. The imaging study showed nomasslesionsinthepancreas,and the patient was clinically diagnosed with IAS.. The patient had an abortion, discontinued methimazole and switched to oral prednisone (30 mg once daily) and propylth- iouracil (100 mg 3 times daily) for 3 months.. At the 3-month follow-up visit, hypoglycemic episodes had disappeared and insulin antibody levels were no longer detectable.. We have described this case and reviewed the relevant literature concerning diagnosis and treatment of IAS. Importantly, this case indicates that clinicians should view pregnancy as another factor of hypoglycemia in IAS.

Topics: Abortion, Spontaneous; Adult; Autoimmune Diseases; Female; Follow-Up Studies; Gestational Age; Graves Disease; Humans; Hypoglycemia; Insulin; Insulin Antibodies; Methimazole; Prednisone; Pregnancy; Pregnancy Complications; Rare Diseases; Risk Assessment; Syndrome

Graves' disease is the most common cause of hyperthyroidism. Both antithyroid medications and radioiodine are commonly used treatments but their frequency of use varies between regions and countries. Despite the commonness of the diagnosis, any possible differences between the two treatments with respect to long-term outcomes remain unknown.. To assess the effects of radioiodine therapy versus antithyroid medications for Graves' disease.. We performed a systematic literature search in the Cochrane Library, MEDLINE and EMBASE and the trials registers ICTRP Search Portal and ClinicalTrials.gov. The date of the last search was September 2015 for all databases.. Randomised controlled trials (RCTs) comparing the effects of radioiodine therapy versus antithyroid medications for Graves' disease with at least two years follow-up.. Two authors independently screened titles and abstracts for relevance. One author carried out screening for inclusion, data extraction and 'Risk of bias' assessment and a second author checked this. We presented data not suitable for meta-analysis as descriptive data. We analysed the overall quality of evidence utilising the GRADE instrument.. We included two RCTs involving 425 adult participants with Graves' disease in this review. Altogether 204 participants were randomised to radioiodine therapy and 221 to methimazole therapy. A single dose of radioiodine was administered. The duration of methimazole medication was 18 months. The period of follow-up was at least two years, depending on the outcome measured. For most outcome measures risk of bias was low; for the outcomes health-related quality of life as well as development and worsening of Graves' ophthalmopathy risks of performance bias and detection bias were high in at least one of the two RCTs.Health-related quality of life appeared to be similar in the radioiodine and methimazole treatment groups, however no quantitative data were reported (425 participants; 2 trials; low quality evidence). The development and worsening of Graves' ophthalmopathy was observed in 76 of 202 radioiodine-treated participants (38%) and in 40 of 215 methimazole-treated participants (19%): risk ratio (RR) 1.94 (95% confidence interval (CI) 1.40 to 2.70); 417 participants; 2 trials; low quality evidence. A total of 35% to 56% of radioiodine-treated participants and 42% of participants treated with methimazole were smokers, which is associated with the risk of worsening or development of Graves' ophthalmopathy. Euthyroidism was not achieved by any participant being treated with radioiodine compared with 64/68 (94%) of participants after methimazole treatment (112 participants; 1 trial). In this trial thyroxine therapy was not introduced early in both treatment arms to avoid hypothyroidism. Recurrence of hyperthyroidism (relapse) in favour of radioiodine treatment showed a RR of 0.20 (95% CI 0.01 to 2.66); P value = 0.22; 417 participants; 2 trials; very low quality evidence. Heterogeneity was high (I² = 91%) and the RRs were 0.61 or 0.06 with non-overlapping CIs. Adverse events other than development of worsening of Graves' ophthalmopathy for radioiodine therapy were hypothyroidism (39 of 41 participants (95%) compared with 0% of participants receiving methimazole, however thyroxine treatment to avoid hypothyroidism was not introduced early in the radioiodine group - 104 participants; 1 trial; very low quality evidence) and drug-related adverse events for methimazole treatment (23 of 215 participants (11%) reported adverse effects likely related to methimazole therapy - 215 participants; 2 trials; very low quality evidence). The outcome measures all-cause mortal. The only antithyroid drug investigated in the two included trials was methimazole, which might limit the applicability of our findings with regard to other compounds such as propylthiouracil. Results from two RCTs suggest that radioiodine treatment is associated with an increased risk of Graves' ophthalmopathy. Our findings suggest some benefit from radioiodine treatment for recurrence of hyperthyroidism (relapse) but there is uncertainty about the magnitude of the effect size.

Topics: Antithyroid Agents; Graves Disease; Graves Ophthalmopathy; Humans; Iodine Radioisotopes; Methimazole; Randomized Controlled Trials as Topic; Recurrence

Neonates born to mothers with Graves' disease are at risk for significant morbidity and mortality and need to be appropriately identified and managed. Because no consensus guidelines regarding the treatment of these newborns exist, we sought to generate a literature-based management algorithm. The suggestions include the following: (1) Base initial risk assessment on maternal thyroid stimulating hormone (TSH) receptor antibodies. If levels are negative, no specific neonatal follow-up is necessary; if unavailable or positive, regard the newborn as "at risk" for the development of hyperthyroidism. (2) Determine levels of TSH-receptor antibodies in cord blood, or as soon as possible thereafter, so that newborns with negative antibodies can be discharged from follow-up. (3) Measurement of cord TSH and fT4 levels is not indicated. (4) Perform fT4 and TSH levels at day 3 to 5 of life, repeat at day 10 to 14 of life and follow clinically until 2 to 3 months of life. (5) Use the same testing schedule in neonates born to mothers with treated or untreated Graves' disease. (6) When warranted, use methimazole (MMI) as the treatment of choice; β-blockers can be added for sympathetic hyperactivity. In refractory cases, potassium iodide may be used in conjunction with MMI. The need for treatment of asymptomatic infants with biochemical hyperthyroidism is uncertain. (7) Assess the MMI-treated newborn on a weekly basis until stable, then every 1 to 2 weeks, with a decrease of MMI (and other medications) as tolerated. MMI treatment duration is most commonly 1 to 2 months. (8) Be cognizant that central or primary hypothyroidism can occur in these newborns.

Topics: Antithyroid Agents; Disease Management; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Infant, Newborn; Methimazole; Mothers; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Thyroid Function Tests

Pediatric hyperthyroidism can be multifactorial, with Graves' disease (GD) being the most common etiology. Treatment focuses on identification of the cause of the hyperthyroidism and achieving a biochemical cure with symptom resolution. This article highlights the clinical presentation, diagnosis, and treatment of a pediatric patient with GD. [Pediatr Ann. 2016;45(5):e171-e175.].

Topics: Adrenergic beta-1 Receptor Antagonists; Antithyroid Agents; Atenolol; Child; Female; Graves Disease; Humans; Methimazole; Thyroidectomy; Thyroxine

Graves' hyperthyroidism is associated with significant morbidity and mortality risk. The thionamides, methimazole, its pro-drug derivative carbimazole, and propylthiouracil, remain a cornerstone of management. Yet despite decades of use, optimal strategies for maximising treatment response and curtailing adverse effect risk remains uncertain.. We reviewed the current literature on the evidence based medical management of Graves' disease. Specifically, we evaluated current approaches to the use of thionamides, adjunctive therapies, and potential novel agents for controlling Graves' hyperthyroidism.. Primary medical therapy is successful in less than 50% of cases and so careful selection of patients for medical treatment based on a combination of pathological and pragmatic considerations is essential. Carbimazole or methimazole is the treatment of choice in the non-pregnant population driven by its more favourable pharmacokinetic and adverse effect profile over propylthiouracil. In pregnancy the choice of treatment is less straightforward and an approach that minimises undue fetal exposure to all thionamides should be adopted. Additional data is needed on the value of adjunctive therapies including potassium perchlorate, iodides, glucocorticoids, lithium, and cholestyramine. Novel agents directed against pathogenetic targets including TSH receptor blocking monoclonal antibodies and small molecule antagonists may hold promise for the future.

Topics: Antibodies, Monoclonal; Antithyroid Agents; Combined Modality Therapy; Graves Disease; Humans; Methimazole; Prodrugs; Propylthiouracil

A 29-year-old pregnant woman with Graves' disease presented with severe persistent hypocalcaemia after thyroidectomy. Six months prior to presentation she was diagnosed with Graves' disease and remained uncontrolled with methimazole. She was confirmed pregnant prior to radioactive iodine ablation (RAI), and underwent total thyroidectomy during her second trimester. After surgery, continuous intravenous calcium infusion was required until delivery of the fetus allowed discontinuation at postoperative day 18, despite oral calcium and calcitriol administration. A total of 38 g of oral and 7.5 g of intravenous elemental calcium was administered. We report an unusual case of recalcitrant hypocalcaemia thought to be due to a combination of postoperative hypoparathyroidism, combined with thyrotoxic osteodystrophy and pregnancy, after surgical correction of Graves' disease. Increased vigilance and early calcium supplementation should be a priority in the management of these patients.

Topics: Administration, Oral; Adult; Antithyroid Agents; Calcium; Drug Administration Schedule; Female; Graves Disease; Humans; Hypocalcemia; Hypoparathyroidism; Infusions, Intravenous; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Second; Thyroidectomy; Thyrotoxicosis; Time Factors; Treatment Outcome

Interferon(IFN)γ-induced protein 10 (IP-10) and its receptor, CXC receptor 3, appear to contribute to the pathogenesis of Graves' disease (GD) and Graves' ophthalmopathy (GO). Under the influence of IFN-γ, IP-10 is secreted by thyrocytes (in GD), fibroblasts and preadipocytes (in GO). Determination of high level of IP-10 in peripheral liquids is therefore a marker of a Th1 orientated immune response. Circulating IP-10 is associated with the active phase of GD in both newly diagnosed and relapsing hyperthyroid patients. Methimazole reduces IP-10 secretion by isolated thyrocytes, decreases serum IP-10 levels, and promotes a transition from Th1 to Th2 dominance in patients with GD active phase. In GD patients the decrease of IP-10 after thyroidectomy and radioiodine strongly suggests that this chemokine is mainly produced by the thyroid itself. In GO patients the increased concentrations of IP-10, at least in part, reflect the activity of orbital inflammation. A significant reductions in IP-10 serum concentrations during corticosteroids and or radiotherapy treatments, as compared both to control group and to basal values in GO patients, suggest that this chemokine could serve as a guideline in therapeutic decision-making in patients with GO. Further studies are needed to evaluate whether IP-10 is a novel therapeutic target in GD and GO.

Topics: Adrenal Cortex Hormones; Chemokine CXCL10; Graves Disease; Graves Ophthalmopathy; Humans; Iodine Radioisotopes; Methimazole; Thyroidectomy

In most patients with hyperthyroidism caused by Graves' disease, antithyroid drug (ATD) therapy is followed by a gradual amelioration of the autoimmune abnormality, but about half of the patients will experience relapse of hyperthyroidism when the ATDs are withdrawn after a standard 1 to 2 years of therapy. This is a major drawback of ATD therapy, and a major concern to patients. We review current knowledge on how to predict and possibly reduce the risk of such relapse.. Several patient and disease characteristics, as well as environmental factors and duration of ATD therapy, may influence the risk of relapse after ATD withdrawal. Depending on the presence of such factors, the risk of relapse after ATD withdrawal may vary from around 10 to 90%. Risk factors for relapse should be taken into account when choosing between therapeutic modalities in a patient with newly diagnosed disease, and also when discussing duration of ATD therapy.. Prolonged low-dose ATD therapy may be feasible in patients with high risk of relapse, such as children and patients with active Graves' orbitopathy, and in patients with previous relapse who prefer such therapy rather than surgery or radioiodine.

Topics: Antithyroid Agents; Drug Administration Schedule; Graves Disease; Humans; Methimazole; Receptors, Thyrotropin; Recurrence; Risk Factors; Smoking; Time Factors; Treatment Outcome

Medical treatment of Graves' hyperthyroidism is based on the use of thionamides; namely, methimazole and propylthiouracil. In the past, methimazole was preferred by European endocrinologists, whereas propylthiouracil was the first choice for the majority of their North American colleagues. However, because of the recent definition of a better side-effect profile, methimazole is nowadays the first choice world while. Although thionamides are quite effective for the short-term control of Graves' hyperthyroidism, a relatively high proportion of patients relapses after thionamide withdrawal. Other possible medical treatments, include iodine and compounds containing iodine, perchlorate, lithium (as an adjuvant in patients undergoing radioiodine therapy), β-adrenergic antagonists, glucocorticoids, and some new molecules still under investigation. Management of Graves' hyperthyroidism using thionamides as well as the other available medical treatments is here reviewed in detail, with a special mention of situations such as pregnancy and lactation, as well as neonatal and fetal thyrotoxicosis.

Topics: Animals; Antithyroid Agents; Graves Disease; Humans; Hyperthyroidism; Methimazole; Propylthiouracil; Treatment Outcome

To bring to the attention of healthcare professionals the additional information on propylthiouracil (PTU)-related hepatotoxicity, based on a reanalysis of medical files reported to the Food and Drug Administration (1982-2008) for acute liver failure in PTU-treated hyperthyroid patients, and propose recommendations for the clinical use of PTU. Thirteen files of PTU-related severe liver adverse effects were analyzed for the pediatric population, seventeen for nonpregnant adults and two for pregnant women.. The recent findings showed that the daily PTU dose administered was high in the children, with a mean of 300 mg/day for an average 10-year-old individual. With regard to treatment duration, PTU administration lasted for at least 4 months in 75% of pediatric cases. Similarly, in a majority of adult cases (64%), PTU-induced liver injury occurred after a relatively long treatment period (4 months to >1 year).. PTU should not be used in children, in whom methimazole (MMI) represents the logical alternative. In adults, PTU should be restricted to those rare patients with Graves' disease for whom no better alternative can be offered and in patients with thyroid storm. For the special circumstance of pregnancy, PTU is the preferred choice during early gestation; switching back to MMI during later gestational stages remains a matter of clinical judgment. It is unknown whether liver function tests monitoring is worthwhile to prevent life-threatening, PTU-related hepatotoxicity.

Topics: Adult; Age Factors; Antithyroid Agents; Child; Drug Administration Schedule; Female; Graves Disease; Humans; Hyperthyroidism; Liver Failure; Male; Methimazole; Patient Selection; Pregnancy; Pregnancy Complications; Propylthiouracil; United States; United States Food and Drug Administration

In the treatment of pregnant patients with Graves' disease, propylthiouracil is preferred over methimazole in early pregnancy because of a possible teratogenicity of methimazole. Methimazole is preferable to propylthiouracil in other time of pregnancy on the basis of severe liver dysfunction occasionally caused by propylthiouracil. Fetal hypothyroidism can be avoided when maternal free T4 levels are maintained at or above the upper normal limit for non-pregnant subjects. However, maternal free T4 should be kept normal for pregnant reference range when pregnancy complications develop. Fetal hypothyroidism in this setting will not affect the infant's development as long as mothers are euthyroid and the infants recover from hypothyroid state within a short time after birth. In hypothyroid women, 1-T4 dose often needs to be increased in pregnancy. Maternal T4 deficiency in early pregnancy has been suggested to affect normal brain development in the offspring. However, it has recently been shown in iodine rich area that no adverse effect on neuropsychological development was seen irrespective of the severity of maternal T4 deficiency. Insufficient iodine intake in the mother can cause low T4 in pregnancy and also inadequate production of T4 in breast-fed infants when sufficient T4 is essential for normal brain development.

Topics: Female; Graves Disease; Humans; Hypothyroidism; Methimazole; Pregnancy; Pregnancy Complications; Time Factors

To elucidate whether incidence of malformation related to 'methimazole (MMI) embryopathy' is increasing associated with exposure to MMI in the first 12 gestational weeks, Graves' women(MMI group/propylthiouracil (PTU) group/non-antithyroidal drug (ATD) group) who noticed pregnancy were registered from several thyroid clinics to Japan Drug Information Institute in Pregnancy since 2008, we were now prospectively collecting outcomes of pregnancy. In June 2011, we announced the interim report which showed extremely higher incidence of MMI-related malformation than expected. Five cases of MMI-related embryopathy in 85 live births of MMI group (95% confidence interval: 1.9-13.2%), while none of this embryopathy was found in neither 121 live births of PTU group nor 83 of non-ATD group. We issued a joint statement with the Japan Thyroid Association about the recommendation to avoid the continuation of MMI during organogenesis period in Graves' women. The final report will be made by 2014.

Topics: Female; Fetal Diseases; Graves Disease; Humans; Japan; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Outcome

Propylthiouracil (PTU), methimazole (MMI) and carbimazole are indicated for the treatment of hyperthyroidism in adult and pediatric patients. The aim of this review is to present all the relevant information regarding the use of antithyroid drugs (ATD) in pediatric thyrotoxic cases, the pediatric toxicology of ATD and the warning which has recently been issued for PTU by the FDA.. Epidemiology, diagnosis and treatment of pediatric thyrotoxicosis are all presented in this article. The authors also extensively discuss the details regarding the pharmacology, bioactivation, biodisposition, bioavailability and pharmacokinetic properties of the two main ATD (MMI and PTU).. The FDA recently reported that use of PTU is associated with a higher risk for clinically serious or fatal liver injury compared to MMI in both adult and pediatric patients. They also found that congenital malformations were reported approximately three times more often with prenatal exposure to MMI compared with PTU and especially with the use of MMI during the first trimester of pregnancy. The authors believe that PTU should not be used in pediatric patients unless the patient is allergic to or intolerant of MMI, and there are no other treatment options available. That being said, PTU may be the treatment of choice during, and just before, the first trimester of pregnancy.

Topics: Agranulocytosis; Animals; Antithyroid Agents; Carbimazole; Child; Child, Preschool; Evidence-Based Medicine; Female; Graves Disease; Humans; Hyperthyroidism; Liver Failure; Methimazole; Pregnancy; Propylthiouracil; Randomized Controlled Trials as Topic; Thyrotoxicosis; Vasculitis

Pediatric Graves' disease accounts for 10-15% of thyroid disorders in patients less than 18 yr of age. The onset of symptoms may be insidious and subsequently associated with a delay in diagnosis. Decreased concentration and poor school performance are frequent complaints and can be quite frustrating for the patient and family. Severe ophthalmopathy is uncommon. The diagnosis is established by the findings of an increased heart rate and goiter in the setting of a suppressed TSH and elevated T(3) and/or T(4). The majority of pediatric patients are initially placed on antithyroid medications and maintained on these medications for prolonged periods of time in hopes of achieving remission. Unfortunately, for many children and adolescents remission is unattainable, ultimately occurring in only 15-30% of patients. Several recent studies have suggested that the age of the patient, the degree of thyrotoxicosis at diagnosis, the initial response to therapy, and the level of TSH receptor antibodies serve as reasonable predictors of remission and relapse. However, a consensus on the utility of these markers has not been reached. The present clinical case describes an adolescent with Graves' disease and highlights the negative impact that prolonged medical therapy can have on quality of life and school performance; it reviews pertinent data on the diagnosis, comorbidities, and treatment options; and it identifies gaps in knowledge for when definitive therapy should be pursued. The case serves as a reminder that earlier discussion and decision for definitive therapy should be more commonplace in caring for our pediatric patients with Graves' disease.

Topics: Adolescent; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Child; Female; Goiter; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Iodine Radioisotopes; Methimazole; Schools

Graves' disease (GD) is the most common cause of thyrotoxicosis in children and adolescents. Caused by immunologic stimulation of the thyroid-stimulating hormone receptor, lasting remission occurs in only a minority of pediatric patients with GD, including children treated with antithyroid drugs (ATDs) for many years. Thus the majority of pediatric patients with GD will need thyroidectomy or treatment with radioactive iodine (RAI; (131)I).. When ATDs are used in children, only methimazole should be used. Propylthiouracil is associated with an unacceptable risk of severe liver injury in children and should never be used as first-line therapy. If remission (defined as normal thyroid function off ATDs) is not achieved after 1 or 2 years of ATD therapy, (131)I or surgery may be considered, with the choice influenced by the age of the individual. When (131)I is used, administered doses should be >150 μCi/g of thyroid tissue. When surgery is performed, near total or total thyroidectomy is recommended.. Choosing a treatment approach for childhood GD is often a difficult and highly personal decision. Discussion of the advantages and risks of each therapeutic option is essential to help the patient and family select a treatment option.

Topics: Antithyroid Agents; Child; Graves Disease; Humans; Iodine Radioisotopes; Methimazole; Propylthiouracil

Hyperthyroidism is characterised by high levels of serum thyroxine and triiodothyronine, and low levels of thyroid-stimulating hormone. The main causes of hyperthyroidism are Graves' disease, toxic multinodular goitre, and toxic adenoma. About 20 times more women than men have hyperthyroidism.. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for primary hyperthyroidism? What are the effects of surgical treatments for primary hyperthyroidism? What are the effects of treatments for subclinical hyperthyroidism? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).. We found 15 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.. In this systematic review we present information relating to the effectiveness and safety of the following interventions: adding thyroxine to antithyroid drugs (carbimazole, propylthiouracil, and thiamazole), antithyroid drugs (carbimazole, propylthiouracil, and thiamazole), radioactive iodine, and thyroidectomy.

Topics: Antithyroid Agents; Graves Disease; Humans; Hyperthyroidism; Incidence; Methimazole; Thyrotropin

We describe a 37-year-old man with a 4-month history of episodic muscular weakness, involving mainly lower-limbs. Hypokalemia was documented in one episode and managed with intravenous potassium chloride. Hyperthyroidism was diagnosed 4 months after onset of attacks because of mild symptoms. The patient was subsequently diagnosed as having thyrotoxic periodic paralysis associated with Graves' disease. Treatment with propranolol and methimazol was initiated and one year later he remains euthyroid and symptom free. Thyrotoxic periodic paralysis is a rare disorder, especially among Caucasians, but it should always be considered in patients with acute paralysis and hypokalemia, and thyroid function should be evaluated.

Topics: Adult; Graves Disease; Humans; Hyperthyroidism; Hypokalemia; Male; Methimazole; Paralyses, Familial Periodic; Potassium Chloride; Propranolol; Treatment Outcome

Hyperthyroidism is characterised by high levels of serum thyroxine and triiodothyronine, and low levels of thyroid-stimulating hormone. The main causes of hyperthyroidism are Graves' disease, toxic multinodular goitre, and toxic adenoma. About 20 times more women than men have hyperthyroidism.. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for primary hyperthyroidism? What are the effects of surgical treatments for primary hyperthyroidism? What are the effects of treatments for subclinical hyperthyroidism? We searched: Medline, Embase, The Cochrane Library and other important databases up to June 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).. We found 14 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.. In this systematic review we present information relating to the effectiveness and safety of the following interventions: adding thyroxine to antithyroid drugs (carbimazole, propylthiouracil, and thiamazole), antithyroid drugs (carbimazole, propylthiouracil, and thiamazole), radioactive iodine, and thyroidectomy.

Topics: Antithyroid Agents; Graves Disease; Humans; Hyperthyroidism; Incidence; Methimazole; Thyrotropin

A 20-year-old woman given a diagnosis of hyperthyroidism (Basedow's disease) had been subsequently treated with methimazole since 1999. As she could not be made euthyroid, surgery was planned to relieve the symptoms. Because of liver dysfunction after discontinuation of methimazole and administration of iodine, she was admitted to the hospital. She was negative for hepatitis A, B and C virus serologies, but positive for anti-nuclear antibodies. A liver biopsy, which showed features of chronic active hepatitis, led to the diagnosis of autoimmune hepatitis (AIH). Interestingly, normalization of serum T4 correlated with improvement of serum aminotransferases. This leads us to speculate that this patient's liver dysfunction may have been AIH exacerbated by the liver dysfunction of hyperthyroidism rather than acute deterioration of AIH itself.

Topics: Adult; Antibodies, Antinuclear; Biomarkers; Female; Graves Disease; Hepatitis, Autoimmune; Humans; Iodine; Liver; Methimazole

To evaluate the evidence supporting the use of propylthiouracil (PTU) versus methimazole for the treatment of Graves' disease during pregnancy.. An English-language literature search was conducted using MEDLINE (1966-March 2007). Identified articles were then reviewed for additional sources. Search terms included hyperthyroidism, Graves' disease, pregnancy, propylthiouracil, and methimazole.. All clinical trials and case reports that were published in English and reported either subjective or objective outcomes were reviewed.. Rationale supporting the use of PTU over methimazole in treatment of Graves' disease during pregnancy is limited. Theories suggesting that PTU has less placental transfer to the fetus than methimazole are not supported by current literature. Studies demonstrating a causal relationship between methimazole use during pregnancy and congenital anomalies and/or fetal hypothyroidism do not exist.. The selection of PTU versus methimazole for the treatment of Graves' disease during pregnancy should not be based solely on the following assumptions: that PTU crosses the placenta less than methimazole, that PTU leads to less fetal hypothyroidism, or that exposure to methimazole during pregnancy leads to decreased intellectual function in children. However, due to a possible association between the use of methimazole during pregnancy and fetal anomalies such as aplasia cutis, esophageal atresia, and choanal atresia, methimazole may be a less desirable first-line treatment for Graves' disease in pregnancy than PTU. Therefore, in the absence of a compelling indication for the use of methimazole, PTU should still be considered as the first-line agent in the treatment of Graves' disease during pregnancy. Methimazole should be considered a viable second choice if the patient is intolerant to PTU, has an allergic reaction to PTU, or fails to become euthyroid while receiving PTU.

Topics: Female; Graves Disease; Humans; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil

Thionamides, selective inhibitors of thyroid peroxidase-mediated iodination by tyrosine residues in thyroglobulin, have been effectively used in the treatment of hyperthyroidism. The choices for initial treatment of patients with Graves' disease differ in various countries, and many physicians around the world prefer to administer thionamide drugs as the first choice of treatment for patients with hyperthyroidism. Although some thyroidologists more often consider radioiodine to be the treatment of choice because of its safety and ease of administration, thionamides remain the mainstay of treatment in thyrotoxic children and adolescents and in hyperthyroid women during pregnancy, postpartum period and lactation. A recent study with continuous thionamide treatment for patients with Graves' disease shows its efficacy, safety and cost-benefit properties. Further studies of the effectiveness of continuous thionamide therapy in patients with thyrotoxicosis need to be designed and implemented to determine indications for such therapy in children, adolescents and adults with diffuse toxic goiter, in particular, in those who have had recurrence of hyperthyroidism after discontinuation of one complete course of treatment.

Topics: Adolescent; Adult; Age Factors; Antithyroid Agents; Child; Drug Administration Schedule; Female; Graves Disease; Humans; Male; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil

Topics: Antithyroid Agents; Autoantibodies; Diagnosis, Differential; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Methimazole; Receptors, Thyrotropin; Thyroid Function Tests; Thyroiditis, Subacute; Thyrotoxicosis

In Graves' patients complicated by pregnancy, both maternal and fetal problems related to the disease can be reduced or avoided by controlling hyperthyroidism. However, optimal treatment for mothers may exert detrimental effects on fetuses. Methimazole may cause "methimazole embryopathy". Antithyroid drug doses that maintain mothers in euthyroid status are sometimes excessive fetuses. Furthermore, successful treatment with surgery or radioiodine occasionally may result in fetal hyperthyroidism due to TSH receptor antibody(TRAb). There are approaches to manage these problems. Propylthiouracil is chosen in treating Graves' disease in early pregnancy. In later pregnancy, maternal free thyroxine is maintained near or somewhat above normal. Ablative therapy is not recommended in women whose TRAb levels are extremely high from the standpoint of fetal thyroid state.

Topics: Antithyroid Agents; Autoantibodies; Congenital Abnormalities; Female; Fetal Diseases; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Immunoglobulins, Thyroid-Stimulating; Infant; Infant, Newborn; Lactation; Maternal-Fetal Exchange; Methimazole; Milk, Human; Pregnancy; Pregnancy Complications; Pregnancy Trimesters; Propylthiouracil

Because of the low frequency of childhood Graves' disease, detailed evidence-based clinical studies have not been reported. Practical clinical work has been performed on the basis of adult clinical references. Therapeutic management includes antithyroid drugs, surgical thyroidectomy and radiologic therapy. Recently in the U.S.A. radiotherapy has become the recommended course of action, even for childhood Graves' disease, whereas in Japan, antithyroid drug therapy is the primary course of action for childhood Graves' disease. In some cases, thyroidectomy is performed following drug therapy. Methimazole (MMI) and propylthiouracil (PTU) have been used, however, MMI is the preferred drug treatment. Compared to PTU, MMI is administered once a day and the frequency of side effects is lower than that of PTU. Evaluation of the TSH receptor antibody value before administration of antithyroid drugs is very useful in estimating the duration of the treatment. No appropriate index has been established guiding when to quit antithyroid drug therapy.

Topics: Antithyroid Agents; Autoantibodies; Biomarkers; Child; Combined Modality Therapy; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Methimazole; Propylthiouracil; Radiotherapy; Thyroidectomy

Topics: Agranulocytosis; Algorithms; Antithyroid Agents; Female; Graves Disease; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Gland; Thyrotoxicosis; Thyroxine; Triiodothyronine

Topics: Animals; Antithyroid Agents; Apoptosis; Fas Ligand Protein; Graves Disease; Humans; Immunoglobulin G; Interleukin-1; Iodide Peroxidase; Iodine Radioisotopes; Membrane Glycoproteins; Methimazole; Prognosis; Receptors, Thyrotropin; Th2 Cells; Thyroglobulin; Thyroiditis, Autoimmune; Thyroxine

We report herein a case of thyroid mucosa-associated lymphoid tissue (MALT) lymphoma in a patient receiving antithyroid drug therapy for Graves' disease. A 75-year-old woman first presented with finger tremor and was diagnosed with Graves' disease on the basis of clinical and laboratory findings. Three years later, she presented with rapid and painless enlargement of the thyroid. Ultrasonography revealed a circumscribed hypoechoic area bilaterally in each lobe of the thyroid, and fine-needle aspiration biopsy showed diffuse monotonous infiltration of small- to medium-sized atypical lymphoid cells. (67)Ga scintigraphy was positive exclusively in the thyroid. After total thyroidectomy, the patient received radiation therapy for treatment of stage IE primary thyroid lymphoma. Results of histological examination, immunohistochemical analysis, and flow cytometric analysis confirmed MALT lymphoma. To our knowledge, there have been few published reports of primary thyroid lymphoma associated with Graves' disease. Our experience with this case, though rare, indicates that an enlarged thyroid in cases of Graves' disease should be examined carefully for primary thyroid lymphoma.

Topics: Aged; Antithyroid Agents; Diagnostic Imaging; Female; Graves Disease; Humans; Lymphoma, B-Cell, Marginal Zone; Methimazole; Radiotherapy; Thyroid Gland; Thyroid Neoplasms; Thyroidectomy

Graves' disease is characterized by hyperthyroidism, diffuse goitre, ophthalmopathy and, rarely, dermopathy. Although diagnostic testing is straightforward once Graves' disease is suspected, physicians need to be aware of heterogeneous and even atypical presentations of the disease, particularly in elderly patients. Because morbidity may be associated with even subtle forms of hyperthyroidism, treatment promoting long-term euthyroidism is necessary. Although all of the available treatments are effective, compliance is best assured by a full discussion of the risks and benefits of each approach. This review focuses on issues of diagnosis and management that will allow the primary care physician to identify patients with Graves' disease and guide them to recovery.

Topics: Adult; Aged; Antithyroid Agents; Female; Graves Disease; Half-Life; Humans; Iodine Radioisotopes; Male; Methimazole; Thyroid Function Tests

Topics: Adult; Antithyroid Agents; Arthritis; Female; Graves Disease; Humans; Methimazole; Propylthiouracil; Syndrome

Topics: Antithyroid Agents; Combined Modality Therapy; Graves Disease; Humans; Iodine Radioisotopes; Lithium Carbonate; Methimazole; Thyroxine; Triiodothyronine

First cause of hyperthyroidism among women of childbearing age, Graves' disease raises the risk of maternal and fetal complications, including eclampsia, cardiac failure, abortion, prematurity, fetal death, all of which can be avoided if maternal hyperthyroidism is closely controlled. The risk of transplacental hyperthyroidism has been shown to correlate to the titre of anti-TSH receptor antibodies and has to be evaluated not only in women treated for Graves' disease during pregnancy, but also in women who have previously received radio iodine treatment or undergone surgery for Graves' disease: TSH-receptor antibodies may indeed remain at a high level several years after initial treatment. Both methimazole and propylthiouracil are equally effective to restore maternal euthyroidism. Accumulation of case-reports relating congenital malformations (mostly aplasia cutis, but in some cases, severe malformations) among the offspring of methimazole-treated women suggests the possibility of a teratogenic effect of methimazole. Despite the fact that the link between severe congenital defects and methimazole exposure during pregnancy is not formally established, propylthiouracil should be preferred to methimazole for the treatment of young hyperthyroid women.

Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Female; Graves Disease; Humans; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil

A 50-year-old woman was admitted because of severe exophthalmos associated with Graves disease. She underwent methimazole (MMI) and methylprednisolone pulse therapy against exophthalmos. She noticed photophobia and blurred vision 3 weeks after the start of pulse therapy and she was diagnosed as having uveitis. Methylprednisolone pulse therapy was performed again for both exophthalmos and uveitis, followed by daily administration of 20 mg of prednisolone and instillation of betamethasone for 2 weeks and the uveitis was improved. Western blot analysis confirmed that human T lymphotropic virus type 1 (HTLV-1) antibody was present in her serum. Propylthiouracil was substituted for MMI and HTLV-1-associated uveitis (HAU) has not recurred. Six months after the beginning of administration of PTU, anti-neutrophil cytoplasmic antibody-related vasculitis developed in the patient. We review 43 cases of HAU with Graves disease, including the present case, in the literature. Only 2 of 27 cases (except unknown cases) (7.4%) had Graves ophthalmopathy. To the best of our knowledge, there has been no investigation of HAU and Graves ophthalmopathy.

Topics: Anti-Inflammatory Agents; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Graves Disease; HTLV-I Infections; Humans; Magnetic Resonance Imaging; Methimazole; Methylprednisolone; Middle Aged; Prednisolone; Propylthiouracil; Severity of Illness Index; Thyroid Hormones; Time Factors; Treatment Outcome; Uveitis; Vasculitis

Radioiodine therapy is now the most common definite treatment for persistent hyperthyroidism. The outcome of radioiodine therapy depends mainly on the absorbed energy dose in the diseased thyroid tissue. The administered activity and the resulting target dose in the thyroid depend on both the biokinetics of radioiodine and the actual therapeutic effect of radioiodine in the thyroid. Thyrostatic drugs have a major influence on the kinetics of radioiodine in the thyroid and may additionally have a radioprotective effect. Pre-treatment with thyrostatic medication lowers the effective half-life and uptake of radioiodine. This can reduce the target dose in the thyroid and have a negative influence on the outcome of the therapy. Discontinuation of medication shortly before radioiodine administration can increase the absorbed energy dose in the thyroid without increasing the whole-body exposure to radiation as much as would a higher or second radioiodine administration. Furthermore, administration of non-radioactive iodine-127 2-3 days after radioiodine administration can also increase the effective half-life of radioiodine in the thyroid. Thus, improving the biokinetics of radioiodine will allow lower activities to be administered with lower effective doses to the rest of the body, while achieving an equally effective target dose in the thyroid.

Topics: Antithyroid Agents; Carbimazole; Combined Modality Therapy; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Drug Interactions; Graves Disease; Half-Life; Humans; Hyperthyroidism; Iodine; Iodine Radioisotopes; Methimazole; Propylthiouracil; Radiation-Protective Agents; Radiopharmaceuticals; Radiotherapy Dosage

A case of Basedow's disease, that developed after successful treatment of ulcerative colitis with a total colectomy, is presented, along with a review of the Japanese literature on the coexistence of hyperthyroidism and ulcerative colitis. A 26-year-old man was referred to our department, complaining of general fatigue, appetite loss, and palpitation. At age 14, blood was discovered in his stool and a diagnosis of ulcerative colitis was made. Since then, he has been treated with salazosulfapyridine and prednisolone. On examination, mild exophthalmos and thyroid swelling were observed. Both serum free T3 and T4 levels were increased along with a positive TSH receptor antibody, while TSH was decreased. Scintigraphic and ultrasonographic examinations of the thyroid gland showed diffuse enlargement. Treatment with thiamazole relieved the symptoms and normalized the thyroid function. Although a high incidence of autoimmune thyroid diseases in association with ulcerative colitis has been suggested, only 6 cases of hyperthyroidism coexisting with ulcerative colitis have been reported in Japan. A common immunological process has been suggested to be implicated in the pathogenesis of this association, however, the exact mechanism remains unclear.

Topics: Adult; Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antithyroid Agents; Autoimmune Diseases; Chronic Disease; Colectomy; Colitis, Ulcerative; Combined Modality Therapy; Comorbidity; Diarrhea; Female; Graves Disease; Humans; Hyperthyroidism; Japan; Male; Methimazole; Middle Aged; Postoperative Complications; Prednisolone; Sulfasalazine; Thyroid Function Tests

We report a rare case of Graves' disease associated with struma ovarii. A 26-year-old Japanese woman had preexisting Graves' disease and was positive for TSH receptor antibody. She had been on antithyroid medication at presentation. She noted a mass in the lower left abdomen, which was diagnosed as a left struma ovarii by radiological work-up including computed tomography, magnetic resonance imaging and scintigraphy. The surgically excised teratomatous tumor, containing cystic spaces with thyroid tissue, was histologically proved to be struma ovarii. Since thyroid function tests and TSH receptor antibody did not change after surgery, her hyperthyroidism was considered to be due to Graves' disease. Our case was diagnosed as struma ovarii before surgery using various imaging studies.

Topics: Adult; Antithyroid Agents; Autoantibodies; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Magnetic Resonance Imaging; Methimazole; Ovarian Neoplasms; Ovariectomy; Radionuclide Imaging; Receptors, Thyrotropin; Struma Ovarii; Thyroid Hormones; Tomography, X-Ray Computed; Ultrasonography

Topics: Aged; Agranulocytosis; Antithyroid Agents; Female; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Methimazole; Neutrophils

We report on a further case of congenital anomalies in a child exposed to methimazole during the first trimester of pregnancy (from first to seventh gestational week), and define a specific malformation pattern related to prenatal methimazole exposure and consisting of choanal and esophageal atresia, scalp defects, minor facial anomalies and psychomotor delay.

Topics: Abnormalities, Drug-Induced; Adult; Antithyroid Agents; Child, Preschool; Choanal Atresia; Esophageal Atresia; Female; Graves Disease; Humans; Male; Maternal-Fetal Exchange; Methimazole; Phenotype; Pregnancy; Pregnancy Trimester, First; Teratogens

Topics: Female; Graves Disease; Humans; Hypothyroidism; Immunosuppressive Agents; Male; Methimazole; Mutation; Propylthiouracil; Receptors, Thyrotropin; Syndrome; Thyroid Gland; Thyroid Hormones

Graves' disease (GD) is extremely rare in children younger than 4 years of age, but if not recognized and treated it can seriously interfere with growth and development. We report three unrelated children, all females, in whom GD occurred before the age of 3. These children presented with goiter, exophthalmos, tachycardia, and hyperactivity. Moreover, one showed a severe psychomotor delay, and had previously undergone surgery due to craniosynostosis; the other two manifested a language delay. All had high thyroid hormones and thyrotropin receptor antibody (TRAb) serum levels that clearly indicated autoimmune hyperthyroidism. In all of them, the disease presumably had developed during the first or second year of life. No maternal history of GD was present in two. The third child was born to a mother affected with GD during pregnancy, but it is likely that her GD began to develop after 6 months of life. These children are being treated with methimazole, and treatment is still necessary after 32 months. TRAb levels were persistently high at follow-up. Psychological evaluation including language development at follow-up was appropriate for age in two children; the third child improved, but severe mental retardation is still evident. GD assessment in early childhood also needs to focus on psychological evaluation. Pediatricians should be aware of the possibility of permanent brain damage and craniosynostosis due to hyperthyroidism in infancy.

Topics: Age of Onset; Antithyroid Agents; Autoantibodies; Child, Preschool; Craniosynostoses; Female; Graves Disease; Humans; Methimazole; Pregnancy; Psychomotor Disorders; Receptors, Thyrotropin; Thyroid Hormones

A 39-year-old female suffered from diffuse goiter, palpitation, finger tremor and body weight loss for about one year. Then she developed acute onset of myalgia and swelling of calves, and muscle weakness of proximal limbs. She could not walk because of myalgia and muscle weakness, and was admitted to our hospital 4 days after the onset of muscle symptoms. On admission, her pulse was 110 per minute and she had finger tremor of 11-12 Hz. The thyroid gland was markedly and diffusely enlarged with an elastic soft surface. She presented muscle weakness of proximal limbs and neck, and had intermittent swelling and myalgia on calves. Deep tendon reflexes were increased in all extremities. The erythrocyte sedimentation rate was 22 mm per hour. Eosinophilia was not recognized. Serum CK level was elevated to 671 IU/l. Serum free T3 was higher than 21.7 pg/ml and free T4 was also elevated to 10.19 ng /dl. Serum TSH was lower than 0.05 microU/ml and thyroid stimulating antibody was 1,302.0%. Muscle biopsy of her left gastrocnemius muscle revealed markedly hypertrophic fascia with inflammatory cellular infiltration on HE staining. Inflammatory change was also recognized in muscle tissue and in perivascular region of perimysium. Variation of fiber size, necrotic fibers, and central nuclei were also seen. From these clinical and laboratory findings she was diagnosed as having Basedow's disease associated with fasciitis and polymyositis. Her thyroid function was improved by anti-thyroid drug, and swelling and myalgia of sural regions and weakness of proximal limbs were also improved by steroid therapy. Only one case of Basedow's disease associated with fasciitis and seven cases of that associated polymyositis have so far been reported. This is the first case report of fasciitis associated with Basedow's disease and polymyositis.

Topics: Adult; Anti-Inflammatory Agents; Antithyroid Agents; Fasciitis; Female; Graves Disease; Humans; Methimazole; Polymyositis; Prednisolone

We report a case of pretibial myxedema with Graves' disease in an 18-year-old Japanese woman. The physical examination revealed waxy indurated plaques with prominent hair follicle openings and nonpitting edema disseminated on her lower legs. Histology from an edematous lesion revealed that the dermis was markedly thickened with abundant mucin, especially hyaluronic acid, and the collagen fibers in this portion were splitting up into fibrils. We also reviewed 112 cases of pretibial myxedema reported in the Japanese literature.

Topics: Adolescent; Antithyroid Agents; Biopsy, Needle; Female; Graves Disease; Humans; Japan; Leg Dermatoses; Methimazole; Myxedema

We describe a recent clinical case experience of antithyroid arthritis syndrome and literature search from 1965 to 1996 on antithyroid medication and associated arthritis using MEDLINE and EMBASE. The antithyroid arthritis syndrome is a transient migratory polyarthritis that occurs within 2 months of starting thionamide treatment, and resolves within 4 weeks of stopping therapy. Discontinuation of medication is necessary. Alternative forms of treatment for hyperthyroidism should be sought. Nonsteroidal antiinflammatory drug or treatment of the rheumatic complaints is recommended or if unsuccessful, corticosteroid treatment.

Topics: Aged; Antithyroid Agents; Arthritis; Female; Graves Disease; Humans; Methimazole; Syndrome

A 36-year-old woman who had had Graves' disease for 6 years was admitted with severe thrombocytopenia. Evans' syndrome was diagnosed. The patient's family history showed multiple cases of Graves' disease but no cases of Evans' syndrome. Both conditions in this patient improved with corticosteroid and thiamazole therapy. Several autoimmune antibodies were found, but a common autoimmune mechanism was not clearly shown. Although the combination of Graves' disease and Evans' syndrome had not occurred previously in her family, genetic factors may play an important role in the pathogenesis of both conditions.

Topics: Adrenal Cortex Hormones; Adult; Anemia, Hemolytic, Autoimmune; Antithyroid Agents; Drug Therapy, Combination; Female; Graves Disease; Humans; Methimazole; Purpura, Thrombocytopenic, Idiopathic; Syndrome

Topics: Animals; Encephalomyelitis, Autoimmune, Experimental; Epitopes; Graves Disease; Humans; Immunotherapy; Incidence; Methimazole; Mice; Myelin Basic Protein; Peptide Fragments; Prevalence; Receptors, Antigen, T-Cell; T-Lymphocyte Subsets; T-Lymphocytes, Helper-Inducer; Thyroiditis, Autoimmune

The relationship between the treatment of Graves' hyperthyroidism and the course of ophthalmopathy is rather unclear. Antithyroid drugs may improve eye manifestations, possibly by restoring normal thyroid function and reducing orbit-directed autoimmune reactions, whereas ophthalmopathy may worsen after radioiodine administration or thyroidectomy. This might occur because of a treatment-related release of thyroid antigens and activation of the autoimmune response that might involve the orbit. On the other hand, some authors suggest that complete thyroid ablation, either by radioiodine or surgery, might be beneficial for ophthalmopathy. However, reported effects of radioiodine and thyroidectomy on Graves' ophthalmopathy are conflicting. This may be due, at least in part, to the retrospective feature of most studies and the lack of precise evaluation of ocular involvement. Two prospective studies were performed in which patients with Graves' disease with mild or no ophthalmopathy were randomly assigned to treatment by radioiodine or subtotal thyroidectomy alone or in association with systemic glucocorticoids. Both treatments were followed by a progression of pre-existing mild ophthalmopathy in a substantial proportion of cases: glucocorticoids prevented such an exacerbation. Ophthalmopathy did not develop in patients without clinical evidence of eye disease prior to therapy. Therefore, it is recommended that a course of glucocorticoids be instituted concomitantly with radioiodine therapy or thyroidectomy in Graves' patients with some degree of ocular involvement.

Topics: Glucocorticoids; Graves Disease; Humans; Iodine Radioisotopes; Methimazole; Thyroidectomy

Topics: Adenoma; Combined Modality Therapy; Graves Disease; Humans; Hyperthyroidism; Methimazole; Thyroid Crisis; Thyroid Function Tests; Thyroid Neoplasms

Topics: Adrenergic beta-Antagonists; Carbimazole; Female; Graves Disease; Humans; Iodine; Iodine Radioisotopes; Lithium; Lithium Carbonate; Male; Methimazole; Pregnancy; Propylthiouracil

Fever is a common clinical manifestation of inflammatory processes of the thyroid and thyroid crisis. On the other hand, fever alone as a presenting symptom of thyrotoxicosis, without other manifestations, is extremely rare. A female patient is described in whom fever persisted for two months prior to hospitalization, but without clinical symptoms or signs to lead to suspicion of thyroid disease. After exhaustive investigation it was found that the patient was suffering from hyperthyroidism. Fever disappeared gradually on antithyroid therapy, recurred when the drugs were withdrawn for a rechallenge trial, and cleared up again after renewal. Four other cases of persistent fever as a presenting symptom of hyperthyroidism were found on a review of previous publications. Thyrotoxicosis should, therefore, be included in the differential diagnosis of pyrexia of unknown origin.

Topics: Female; Fever of Unknown Origin; Graves Disease; Humans; Methimazole; Middle Aged

Propylthiouracil and methimazole are frequently used in the management of hyperthyroidism. Two patients in whom adverse immunologic effects other than isolated agranulocytosis developed during treatment with propylthiouracil are described. A review of the literature revealed 53 similar cases over a 35-year period. Rash, fever, arthralgias and granulocytopenia were the most common manifestations. Vasculitis, particularly with cutaneous manifestations, occurs and may be fatal. The clinical evidence suggests that an immunologic mechanism is involved. A number of different autoantibodies were reported, but antinuclear antibodies were infrequent, and none of the cases met the criteria for a diagnosis of systemic lupus erythematosus. Thus, the reactions do not represent a true drug-induced lupus syndrome. Current hypotheses and experimental data regarding the cause of the reactions are reviewed. No specific clinical subgroup at high risk can be identified, and manifestations may occur at any dosage and at any time during therapy. Cross-reactivity between the two antithyroid drugs can be expected. Except for minor symptoms (e.g., mild arthralgias or transient rash), such reactions are an indication for withdrawal of the drug and the use of alternative methods to control the hyperthyroidism. In rare cases of severe vasculitis a short course of high-dose glucocorticoid therapy may be helpful.

Topics: Adult; Agranulocytosis; Antibody Formation; Cross Reactions; Drug Hypersensitivity; Female; Graves Disease; Humans; Hyperthyroidism; Immunity, Cellular; Methimazole; Middle Aged; Propylthiouracil

In the United Kingdom, about half the patients with Graves' disease who are given antithyroid drugs are still in remission one year after treatment is stopped. The most widely held view is that such remission rates are due only to the biochemical effects of the drugs, the disease either spontaneously remitting or abating when the immune system is no longer subject to the stimulatory effects of excessive thyroid hormone. We review here the accumulating evidence against both of these alternatives. In contrast, there is now a large body of work which shows that thyrotrophin receptor antibody levels, central to the aetiology of Graves' hyperthyroidism, fall during antithyroid treatment and that remission may be related to this fall in a fashion which is dependent on the dose and duration of treatment. This immunosuppressive effect is supported by experimental data and on the basis of these results we propose that antithyroid drugs may modify the natural history of Graves' disease and contribute to the remission which occurs in a proportion of treated patients.

Topics: Antithyroid Agents; Autoantibodies; Female; Graves Disease; Humans; Hyperthyroidism; Immunosuppression Therapy; Male; Methimazole; Propranolol; Remission, Spontaneous

Over the past four decades, a great deal has been learned about the pharmacology and mechanisms of action of antithyroid drugs. Their ability to inhibit hormone biosynthesis involves complex interactions with thyroid peroxidase and thyroglobulin, many of which are still poorly understood. Their spectrum of activity is much wider than previously thought, and a number of clinically important extrathyroidal actions have been identified. Despite a greater appreciation for the intricacies of antithyroid-drug pharmacology, controversies still surround the use of these agents in the treatment of thyrotoxicosis. These controversies are apt to continue until the pathophysiology of Graves' disease is fully elucidated.

Topics: Adult; Agranulocytosis; Autoimmune Diseases; Chemical and Drug Induced Liver Injury; Child; Female; Fetus; Graves Disease; Humans; Hyperthyroidism; Immunity; Immunoglobulins; Infant, Newborn; Insulin Antibodies; Leukopenia; Lupus Vulgaris; Methimazole; Milk, Human; Pregnancy; Pregnancy Complications; Propylthiouracil; Vascular Diseases

Topics: Adolescent; Adult; Antithyroid Agents; Carbimazole; Child; Female; Goiter; Graves Disease; Humans; Hyperthyroidism; Iodine; Iodine Radioisotopes; Lithium; Methimazole; Pregnancy; Propranolol; Propylthiouracil; Thyroidectomy

Topics: Adenocarcinoma; Dose-Response Relationship, Drug; Female; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Pregnancy; Propylthiouracil; Thyroid Neoplasms

Topics: Eye Diseases; Graves Disease; Humans; Iodine Isotopes; Long-Acting Thyroid Stimulator; Methimazole; Propylthiouracil; Thyroid Function Tests; Thyroxine

This study aimed to compare the time to achieve euthyroidism and sustained control of hyperthyroidism after treatment with radioactive iodine (RAI) or long-term methimazole (LT-MMI) in patients with post-RAI relapsed hyperthyroidism.. Sixty four patients with recurrence of hyperthyroidism after RAI treatment were randomly assigned to either RAI or LT-MMI treatment. Both groups were followed every 1-3 months in the first year and then every 6 months for a total of 60 months.. In RAI and LT-MMI groups, mean age was 49.0 ± 12.1 and 50.1 ± 14.6 years and time of relapse of hyperthyroidism after previous RAI treatment was 23.2 ± 18.8 and 20.8 ± 17.1 months, respectively. At the end of study, in the LT-MMI group, 31 (97%) and 1 (3%) were euthyroid and hypothyroid, respectively; in the RAI group, 8 (25%) patients were euthyroid, whereas 18 (56%), 3 (9.5%) and 3 (9.5%) had overt hypothyroidism, subclinical hypothyroidism and hyperthyroidism, respectively. Mean time to euthyroidism was 9.4 ± 5.0 months in the RAI group and 3.5 ± 2.8 months in the LT-MMI group (p < 0.001). Patients in the RAI group spent 77.7 ± 14.0 percent and those in the LT-MMI group spent 95.2 ± 5.9 percent of 60 months in the euthyroid state (p < 0.001).. In patients with post-RAI relapse of hyperthyroidism, LT-MMI treatment was superior to radioiodine because of faster achievement of euthyroidism and more sustained control of hyperthyroidism during 60 months of follow-up.

Topics: Adult; Antithyroid Agents; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Methimazole; Middle Aged; Neoplasm Recurrence, Local; Thyroid Neoplasms

Prompt and stable control of hyperthyroidism is fundamental to avoid the detrimental effects of thyroid hormone excess, and antithyroid drugs, mainly methimazole (MMI), represent the first-line treatment for Graves' disease (GD) hyperthyroidism. Decreased serum concentrations of selenium (Se) and calcifediol (25(OH)D, VitD) have been reported in newly diagnosed GD patients in observational studies. Low Se levels might exacerbate oxidative stress by compromising the antioxidant machinery's response to reactive oxygen species, and low VitD levels might hamper the anti-inflammatory immune response. We performed a randomized controlled clinical trial (EudraCT 2017-00505011) to investigate whether Se and cholecalciferol (VitD) addition to MMI is associated with a prompter control of hyperthyroidism. Forty-two consecutive patients with newly-onset GD and marginal/insufficient Se and VitD levels were randomly assigned to treatment with either MMI monotherapy or MMI combined with Se and VitD. Se treatment was withdrawn after 180 days, while the other treatments were continued. Combination therapy resulted in a significantly greater reduction in serum FT4 concentration at 45 days (-37.9 pg/ml, CI 95%, -43.7 to -32.2 pg/ml) and 180 days (-36.5 pg/ml, CI 95%, -42 to -30.9 pg/ml) compared to MMI monotherapy (respectively: -25.7 pg/ml, CI 95%, -31.6 to -19.7 pg/ml and -22.9 pg/ml, CI 95%, -28 to -17.3 pg/ml, p 0.002). Data at 270 days confirmed this trend (-37.8 pg/ml, CI 95%, -43.6 to -32.1 pg/ml vs -24.4 pg/ml, CI 95%, -30.3 to -18.4 pg/ml). The quality of life (QoL) score was investigated by the validated "Thyroid-related Patient-Reported Outcome" questionnaire (ThyPRO). ThyPRO composite score showed a greater improvement in the intervention group at 45 days (-14.6, CI 95%, -18.8 to -10.4), 180 (-9, CI 95%, -13.9 to -4.2) and 270 days (-14.3, CI 95%, -19.5 to -9.1) compared to MMI group (respectively, -5.2, CI 95%, -9.5 to -1; -5.4, CI 95%, -10.6 to -0.2 and -3.5, CI 95%, -9 to -2.1, p 0-6 months and 6-9 months <0.05). Our results suggest that reaching optimal Se and VitD levels increases the early efficacy of MMI treatment when Se and VitD levels are suboptimal.

Topics: Dietary Supplements; Graves Disease; Humans; Hyperthyroidism; Methimazole; Quality of Life; Selenium; Vitamin D; Vitamins

Hyperthyroidism is related to vascular atherosclerosis. Propylthiouracil (PTU) and methimazole, other than their antithyroid effects, may have different mechanisms in preventing atherogenesis in Graves' disease.. This study aimed to investigate the effect of antithyroid drugs on markers of vascular atherosclerosis in Graves' hyperthyroidism.. This study was a single-blind, randomized clinical trial conducted on 36 patients with Graves' disease in Cipto Mangunkusumo General Hospital, Jakarta, Indonesia, from June 2019 until July 2020. Graves' disease was diagnosed from clinical manifestation of hyperthyroidism with diffuse goiter and then confirmed by thyroid stimulation hormone (TSH), free T4 (fT4), and TSH-receptor antibody (TRAb) measurements. Participants were randomly assigned to either a PTU or a methimazole treatment group and followed up for 3 months. Markers of vascular atherosclerosis were represented by adhesion molecules [intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin], carotid artery stiffness [pulse wave velocity (PWV)], and thickness [carotid intima media thickness (cIMT)].. By the end of the study, 24 participants reached euthyroid condition (13 from the PTU group and 11 from the methimazole group). After 3 months of follow-up, in the PTU group, we noticed an improvement of ICAM-1 [pretreatment: 204.1 (61.3) vs. posttreatment: 141.6 (58.4) ng/ml; p = 0.001], VCAM-1 [837 (707-977) vs. 510 (402-630) ng/ml; p < 0.001] and E-selectin [32.1 (24.1-42.7) vs. 28.2 (21.6-36.8) ng/ml; p = 0.045] in the PTU group. In the methimazole group, only VCAM-1 improvement [725 (565-904) vs. 472 (367-590); p = 0.001] was observed. Meanwhile, we found no significant changes in PWV or cIMT in either group.. Antithyroid treatment in Graves' disease leads to improvement in adhesion molecules, with a lesser effect on methimazole, whereas there were no significant changes in PWV or cIMT. PTU may have a better mechanism compared with methimazole in terms of improving adhesion molecules.

Topics: Adult; Antithyroid Agents; Atherosclerosis; Biomarkers; Female; Follow-Up Studies; Graves Disease; Humans; Intercellular Adhesion Molecule-1; Male; Methimazole; Middle Aged; Propylthiouracil; Pulse Wave Analysis; Single-Blind Method; Thyroid Hormones; Treatment Outcome; Vascular Cell Adhesion Molecule-1

Effective control of autoimmune inflammation in Graves' disease determines necessity to study the T helper (Th) and cytotoxic T-lymphocytes dysfunction, as well as the level of regulatory T-cells (Treg) activation in patients with Graves' disease on thyrostatic medication, which will clarify the immunomodulatory effects of long-term thiamazole treatment serve as targets for more specific therapies.. To study the phenotypic composition of T-lymphocytes in the peripheral blood of patients with Graves' disease to assess the direction of immune response depending on thimazole-induced euthyroidism duration.. A single-center, cohort, continuous, open-label, controlled trial was conducted to assess the phenotypic composition of T-lymphocytes in peripheral blood in women with Graves' disease on long-term thiamazole treatment. The phenotypic composition of T-lymphocytes was determined by flow cytometry using direct immunofluorescence with conjugated FITC monoclonal antibodies depending on the duration of thimazole-induced euthyroidism of long-term thiamazole treatment.. The study included 135 women with Graves' disease, mean age 43.09±12.81 years, 120 (88.91%) with a relapse of the disease and 15 (11.09%) with newly diagnosed hyperthyroidism. An increase of activated CD3+CD4+CD25+ was found in patients with Graves' disease with a duration of thimazole-induced euthyroidism 5-8 months and 9-12 months, respectively, Me=0.94 (0.48-1.45), p=0.020) and Me=0.95 (0.41-1.80), p=0.025), in control group - Me=0.12 (0.03-0.68). Compared to the control an increase of CD4+CD25+CD127Low (Treg) was found in patients with a duration of thimazole-induced euthyroidism 5-8 and 9-12 months. The content of Treg in peripheral blood in Graves' disease patients with a duration of thimazole-induced euthyroidism more than 12 months decreases, but remains elevated relative to the control.. In patients with Graves' disease with a duration of thimazole-induced euthyroidism 5-8 months and 9-12 months the level of Treg has been increased. The increase of activated Th (CD3+CD4+CD25+) persists independently of thimazole-induced euthyroidism. In patients with Graves' disease with a duration of thimazole-induced euthyroidism for more than 12 months, there is a compensatory increase in regulatory T-lymphocyte, and the total number of T-helpers is restored to the control.

Topics: Conservative Treatment; Female; Graves Disease; Humans; Hyperthyroidism; Methimazole; T-Lymphocytes, Regulatory

Long-term antithyroid drug therapy has become one of the options for treatment of Graves' hyperthyroidism. The aim of this study was to compare thyroid status in those who discontinued methimazole (MMI) treatment after 12.8 years with those who continued MMI as long as 24 years.. Fifty nine patients with Graves' disease on long-term MMI for 14.2 ± 2.9 years were recruited; 32 patients (54%) decided to discontinue MMI and 27 (46%) preferred additional years of MMI treatment. All patients were followed for a mean of 6 additional years.. Of 27 patients who continued MMI up to 24 years, suppressed serum thyrotropin (TSH) was not observed in any patient after the seventh year of treatment. Serum free thyroxine, triiodothyronine, TSH and TSH receptor antibody concentrations remained normal up to the length of the study. Mean daily dose of MMI to maintain TSH in the reference range decreased gradually and reached to 2.8 ± 1.7 mg by 24 years of MMI treatment. No adverse reaction related to MMI occured during additional years of therapy. In 32 patients who discontinued MMI, hyperthyroidism relapsed in 6 patients (19%), one left follow-up and 25 (78%) remained euthyroid during the study.. Long-term low dose MMI treatment may be a lifelong effective and safe therapeutic modality in patients with Graves' hyperthyroidism for prevention of relapse, if studies from other centers confirm findings of this research.. IRCT201009224794N1, 2010-10-25. Retrospectively registered. https://www.irct.ir/trial/5143 .

Topics: Adult; Aged; Antithyroid Agents; Female; Follow-Up Studies; Graves Disease; Humans; Kaplan-Meier Estimate; Male; Methimazole; Middle Aged; Recurrence; Thyroid Hormones; Treatment Outcome

Brown adipose tissue (BAT) controls metabolic rate through thermogenesis. As its regulatory factors during the transition from hyperthyroidism to euthyroidism are not well established, our study investigated the relationships between supraclavicular brown adipose tissue (sBAT) activity and physiological/metabolic changes with changes in thyroid status.. Participants with newly diagnosed Graves' disease were recruited. A thionamide antithyroid drug (ATD) such as carbimazole (CMZ) or thiamazole (TMZ) was prescribed in every case. All underwent energy expenditure (EE) measurement and supraclavicular infrared thermography (IRT) within a chamber calorimeter, as well as 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging scanning, with clinical and biochemical parameters measured during hyperthyroidism and repeated in early euthyroidism. PET sBAT mean/maximum standardized uptake value (SUV mean/max), MR supraclavicular fat fraction (sFF) and mean temperature (Tscv) quantified sBAT activity.. Twenty-one (16 female/5 male) participants aged 39.5 ± 2.5 years completed the study. The average duration to attain euthyroidism was 28.6 ± 2.3 weeks. Eight participants were BAT-positive while 13 were BAT-negative. sFF increased with euthyroidism (72.3 ± 1.4% to 76.8 ± 1.4%; P < 0.01), but no changes were observed in PET SUV mean and Tscv. Significant changes in serum-free triiodothyronine (FT3) levels were related to BAT status (interaction P value = 0.04). FT3 concentration at hyperthyroid state was positively associated with sBAT PET SUV mean (r = 0.58, P = 0.01) and resting metabolic rate (RMR) (P < 0.01).. Hyperthyroidism does not consistently lead to a detectable increase in BAT activity. FT3 reduction during the transition to euthyroidism correlated with BAT activity.

Topics: Adipose Tissue, Brown; Adult; Aged; Antithyroid Agents; Body Composition; Carbimazole; Energy Metabolism; Female; Fluorodeoxyglucose F18; Graves Disease; Humans; Hyperthyroidism; Magnetic Resonance Imaging; Male; Methimazole; Middle Aged; Positron-Emission Tomography; Remission Induction; Singapore; Thermogenesis; Thyroid Gland; Young Adult

Background The management options for Graves' disease in children are limited and there is controversy regarding optimal treatment. Remission rate with anti-thyroid drug (ATD) treatment in children is said to be lower than in adults. Definitive treatments are effective, but they often result in permanent hypothyroidism. The objective of this study was to investigate the outcome of methimazole treatment, identify significant predictors of a remission and evaluate the adverse effects of methimazole in a pediatric population of GD patients. Methods Medical records of the patients who had been diagnosed with Graves' disease were screened retrospectively. Diagnostic criteria included elevated free thyroxine (fT4) and total triiodothyronine (T3), suppressed thyroid-stimulating hormone (TSH) and either positive thyroid-stimulating immunoglobulin (TSI) or thyroid receptor antibodies (TRABs) or clinical signs suggestive of Graves' disease, for example, exophthalmos. Remission was defined as maintenance of euthyroidism for more than 12 months after discontinuing methimazole treatment. Results Of the 48 patients, provisional remission was achieved in 21 patients. Of the 21 patients, 14 experienced a relapse (66.6%). Remission was achieved in seven (24.1%) of 29 patients who received methimazole treatment for more than 2 years. In patients who achieved long-term remission, the male sex ratio and fT4 levels at diagnosis were significantly lower than the relapsed and non-remission groups, whereas the free triiodothyronine (fT3)/fT4 ratio and duration of methimazole treatment were significantly higher than the relapse group. Conclusions Long-term methimazole treatment in pediatric Graves' disease would be appropriate. High fT4 levels at the time of diagnosis and male sex were associated with a risk of relapse.

Topics: Adolescent; Adult; Antithyroid Agents; Child; Female; Follow-Up Studies; Graves Disease; Humans; Male; Methimazole; Prognosis; Remission Induction; Retrospective Studies; Thyroid Function Tests; Thyroid Hormones; Young Adult

The aim of this study was to assess the effect of a combination use of methimazole (MMI) and selenium (Se) in the treatment of Graves’ disease (GD).. A total of 103 newly diagnosed hyperthyroidism patients were randomized to MMI and MMI + Se combination groups. After treatment for 6 months, the levels of triiodothyronine (FT3), free thyroxine (FT4), thyrotropin receptor antibody (TRAb), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TGAb) were observed. An in vitro culture model of thyroid cells was established and the protein expression and mRNA levels of TRAb, TPOAb, and TGAb were determined by western blot and RT-PCR.. A significant decrease in the levels of FT3, FT4, TRAb, TPOAb, and TGAb were observed in both groups along with a marked increase in TSH levels. Furthermore, the in vitro experiments showed that the protein expression and mRNA levels of TRAb, TPOAb, and TGAb decreased significantly. Also, compared to the MMI group, there was a greater improvement of these indices in the MMI + Se group.. We suggest that the combined use of MMI and Se could improve the thyroid activity in patients, which may provide an effective therapy for the treatment of GD in clinical settings.

Topics: Adult; Antithyroid Agents; Autoantibodies; Cell Survival; Cells, Cultured; Dietary Supplements; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Pilot Projects; Receptors, Thyrotropin; Selenium; Thyroid Gland; Thyroid Hormones

Recent studies show that long-term (LT) antithyroid drugs reduce relapse of hyperthyroidism in patients with Graves' disease. Our objective was to evaluate the effectiveness and safety of LT methimazole treatment and to compare remission rates in Graves' disease patients after LT and short-term (ST) therapy.. In this randomized, parallel group trial, 66 consecutive patients with untreated juvenile Graves' hyperthyroidism were enrolled. After a median 22 months of methimazole treatment, 56 patients were randomly assigned to either continue low-dose methimazole treatment (. Except for 3 cases of cutaneous reactions, no other adverse events were observed throughout 120 months of methimazole therapy. Serum free thyroxine, triiodothyronine, thyrotropin, and thyrotropin receptor antibody remained normal, and the required daily dosage of methimazole was gradually decreased from 5.17 ± 1.05 mg at 22 months to 3.5 ± 1.3 mg between 96 and 120 months of treatment (. LT methimazole treatment of 96 to 120 months is safe and effective for treatment of juvenile Graves' disease. The four-year cure rate of hyperthyroidism with LT methimazole treatment is almost 3 times more than that of ST methimazole treatment.

Topics: Adolescent; Antithyroid Agents; Drug Administration Schedule; Female; Graves Disease; Humans; Male; Methimazole; Thyroid Function Tests

Hyperthyroidism is associated with alterations in metabolism that are currently only partially understood. The objective of the study was to investigate changes in metabolism associated with reinstatement of euthyroidism in Swedish patients.. Eighty metabolites in plasma were profiled from 10 subjects with Graves' disease (GD) at baseline and after 9 and 15 months of treatment to reinstate euthyroidism. Thyroid parameters, thyrotropin (TSH), TSH receptor antibodies, free triiodothyronine, and free thyroxine were followed. Main findings were validated in plasma from 20 subjects with GD at baseline and at three, six, and nine months. The study was conducted at the endocrinology clinic in Malmö, Sweden.. Euthyroidism was reinstated at three months, and thyroid status did not change further during the 15-month follow-up. This was paralleled by altered levels of 9/19 detected acylcarnitines (p < 0.05 after adjustment for multiple testing). Levels of short-chain acylcarnitines were decreased, intermediate-chain acylcarnitines elevated, and long-chain acylcarnitines unaltered.. GD and treatment of the disease is associated with pronounced acyl chain length-dependent alterations in acylcarnitine levels. These changes may be impacted by ethnicity and or dietary differences.

Topics: Adult; Antithyroid Agents; Carnitine; Combined Modality Therapy; Fatty Acids; Fatty Acids, Volatile; Female; Follow-Up Studies; Graves Disease; Hormone Replacement Therapy; Humans; Male; Metabolomics; Methimazole; Middle Aged; Molecular Weight; Principal Component Analysis; Sweden; Thyroid Gland; Thyroxine

In spite of previous conflicting results, an adjuvant role of selenium in the treatment of Graves' disease (GD) hyperthyroidism has been proposed. To address this issue, a randomized clinical trial was carried out aimed at investigating whether selenium is beneficial on the short-term control of GD hyperthyroidism treated with methimazole (MMI).. Thirty newly diagnosed hyperthyroid GD patients were randomly assigned to treatment with: (i) MMI or (ii) MMI plus selenium. Primary outcomes were: control of hyperthyroidism and clinical and biochemical manifestations of hyperthyroidism [heart rate, cholesterol, sex hormone-binding globulin (SHBG), hyperthyroidism symptoms] at 90 days.. Baseline features of the two groups did not differ. Serum selenium at baseline was similar in the two groups and within the recommended range to define selenium sufficiency. Selenium increased with treatment in the MMI-selenium group and became significantly higher than in the MMI group. Serum malondialdehyde, a marker of oxidative stress, was similar in the two groups and decreased significantly with treatment, with no difference between groups. Administration of MMI was followed by a reduction of FT. Our study, carried out in a selenium-sufficient cohort of GD patients, failed to show an adjuvant role of selenium in the short-term control of hyperthyroidism. However, selenium might be beneficial in patients from selenium-deficient areas, as well as in the long-term outcome of antithyroid treatment.

Topics: Adult; Antioxidants; Antithyroid Agents; Female; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Selenium; Sex Hormone-Binding Globulin; Thyroxine; Treatment Outcome; Triiodothyronine

Yingliu mixture was developed in 1990s by Affiliated Longhua Hospital of Shanghai University of Traditional Chinese Medicine, for treating diffuse goitre with hyperthyroidism (Graves' disease, GD). Former studies have shown Yingliu mixture combined with methimazole (Y-M) can effectively improve thyroid function and decrease thyrotropin-receptor antibody level. Furthermore, we researched its impact on related cytokines to prove that Y-M improve patients' immunity status.. To observe the clinical efficacy of Y-M for treating GD.. A total of 120 GD patients were randomly divided into two groups, the treatment and the control groups (n = 60). The treatment group's patients were treated with Y-M. The control group's patients were treated with methimazole alone. Yingliu mixture was orally administered, 25 mL three times daily. Methimazole was administered at 5-25 mg/day. After 12 weeks of the treatment, the cytokines, antibodies related to thyroid function, and Chinese medical syndromes were evaluated.. After the treatment, the free triiodothyronine and thyroxine levels in both groups decreased. The thyroid-stimulating hormone level increased in the treatment group. The thyrotropin-receptor antibody levels and TNF-α levels decreased in both groups. In the control group, IL-6 and IFN-γ levels were lower than that before the treatment. In the treatment group, CD4. the total CMS scores for both groups decreased.. The Y-M combination can improve thyroid function, and decrease autoantibodies, cytokines, and clinical symptoms, so its efficacy may surpass that of methimazole alone.

Topics: Adult; Antithyroid Agents; Autoantibodies; Biomarkers; China; Cytokines; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Recovery of Function; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones; Time Factors; Treatment Outcome

Despite the efficacy and safety, antithyroid drug (ATD) therapy for Graves' disease (GD) is associated with a high risk of relapse, especially within the first year. The inability to predict whether and when relapse may occur is a major problem for ATD therapy. This study was aimed to investigate potential predicative factors for GD patients after ATD withdrawal. Consecutive patients newly diagnosed with GD and treated with ATD [methimazole (MMI)] were enrolled in this study. Univariate and multivariate Cox proportional hazard analyses were used for the analysis of predicative parameters for GD relapse after MMI withdrawal. Kaplan-Meier survival analysis and log-rank test were utilized for presenting the risk of relapse. Of the 103 patients included, 67 (65.0%) remained in remission and 36 (35.0%) had a relapse within 1 year after the MMI withdrawal. The multivariate analysis suggested significant predictive factors for GD relapse: patients with higher miR-346 expressions (≥median value) at diagnosis and at cessation, and lower TRAb levels at cessation. MiR-346 at diagnosis and cessation, and TRAb at cessation could serve as predictive factors for GD relapse within 1 year after drug withdrawal.

Topics: Adult; Disease-Free Survival; Female; Follow-Up Studies; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; MicroRNAs; Middle Aged; Recurrence; Survival Rate

Methimazole (MMI) is usually used at an initial dose of 30 mg/day for severe Graves' disease (GD) hyperthyroidism, but adverse effects are more frequent at this dose than at MMI 15 mg/day.. We designed a regimen to address the lack of a primary therapeutic effect of the MMI 15 mg/day by combining it with inorganic iodine at 38.2 mg/day. Our aim was to compare the two regimens (MMI 15 mg+inorganic iodine at 38.2 mg/day (M15+I) vs. MMI 30 mg/day (M30)) in terms of therapeutic effect, adverse effects, and remission rate.. In a prospective study, 310 patients with untreated GD (serum free thyroxine (fT4) ≥5 ng/dL) were assigned to one of the two regimens. Potassium iodide was discontinued in the M15+I group as soon as the serum fT4 level was within the reference range (0.8-1.6 ng/dL).. Percentages of patients achieving an fT4 level within reference range in ≤30, ≤60, or 90 days on the study treatment regimens were 45.3%, 73.9%, and 82.0% respectively for the M15+I group, and 24.8%, 63.1%, and 75.2% respectively for the M30 group. Hence, the proportions of patients achieving this goal in ≤30 or ≤60 days were significantly larger in the M15+I group. Adverse effects that required discontinuation of MMI were more frequent in the M30-treated than in the M15+I-treated group (14.8% vs. 7.5%; p=0.0387). The remission rates in the M15+I and M30 groups were 19.9% and 14.8%-higher in the former, but the difference did not reach statistical significance.. The results of this study raise the possibility that M15+I is superior to M30 as a primary treatment for moderate to severe hyperthyroidism caused by GD.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Child; Drug Administration Schedule; Drug Therapy, Combination; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Potassium Iodide; Thyroid Function Tests; Thyroxine; Treatment Outcome; Triiodothyronine; Young Adult

Although radioiodine therapy (RIT) has been used for the treatment of hyperthyroidism for many decades, there is no consensus on the optimal time of methimazole (MMI) discontinuation before RIT. The aim of this clinical trial is to study the effect of three different time points of MMI discontinuation on response to RIT.. Overall, 151 patients (18-65 years old), with Graves' disease who were taking MMI and referred to I-131 therapy, were consecutively assigned to one of three groups, and MMI was discontinued for 24-48, 48.1-72, and 72.1-168 h in group, 1, 2, and 3, respectively. Radioiodine uptake was measured in all patients and the radioiodine dose was calculated according to the Quimby formula to deliver 7.4 MBq of I-131 per gram of thyroid weight. Response to RIT was assessed at 1, 3, 6, and 12 months after RIT.. A total of 102 women and 49 men were included in the study. The mean administered dose of I-131 was 362.9±188.7 MBq (9.8±5.1 mCi) and the mean time to response for radioiodine was 4.1±3.6 months. There was no significant difference between the three groups in age, thyroid weight, anti-TPO level, radioactive iodine uptake level, and radioiodine dose (P>0.1). Response to RIT at 1, 3, 6, and 12 months after administration was also not different between the three groups (P>0.57).. No difference was found in the response to treatment between patients with MMI discontinuation for 24-48, 48.1-72, and 72.1-96 h before RIT. Shorter discontinuation of MMI before RIT may be preferable in most patients. Video Abstract: http://links.lww.com/NMC/A39.

Topics: Adolescent; Adult; Aged; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Time Factors; Withholding Treatment; Young Adult

Antithyroid drug therapy is one of the main medical treatments for Graves' disease. There have been conflicting reports as to whether the addition of exogenous L-thyroxine improves remission rates more than antithyroid drugs alone. This randomized, controlled and prospective clinical trial was undertaken to investigate the long-term outcome of methimazole treatment with or without exogenous L-thyroxine in Chinese patients.. 145 patients with Graves' disease were randomly divided into 3 groups and all patients initially received 30 mg of methimazole daily for at least 1 month and then followed the titration -regimen with or without L-thyroxine: group 1 (30 mg→20 mg→15 mg→10 mg→5 mg); group 2 (30 mg→20 mg→15 mg→10 mg+L-thyroxine→5 mg+L-thyroxine); group 3 (30 mg→20 mg→15 mg→10 mg+L-thyroxine→5 mg+L-thyroxine→2.5 mg+L-thyroxine). The drug therapy was discontinued after 5 months of the final dose.. 16 out of 46 patients in group 1 (34.8%), 12 out of 47 in group 2 (25.5%) and 16 out of 52 in group 3 (30.8%) had a recurrence of Graves' disease within 6-year follow-up after drug withdrawal. Survival Analysis showed no significant differences in the remission rates between any 2 groups, despite the remission rates in group 2 and 3 were slightly higher than that in group 1.. The addition of L-thyroxine to methimazole treatment in patients with Graves' disease neither improves nor prevents the remission or recurrence of Graves' disease in China.

Topics: Adolescent; Adult; Antithyroid Agents; Child; China; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Graves Disease; Humans; Male; Methimazole; Middle Aged; Recurrence; Thyroxine; Treatment Outcome; Young Adult

Thyrotoxicosis is a rare condition in pediatric patients, and optimal treatment can be difficult to achieve in some children. To our knowledge, no studies have evaluated sex hormone-binding globulin (SHBG) levels in hyperthyroid children and adolescents in relation to age- and gender-related normative data.. SHBG serum levels were determined before and after 4 months of antithyroid therapy (ATT) in 10 children and adolescents with Graves' disease. A total of 903 healthy children and adolescents served as controls.. Serum SHBG levels were elevated (>2 SD) at diagnosis in all hyperthyroid children but normalized rapidly following ATT. At diagnosis, median SHBG was +2.51 SD (interquartile range 2.20-3.27) compared to healthy children without thyroid illness, and it declined significantly during ATT (-0.16 SD, -0.66 to 1.64; p < 0.05).. This is the first study to demonstrate that serum SHBG levels are markedly increased in children with Graves' disease, and we suggest that SHBG may be an additional marker of thyroid hormone action in children, as has been shown in adults.

Topics: Adolescent; Child; Female; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Reference Values; Sex Factors; Sex Hormone-Binding Globulin; Thyrotoxicosis

Potassium bromide is used as a sedative and an anti-epileptic drug for children and adolescents. Rodent animal studies have shown that bromide ions inhibit thyroid hormone synthesis by decreasing the iodine concentration in thyroid tissue.. To observe the short-term clinical effects of combined treatment with potassium bromide and methimazole in patients with Graves' disease.. Sixty patients with Graves' diseases were randomized in groups. Thirty patients in the combined treatment group were treated with methimazole (10 mg, tid) and potassium bromide (1 g, tid); 30 patients in the methimazole only group were treated with methimazole (10 mg, tid) and starch placebo (1 g, tid). All the patients were treated with metoprolol tartrate (25 mg, bid) to control the symptoms and signs of hyperthyroidism. Patients were treated for one month. Clinical symptoms and potential side effects were monitored. Serum thyroid hormone levels were measured before and after the treatments.. Clinical hyperthyroidism symptoms were improved in both groups, with or without potassium bromide. Patients in the combined treatment group displayed improved clinical hyperthyroidism symptoms 10 days earlier on average (p<0.05). Furthermore, blood thyroid hormone levels decreased to normal levels in 93% (28/30) of patients in the combined treatment group, compared with only 37% (5/30) of patients in the methimazole only group (p<0.05).. Treatment of patients with Graves' disease with a novel combination therapy consisting of potassium bromide and methimazole resulted in a rapid improvement in clinical symptoms and decreased blood thyroid hormone levels to homeostatic levels faster than methimazole treatment alone.

Topics: Adult; Antithyroid Agents; Bromides; Drug Therapy, Combination; Female; Graves Disease; Humans; Male; Methimazole; Potassium Compounds; Thyroid Hormones; Young Adult

Use of the antithyroid drugs (ATDs) thiamazole (MMI) and propylthiouracil (PTU) is associated with a high frequency of side effects. When patients experience side effects with one (the 1st) ATD, it is usually discontinued and another is administered (the 2nd ATD). We investigated side effects associated with the 1st and 2nd ATDs.. Four hundred forty-nine patients with untreated Graves' disease (GD) were randomly assigned to three groups according to ATD type and/or dosage: 15 mg/day MMI, 30 mg/day MMI and 300 mg/day PTU. The type, frequency and onset of side effects were assessed. We also studied the side effects associated with the 2nd ATD after cessation of the 1st ATD.. Cutaneous reactions, liver dysfunction and other side effects were examined every 2 weeks after starting ATD administration.. The overall frequency of side effects in patients taking 15 mg/day MMI was low. The frequencies of cutaneous reactions in patients taking 30 mg/day MMI and hepatotoxicity in those taking 300 mg/day PTU were high. Hepatotoxicity developed later than cutaneous reactions with PTU. Hepatotoxicity developed earlier in the 30 mg/day MMI group than in the other two groups. The frequency of side effects did not differ between the 2nd and 1st ATDs. Hepatotoxicity occurred at a higher frequency in patients who were switched from MMI to PTU because of hepatotoxicity of the former.. Attention to the onset times of side effects and cross-reactivity of ATDs can lead to safer treatment of GD.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Drug Administration Schedule; Female; Graves Disease; Humans; Liver; Male; Methimazole; Middle Aged; Propylthiouracil; Skin; Young Adult

The effect of supplementation with a fixed combination of antioxidants (beta-carotene, selenium, vitamins C and E) on serum lipids was monitored in patients with newly detected Graves' disease. Measurements were made prior to the commencement of therapy and after 30 and 60 days. Patients were randomized into two groups. Test group comprised patients who received antioxidant supplementation in addition to methimazole, while patients treated with methimazole only were in the control group. The concentration of total and HDL-cholesterol increased significantly in test and control groups (p < 0.05) but these groups did not differ significantly. Concentration of LDL-cholesterol increased significantly in the test group only (p < 0.005) and was significantly different from the control group 60 days after the commencement of therapy (p < 0.005). Significant increase in the LDL-cholesterol concentration in the test group requires further investigations.

Topics: Adolescent; Adult; Antioxidants; Antithyroid Agents; Ascorbic Acid; beta Carotene; Cholesterol, LDL; Croatia; Dietary Supplements; Drug Combinations; Drug Therapy, Combination; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Selenium; Thyroid Hormones; Time Factors; Treatment Outcome; Vitamin E; Young Adult

Interleukine-16 (IL-16) and RANTES (regulated upon activation, normal T cell expressed and secreted) are 2 cytokines with the function of T helper cell recruitment, which might play a key role in pathogenesis of autoimmune thyroid diseases (AITD). This study was aimed to evaluate the IL-16 and RANTES in patients with AITD. Serum IL-16 and RANTES levels were measured in patients with Graves' disease (GD; n=45), Hashimoto's thyroiditis (HT; n=68), nontoxic multinodular goiter (NTMNG; n=20), and healthy individuals (n=61). The results showed that serum IL-16 and RANTES levels were elevated both in HT and higher in untreated GD patients when compared to NTMNG patients and the healthy individuals, which were decreased after MMI therapy in untreated GD patients. However, in HT patients, serum IL-16 and RANTES levels were comparable among the conditions of hyperthyroid and euthyroid received by l-thyroxine therapy and untreated hypothyroid. Furthermore, serum IL-16 levels were correlated with FT3, FT4, TRAb in GD, but not in HT patients. The data did not show any correlation between RANTES levels and clinical factors. In conclusion, IL-16 and RANTES might be involved in the pathogenesis of GD and HT, and serum IL-16 levels in GD maybe a potential marker of disease activity and severity.

Topics: Adult; Antithyroid Agents; Case-Control Studies; Chemokine CCL5; Female; Goiter, Nodular; Graves Disease; Hashimoto Disease; Humans; Interleukin-16; Male; Methimazole; Thyroid Function Tests

β-adrenergic antagonists (β-blockers) are often used to attenuate the hyperadrenergic symptoms of Graves' disease (GD), including palpitation. Although β-blockers reduce the heart rate, cardiac output and oxygen consumption, no firm evidence exists regarding the effects of combined therapy with β-blockers and anti-thyroid drugs. The objective is to elucidate the effects of β-blockers on anti-thyroid drug therapy in GD.. Patients newly diagnosed with mild GD were randomly assigned to receive methimazole with or without β-blockers in a prospective multi-center survey. The heart rate and thyroid function were measured and the quality of life was assessed using original and SF-36 questionnaires at 0 and 4 weeks.. A total of 28 patients were enrolled in the study. Fourteen patients (one man, 13 women) were randomly assigned to the group treated with β-blockers and 14 patients (one man, 13 women) were randomly assigned to the group not treated with β-blockers. Although no significant differences in the improvement of thyroid function were observed between the two groups, the heart rates improved more significantly in the group treated with β-blockers. Specific symptoms, such as easy fatigability and shortness of breath, also improved more significantly with the β-blocker treatment. In addition, 'physical functioning' assessed with the SF-36 questionnaires significantly improved only in the group treated with β-blockers.. Although β-blockers may not reinforce the effects of anti-thyroid drugs on thyroid function, at least during the course of one month, they are effective in reducing heart rates and ameliorating specific symptoms in patients with mild GD.

Topics: Adrenergic beta-Antagonists; Adult; Antithyroid Agents; Drug Therapy, Combination; Dyspnea; Fatigue; Female; Graves Disease; Heart Rate; Humans; Incidence; Male; Methimazole; Middle Aged; Prospective Studies; Quality of Life; Surveys and Questionnaires; Thyroid Gland; Thyrotoxicosis; Treatment Outcome

Lack of consensus regarding the antithyroid drug regimen in relation to radioiodine ((131) I) therapy of hyperthyroidism prompted this randomized trial comparing two strategies.. Patients with Graves' disease (GD, n = 51) or toxic nodular goitre (TNG, n = 49) were randomized to (131) I either 8 days following discontinuation of methimazole (-BRT, n = 52, median dose: 5 mg) or while on a continuous block-replacement regimen (+BRT, n = 48, median dose 15 mg methimazole and 100 μg levothyroxine). results: Patients in the +BRT group required more radioactivity. In this group, thyroid function did not change in the early post (131) I period, while serum-free T3 index was higher in the -BRT group (P < 0·05). One year posttherapy, the fraction of cured patients (euthyroid or hypothyroid) was 48% and 61% in the +BRT and -BRT group, respectively (P = 0·014 unadjusted; P = 0·004 adjusted), but the outcome depended on the type of disease. In GD, treatment failure in the +BRT group correlated positively with the 24-h thyroid (131) I uptake (P = 0·017), while no correlations existed in the -BRT group. In addition to +BRT allocation, patients with TNG were at higher risk of treatment failure with lower thyroid radiation doses (P = 0·048), higher doses of methimazole (P = 0·026) and lower levels of serum TSH (P = 0·009).. A continuous block-replacement regimen results in a stable thyroid function during (131) I therapy but is hampered by the higher amounts of radioactivity required. The study demonstrates that the outcome in GD is highly unpredictable, while treatment failure in patients with TNG is correlated with a number of factors.

Topics: Adult; Aged; Antithyroid Agents; Combined Modality Therapy; Drug Administration Schedule; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Radiotherapy Dosage; Thyroid Hormones; Thyroxine; Treatment Outcome

The chemokine CXCL10 plays an important role in Graves' disease (GD); however, data regarding the effectiveness of therapy are contradictory. Serum CXCL10 levels in 31 hyperthyroid patients were measured before and after establishing euthyroidism: 16 newly diagnosed GD patients received methimazole (MMI), 15 relapsed GD patients were treated with radioactive iodine (RAI), and 18 healthy subjects served as a control group. Baseline serum CXCL10 levels were higher than in controls (MMI group 144.0 ± 48.24, RAI group 156.3 ± 71.81 and control 71.32 ± 26.03 pg/ml; p < 0.01). In the MMI group, serum CXCL10 levels decreased following euthyroidism at 6 months (76.51 ± 22.06 pg/ml; p < 0.01) and 12 (76.42 ± 34.07 pg/ml; p < 0.01). In the RAI group, serum CXCL10 levels decreased after 3, 6, 9, and 12 months of RAI administration (82.37 ± 55.01, 66.35 ± 48.62, 68.76 ± 28.87, and 74.94 ± 49.74 pg/ml, respectively; p < 0.05). Elevated serum TRAb levels in the MMI group (33.15 ± 30.84) decreased at 6 months (14.64 ± 16.57 IU/l; p = 0.0070), whereas in the RAI group (44.61 ± 60.66 IU/l) they increased to a peak level at 6 months (66.40 ± 104.2 IU/l; p = 0.003), which was significantly higher than those of the MMI group, but were decreased at 12 months (28.91 ± 35.13 IU/l). Serum CXCL10 levels correlated with FT3 (r = 0.48, p < 0.0001), FT4 (r = 0.47, p < 0.0001) and TRAb (r = 0.37, p = 0.0014). In conclusion, these data show a relationship between serum CXCL10 and GD activity and suggest that a more complex mechanism is involved in the generation of the thyroid auto-antibodies TPOAb and TRAb.

Topics: Adult; Antithyroid Agents; Case-Control Studies; Chemokine CXCL10; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged

The aim of this study was to compare the efficacy and adverse reactions during initial treatment and long-term outcome between children and adolescents with Graves' disease (GD) treated with propylthiouracil (PTU) and those treated with methimazole (MMI).. Retrospective and collaborative study. Children and adolescents with GD were divided into group M (MMI: n=64) and group P (PTU: n=69) and into four subgroups by initial dose: group M1 (<0.75 mg/kg of MMI, n=34), group M2 (> or = 0.75 mg/kg, n=30), group P1 (<7.5 mg/kg of PTU, n=24) and group P2 (> or = 7.5 mg/kg, n=45).. The duration for normalization of serum T4 on initial treatment, the incidence of adverse effects for one year and outcomes at 10 years after were compared.. Mean durations for normalization of T4 (+/- SD) were 1.7 +/- 1.0 months in group M and 2.3 +/- 2.4 in group P [not significant (NS)], while the mean duration in group P1 (3.1 +/- 3.3) was significantly longer than those in the other subgroups (M1: 1.9 +/- 1.2; M2: 1.4 +/- 0.7; P2; 1.7 +/- 1.3). No major adverse reaction was observed. Minor adverse effects occurred in 25.0% of cases in group M and 31.9% in group P (NS). The incidence in group P2 (44.4%) was significantly higher than those in group M1 (20.6%) and group P1 (8.3%). Remission rates did not differ between the MMI-treated group (35.0%, n=20) and PTU-treated group (50.0%, n=40).. PTU may not be suitable for initial use in children and adolescents with GD, even with the risk of major adverse reactions such as liver failure excluded.

Topics: Adolescent; Antithyroid Agents; Child; Drug Eruptions; Female; Graves Disease; Humans; Liver; Male; Methimazole; Propylthiouracil; Retrospective Studies; Thyroxine; Time Factors; Treatment Outcome

To study the effects of Radix Astragali on serum cytokines IL-1beta, TNFalpha and antigen expression of peripheral blood mononuclear cells (PBMCs) in patients with Graves disease (GD).. Eighty GD patients at their first visit were randomly assigned to the methimazole (MMI) group (Group A) and the MMI combined Radix Astragali group (Group B), 40 in each. The improvement of clinical symptoms and thyroid functions were observed after one-month treatment. The serum IL-1beta and TNF-alpha levels in the peripheral blood were determined using radioimmunoassay. The expression levels of surface antigen CD80, CD54, and HLA-DR of PBMCs were detected using flow cytometry.. The improvement of the thyroid gland function was similar in the two groups. There was no obvious change in the levels of autoantibody TGAb or TPOAb of the two groups. Symptoms such as fear of heat, hidrosis, palpitation, and so on were more obviously improved in Group B than in Group A (P < 0.05). The serum IL-betaP, TNFalphaa, CD00 levels in the peripheral blood were all improved in the two groups after treatment when compared with before treatment ( P < 0.05 or P < 0.01). But the serum levels of IL-beta and TNFalpha decreased more obviously in Group B than in Group A ( P < 0.05). The expression of CD54 decreased more obviously in Group B (P < 0.01), showing statistical difference when compared with Group A at the same time point (P < 0.05).. Radix Astragali could significantly relieve the clinical symptoms such as hidrosis and palpitation, regulate the immune function of GD patients, playing an important role in the adjuvant therapy for GD.

Topics: Adult; Astragalus Plant; Astragalus propinquus; Drugs, Chinese Herbal; Female; Graves Disease; HLA Antigens; Humans; Interleukin-1beta; Leukocytes, Mononuclear; Male; Methimazole; Middle Aged; Tumor Necrosis Factor-alpha

Combined treatment with anti-thyroid drugs (ATDs) and potassium iodide (KI) has been used only for severe thyrotoxicosis or as a pretreatment before urgent thyroidectomy in patients with Graves' disease. We compared methimazole (MMI) treatment with MMI + KI treatment in terms of rapid normalization of thyroid hormones during the early phase and examined the later induction of disease remission.. A total of 134 untreated patients with Graves' disease were randomly assigned to one of four regimens: Group 1, MMI 30 mg; Group 2, MMI 30 mg + KI; Group 3, MMI 15 mg and Group 4, MMI 15 mg + KI. For easy handling, KI tablets were used instead of saturated solution of KI. KI was discontinued when patients showed normal free thyroxine (FT4) levels but MMI was continued with a tapering dosage until remission. Remission rate was examined during a 4- to 5-year observation.. Serum FT4, FT3 and TSH were measured by chemiluminescent immunoassays. TSH receptor antibody (TRAb) was assayed with TRAb-ELISA. Goitre size was estimated by ultrasonography.. After 2 weeks of treatment, normal FT4 was observed in 29% of patients in Group 1 and 59% (P < 0.05) of patients in Group 2. Furthermore, normal FT4 after 2 weeks of treatment was observed in 27% of patients in Group 3 and 54% (P < 0.05) of patients in Group 4. Similarly, FT3 normalized more rapidly in Groups 2 and 4 than in Groups 1 and 3. None of the patients showed an increase in thyroid hormones or aggravation of disease during combined treatment with MMI and KI. The remission rates in Groups 1, 2, 3 and 4 were 34%, 44%, 33% and 51%, respectively, and were higher in the groups receiving combined therapy but differences among four groups did not reach significance.. Combined treatment with MMI and KI improved the short-term control of Graves' hyperthyroidism and was not associated with worsening hyperthyroidism or induction of thionamide resistance.

Topics: Adult; Antithyroid Agents; Drug Administration Schedule; Drug Therapy, Combination; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Potassium Iodide; Remission Induction; Risk Assessment; Thyroid Function Tests; Thyroid Hormones; Thyrotoxicosis; Time Factors; Treatment Outcome; Young Adult

The objective of this study was to investigate quality of life (QoL) in patients with Graves' disease treated with radioiodine or antithyroid drugs.. The design of the study consists of an open, prospective, randomized multicenter trial between radioiodine and medical treatment. A total of 308 patients were included in the study group: 145 patients in the medical group and 163 patients in the radioiodine group. QoL was measured with a 36-item Short Form Health Status Survey questionnaire (SF-36) at six time points during the 48-month study period.. Patient who developed or got worse of thyroid-associated ophthalmopathy (TAO) at any time point during the 4-year study period (TAO group) had lower QoL when no respect was paid to the mode of treatment. TAO occurred in 75 patients who had radioiodine treatment at some time point during the study period as compared with TAO in 40 medically treated patients (P<0.0009). Comparisons between the group of patients who have had TAO versus the group without TAO, in relation to treatments and time, showed significantly decreased QoL scores for the TAO groups at several time points during the study. In patients without TAO, there were no differences in QoL related to mode of treatment.. The QoL in patients with Graves' ophthalmopathy was similar in radioiodine and medically treated patients, but patients who developed or had worsening of TAO had decreased QoL independent of mode of treatment. Furthermore, patients with TAO recovered physically within 1 year but it took twice as long for them to recover mentally.

Topics: Adult; Aged; Antithyroid Agents; Female; Graves Disease; Graves Ophthalmopathy; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Quality of Life; Treatment Outcome

Some precursor P wave changes on electrocardiogram (ECG) before the atrial fibrillation (AF) episodes occur in the hyperthyroidism. Our aim was to compare the effect of two antithyroid drugs (ATD) on P wave duration and dispersion (PWD) in patients with hyperthyroidism.. Fifty patients (13 men, 37 women; mean age 39.2+/-13.2 years) with newly diagnosed overt hyperthyroid patients with Graves' disease (GD) were enrolled in the prospective, randomized study. The maximum P wave duration (Pmax) and the minimum P wave duration (Pmin) were measured in all 12-lead surface ECGs. The patients were consecutively randomized to propylthiouracil (PTU) (n=24) and methimazole (MMZ) (n=26) groups. Electrocardiogram was repeated within euthyroid state after the 18-month ATD treatment. Student t-test, Mann-Whitney U and Pearson Chi-square tests were used for comparisons of the data between groups. The differences between pre- and post-treatment measurements within groups were evaluated by Wilcoxon Sign Rank test. The correlation of data was tested by using Spearman correlation analysis.. The maximum P wave duration (Pmax) was 90 (80-110) and 90 (90-110) msec, (p=0.586), and PWD was 35 (22.5-48.7) and 40 (30-40) msec, respectively (p=0.952) in PTU and MMZ groups. After euthyroidism was achieved, Pmax was 80 (80-90) and 87.5 (80-90) msec (p=0.676), and PWD was 27.5 (20-35) and 27.5 (20-30) msec in PTU and MMZ groups, respectively (p=0.540). After ATD treatment PWD decreased (p=0.009 and p<0.001, respectively) in both of PTU and MMZ groups. However effects of ATD on PWD change were similar (p=0.486).. P wave duration and PWD are found to be prolonged in hyperthyroid patients with GD. Both propylthiouracil and methimazole reduce the P wave duration and dispersion. Thus, we can conclude that improvements in atrial conduction properties are not associated with the type of ATD but with only achievement of euthyroidism.

Topics: Adult; Antithyroid Agents; Atrial Fibrillation; Electrocardiography; Female; Graves Disease; Heart Conduction System; Humans; Male; Methimazole; Propylthiouracil; Prospective Studies; Thyroid Hormones

Antithyroid drugs are widely used in the treatment of Graves' disease (GD), but the relapse rate is very high after therapy withdrawal. We evaluated the reduction effects of intrathyroid injection of dexamethasone (IID) on the relapse rate of hyperthyroidism in patients with newly diagnosed GD.. A total of 191 patients with GD completed the study. After 6 months of treatment with methimazole (MMI), the patients were randomly assigned to receive either MMI (96 patients) alone or MMI combined with IID (MMI+IID; 95 patients) treatment for 3 months, followed by continuing a dose of MMI that would maintain euthyroidism for the next 9 months in all of the patients. After withdrawal of the medical therapy, patients were followed for 24 months, and the relapse rate of hyperthyroidism was evaluated.. No statistical difference was observed in the levels of serum FT(4), TSH, or TSH receptor antibodies (TR-Ab), the thyroid volume, or the TR-Ab positive rate between the two groups at month 6. After the next 3 months of treatment with MMI+IID or MMI alone, the levels of TSH increased significantly, and the levels of serum TR-Ab, the TR-Ab positive rate, and thyroid volume decreased significantly in the MMI+IID group compared with the MMI group. Seven patients (7.4%) experienced a relapse of overt hyperthyroidism in the MMI+IID group and 49 patients (51%) in MMI group during the 2-yr follow-up period (P < 0.001).. MMI+IID treatment is helpful to prevent relapse of hyperthyroidism in GD after medical therapy withdrawal.

Topics: Adult; Anti-Inflammatory Agents; Antithyroid Agents; Dexamethasone; Drug Therapy, Combination; Female; Follow-Up Studies; Goiter; Graves Disease; Humans; Injections; Male; Methimazole; Middle Aged; Secondary Prevention; Thyroid Gland; Thyroid Hormones; Thyrotropin; Treatment Outcome; Young Adult

Preoperative preparation of the patient with Graves' disease (GD) is crucial to avoid intraoperative or postoperative complications associated with anesthesia or surgery. We aimed to evaluate thyroid blood flow and microvessel density in patients with GD according to antithyroid drug (ATD) treatment, preoperatively.. Forty-three patients were divided into two groups according to the ATD type. Patients in group 1 (n = 25) were treated with methimazole, whereas patients in group 2 (n = 18) were treated with propylthiouracil, preoperatively. Blood flow through the thyroid arteries was measured by color flow Doppler ultrasonography. The microvessel density (MVD) was assessed immunohistochemically and via Western blot analysis using the level of CD-34expression in thyroid tissue.. There was a positive correlation between blood loss and thyroid volume (r(s) = 0.953, P = .0001) and blood flow (r(s) = 0.720, P = .0001) and CD-34 expression (r(s) = 0.331, P = .03) and MVD (r(s) = 0.442, P = .003). No correlation was observed between ATD type and thyroid vascularity. In patients with longer treatment duration before operation, thyroid vascularity was significantly lower relative to patients with shorter treatment durations. According to logistic regression analysis, longer treatment duration had a 142-fold decreased rate of intraoperative blood loss independent of ATD type.. Preoperative ATD treatment duration may predict intraoperative blood loss during thyroidectomy. Longer treatment duration might be useful in reducing intraoperative bleeding, allowing better visualization and preservation of the nerves and parathyroid glands.

Topics: Adolescent; Adult; Antithyroid Agents; Blood Flow Velocity; Blood Loss, Surgical; Female; Graves Disease; Humans; Male; Methimazole; Microcirculation; Middle Aged; Preoperative Care; Propylthiouracil; Reference Values; Thyroid Gland; Thyroidectomy; Ultrasonography, Doppler, Color

This study evaluated the thyroidal kinetics of radioiodine in Graves' disease under continued thiamazole medication and after discontinuation of thiamazole for 1-2 days, with a view to keeping the period of discontinuation as short as possible and to exploring the underlying mechanism of a postulated radioprotective effect of antithyroid drugs.. In 316 patients, diagnostic and therapeutic radioiodine kinetics were followed up for 2 days by ten uptake measurements each and were defined mathematically by a two-compartment model.. Without thiamazole or when thiamazole was discontinued for at least 2 days, all uptake curves could be fitted perfectly by a simple in- and output function; the mean square error (mse) was 0.38 (test) and 0.28 (therapy). Under continued thiamazole medication (11.0+/-7.0 mg/day), the energy dose delivered to the thyroid was lowered by factor of 2.5. Uptake curves were deformed (mse: 1.06, test and 0.86, therapy) and appeared two peaked, suggesting coexistence of follicles with blocked and follicles with intact hormone synthesis and hence heterogeneous radioiodine uptake in the thyroid. In patients with maximally altered uptake curves, the success rate was as low as 31%. One day after discontinuation of thiamazole, mse was still increased (0.78, test), while 2 days afterwards it had normalised (0.36, test) and 3 days afterwards (mse: 0.24, therapy) the success rate was 87%.. Efficacy of radioiodine therapy under continued thiamazole medication is reduced not only by a lower uptake and shorter half-life of radioiodine, but also by a heterogeneous energy dose distribution in the thyroid. Discontinuation of thiamazole (but probably not of propylthiouracil) for at least 2 days is required to restore the efficacy of radioiodine.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antithyroid Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Metabolic Clearance Rate; Methimazole; Middle Aged; Radiopharmaceuticals; Thyroid Gland; Treatment Outcome

Graves' disease (GD) is a common TSH receptor autoantibody (TRAb)-mediated disorder. Because B lymphocytes are important self-antigen presenting cells and precursors for antibody-secreting plasma cells, temporary B-lymphocyte depletion with the monoclonal antibody rituximab (RTX) might be of benefit in GD.. The objective of this prospective, controlled, nonrandomized study was to investigate the effect of RTX in GD.. We studied 20 outpatients referred to a university clinic with newly diagnosed (four with relapse) untreated GD. Ten received RTX (+RTX), whereas 10 did not (-RTX).. The patients received methimazole (MMI) for a median of 102 d (+RTX) and 110 d (-RTX) before the study. Patients in the +RTX group received 375 mg RTX/m(2) iv on d 1, 8, 15, and 22, and all patients were withdrawn from methimazole (MMI) at d 22.. We measured time to relapse of hyperthyroidism and changes in autoantibody levels.. Four patients in the +RTX group remained in remission with a median follow-up of 705 d (range, 435-904 d), whereas all the patients in the -RTX group had relapsed by d 393 (P < 0.05). All of the patients in remission had initial TRAb levels below 5 IU/liter (normal, <0.7 IU/liter). However, none of the five patients in the -RTX group with correspondingly low TRAb levels were in remission (P < 0.01). RTX treatment did not affect autoantibody levels to a greater extent than did MMI monotherapy. Two patients received glucocorticoids for joint pain after RTX therapy.. RTX treatment may induce sustained remission in patients with GD with low TRAb levels. However, RTX did not affect autoantibody levels and seems ineffective in patients with high TRAb levels. At present, high cost, low efficacy, and potential side effects do not support use in uncomplicated GD.

Topics: Adolescent; Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antithyroid Agents; Autoantibodies; B-Lymphocytes; Female; Graves Disease; Graves Ophthalmopathy; Humans; Immunosuppressive Agents; Iodide Peroxidase; Lymphocyte Depletion; Male; Methimazole; Middle Aged; Pilot Projects; Prospective Studies; Receptors, Thyrotropin; Recurrence; Rituximab; Thyroid Hormones

Although methimazole (MMI) and propylthiouracil (PTU) have long been used to treat hyperthyroidism caused by Graves' disease (GD), there is still no clear conclusion about the choice of drug or appropriate initial doses.. The aim of the study was to compare the MMI 30 mg/d treatment with the PTU 300 mg/d and MMI 15 mg/d treatment in terms of efficacy and adverse reactions.. Patients newly diagnosed with GD were randomly assigned to one of the three treatment regimens in a prospective study at four Japanese hospitals.. Percentages of patients with normal serum free T(4) (FT4) or free T(3) (FT3) and frequency of adverse effects were measured at 4, 8, and 12 wk.. MMI 30 mg/d normalized FT4 in more patients than PTU 300 mg/d and MMI 15 mg/d for the whole group (240 patients) at 12 wk (96.5 vs. 78.3%; P = 0.001; and 86.2%, P = 0.023, respectively). When patients were divided into two groups by initial FT4, in the group of the patients with severe hyperthyroidism (FT4, 7 ng/dl or more, 64 patients) MMI 30 mg/d normalized FT4 more effectively than PTU 300 mg/d at 8 and 12 wk and MMI 15 mg/d at 8 wk, respectively (P < 0.05). No remarkable difference between the treatments was observed in patients with initial FT4 less than 7 ng/dl. Adverse effects, especially mild hepatotoxicity, were higher with PTU and significantly lower with MMI 15 mg/d compared with MMI 30 mg/d.. MMI 15 mg/d is suitable for mild and moderate GD, whereas MMI 30 mg/d is advisable for severe cases. PTU is not recommended for initial use.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Propylthiouracil; Prospective Studies; Thyroxine; Treatment Outcome; Triiodothyronine

Topics: Antithyroid Agents; Chloroquine; Double-Blind Method; Drug Therapy, Combination; Female; Graves Disease; Humans; Immunologic Factors; Male; Methimazole; Pilot Projects; Prospective Studies; Time Factors

In most trials, at least 30-60% of patients with Graves' disease treated with antithyroid drugs relapse within 2 years after therapy withdrawal. At present, there are no prognostic parameters available early in treatment to indicate patients likely to achieve long-term remission. Because thyrotropin receptor autoantibodies (TRAb) are specific for Graves' disease, we evaluated the ability of their levels and of their rate of change to predict long-term prognosis. In our study 216 consecutive patients with newly diagnosed Graves' disease started a therapy with methimazole. Patients were treated until they achieved euthyroidism and TRAb were measured at 6-month intervals throughout a follow up of 120 months. Our study demonstrated that at the onset of hyperthyroidism patients' age, sex, fT4 levels and goiter size had no prognostic value in predicting long-term prognosis (respectively p = 0.79; p = 0.98; p = 0.83; p = 0.89). On the contrary, at the time of diagnosis TRAb titer was a good predictor of the final outcome (p<0.001); a titer equal to (or) more than 46.5 UI/L could identify patients who had never achieved long-term remission with a sensitivity of 52% and a specificity of 78%. Also fall rate of TRAb at 6 months of follow up and after therapy withdrawal were useful to predict the final outcome (p<0.001). At 6 months of follow up the time of therapy withdrawal, a decrease of TRAb lower than 52.3% or even its increase could identify patients who had never achieved permanent remission with a sensitivity of 55% and a specificity of 79.1%. No single parameter among TRAb, satisfactory identified a sub-set of patients who achieved long remission. Accordingly to our data, the best result in predicting long term remission is probably given by the presence of at least one of the two features evaluated at 6 months (TRAb titer and/or percentage of TRAb fall rate), with a sensitivity of 63% and specificity of 88%. TRAb titers evaluated both at the onset of hyperthyroidism that at 6 months of therapy or their rate of fall at 6 months and at ATD withdrawal are predictors of outcome. However, the presence of at least one, between titers of TRAb or their rate of fall at six months, resulted to be the best predictor of remission with the higher sensitivity and specificity.

Topics: Adult; Antithyroid Agents; Female; Follow-Up Studies; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Prognosis; Receptors, Thyrotropin; Recurrence; Remission Induction; Withholding Treatment

To observe the clinical effects of prunrllae oral solution in treating hyperthyrea.. 56 cases with hyperthyrea were randomized into two groups; group A1 was treated by classic method, B1 was treated by classic method combined with prunrllae oral solution. The size, vessel caliber of thyroidea, volume of blood flow and blood flow rate pre-and post-treatment were measured by color supersonic, meanwhile, 20 normal thyroidea were measured as control group.. The size and vessel caliber of thyroidea of the two groups pre-treatment were obviously bigger than those of the control group, the volume of blood flow and blood flow rate were obviously slower than those of the control group (P < 0.001), the sizes of thyroidea of the two groups became smaller, especially the group B1 was more obvious, and there was no significant difference in the size of thyroidea between group B1 and control group.. It is indicated that combined treatment of traditional Chinese medicine (prunrllae oral solution) and western medicine is superior to western medicine in treating hyperthyrea.

Topics: Administration, Oral; Adult; Antithyroid Agents; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Phytotherapy; Plants, Medicinal; Prunella; Thyroid Gland

Patients with hyperthyroidism occasionally need rapid restoration to the euthyroid state. In view of the increased enterohepatic circulation of thyroxine (T4) and triiodothyronine (T3) in thyrotoxicosis, and metabolic effects of konjac glucomannan in gastrointestinal system, we aimed to determine the activity of glucomannan in treatment of hyperthyroidism.. A prospective, randomized, placebo-controlled, one-blind study design was used with newly diagnosed 48 hyperthyroid patients (30 patients with Graves' disease and 12 with multinodulary goitre). They were assigned to one of the following treatment groups: I) methimazole 2 x 10 mg, propranolol 2 x 20 mg, and glucomannan (Propol) 2 x 1.3 gr daily for two months; II) methimazole 2 x 10 mg, propranolol 2 x 20 mg, and placebo powder daily for two months.. No differences were detected from the point of view of the baseline thyroid hormone levels between groups (p > 0.05). Further analyses revealed that the patients receiving glucomannan at the end of the second, fourth and sixth weeks of the study had significantly lower serum T3, T4, FT3 and FT4 levels than the patients who received placebo (p < 0.05). TSH was not different between the two groups at any specific time (p > 0.05). At week 8, thyroid hormone levels were not shown any differences. The glucomannan-treated group had a more rapid decline in all four serum thyroid hormone levels than the placebo-treated group.. We believe our preliminary results indicate that glucomannan may be a safe and easily tolerated adjunctive therapeutic agent in the treatment of thyrotoxicosis. This combination therapy seems most effect during first weeks of treatment of a hyperthyroid patient.

Topics: Adult; Antithyroid Agents; Drug Therapy, Combination; Female; Graves Disease; Humans; Hyperthyroidism; Male; Mannans; Methimazole; Middle Aged; Propranolol; Prospective Studies; Thyroid Hormones; Thyrotoxicosis; Thyroxine; Treatment Outcome; Triiodothyronine

The close relationship between iodine intake and the effects of anti-thyroid drugs (ATD) for Graves' disease (GD) has been well established. However, it remains unknown whether restriction of dietary iodine improves the effect of ATD. This study aimed to clarify this issue in Japanese patients with GD who routinely ingest large amounts of dietary iodine. We performed a prospective clinical study in 81 patients with newly diagnosed GD who were divided into an iodine restricted group and a control group. Urinary iodine, thyroid hormones and TSH receptor antibody were measured during the first 8 weeks of ATD therapy. Urinary iodine concentrations in the iodine restricted group were significantly lower than in the control group (p=0.043). However, there were no significant differences in the decrease of thyroid hormones and TSH receptor antibody between the two groups. Restriction of dietary iodine does not ameliorate the effect of ATD therapy for GD in an area of excessive iodine intake.

Topics: Adult; Antithyroid Agents; Diet; Female; Graves Disease; Humans; Iodine; Male; Methimazole; Middle Aged; Receptors, Thyrotropin; Thyroxine; Triiodothyronine

A randomized clinical trial was performed to clarify whether continuous use of methimazole (MTZ) during radioiodine ((131)I) therapy influences the final outcome of this therapy.. Consecutive patients with Graves' disease (n = 30) or a toxic nodular goiter (n = 45) were rendered euthyroid by MTZ and randomized to stop MTZ 8 d before (131)I (-MTZ; n = 36) or to continue MTZ until 4 wk after (131)I (+MTZ; n = 39). Calculation of the (131)I activity included an assessment of the (131)I half-life and the thyroid volume.. The 24-h thyroid (131)I uptake was lower in the +MTZ group than in the -MTZ group (44.8 +/- 15.6% vs. 62.1 +/- 9.9%, respectively; P < 0.001). At 3 wk after therapy, no significant change in serum free T(4) index was observed in the +MTZ group (109 +/- 106 vs. 83 +/- 28 nmol/liter at baseline; P = 0.26), contrasting an increase in the -MTZ group (180 +/- 110 vs. 82 +/- 26 nmol/liter; P < 0.001). The number of cured patients was 17 (44%) and 22 (61%) in the +MTZ and -MTZ groups, respectively (P = 0.17). Cured patients tended to have a lower 24-h thyroid (131)I uptake (50.1 +/- 13.8% vs. 56.4 +/- 17.1%; P = 0.09). By adjusting for a possible interfactorial relationship through a regression analysis (variables: randomization, 24- and 96-h thyroid (131)I uptake, type and duration of disease, age, gender, presence of antithyroid peroxidase antibodies, thyroid volume, dose of MTZ), only the continuous use of MTZ correlated with treatment failure (P = 0.006), whereas a low 24-h thyroid (131)I uptake predicted a better outcome (P = 0.006).. Continuous use of MTZ hinders an excessive increase of the thyroid hormones during (131)I therapy of hyperthyroid diseases. However, such a strategy seems to reduce the final cure rate, although this adverse effect paradoxically is attenuated by the concomitant reduction of the thyroid (131)I uptake.

Topics: Adult; Aged; Antithyroid Agents; Combined Modality Therapy; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Logistic Models; Male; Methimazole; Middle Aged; Recurrence; Thyrotropin; Treatment Outcome

In this study we confirmed our previous findings on the importance of IgE in Graves' disease and further investigated the relationships existing among Graves' disease, IgE, and interleukin-4. Two hundred and thirty-two newly diagnosed Graves' disease patients were treated with methimazole for 2 years, and were classified into 3 groups according to their response to the therapy. Incidence of IgE elevation (IgE> or =170 IU/ml) before treatment was lowest, 23.8%, in the group who achieved remission without recurrence, while it was 41.7% in the group who achieved remission but recurrence occurred within 4 years. Incidence of IgE elevation before treatment was highest, 60.7%, in the group who failed to achieve remission, significantly higher than that of the group without recurrence. Incidence of IgE elevation before treatment in all these patients of Graves' disease were 35.3%, significantly higher than those of Hashimoto's thyroiditis (17.5%) and of simple goiter (7.0%). Serum IL-4 levels before treatment were significantly higher in the patients of Graves' disease with IgE elevation than in those without IgE elevation. Serum T4 concentration and TSAb titration before treatment were also significantly higher in elevated IgE group than in normal IgE group. These results support our previous findings and suggest that IL-4 may play important roles in the elevation of IgE, TBII, and TSAb in patients of Graves' disease, and that IL-4 and IgE may be involved in the development, progression, and maintenance of Graves' disease.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antithyroid Agents; Autoantibodies; Female; Graves Disease; Humans; Immunoglobulin E; Immunoglobulins, Thyroid-Stimulating; Interleukin-4; Male; Methimazole; Middle Aged; Thyroid Function Tests; Thyroid Gland; Time Factors

Aiming at evaluating the effect of antithyroid drugs on the efficacy of radioiodine treatment (RAI) we retrospectively analyzed 226 patients with Graves disease hyperthyroidism submitted to RAI between 1990 and 2001: 58 patients without any antithyroid drug (ATD) prior to RAI, 119 patients using propylthiouracil (PTU) and 49 patients using methimazole (MMI) prior to RAI. Clinical and laboratory parameters 1 year after RAI defined their clinical status (cured or not cured). High serum free T4 and 131-iodine uptake were negatively related with cure as well as lower RAI doses (mCi) and larger goiters (p< 0.05). The percentage of cured patients on PTU prior to RAI was 70.2% (84/119), while those on MMI was 85.7% (42/49), and 84.5% (49/58) of those without ATD prior to RAI (p= 0.034). On logistic regression analysis, free T4 > 4 ng/dl, large goiter, RAI dose < 10 mCi and PTU prior to RAI were related to lower cure rates. Compared to patients with no ATD prior to RAI, we concluded that the previous use of PTU implies in higher failure rates after RAI (OR= 3.13), an effect not observed in patients on MMI (OR= 1.28).

Topics: Adult; Antithyroid Agents; Combined Modality Therapy; Dose-Response Relationship, Radiation; Female; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Logistic Models; Male; Methimazole; Propylthiouracil; Radiation-Protective Agents; Radiography; Retrospective Studies; Thyroid Function Tests; Thyroid Hormones; Treatment Outcome

We have postulated that metabolic oxidation could be the source of signs and symptoms of hyperthyroidism. The present study was designed to evaluate urinary malondialdehyde levels in Graves' disease and compare this oxidative stress biomarker with the clinical evolution of patients suffering this illness.. We evaluated the concentration of urinary and serum malondialdehyde (MDA) in 36 patients with Graves' disease. Patients were treated with the antithyroid drug methimazole (MMI; Group A) or antioxidant mixture (200 mg vitamin E, 3 mg beta-carotene, 250 mg vitamin C, 1 mg Cu, 7.5 mg Zn, 1.5 mg Mn, and 15 microg Se; Group B).. MDA concentrations were higher in hyperthyroid patients compared to euthyroid controls, and a positive correlation was observed between serum and urinary MDA levels. Group A decreased urinary MDA to control values. There was a positive correlation between the clinical score and the heart rate of patients with urinary MDA before and during the treatment with MMI (Group A). Similar results were observed after treatment with the antioxidant mixture.. Urinary MDA might be a good parameter in the follow-up of patients during MMI treatment. We proposed that oxidative stress correlates with signs and symptoms of hyperthyroidism.

Topics: Adult; Antioxidants; Double-Blind Method; Female; Follow-Up Studies; Graves Disease; Heart Rate; Humans; Male; Malondialdehyde; Methimazole; Middle Aged; Oxidative Stress

The effects of supplementation with a fixed combination of antioxidants (vitamins C and E, beta-carotene and selenium) on superoxide dismutase activity, copper and zinc concentrations, and total antioxidant status were monitored in erythrocytes derived from a group of patients with Graves' disease treated with methimazole, with respect to the rate of achieving euthyroidism. Thyroid-stimulating hormone (TSH), thyroid hormones and the above-mentioned parameters were measured before therapy, and on days 30 and 60 after therapy initiation. The patients receiving antioxidant supplementation along with methimazole therapy (group A, n = 27) achieved euthyroidism at a faster rate than those treated with methimazole alone (group B, n = 28). The activity of superoxide dismutase decreased significantly in both patient groups during the treatment; however, there was no significant difference between the groups. There was no significant change in the erythrocyte concentration of copper, whereas the zinc concentration and total antioxidant status showed significant between-group differences. The study results clearly show that antioxidant supplementation in the treatment of Graves' disease is justified, while zinc and total antioxidant status in erythrocytes seem to be sensitive indicators of the efficacy of supplemental therapy.

Topics: Adolescent; Adult; Aged; Antioxidants; Antithyroid Agents; Copper; Dietary Supplements; Drug Combinations; Enzyme Activation; Erythrocytes; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Superoxide Dismutase; Thyroid Hormones; Thyrotropin; Zinc

Recent studies have indicated the existence of causal links between the endocrine and immune systems and cardiovascular disease. Mannan-binding lectin (MBL), a protein of the innate immune system, may constitute a connection between these fields.. To test whether thyroid hormone regulates MBL levels, we studied eight patients with Graves' hyperthyroidism before and after methimazole therapy, eight healthy subjects before and after short-term experimental hyperthyroidism, and eight hypothyroid patients with chronic auto-immune thyroiditis before and after L-thyroxine substitution.. In all hyperthyroid patients, MBL levels were increased--median (range), 1886 ng/ml (1478-7344) --before treatment and decreased to 954 ng/ml (312-3222) after treatment (P = 0.01, paired comparison: Wilcoxon's signed ranks test). The healthy subjects had MBL levels of 1081 ng/ml (312-1578). Administration of thyroid hormones to these persons induced mild hyperthyroidism and increased MBL levels significantly to 1714 ng/ml (356-2488) (P = 0.01). Two of the eight hypothyroid patients had undetectably low levels of MBL both before and after L-thyroxine substitution. The other six hypothyroid patients had decreased levels of MBL of 145 ng/ml (20-457) compared with 979 ng/ml (214-1533) after L-thyroxine substitution (P = 0.03, paired comparison: Wilcoxon's signed ranks test).. Our data show that thyroid hormone increases levels of MBL. MBL is part of the inflammatory complement system, and this modulation of complement activation may play a role in the pathogenesis of a number of key components of thyroid diseases.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Male; Mannose-Binding Lectin; Mannose-Binding Protein-Associated Serine Proteases; Methimazole; Middle Aged; Single-Blind Method; Thyroid Hormones; Thyroiditis, Autoimmune; Thyroxine; Triiodothyronine

Optimal treatment of Graves' disease in paediatric patients is still a matter of controversy. Antithyroid drugs, radioiodine and thyroidectomy are the three therapeutic options available.. To report our experience of long-term medical treatment and outcome of paediatric Graves' disease.. A 5-y-long medical protocol was implemented in 20 children and adolescents with Graves' disease. All patients received antithyroid drugs as the first therapeutic option; patients who did not enter long-term remission received I(131) and/or surgery as the definitive treatment.. The mean age at diagnosis was 12.1+/-4 y. Only two patients were males, both presenting concomitant type 1 diabetes. Mean follow-up was 13.8+/-5.5 y. Forty per cent of patients achieved long-term remission with low antithyroid drugs doses (mean treatment time: 5.4+/-1.4 y). Six patients received I(131) as definitive treatment and another six underwent surgery after completing medical treatment for 6.8+/-4.1 and 5.1+/-2 y, respectively. No patients requiring high antithyroid drugs doses to maintain euthyroidism reached long-term remission and needed I(131) and/or surgery.. Implementation of a long-term antithyroid drug protocol achieved 40% long-term remissions in paediatric patients with Graves' disease. Need for maintained high doses of antithyroid drugs could be considered a predictive factor for no remission. When permanent remission was not obtained by medical treatment, I(131)and/or surgery allowed healing in all cases.

Topics: Adolescent; Analysis of Variance; Antithyroid Agents; Child; Clinical Protocols; Combined Modality Therapy; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Thyroidectomy

The effect of supplementation with a fixed combination of antioxidants (vitamins C and E, beta-carotene and selenium) was monitored on the speed of attaining euthyroidism in a group of patients with Graves' disease, treated with methimazole.. The activity of glutathione peroxidase in whole blood and the concentrations of selenium, pituitary and thyroid hormones in serum were measured, prior to commencement of therapy and after 30 and 60 days. RESULTS Patients who received supplementation with antioxidants in addition to therapy with methimazole (Group A, n=29) attained euthyroidism faster than the patients treated with only methimazole (Group B, n=28). The concentration of selenium in the serum of patients in Group A increased significantly during treatment (p<0.001), while there was no statistically significant change in the patients in Group B. The concentration of selenium in the serum between the groups differed statistically significantly 30 days (p<0.05) and 60 days (p<0.01) after the commencement of therapy. Activity of glutathione peroxidase in whole blood increased during treatment in both groups of patients. However, a statistically more significant increase occurred in Group A compared to Group B, 30 days after the commencement of therapy (p<0.01).. The results of the study clearly indicate that supplementation with antioxidants in the treatment of Graves' disease is justified, particularly those containing selenium.

Topics: Adult; Antioxidants; Antithyroid Agents; Drug Therapy, Combination; Female; Glutathione Peroxidase; Graves Disease; Hemoglobins; Humans; Male; Methimazole; Selenium; Spectrophotometry, Atomic; Thyrotropin; Thyroxine; Triiodothyronine

Hyperthyroidism is associated with altered growth hormone (GH) secretion. Many patients with thyroid dysfunction experience several poorly described complications such as symptoms and signs also seen in patients with growth hormone deficiency (GHD). We have therefore prospectively evaluated a possible relationship between the thyroid function, body composition, leptin levels and insulin-like growth factor (IGF) related peptides in patients with Graves' disease. DESIGN, PATIENTS, AND MEASUREMENTS: In a prospective group of 24 fasting female patients with Graves' disease (mean age (CI 95%): 40 years (33-47)), we measured serum thyroxine, triiodothyronine, thyrotropine (TSH), TSH receptor antibodies, anti-thyroid peroxidase, leptin, body composition, body mass index (BMI) and IGF-related peptides at diagnosis and after 12 months of treatment with thiamazol (ATD).. In thyrotoxic patients IGF-I plus IGF-II correlated positively with IGFBP-3 at baseline (r = 0.90, p < 0.1 x 10(16)) and after 12 months follow-up (r = 0.87, p < 0.1 x 10(-16)). In the thyrotoxic state total IGF-I, IGF-II, IGF binding protein 3 (IGFBP-3) and acid-labile subunit (ALS) but not free IGF-I decreased significantly from 223 microg/L (189-260) (mean (CI 95%), 877 microg/L (801-953), 4165 microg/L (3772-4577) and 22 mg/L (18-26)) to 198 microg/L (172-226), 788 microg/L (711-865), 3431 microg/L (3135-3741) and 19 mg/L (16-26) (p <0.006), respectively, after 12 months of ATD despite an increase in BMI from 22 (21-23) to 23 kg/m(2) (22-25) (p < 0.0004) but no significant changes in leptin.. The complex IGF systems seemed intact in thyrotoxic patients but change in body composition and the regulation of leptin and insulin secretion during treatment of autoimmune thyroid disease influence IGF-related peptides leaving the patient in a state somewhat similar to partial GHD, but the mechanism behind these alterations remains unclear.

Topics: Adult; Body Composition; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Iodide Peroxidase; Leptin; Male; Methimazole; Middle Aged; Somatomedins; Thyroid Hormones; Thyrotoxicosis

The present study was to compare the efficacy of a single daily dose of methimazole (MMI) and propylthiouracil (PTU) in the treatment of Graves' hyperthyroidism.. Antithyroid drugs, MMI and PTU, are widely used in the treatment of hyperthyroidism. Previous studies in the treatment of hyperthyroidism with a single daily dose of antithyroid drugs have demonstrated a more favourable result with MMI. However, the efficacy of a single daily dose of PTU was inconsistent. In this study, we examined the therapeutic efficacy of single daily doses of MMI and PTU on the change of thyroid hormones and thyrotropin receptor antibodies (TRAb) levels.. Thirty patients with newly diagnosed Graves' hyperthyroidism were randomly divided into two groups, each receiving a single dose of either 15 mg MMI or 150 mg PTU daily for 12 weeks. The therapeutic efficacy was determined by serum total triiodothyronine (TT3), total thyroxine (TT4), thyrotropin (TSH), free thyroxine (FT4), and TRAb levels at baseline and at the end of 4, 8 and 12 weeks during the study period.. There was no significant difference in baseline thyroid function parameters. Serum TT3, TT4 and FT4 levels in the MMI-treated group were significantly lower than those of the PTU-treated group after 4 weeks and through the end of the study. MMI also has superior effect on reducing serum TRAb levels than PTU after 8 weeks and at the end of the study.. During the 12-week treatment of Graves' hyperthyroidism, a single daily dose of 15 mg MMI was much more effective in the induction of euthyroidism than a single daily dose of 150 mg PTU. In the doses used in this study, MMI is preferable to PTU when a once-daily regimen of antithyroid drug is considered for the treatment of Graves' hyperthyroidism.

Topics: Adolescent; Adult; Analysis of Variance; Antibodies, Monoclonal; Antithyroid Agents; Drug Administration Schedule; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Propylthiouracil; Receptors, Thyrotropin; Thyroxine; Triiodothyronine

Despite extensive use of (131)I therapy for Graves' hyperthyroidism the treatment regimen with (131)I and antithyroid drugs remain under discussion. In our prospective clinical study we followed acute thyroid hormone changes after (131)I in patients not pretreated with methimazole (MMI) and in patients with different MMI pretreatment regimens.. 187 patients were treated with fixed activity of 550 or 740 MBq of (131)I. First group (71 patients) received (131)I alone. In the second group (57 patients) MMI was stopped seven days before (131)I. The third group (59 patients) received MMI until (131)I application. Initial free triiodothyronin and free thyroxin were measured in the second group 7 and 2 days before (131)I therapy and in all three groups on the day of (131)I application as well as 2, 5, 12, and 30 days afterwards. Absorbed dose was measured in each patient.. In the non-pretreated group (131)I application was followed by a significant decrease of fT4 in 5 days and of fT3 in 2 days, higher reduction was detected in patients with higher baseline values. In MMI pretreated patients significant but clinically irrelevant increase of both thyroid hormones was detected with maximum value 7 days after discontinuation in the second group and 5 days after discontinuation in the third group. Additionally, in patients of the third group absorbed dose of (131)I was significantly lower relative to other two groups. We found no correlation between absorbed dose of (131)I and thyroid hormone changes.. Our study demonstrates that (131)I application alone does not result in exacerbation of hyperthyroidism and therefore it may be considered as safe. Additionally, MMI withdrawal causes significant but clinically irrelevant elevation of thyroid hormones.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antithyroid Agents; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Regression Analysis; Thyroid Hormones; Thyroxine; Time Factors; Triiodothyronine

Oxidative stress plays an important role in hyperthyroidism-induced tissue damage, as well as in development of autoimmune disorders. To clarify influence of thyroid metabolic status and autoimmune factors on blood extracellular indices of reactive oxygen species (ROS) generation and free radical scavenging in hyperthyroidism, we studied patients with newly diagnosed and untreated Graves' disease without infiltrative ophthalmopathy (17 female and 8 male, aged 41.8 +/- 8.9) and toxic multinodular goiter (15 female and 9 male, aged 48.4 +/- 10.1) under the same antithyroid treatment protocol. Initially and after achievement of stable euthyroidism with methimazole, plasma levels of hydrogen peroxide (H202), lipid hydroperoxides (ROOH) and ceruloplasmin (CP) and serum concentrations of thiobarbituric acid-reacting substances (TBARS) were determined. Similarly, activities of plasma superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) were assayed. The results were compared to those of age- and sex-matched controls. Average duration of hyperthyroidism and treatment period were similar in both patients groups. H202, ROOH and TBARS concentrations were significantly higher in hyperthyroid patients compared to controls. Hyperthyroidism caused an evident increase in SOD and CAT activities and CP level, as well as a decrease in GPx and GR activities. Achievement of euthyroidism resulted in normalization of all analyzed parameters in both hyperthyroid patients groups. These findings suggest that the changes in blood extracellular indices of oxidative stress and free radical scavenging in hyperthyroid patients are influenced by thyroid metabolic status, and are not directly dependent on autoimmune factors present in Graves' disease.

Topics: Adult; Age Factors; Antioxidants; Antithyroid Agents; Biomarkers; Female; Free Radicals; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Oxidation-Reduction; Reactive Oxygen Species; Sex Factors

Radioiodine therapy (131I) in hyperthyroid Graves' disease is generally followed by a transitory increase in levels of thyrotropin receptors antibodies (TRAb). Immunosuppressive effects of antithyroid drugs are still a matter of debate. In this study we evaluated the effect of methimazole pretreatment on the TRAb boost induced by 131I.. A randomized, prospective clinical trial.. 61 patients were randomly assigned to receive 131I alone (32 patients) or 131I plus pretreatment with methimazole (30 mg/day; 29 patients). Serum TRAb levels were measured on the day of 131I dosing (D0), and at 1, 3, 6 and 12 months after 131I administration.. The mean serum TRAb levels decreased significantly from baseline to D0 in patients treated with methimazole (80.8 vs 48.8 U/l; P<0.05). After 131I treatment, TRAb levels increased at 3 months (48.8 to 60 U/l; 19%) and they were still elevated at 6 months compared with D0 values (99.9 U/l; 105%). Thereafter, TRAb levels decreased to baseline values (47.8 U/l) at 12 months. In hyperthyroid patients, TRAb levels increased significantly from D0 to 1 month (45.0 to 78 U/l; 73%) reaching their highest levels at 3 months (225 U/l; 400%). After this, we observed a progressive decrease to the baseline levels at 12 months (40.0 U/l). The course of TRAb levels after 131I treatment was significantly different between the two groups (P<0.05). Multiple regression analysis identified serum TRAb levels on D0 as independent predictors of TRAb increment after 131I therapy (r2=0.34; P=0.001). A higher increment in serum TRAb levels was associated with hypothyroidism after 1 year of follow-up.. Methimazole pretreatment attenuates the 131I-induced rise in serum TRAb levels. The effects of methimazole could be attributed to a direct immunomodulatory action or may be due to its effects on the control of hyperthyroidism, which is a known cause of immune dysregulation.

Topics: Adult; Antithyroid Agents; Autoantibodies; Combined Modality Therapy; Female; Follow-Up Studies; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Prospective Studies; Receptors, Thyrotropin

Regardless the autoimmune origin of Graves' disease, the preferred method of its treatment remains antithyroid drug administration. Use of immunosuppressive agents (mostly steroids) is still limited to the therapy of disease complications, such as proliferative ophthalmopathy. The aim of the study was to assess the influence of early immunosuppressive treatment of autoimmune thyrotoxicosis with azathioprine on the course of the disease and the incidence of its complications. The study comprised 64 patients (47 females and 17 males aged 20-43 years) for the first time diagnosed with Graves' disease. The subjects were randomised into two groups. Group I consisted of 28 patients treated only with antithyroid drugs, the remaining 36 subjects additionally receiving azathioprine were included into group II. The dose of both drugs was adjusted during the treatment according to metabolic status of each patients. The treatment was continued for 8-14 months, the follow-up duration after therapy withdrawal was 5 years. Euthyreosis was achieved in all patients 2-8 weeks after treatment initiation. No drug intolerance symptoms were observed in group I. In four patients additionally treated with azathioprine, gastrointestinal side effects or leucopenia were present. The disease relapse was observed during the follow-up period in 15 (53.5%) patients of group I and in 3 (8.3%) of group II, the difference was statistically significant (p<0.01). Only one patient receiving additionally azathioprine presented ophthalmic symptoms compared with seven subjects (25%) treated only with antithyroid drugs (p<0.001). The patients of group I were also more frequently referred to surgical treatment due to rapid goitre growth (accordingly 5 (17.8%) and 1 (2.7%) patients, p=0.07), the difference between both groups not being statistically significant.. Additional early immunosuppressive treatment significantly decreased frequency of Graves' disease complications and thyrotoxicosis recurrence. The use of azathioprine may be advised in patients with contraindications to the radical Graves' disease treatment and in prophylaxis of its complications.

Topics: Adrenergic beta-Antagonists; Adult; Antithyroid Agents; Azathioprine; Drug Therapy, Combination; Female; Graves Disease; Humans; Immunosuppressive Agents; Male; Methimazole; Thyrotoxicosis; Treatment Outcome

Although many researchers have reported clinical and laboratory parameters for prediction of remission in Graves' disease during or after anti-thyroid drug therapy, there is no reliable one to assure the complete remission. We prospectively examined a practical therapy with minimum maintenance dose of anti-thyroid drugs for prediction of remission in Graves' disease. Fifty-seven patients with Graves' disease were treated with anti-thyroid drugs at the initial dose of 30 mg/day of methimazole (MMI) or 300 mg/day of propylthiouracil (PTU). Then, doses were gradually decreased, and finally discontinued when the patients were able to maintain euthyroid (normal FT4 and TSH) for at least 6 months with the minimum maintenance dose (MMI 5 mg every other day or PTU 50 mg every other day). After discontinuation of drugs, FT4, FT3, TSH and TSH-binding inhibitory immunoglobulin (TBII) were measured every one to two months for the first 6 months and every 3-4 months for the next 18 months to confirm continuous remission. After 2 years of drug cessation, 46 (81%) of 57 patients were in remission and the other 11 patients had relapsed into thyrotoxicosis. At the time of drug discontinuation, the serum concentration of FT4, FT3 and TSH, titers of anti-thyroglobulin antibodies and anti-thyroid microsomal antibodies, goiter size were not different between the remission and relapse groups. At the time of drug cessation, the activities of TBII and thyroid-stimulating antibodies (TSAb) overlapped between the two groups, although they were significantly lower in the remission group than in the relapse group (p<0.01). Forty percent (4/10) of TBII positive patients and 71% (23/32) of TSAb positive patients continued to be in remission. On the other hand, thyrotoxicosis relapsed in 5 (11%) of 47 TBII negative and 2 (8%) of 25 TSAb negative patients. These data indicate that minimum maintenance therapy to keep euthyroid (normal FT4 and TSH) for 6 months is a practical measure for 81% prediction of remission in Graves' disease. The measurement of TBII or TSAb gave little additional information for predicting remission.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Predictive Value of Tests; Propylthiouracil; Prospective Studies; Recurrence; Remission Induction

Topics: Adult; Antithyroid Agents; Autoantibodies; Drugs, Chinese Herbal; Female; Glycosides; Graves Disease; Humans; Immunosuppressive Agents; Male; Methimazole; Middle Aged; Phytotherapy; Tripterygium

Antithyroid treatment effectively restores euthyroidism in patients with Graves' hyperthyroidism. After a few months of treatment, patients are clinically euthyroid with normal levels of thyroid hormones, but in many patients TSH levels remain suppressed. We postulated that TSH receptor autoantibodies could directly suppress TSH secretion, independently from thyroid hormone levels, via binding to the pituitary TSH receptor. To test this hypothesis, we prospectively followed 45 patients with Graves' hyperthyroidism who were treated with antithyroid drugs. Three months after reaching euthyroidism, blood was drawn for the analysis of thyroid hormones, TSH, and TSH binding inhibitory Ig (TBII) levels. After 6.7 +/- 1.5 months since start of antithyroid treatment, 20 patients still had detectable TBII levels, and 25 had become TBII negative. The two groups had similar levels of free T(4) and T(3), but TBII-positive patients had lower TSH values than TBII-negative patients: median 0.09 (range < 0.01-4.30) mU/liter vs. 0.84 (0.01-4.20; P = 0.015). In addition, TSH levels correlated only with TBII titers (r = -0.424; P = 0.004), and not with free T(4) or T(3) values. Our findings suggest that TBII suppress TSH secretion independently of thyroid hormone levels, most likely by binding to the pituitary TSH receptor.

Topics: Adult; Aged; Antithyroid Agents; Autoantibodies; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Prospective Studies; Receptors, Thyrotropin; Thyroid Function Tests; Thyrotropin; Thyroxine; Triiodothyronine

Retrospective studies have indicated that anti-thyroid drugs (ATD) might possess a radioprotective effect, leading to a higher rate of recurrence of hyperthyroidism after iodine-131 ((131)I) therapy.. A randomized clinical trial was performed to clarify whether resumption of methimazole after (131)I influences the final outcome of this treatment.. We assigned 149 patients with Graves' disease or a toxic nodular goitre to groups either to resume (+ATD) or not to resume (-ATD) methimazole 7 days after (131)I. Before (131)I therapy, all patients were rendered euthyroid by methimazole, which was discontinued 4 days before the (131)I therapy.. During the follow-up period of 12 Months, 13 patients developed hypothyroidism, 42 were euthyroid, and 18 had recurrence of hyperthyroidism in the +ATD group; the respective numbers in the -ATD group were 16, 42 and 18 (P=0.88). At 3 weeks after (131)I therapy, the serum free-thyroxine index was slightly decreased (by 5.7%; 95% confidence interval (CI) -15.5 to 5.4%) in the +ATD group, in contrast to an increase of 35.9% (95% CI 18.8 to 55.5%) in the -ATD group (P<0.001 between groups). In the subgroup that remained euthyroid during follow-up, thyroid Volume reduction, assessed by ultrasonography, was smaller in the +ATD group [38.7% (95% CI 33.3 to 44.1%)] than in the -ATD group [48.6% (95% CI: 41.5-55.6%)] (P<0.05).. No radioprotective effect could be demonstrated, with regard to final thyroid function, for the resumpton of methimazole 7 days after (131)I therapy. Although resumption of methimazole slightly reduced the magnitude of shrinkage of the goitre obtained by (131)I, the prevention of a temporary thyrotoxicosis in the early period after radiation favours this regimen.

Topics: Aged; Antithyroid Agents; Combined Modality Therapy; Female; Follow-Up Studies; Goiter, Nodular; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Radiation-Protective Agents; Recurrence; Treatment Outcome

To observe the therapeutic effect of Xiehuo Yangyin powder (XHYY) in treating the initial stage of toxic and diffuse goiter (Graves' disease).. Sixty patients were randomly divided into two groups, the treated group (n = 30) was treated with XHYY and methimazole, while the control group (n = 30) was treated with methimazole alone. The TCM syndrome score and thyroxin level in the two groups were compared and analyzed before, and 2 weeks, 12 weeks after treatment.. The syndrome score and thyroxin level in the treated group 2 weeks, 4 weeks, 12 weeks after treatment were reduced in comparing with before treatment, with the improvement better than those in the control group in the corresponding stages (P < 0.05).. The Chinese herbal medicine XHYY plus methimazole, in treating Graves' disease, could rapidly and effectively improve the patients' clinical symptoms and lower the thyroxin level, reduce the daily taken of methimazole.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Phytotherapy; Powders; Thyroxine

The aim of the study was to assess the usefulness of determining the thyroid size, TRAb level and their correlation as markers for predicting the effectiveness of conservative treatment in Graves-Basedow's disease. The study included 100 patients with Graves-Basedow's disease; group I treated with thiamazole, group II treated with 131I. The biggest thyroid size, x -42.09+/-13.94ml, was found in the group unsuccessfully treated with thiamazole and was statistically significant compared to that in the euthyreosis group, x -31.65+/-11.74ml (p<0.01) and controls x -14.45+/-2.37ml (p<0.001). It is noteworthy that the initial TRAb level in the group with persistent hyperthyroidism was higher (x -54.39+/-31.21 U/I) than that in the euthyreosis group (x -29.13+/-19.44 U/I) and controls (x -2.75+/-2.06 U/l), p<0.001 for both parameters. Elevated antibody levels were also found after 12 and 18 months of treatment. Moreover, in the 131 I patients, the biggest thyroid size before iodine administration was found in the group with persistent hyperthyroidism, x -56.56+/-24.19 ml. It was statistically significantly different compared to the thyroid size in the euthyreosis patients x -37.922+/-20.69 ml (p<0.001) and in the hypothyreosis patients, x -43.47+/-18.09 ml (p<0.05). Before 131I administration, the highest antibody levels were observed in the group with persistent hyperthyroidism, x -103.61+/-43.90 U/I (p<0.001) compared to euthyreosis, hypothyreosis and control groups. The significance of differences in TRAb levels in the examined groups was still observed 18 months after 131I administration. In the groups of patients treated with thyreostatics and radioactive iodine, the positive correlation between the thyroid size and TRAb level was found before as well as 12 and 18 months after the onset of treatment.. 1.The TRAb levels and thyroid sizes are important parameters that should be considered in predicting the effectiveness of treatment. 2. The TRAb level correlates with the thyroid size.

Topics: Adult; Aged; Antithyroid Agents; Autoantibodies; Biomarkers; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Receptors, Thyrotropin; Thyroid Gland; Time Factors; Treatment Outcome; Ultrasonography

The aim of the study was to evaluate the usefulness of TRAb determinations in predicting and monitoring the effectiveness of various forms of treatment in Graves-Basedow's disease. 144 patients with Graves-Basedow's disease aged 18-76 years, x-44 were studied. Group I--54 patients treated with methizole, group II--45 patients treated with 131 I, group III--45 patients subjected to operative procedures. The TSH receptor antibodies were determined using the radioimmunoassay (TRAK-assay, Henning). The examinations were performed before, 12 and 18 months after treatment. Irrespective of the treatment type, the highest initial TRAb values were observed in the groups of patients with ineffective treatment (thiamazole x- 54.39+/-31.23 U/l, radioiodine x- 103.61+/-43.90 U/l, operative procedures x- 104.00+/- 52.34 U/l). During the 12-month follow-up of the patients subjected to surgery and 18-month follow-up of those undergoing conservative treatment, the level of antibodies did not normalize (x- 40.17+/-33.06, x- 77.18+/-44.92, x- 58.77+/-54.67, respectively). In the groups with effective treatment, the TRAb levels normalized. 1. The level of TSH receptor antibodies is a good marker for monitoring the effectiveness of treatment in Graves-Basedow's disease. 2. The high initial antibody level, irrespective of the kind of treatment instituted, is a bad prognostic feature. 3. The TRAb determinations performed 12 months after the institution of treatment also show some prognostic value. 4. The lack of normalization of antibody levels during treatment is associated with persistent hyperthyroidism, irrespective of the form of therapy.

Topics: Adult; Aged; Antithyroid Agents; Autoantibodies; Biomarkers; Female; Follow-Up Studies; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Predictive Value of Tests; Receptors, Thyrotropin; Sensitivity and Specificity; Thyroidectomy; Time Factors; Treatment Outcome

To investigate the clinical effect of prednisone on hyper thyroid atrial fibrillation associated with Graves disease (HAFGD).. Twenty-four patients with hyperthyroid atrial fibrillation associated with Graves disease were divided into two groups: traditional antithyroid group (10 cases, with 2 males and 8 females, treated by methimazole 15 approximately 30 mg/d and propranolol 15 approximately 30 mg/d) and prednisone group (14 cases with 3 males and 11 females, treated by methimazole 15 approximately 30 mg/d, propranolol 15 approximately 30 mg/d, and prednisone 30 mg/d). The effects of these two remedies on reversion from atrial fibrillation to sinus rhythm were compared.. The cardiac rhythm reverted to sinus rhythm in 12 out of the 14 cases in prednisone group with a reversion rate of 86% and the mean reversion time of 3.8 months (range 3.8 +/- 2.6 months), and in 4 out of the 10 cases in traditional antithyroid remedy group with the mean reversion rate of 40% and mean reversion time of 2.8 months (range 2.8 +/- 1.0 months). The reversion rate was significantly higher in prednisone group than in the traditional remedy group (P < 0.05).. Treatment of prednisone is more beneficial to reversion of atrial fibrillation into sinus rhythm among patients with HARGD.

Topics: Adult; Aged; Atrial Fibrillation; Female; Glucocorticoids; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Prednisone; Thyrotropin

Serum thyroid hormone concentrations increase after radioiodine (RAI) therapy for Graves' disease. This phenomenon has been ascribed to either antithyroid drug withdrawal before RAI therapy or release of preformed thyroid hormones into the bloodstream from the RAI-damaged thyroid. Lithium blocks the release of iodine and thyroid hormones from the thyroid, thus enhancing the effectiveness of RAI therapy. Changes in serum-free thyroxine (FT4) and triiodothyronine (FT3) levels after methimazole (MMI) discontinuation and RAI therapy were evaluated in a prospective, randomized, control study of 36 patients with Graves' disease. After a 3- to 4-month course of MMI, patients were assigned to one of three groups: G1 (RAI alone); G2 (RAI plus lithium for 6 d starting on the day of RAI therapy); or G3 (RAI plus lithium for 19 d starting on the day of MMI withdrawal). G1-G2 patients had an increase in serum FT4 and FT3 levels from 13.5 +/- 6.5 to 19.8 +/- 9.2 pmol/liter and 5.0 +/- 2.0 to 8.0 +/- 4.8 pmol/liter, respectively (P < 0.0001), 2-5 d after MMI withdrawal, but G3 patients showed no changes. In the 30 d after RAI therapy, mean serum FT4 values increased in G1 patients (P = 0.02), peaking at 3-7 d (P < 0.05) but not in G2 and G3 patients. Serum FT3 levels decreased in G1, G2, and G3 (P = 0.03, P = 0.001, P = 0.02, respectively). Hyperthyroidism was cured in 8 of 12 G1 patients, 11 of 12 G2 patients, and 11 of 12 G3 patients (P = 0.31). Control of hyperthyroidism was prompter in G2 (P = 0.08) and G3 (P < 0.05) than in G1 patients. Patients in the three groups received a similar dose of RAI, but the committed radiation to the thyroid was higher in G3 (563 +/- 174 Gray) and G2 (588 +/- 347 Gray) than in G1 (429 +/- 204 Gray) (P < 0.03). In conclusion, the results of the present study demonstrate that: 1) MMI withdrawal is associated with a slight rise in serum thyroid hormone levels; 2) a further increase occurs after RAI therapy; 3) changes in serum thyroid hormone concentrations are prevented by lithium; and 4) the increased effectiveness of RAI therapy in lithium-treated patients is related to the increased RAI retention in the thyroid gland. Accordingly, a short course of lithium therapy can be considered a useful adjunct to RAI therapy to obtain a prompter control of thyrotoxicosis and avoid its transient exacerbation because of MMI withdrawal and RAI administration.

Topics: Antithyroid Agents; Graves Disease; Humans; Iodine Radioisotopes; Lithium; Methimazole; Prospective Studies; Thyroid Hormones; Thyroxine; Treatment Outcome; Triiodothyronine

The study was so designed as to determine the effect of low to medium daily doses of methimazole (10-20 mg per day) on the number and function of different types of immunocompetent cells in peripheral blood of patients with Graves' disease administered methimazole for the treatment of hyperthyroidism. The study included 127 patients with Graves' disease divided into three groups: group I of 29 thyrotoxic patients before the beginning of treatment; group II of 73 euthyroid patients under antithyroid treatment; and group III of 25 patients who remained euthyroid 8 weeks after therapy discontinuation. In group I, the proportion of CD4+ cells, proportion and number of granulocytes, and their ingestion and microbicidity as well as monocyte phagocytic activity and ingestion were decreased. The mentioned alterations were concluded to most likely be the consequence of the underlying autoimmune process. In group II, the proportion and number of CD8+ cells were increased, while the natural killer cell activity was impaired. Granulocyte microbicidity was suppressed as compared to group I, while the granulocyte phagocytic activity was impaired as compared to normal values. Compared to normal, monocyte microbicidity and phagocytic activity were also suppressed. Monocyte ingestion was suppressed as compared to groups I and III, regardless of the patients' thyroid hormone status. Study results strongly support the hypothesis of a direct immunosuppressive effect of methimazole in patients with Graves' disease rather than the theory favoring concomitant immunomodulation due to thyroid hormone decrease.

Topics: Antithyroid Agents; Female; Graves Disease; Humans; Immunity, Cellular; Immunosuppression Therapy; Killer Cells, Natural; Leukocyte Count; Male; Methimazole; Middle Aged; Phagocytosis

Forty-two newly diagnosed patients with Graves' hyperthyroidism were randomly assigned to receive 131I therapy after pretreatment with methimazole (21) or beta-blocker alone (21) and prospectively evaluated, to determine possible effects of methimazole on 131I treatment outcome. After randomization, 8 patients were excluded from the study (5 from pretreatment group and 3 from nonpretreatment group). Radioactive iodine (baseline dose 15 mCi, adjusted for goiter size and/or 131I uptake) was administered after pretreatment with methimazole (30 mg initial dose for at least 2 months and stopped 6 days before treatment) and beta-blocker or pretreatment with beta-blocker alone (atenolol 50-100 mg/d). All but one patient in each group became hypothyroid. A similar length of time was required by both groups to achieve hypothyroidism (112 days, [95% confidence interval [CI] = 28 to 196 days) in the pretreated group and 106 days, [95% CI = 45 to 167 days] in nonpretreated patients). Free thyroxine (T4) normalized 44 +/- 39 days after therapy in the nonpretreated group and 35 +/- 30 days in the pretreated group (p = 0.57) and decreased to subnormal levels 80 +/- 70 days in nonpretreated and 65 +/- 32 days in pretreated patients (p = 0.46). We conclude that pretreating patients with methimazole before radioactive iodine therapy does not interfere with the final outcome. Similar cure rates and time required to achieve hypothyroidism after radioiodine were observed when patients were pretreated with methimazole compared to nonpretreated patients.

Topics: Adult; Animals; Antithyroid Agents; CHO Cells; Combined Modality Therapy; Cricetinae; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Thyroxine; Time Factors; Treatment Outcome

Previous studies of the treatment of hyperthyroidism with a single daily dose of antithyroid drugs have demonstrated a favourable result with methimazole (MMI). However, the efficacy of a single daily dose of propylthiouracil (PTU) was inconsistent. The present prospective randomized study was conducted to compare the efficacy of a single daily dose of MMI and PTU in the induction of euthyroidism in patients with Graves' disease.. Seventy-one patients with newly diagnosed Graves' disease were studied.. Patients were randomized to two groups to receive once daily dose of either 15 mg MMI or 150 mg PTU for 12 weeks. The therapeutic efficacy was determined biochemically by serum total T3, total T4 and TSH levels at baseline and at 4, 8 and 12 weeks during the study period.. There was no significant difference in baseline characteristics. Serum total T3 levels of the MMI group were significantly lower than those of the PTU group after four weeks of the treatment (3.54 +/- 0.72 vs. 5.49 +/- 2.74 nmol/l, P < 0.05) through the end of the study (2.22 +/- 1.42 vs. 4.30 +/- 1.78 nmol/l, P < 0.05). The changes in serum total T4 levels occurred in the same direction as serum total T3 levels but a significant difference was observed only after eight weeks of the treatment (MMI vs. PTU; 101.67 +/- 54.05 vs. 176.32 +/- 66.92 nmol/l, P < 0.05). At the end of the study, more patients in the MMI group had both serum total T3 and T4 levels less than the upper limit of the normal range compared to the PTU group (77.1% vs. 19.4%). Hypothyroidism was observed in 31.4% of the patients in the MMI group but not in the PTU group.. During 12-weeks' treatment of Graves' hyperthyroidism, a single daily dose of 15 mg of MMI was much more effective in the induction of euthyroidism than a single daily dose of 150 mg of PTU. Once daily regimen of MMI not only decreased serum T3 and T4 levels more rapidly but also induced euthyroidism four times more effectively than did the once daily regimen of PTU. In the doses used in this study, MMI is preferable to PTU when a once-daily regimen of antithyroid drug is considered for the treatment of hyperthyroidism.

Topics: Adult; Antithyroid Agents; Chi-Square Distribution; Drug Administration Schedule; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Propylthiouracil; Thyrotropin; Thyroxine; Triiodothyronine

Acute changes in thyroid hormone levels before and after radioiodine therapy for Graves' disease were compared in 42 patients randomized to receive either antithyroid drug pretreatment or no pretreatment. Five patients (11.9%), including 3 in the pretreatment arm and 2 in the no pretreatment arm experienced a late exacerbation of thyrotoxicosis after radioiodine therapy. The majority (19 of 21, 90.5%) of pretreated patients experienced a transient increase in free T(4) and free T(3) after discontinuation of antithyroid drugs, with little further elevation after radioiodine therapy. After stopping antithyroid drugs and before radioiodine administration, mean serum free T(4) values rose from 14.7 +/- 6.9 to 21.6 +/- 12.1 pmol/L, representing a 46.9% increase, whereas serum free T(3) levels rose from 4.9 +/- 1.7 to 8.1 +/- 6.3 pmol/L, representing a 65.3% increase. The average pretreated patient experienced a 52.4% increase [95% confidence interval (CI), +26.4% to +78.5%] in free T(4) and a 61.8% increase (95% CI, +23.5% to +100.0%) in free T(3). Conversely, the majority (19 of 21, 90.5%) of nonpretreated patients experienced a rapid decline in thyroid hormone levels after radioiodine treatment. Over the 14 days after radioiodine therapy mean free T(4) values in nonpretreated patients fell from 85.8 +/- 60.4 to 58.0 +/- 76.5 pmol/L, representing a 32.4% decrease, whereas mean free T(3) levels fell from 16.1 +/- 8.0 to 10.8 +/- 11.1 pmol/L, representing a 32.9% decrease. The average nonpretreated patient experienced a 20.6% decrease (95% CI, -47.3% to +7.0%) in free T(4) and a 24.3% decrease (95% CI, -1.2% to -47.4%) in free T(3) during this time period. Excluding 2 patients with a late exacerbation after radioiodine, 19 nonpretreated patients experienced a decrease in mean free T(4) values from 76.8 +/- 46.6 to 36.6 +/- 19.8 pmol/L, representing a 52.3% decrease, whereas mean free T(3) levels fell from 15.5 +/- 7.7 to 7.8 +/- 3.6 pmol/L, representing a 49.7% decrease. The average decrease in free T(4) levels among this subgroup of patients was 30.1% (95% CI, -4.6% to -55.6%), whereas the average decrease in free T(3) was 34.4% (95% CI, -13.7% to -55.1%). High levels of TSH receptor autoantibodies at diagnosis were associated with an acute worsening of thyrotoxicosis after stopping antithyroid drug pretreatment. We conclude that pretreatment with antithyroid drugs does not protect against worsening thyrotoxicosis after radioiodine, but may allow such patients

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Prospective Studies; Thyroid Hormones; Thyrotoxicosis; Thyroxine; Triiodothyronine

The effect of antithyroid drugs on the efficacy of radioiodine (131I) treatment is still controversial. This study evaluated the effect of methimazole pretreatment on the efficacy of 131I therapy in Graves' hyperthyroidism. Sixty-one untreated patients were randomly assigned to receive 131I alone (32 patients) or 131I plus pretreatment with methimazole (30 mg/d; 29 patients). 131I was administered 4 d after drug discontinuation. The calculated 131I dose was 200 microCi/g thyroid tissue as estimated by ultrasound, corrected by 24-h radioiodine uptake. Serum TSH, T4, and free T4 were measured 4 d before 131I therapy, on the day of treatment, and then monthly for 1 yr. Considering cure as euthyroidism or hypothyroidism, based on free T4 measurement, approximately 80% of patients from both groups were cured 3 months after beginning 131I treatment. After 1 yr the groups were similar in terms of persistent hyperthyroidism (15.6% vs. 13.8%), euthyroidism (28.1% vs. 31.0%), or hypothyroidism (56.3% vs. 55.2%). Relapsed patients presented larger thyroid volume (P = 0.002), higher 24-h radioiodine uptake (P = 0.022), and T3 levels (P = 0.002). Multiple logistic regression analysis identified T3 values as an independent predictor of therapy failure. In conclusion, pretreatment with methimazole had no effect on either the time required for cure or the 1-yr success rate of 131I therapy.

Topics: Adult; Antithyroid Agents; Combined Modality Therapy; Female; Follow-Up Studies; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Prospective Studies; Radiotherapy Dosage; Regression Analysis; Thyroid Gland; Thyroxine; Time Factors; Triiodothyronine

To investigate the effect of thyroxine upon the prevention of recurrence of Graves disease after treatment by antithyroid drugs.. Sixty patients newly diagnosed as Graves disease were treated with methimazole for 6 months and then randomly distributed into three groups. Patient in group A and group C received small dose of methimazole plus L-T(4) 50 microgram/d, and patients in group B were treated with methimazole in small dose only. Twenty four months later, only L-T(4) 50 microgram/d, without methimazole, was administered to the patients of group A; methimazole in maintenance dose was administered continuously to the patients of group B, and patients in group C were treated with methimazole in maintenance dose plus L-T(4) 50 microgram/d. Such treatments lasted 6 months. Post-treatment follow-up survey was conducted to the three groups.. The titers of thyroid-stimulating Ab (TSAb) in groups A and C were lower than that in group B. However, the recurrence rates among the three groups (4/20, 20%; 4/20, 25%; and 4/20, 20% respectively) were not significantly different.. Both treatment of Graves' disease with methimazole plus L-T4 and treatment with prolonged use of methimazole cannot reduce the recurrence rate more effectively than treatment with only methimazole. The level of TSAb is not the only factor that influences the recurrence of Graves disease.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Drug Therapy, Combination; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Secondary Prevention; Thyrotropin; Thyroxine; Treatment Outcome; Triiodothyronine

In a prospective, randomized study of 135 newly diagnosed patients with hyperthyroidism due to Graves' disease we compared the effect on remission rates of additional triiodothyronine (T3) with conventional antithyroid drug therapy. To this end 114 patients were followed for at least 12 months (15.7+/-4.9, mean+/-s.d.) after the discontinuation of any therapy. After return of thyroid function to normal (8.5+/-7.4 weeks, mean+/-s.d.) patients were maintained on antithyroid medication for 9.0+/-2.5 months. They were then randomly assigned to one of three groups: group 1 (n=44) stopped methimazole, groups 2 (n=39) and 3 (n=31) continued with exogenous T3 (not exceeding 75 microgram/day in any patient) for a further 6 months either with (group 2) or without (group 3) a fixed dose of 10mg methimazole daily. The T3 dose was kept variable to keep TSH suppressed (<0. 1mU/l), which could be achieved in 82% of patients on 100% of their monthly visits. No serious side-effect requiring the discontinuation of the study occurred in any patient. Total T3, TSH-receptor antibodies and some previously suggested potential predictors of relapse including thyroid size by ultrasound, 24h urinary iodine excretion, history of cigarette smoking and ophthalmopathy were determined at the outset of the study and subsequently every 6 months (and total T3 every 4 weeks). No significant difference (P>0.05, Chi square) was seen in relapse of hyperthyroidism after a mean follow-up of 16 months (range: 12-31 months; groups 1:52%, 2:44% and 3:42%) in an area of low-to-moderate iodine intake (prevalence of 24h urinary iodine excretion <100 microgram/24h: 17 and 25% at two different measurements respectively). Concomitantly, no predictor of recurrence of disease could be identified, irrespective of treatment modality.

Topics: Adolescent; Adult; Aged; Antibodies; Antithyroid Agents; Drug Combinations; Female; Goiter; Graves Disease; Humans; Iodine; Male; Methimazole; Middle Aged; Prospective Studies; Receptors, Thyrotropin; Recurrence; Remission Induction; Smoking; Thyroxine; Triiodothyronine

It is important to know whether a patient with Graves' disease will get into remission or not during antithyroid drug (ATD) treatment. Thyrotropin (TSH) receptor antibodies (TRAb) cause Graves' disease. Thyroid-stimulating antibody (TSAb) and TSH-binding inhibitor immunoglobulin (TBII) have been measured as TRAb to diagnose Graves' disease and to follow Graves' patients. Smooth decreases of TSAb and TBII during ATD treatment predict the remission of Graves' hyperthyroidism. We followed serial changes of TSAb and TBII in 58 Graves' patients before, during, and after ATD treatment; TSAb was measured as a stimulator assay, using porcine thyroid cells, and TBII as a receptor assay. Patterns of TSAb and TBII changes during ATD treatment differ from one patient to another. TSAb and TBII activities decreased and disappeared in 52 (group A) but continued to be high in the other 6 (group B); 39 of the 52 group A patients achieved remission, but all of the 6 group B patients with persistently positive TSAb and TBII continued to have hyperthyroidism. No differences in the initial TSAb and TBII activities were noted between the 52 group A patients and the 6 group B patients. Of the 52 group A patients in whom TSAb and TBII had disappeared, 44 had smooth decreases of TSAb and TBII (group A1), and 8 had complex changes of TSAb and/or TBII (group A2); 36 of the 44 group A1 patients (82%) but only 3 of the 8 group A2 patients (37%) continued to be in remission more than 1 year after ATD discontinuation. The number of remission in group A1 was significantly larger than that in group A2. No differences in the initial TSAb and TBII activities were noted between group A1 and group A2. More than 80% of group A1 patients, who had smooth decreases of TSAb and TBII, continued to be in remission longer than 1 year. We demonstrated that smooth decreases of TSAb and TBII during ATD treatment predicted the remission of Graves' hyperthyroidism. The Graves' patients can be classified into A1, A2, and B groups according to the patterns of TSAb and TBII changes during ATD treatment. Group A1 patients, who had smooth decreases of TSAb and TBII, had higher rate of remission than the others. Smooth decreases of TSAb and TBII during the early phase of ATD treatment are a reliable predictor of the remission.

Topics: Adult; Antithyroid Agents; Autoantibodies; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Predictive Value of Tests; Receptors, Thyrotropin; Remission Induction; Treatment Outcome

To study the therapeutic effect of Jiayanxiao (JYX) on thyrotoxic exophthalmos.. Forty-three patients were divided randomly into two groups, the 31 Patients in the treated group were treated with JYX plus tapazole, and the 12 patients in the control group were treated with prednisone plus tapazole. The therapeutic course of both groups was 3 months. The symptoms, eye signs, thyroxin level, and other routine laboratory parameters as well as the adverse effect of the therapy were observed and compared between two groups.. The total effective rate in the treated group was 80.6%, which was obviously higher than that in the control group (50.0%, P < 0.05). Effect of the treated group in lowering degree of exophthalmos was superior to that of the control group. Effects in elevating vision, decreasing palpebral fissure altitude and lowering serum T3, T4 contents in the two groups were similar (P > 0.05). Moreover, the treated group showed better efficacy in improving clinical symptoms with less adverse effect.. The therapeutic effect of JYX in treating thyrotoxic exophthalmos is ensured.

Topics: Adolescent; Adult; Antithyroid Agents; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Phytotherapy

Methimazole (MMI) has been reported to affect prognosis in hyperthyroid Graves' disease patients treated with radioiodine (131I). In the present study, serum concentrations of thyroxine (T4), triiodothyronine (T3), thyroglobulin (Tg), thyrotropin-binding inhibitory immunoglobulin (TBII), thyroglobulin antibody (TgAb), and thyroid-peroxidase antibody (TPOAb) were measured serially for 1 year in patients with Graves' disease after 131I treatment either given alone (group 1, 41 patients) or followed by an antithyroid drug (group 2, 19 patients). The effect of antithyroid drugs on these parameters was analyzed retrospectively. Mean serum concentrations of T4 and T3 both decreased to normal within 3 months after 131I treatment in both groups. Serum Tg concentrations in group 1 showed significant transient increases (about four times the basal value) 1 month after 131I administration. Titers of TBII, TgAb, and TPOAb in group 1 also increased transiently after 131I treatment, with the maximum increase at 3 months. Antithyroid drugs significantly lessened 131I-induced increases in serum concentrations of Tg and all thyroid autoantibodies tested. One year after 131I treatment, 33 of 41 patients (80%) were euthyroid or hypothyroid in group 1; this was true for only 4 of 19 group II patients (22%). The results indicate that administering antithyroid drugs after 131I treatment reduced 131I-induced damage to the thyroid and reduced therapeutic efficacy of 131I in hyperthyroidism. Drug treatment also inhibited release of Tg and blunted 131I-induced increases in titers of thyroid autoantibodies.

Topics: Adult; Aged; Antithyroid Agents; Autoantibodies; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Iodide Peroxidase; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Organ Size; Receptors, Thyrotropin; Thyroglobulin; Thyroid Gland; Time Factors

Radioiodine (131I) is the preferred definitive treatment for Graves' hyperthyroidism. Pretreatment with antithyroid drugs is often used to avoid thyroid hormone discharge after 131I ablation. However, this may represent an unnecessary increase in risk and costs. Fifty-one patients with Graves' disease were randomly assigned to receive 131I alone (28 patients) or 131I plus pretreatment with methimazole (30 mg/day; 23 patients). Methimazole was interrupted 4 days before 131I therapy. Serum T4, free T4 (FT4), and T3 were measured on days -4 and -1, on the day of treatment, and on days 2, 5, 7, 14, 20, and 30. In patients receiving 131I alone, mean serum T4 levels did not change after therapy. Mean serum FT4 and T3 levels decreased significantly 5 days after 131I administration (15% and 18%, respectively). Serum T3 reached its lowest level on day 30 (38%). With pretreatment, mean serum T4, FT4, and T3 levels increased (38%, 39%, and 70%, respectively) after methimazole discontinuation and before 131I administration. After 131I, serum T4 levels peaked on day 7 (23% vs. treatment day; 70% vs. baseline); FT4 levels peaked on day 14 (53% vs. treatment day; 107% vs. baseline). The serum T3 concentration increased 9% on day 2 (85% vs. baseline) and decreased from day 14 (15%) to day 30 (21%). We conclude that interruption of antithyroid drugs causes a short term increase in serum thyroid hormone levels in patients with Graves' hyperthyroidism receiving 131I. Thyroid hormone levels stabilize or decrease during the first 30 days after 131I therapy.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Thyroxine; Triiodothyronine

Oxygen free radicals (OFR) play a role in the pathogenesis of tissue damage in many pathological conditions via the peroxidation of membrane phospholipids. Experimental studies showed an elevated oxidative stress during hyperthyroidism, which is reduced by treatment. Therapy per se might decrease oxidative stress.. Fasting plasma levels of thiobarbituric acid reacting substances (TBARS), vitamin E and coenzyme Q10 were measured in 22 hyperthyroid patients, before treatment for their thyroid disease, after 13.9 [SD 9.2] weeks, when they achieved an euthyroid state on thyrostatic drugs, and again after 47.7 [21.0] weeks, off therapy. No patient presented additional risk factors for increased lipoperoxidation and/or increased OFR levels. Smokers were asked to abstain from smoking overnight.. All analytes were measured by HPLC.. In hyperthyroidism, plasma levels of TBARS were increased, whereas vitamin E and coenzyme Q10 were reduced. Average levels of TBARS and antioxidant agents returned to normal in euthyroid patients, without differences in relation to stop of thyrostatic therapy.. Our data confirm the presence of oxidative stress and decreased anti-oxidant metabolites in hyperthyroid patients, which are corrected in euthyroidism, without any influence of thyrostatic drugs per se. Nutritional support with antioxidant agents, which are defective during hyperthyroidism, is warranted.

Topics: Adult; Aged; Aged, 80 and over; Antithyroid Agents; Coenzymes; Female; Graves Disease; Humans; Lipid Peroxidation; Male; Methimazole; Middle Aged; Oxidative Stress; Propylthiouracil; Thiobarbituric Acid Reactive Substances; Thyroiditis, Autoimmune; Treatment Outcome; Ubiquinone; Vitamin E

The chief clinical characteristics of Graves' disease are hyperthyroidism and ophthalmopathy. The relation between the two and the effect of treatment for hyperthyroidism on ophthalmopathy are unclear.. We studied 443 patients with Graves' hyperthyroidism and slight or no ophthalmopathy who were randomly assigned to receive radioiodine, radioiodine followed by a 3-month course of prednisone, or methimazole for 18 months. The patients were evaluated for changes in the function and appearance of the thyroid and progression of ophthalmopathy at intervals of 1 to 2 months for 12 months. Hypothyroidism and persistent nyperthyroiaism were promptly corrected.. Among the 150 patients treated with radioiodine, ophthalmopathy developed or worsened in 23 (15 percent) two to six months after treatment. The change was transient in 15 patients, but it persisted in 8 (5 percent), who subsequently required treatment for their eye disease. None of the 55 other patients in this group who had ophthalmopathy at base line had improvement in their eye disease. Among the 145 patients treated with radioiodine and prednisone, 50 (67 percent) of the 75 with ophthalmopathy at base line had improvement, and no patient had progression. The effects of radioiodine on thyroid function were similar in these two groups. Among the 148 patients treated with methimazole, 3 (2 percent) who had ophthalmopathy at base line improved, 4 (3 percent) had worsening of eye disease, and the remaining 141 had no change.. Radioiodine therapy for Graves' hyperthyroidism is followed by the appearance or worsening of ophthalmopathy more often than is therapy with methimazole. Worsening of ophthalmopathy after radioiodine therapy is often transient and can be prevented by the administration of prednisone.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antithyroid Agents; Combined Modality Therapy; Disease Progression; Exophthalmos; Female; Glucocorticoids; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Prednisone; Prospective Studies; Treatment Outcome

Medical treatment of Graves' disease involves antithyroid drugs with or without the addition of exogenous T4. There have been conflicting reports as to whether the addition of T4 improves remission rates or delays relapse. To evaluate this issue in a North American population, 199 patients were treated with methimazole until they were euthyroid. They were then randomized to either methimazole alone in a dose sufficient to normalize TSH (group 1), or to 30 mg methimazole daily plus sufficient T4 to maintain TSH in the upper normal range (group 2), or to 30 mg methimazole daily plus sufficient T4 to suppress TSH below 0.6 mIU/L (group 3). After 18 months, methimazole was stopped, and T4 was continued in groups 2 and 3. Because not all patients in groups 2 and 3 achieved their target TSH concentration, they were reassigned to group A (TSH > or = 1.0) or group B (TSH < 1.0), based on the mean TSH achieved during methimazole treatment. One hundred forty-nine patients have been followed for at least 6 months after stopping methimazole (mean 27 months). Fifty-eight percent of patients have relapsed. There were no significant differences in relapse rates after stopping methimazole. Among those patients who did relapse, however, there was a significant difference in the months to relapse after stopping methimazole between groups B and 1 (group 1: 3.3 +/- 0.7, group A: 5.6 +/- 0.8, group B: 7.4 +/- 1.7; P = 0.01 for the comparison between groups B and 1). We conclude that the addition of T4 to methimazole does not improve long-term remission rates in Graves' disease.

Topics: Adult; Antibodies; Antithyroid Agents; Drug Therapy, Combination; Female; Graves Disease; Humans; Male; Methimazole; Receptors, Thyrotropin; Recurrence; Remission Induction; Thyroglobulin; Thyroid Hormones; Thyroxine; Treatment Outcome

It is commonly recognized that a few patients with Graves' disease (GD) develop an overt ophthalmopathy, although most of them show subclinical extraocular muscle enlargement by appropriate imaging techniques. At present, it is not possible to identify the subgroup of GD patients with subclinical retroorbital connective involvement. Recently, it has been shown that increase of soluble intercellular adhesion molecule-1 (sICAM-1) serum levels is correlated to clinical activity score in active Graves' ophthalmopathy (GO) patients with or without hyperthyroidism, suggesting that sICAM-1 serum values could reflect the degree of ocular inflammatory activity. The aim of this longitudinal study was to evaluate sICAM-1 serum levels in GD patients without clinical ophthalmopathy and to assess their possible relationship with occurrence of GO. We measured sICAM-1 serum levels in 103 initially hyperthyroid GD patients without clinical ophthalmopathy and in 100 healthy subjects. All patients were treated with methimazole for 2 yr. Sera were collected from all patients before treatment and then monthly for the first 6 months of therapy, every 2 months in the following 6 months, and finally at the end of the follow-up study. Patients developing GO were excluded from the follow-up at the onset of ophthalmopathy. During the follow-up 17 GD patients (16.5%, group 1) developed overt eye involvement (14 as active inflammatory ophthalmopathy and 3 as ophthalmopathy without clinical retroorbital connective inflammation) and 86 (83.5%, group 2) did not. At start of the study, the mean of sICAM-1 serum concentrations did not differ significantly between the 2 groups, but it was significantly higher than in controls in both groups. No significant correlation between serum sICAM-1 concentrations and free thyroid hormone levels was found in the 2 groups of patients. During the follow-up study, a further increase of sICAM-1 serum levels was observed in 12 of the 14 patients (85.7%) of group 1 who developed active inflammatory ophthalmopathy not only at the onset but also before clinical GO appearance. On the contrary, the 3 patients of group 1 that developed ophthalmopathy without clinical retroorbital inflammation did not show any further increase of sICAM-1 levels at every time of follow-up in comparison with the starting values, even if their sICAM-1 levels were always higher than in normal controls. Finally, group 2 patients showed significantly decreased sICAM-1 levels througho

Topics: Adult; Antithyroid Agents; Eye Diseases; Female; Follow-Up Studies; Graves Disease; Humans; Intercellular Adhesion Molecule-1; Male; Methimazole; Middle Aged; Solubility

The patients' views and costs of three different forms of treatment for Graves' hyperthyroidism were investigated. The study comprises 174 patients with Graves' hyperthyroidism who were stratified into two age groups: 20 to 34 years and 35 to 55 years. The younger group was randomly assigned to treatment with antithyroid drug plus thyroxine for 18 months or subtotal thyroidectomy, and in the older group iodine-131 was added as a third alternative. The patients' views of their therapy were based on a questionnaire formulated to identify possible differences between the three treatment forms. The costs were assessed by analyzing the official hospital reimbursement system for both outpatient and inpatient costs for a period of 2 years from the day of randomization. The results show that no significant differences in opinion were found between the five treatment groups with regard to any of the questions. Furthermore, only 10% of the patients expressed slight and 3% major hesitation to recommend the treatment form received to a friend with similar disease. Twenty percent of the patients with endocrine ophthalmopathy reported the eye problems to be much more troublesome and 14% somewhat more troublesome than the thyroid problems. The cost proportion between the medical and surgical treatment in the young group was 1:2.5 (1 = 1126 United States dollars [USD]) before and 1:1.3 (1 = 2284 USD) after inclusion of the relapse costs. The proportion between the medical, surgical, and iodine-131 treatment in the older group was 1:2.5:1.6 (1 = 1164 USD) before and 1:1.6:1.4 (1 = 1972 USD) after inclusion of the relapse costs.

Topics: Adult; Costs and Cost Analysis; Female; Graves Disease; Health Care Costs; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Prospective Studies; Quality of Life; Recurrence; Surveys and Questionnaires; Thyroidectomy

The distribution of peripheral blood CD16/56 cytotoxic T and natural killer (NK) cells in Graves' disease patients is analyzed in order to correlate them with disease activity and with prognosis. Eighteen patients with Graves' disease, twenty-four patients with Hashimoto's thyroiditis and thirty-two sex- and age-matched healthy control subjects were studied. Peripheral blood CD16/56 (cytotoxic T and NK) cells were analyzed by cytofluorometry. A decreased proportion of CD16/56+ and CD16/ 56+CD3+ cells were detected in Graves' disease patients when compared with thyroiditis patients and healthy control groups. No correlation was detected with serum free thyroxine. On diagnosis, patients who would require a radical treatment for thyrotoxicosis control showed a significant decrease of cytotoxic CD56+ T (CD3+) and NK (CD3-) cells compared with those who would maintain the euthyroid state after methimazole. These results suggest that the cytotoxic compartment, both T and NK cells, of the immune system is altered in patients with Graves' disease, independently of the functional thyroid status. Changes in peripheral blood lymphocytes in Graves' disease patients could be useful as predictive markers of an unfavorable outcome.

Topics: Adult; Antithyroid Agents; Autoantibodies; Biomarkers; CD56 Antigen; Female; Graves Disease; Humans; Killer Cells, Natural; Male; Methimazole; Receptors, IgG; T-Lymphocytes, Cytotoxic; Thyroid Hormones; Thyroiditis, Autoimmune

We have prospectively examined the percentage of peripheral blood lymphocytes which expressed adhesion molecules in untreated Graves' disease patients. Eighteen patients with Graves' disease, twenty-four patients with Hashimoto's thyroiditis and thirty-two sex- and age-matched healthy control subjects were studied. The expression of the lymphocyte adhesion molecules beta-1 integrin CD29, beta-2 integrin CD11b and L-selectin Leu8 (CD62L) was analyzed by cytofluorometry. A decreased percentage of CD29+ and CD11b+ lymphocytes was observed in hyperthyroid patients in comparison with Hashimoto's thyroiditis patients and healthy controls. However, there was no difference in the percentage of CD62L+ lymphocytes in the three groups. Percentages of lymphocyte activation markers, hyperthyroid status, presence or absence of ophthalmopathy or serum levels of antithyroid antibodies were not related to the proportions of CD29+ or CD11b+ lymphocytes. Four Graves' patients required radical therapy but after the treatment, there was no modification in the percentages of CD29+ and CD11b+ lymphocytes compared with those determined at diagnosis. Our findings suggest that the decrease in beta-1 and beta-2 integrins could be a predisposing marker of development of Graves' disease.

Topics: Adolescent; Adult; Antithyroid Agents; Biomarkers; CD18 Antigens; Female; Graves Disease; Humans; Integrin beta1; Lymphocytes; Macrophage-1 Antigen; Male; Methimazole; Middle Aged; Prospective Studies; Thyroid Hormones; Thyroiditis, Autoimmune

The optimal antithyroid drug regimen for Graves' disease remains a matter of controversy. The European Multicentre Trial Group has investigated the effects of methimazole drug dose on the long-term outcome of Graves' disease.. Extended follow-up of patients from a prospective multicentre trial, designed to study methimazole dose effects on the outcome of Graves' disease. We have reported previously that the relapse rates did not differ after a medication-free observation period of 12 months; the relapse rates were 37% and 38%, respectively. In this paper, we describe the outcome in these patients after a mean observation period of 4.3 +/- 1.3 years and have looked for potential predictors of this outcome.. Three hundred and thirteen patients with Graves' disease were randomized to treatment with a constant dose of 10 or 40 mg of methimazole for 1 year, with levothyroxine supplementation as required.. At the time of inclusion into the trial: thyroid size, T4, T3, TSH-binding inhibiting immunoglobulins, urinary iodide excretion, thyroid uptake, Crook's therapeutic index of hyperthyroidism (a measure of clinical disease severity). At the time of follow-up examination: TSH, T4, T3, thyroid size, thyroid ultrasound, THS-binding inhibiting immunoglobulins.. The overall relapse rate was 58%. There was no difference in relapse rates between patients treated with either 10 or 40 mg of methimazole (58.3 vs. 57.8%). Five patients had become spontaneously hypothyroid, without obvious relationship to antithyroid drug dose. Patients who relapsed and patients who remained in remission did not differ with respect to: age, goitre size, ophthalmopathy, median iodine excretion, serum T4 or serum T3, Crook's therapeutic index and thyroid uptake at the time of study entry. Thus, none of these variables was potentially suitable for predicting outcome. This finding was confirmed by Cox's proportional hazard regression. Thyroid volume, measured by ultrasound, did not differ between patients in remission and patients with relapse. There was no difference in the course of endocrine eye signs, in the requirement for steroid and radiotherapy for eye signs, or in thyroid echostructure between patients in the 10 and in the 40 mg group, nor was serum TSH different in patients who had remained in remission (0.8 +/- 0.6 mU/l in the 10 mg group, 1.0 +/- 0.8 mU/l in the 40 mg group).. The dose of methimazole in Graves' disease therapy can safely be kept to the minimal required dose. This will provide the same chance of remission as higher doses, and provide the best balance of risk and benefit.

Topics: Adult; Antithyroid Agents; Drug Administration Schedule; Follow-Up Studies; Graves Disease; Humans; Methimazole; Middle Aged; Prospective Studies; Recurrence; Time Factors; Treatment Outcome

The enterohepatic circulation of thyroxine (T4) and triiodothyronine (T3) is higher in thyrotoxicosis. Bile-salt sequestrants bind iodothyronines and thereby increase their fecal excretion. We, therefore, evaluated the effect of colestipol-hydrochloride administration on clinical and biochemical indices of patients with hyperthyroidism. In a prospective, controlled trial, ninety-two adult volunteers with Graves' disease, toxic autonomous nodule or toxic multinodular goiter were randomly assigned into the following treatment protocols: Group 1, 30 mg of methimazole (MMI) and 20 g of colestipol-hydrochloride (COL) daily; Group 2, 30 mg of MMI daily; and Group 3, 15 mg of MMI 20 g of COL daily. The patients were further classified into Group A, severe hyperthyroidism (baseline levels of total T3 (TT3) > or =5 nmol/l) and Group B, mild to moderate thyrotoxicosis (baseline levels of TT-3<5 nmol/l). Crook's clinical index, serum free T4 (FT4), TT3 and thyroid stimulating hormone (TSH) levels were determined before (WO), following one week (W1) and two weeks (W2) of treatment. Serum TT3 level decreased (mean+/-SE) at W1 by 40.8+/-2.6% of WO in Group1 and by 29.2+/-2.4% in Group 2 (p<0.001), and down further to 47.8+/-3.0% at W2 in Group 1, and 40.6+/-2.8% in Group 2 (p=0.01). Serum FT4 level decreased (mean+/-SE) from WO to W1 by 31.7+/-2.7% in Group 1 and by 16.2+/-3.1% in Group 2 (p=0.005), and down to 49.1+/-2.8% of WO at W2 in Group 1 and to 38.7+/-3.5% in Group 2 (p=0.07). In sub groups B COL was not effective in reducing thyroid hormone levels nor in ameliorating the clinical status of the patients. However, in Group A3 COL lowered FT4 (p=0.001) and TT3 (p=0.05) levels as compared to group A2. At W2 the clinical hyperthyroidism score improved faster in Group A1 (p<0.001) and Group A3 (p=0.012) as compared to the control Group A2. In conclusion, COL is an effective and well tolerated adjunctive agent in the treatment of hyperthyroidism. Its main effect is in severe cases of thyrotoxicosis, and in the first phase of treatment. As adjunctive COL treatment in hyperthyroidism allows reducing MMI dosage it may decrease the rate of dose dependent MMI side effects.

Topics: Adult; Antithyroid Agents; Colestipol; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Ion Exchange Resins; Male; Methimazole; Middle Aged; Prospective Studies; Thyroid Nodule; Thyrotropin; Thyroxine; Treatment Outcome; Triiodothyronine

The clinical course of 306 Graves' patients treated with methimazole (MMI) was reviewed with the aim of establishing criteria able to predict remission of hyperthyroidism after medical treatment. One hundred and ninety-four (149 females, 45 males) of 306 (63.4%) patients had relapse of hyperthyroidism after antithyroid drug (ATD) withdrawal. Relapse was more frequent during the first months of the follow-up, but still it was observed 3 years after MMI withdrawal. The relapse rate was dependent on the age of the patient, the size of goiter, and the level of TSH-receptor antibody (TRAb) at diagnosis, being observed in 40 of 47 (85%) patients with high (> 30 U/L) TRAb level and in 54 of 101 (53%) patients with low TRAb level (< or = 30 U/L; p <.0002). Remission was more frequent (43.3%) in patients having the combination goiter size < or = 40 mL, TRAb level < or = 30 U/L, than in patients with goiter size > 40 mL and high TRAb levels (9%). In the subgroup of patients with the combination: goiter < or = 40 mL- TRAb < or = 30 U/L - age at onset > 40 years, the remission rate was 80%, and all relapses occurred within the first 9 months after MMI withdrawal. In conclusion, our study confirms that hyperthyroidism relapses in the majority of patients with Graves' disease treated with ATD. Among different clinical and laboratory features, age at onset of hyperthyroidism, goiter size and TRAb level are particularly helpful in identifying those patients who are more prone to undergo a remission of hyperthyroidism after medical treatment and may be useful to select the minority of Graves' patients who will benefit from antithyroid drug treatment as a first choice.

Topics: Adult; Age of Onset; Antithyroid Agents; Female; Follow-Up Studies; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Receptors, Thyrotropin; Recurrence; Retrospective Studies; Thyroid Hormones; Thyroiditis, Autoimmune

Thyrotoxic patients exhibit increased levels of immune activation molecules (soluble interleukin-2 receptor [sIL-2R], intercellular adhesion molecule-1 [ICAM-1], and endothelial-leukocyte adhesion molecule-1 [ELAM-1]) in serum, although the clinical significance of these measurements remains unclear. In a randomized 4-week study, we have recently shown that in the treatment of hyperthyroidism, the combination of cholestyramine and methimazole (MMI) resulted in faster lowering of serum thyroid-hormone levels than did MMI alone. Stored serial serum samples from patients participating in this randomized treatment trial were analyzed for sIL-2R, soluble ICAM-1 (sICAM-1), and soluble ELAM-1 (sELAM-1). The levels of all three molecules were elevated in patients with hyperthyroidism. Although the levels of sICAM-1 and sELAM-1 remained elevated through the 4-week follow-up period in both groups of patients, the sIL-2R levels (normal levels, 1.0 to 4.2 ng/ml) decreased significantly in the 10 patients who received cholestyramine in addition to MMI (week 0, 14.2 +/- 1.5 ng/ml; week 2, 10.8 +/- 1.2 ng/ml; week 4, 8.9 +/- 1.5 ng/ml). In eight patients who received MMI alone, sIL-2R decreased less rapidly (week 0, 12.3 +/- 1.4 ng/ml; week 2, 12.3 +/- 1.3 ng/ml; week 4, 10.9 +/- 1.3 ng/ml). sICAM-1 and sELAM-1 were elevated at baseline but did not decrease during therapy. In the former group, free thyroxine and free triiodothyronine decreased faster. These data show that levels of sIL-2R in serum, but not those of sICAM-1 and sELAM-1, may be of clinical use in the early follow-up evaluation of medically treated patients.

Topics: Antithyroid Agents; Biomarkers; Cholestyramine Resin; E-Selectin; Female; Graves Disease; Humans; Intercellular Adhesion Molecule-1; Male; Methimazole; Multivariate Analysis; Randomized Controlled Trials as Topic; Receptors, Interleukin-2; Thyroid Hormones; Thyrotoxicosis

We performed a randomized, open prospective study to determine the effect of 1 alpha-hydroxyvitamin D3 [1 alpha (OH)D3] on hyperthyroidism in patients with untreated Graves' disease. At the time of entry into the study, 30 patients were randomly assigned to receive a daily dose of 30 mg methimazole (MMI) (group A, n = 15) or the same dose of MMI supplemented with 1.5 micrograms 1 alpha (OH)D3 (group B, n = 15). These treatment regimens were continued for 24 weeks, and physicians were allowed to adjust MMI dosage during follow-up visits. Blood samples were collected, and serum concentrations of free triiodothyronine (FT3), free thyroxine (FT4), T3, T4, thyrotropin (TSH), alkaline phosphatase (ALP), and TSH-receptor antibody (TRAb) were determined. During the follow-up periods, all patients became euthyroid. The dose of MMI was not significantly different between these two groups. In contrast, decreases in mean serum FT3 and FT4 levels, as well as in mean serum T3 and T4 levels, were greater in group B. Correspondingly, the reciprocal increase in the mean TSH level was more prominent in group B. Mean TRAb levels did not differ between the two groups. Mean serum ALP levels in group B were significantly lower than in group A at 24 weeks. Thus, we suggest that concomitant administration of 1 alpha (OH)D3 is useful for treating hyperthyroidism in patients with Graves' disease.

Topics: Adolescent; Adult; Aged; Alkaline Phosphatase; Antithyroid Agents; Autoantibodies; Female; Graves Disease; Humans; Hydroxycholecalciferols; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Receptors, Thyrotropin; Thyrotropin; Thyroxine; Time Factors; Triiodothyronine

Topics: Adolescent; Adult; Antithyroid Agents; Drug Therapy, Combination; Female; Follow-Up Studies; Graves Disease; Humans; Intercellular Adhesion Molecule-1; Male; Methimazole; Middle Aged; Prognosis; Prospective Studies; Recurrence; Thyroxine; Treatment Outcome

A prospective long-term follow-up study was performed with conventional divided doses (group C: 10 mg 3 times daily, N = 58) and a small single daily dose (group S: 15 mg once daily, N = 54) of methimazole (MMI) for the treatment of Graves' hyperthyroidism. Within 8 weeks, almost 80% of the patients in both groups became euthyroid. The mean time required to achieve a euthyroid state was 5.6 +/- 2.7 weeks in group C and 5.8 +/- 3.1 in group S. TSH binding inhibitor immunoglobulin (TBII) levels before therapy were 44.2 +/- 22.7% and 47.1 +/- 23.9% in group C and group S, respectively. A similar gradual fall in TBII levels was observed in both groups over a two-year period of treatment. MMI doses were gradually reduced to a maintenance dose (5 mg daily) after the patients became euthyroid. The patients were treated for 28 +/- 9 months and were followed up after therapy was stopped (observation period in patients who remained in remission was 12-130 (75 +/- 34) months and the interval to relapse in recurred cases was 1-98 (20 +/- 27) months). The rates of recurrence in group C were 41% at 1 yr, 54% at 2 yrs, 56% at 4 yrs and 61% at 6 yrs. In group S, these were 44%, 53%, 56% and 63%, respectively. No differences between relapse rates were observed with the two different dosage regimens. Adverse effects occurred more frequently in group C patients (24%) than in group S patients (13%). These results show that there is no difference in the clinical and immunological course or in the long-term remission rate of Graves' hyperthyroidism when the treatment is initiated with either a small single daily dose (15 mg) or the conventional regimen (10 mg 3 times daily).

Topics: Adult; Antithyroid Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Graves Disease; Humans; Male; Methimazole; Middle Aged; Prospective Studies; Recurrence

To investigate possible correlations between thyroid vascularization and activity of Graves' disease, we measured blood flow (TBF) at the inferior thyroid artery and intraparenchymal vascularization (number of vessels per square centimeter) by color Doppler ultrasonography (CDU) on Graves' patients at different phases of the disease. We studied 88 patients cross sectionally: 22 untreated; 17 euthyroid after 6 months of methimazole; 49 euthyroid at drug withdrawal after 12 to 24 months of treatment. The patients of the latter group were followed up for 29.1 +/- 6.3 months after discontinuation of treatment. On the day of CDU examination, free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), antiperoxidase and anti-TSH receptor (TRAb) antibodies were measured. Vascularization indices were significantly higher in the Graves' patients than in controls. In the patients euthyroid under treatment, vascularization was not significantly lower than in the untreated group, but TBF and vessel number both appeared clearly reduced in the patients tested at drug withdrawal. The vascularization indices at drug withdrawal were significantly higher in the patients who relapsed than in those in stable remission: TBF (mL/min) 50.6 +/- 36.8 vs. 23.8 +/- 17.5, p = 0.001; vessel number/cm2 1.8 +/- 0.8 vs. 0.8 +/- 0.5, p = 0.002. A multivariate analysis, evaluating the predictive value of vascularization, hormonal and immunological parameters for relapse, demonstrated a significant predictive value for TRAb (RR 8.2; p = 0.001) and a weak predictive value for TBF (RR 1.1; p = 0.02). In conclusion, CDU examination confirms that thyroid hypervascularization in Graves' disease is not related to thyroid hormone circulating levels. The association of increased TBF and high levels of TRAb in the relapsing forms of disease suggests that thyroid hypervascularization is probably related to the activity of the underlying autoimmune processes.

Topics: Adult; Aged; Antibodies; Antithyroid Agents; Arteries; Female; Graves Disease; Hormones; Humans; Iodide Peroxidase; Male; Methimazole; Middle Aged; Organ Size; Prognosis; Receptors, Thyrotropin; Recurrence; Regional Blood Flow; Thyroid Gland; Thyrotropin; Thyroxine; Time Factors; Treatment Outcome; Triiodothyronine; Ultrasonography, Doppler, Color

To explore the therapeutic effect and its mechanism mainly using traditional Chinese medicine (TCM) of replenishing Qi and nourishing Yin (RQNY) with a small dosage of Tapazol for treatment of Graves disease (GD).. The changes of thyroid function and the activity of sodium pump of human erythrocyte in the patients with Graves disease were observed and compared before and after treatment between the treated group (42 cases) by combining treatment mainly using TCM of RQNY and a small amount of Tapazol, and a control group (42 cases) by Tapazol alone.. After treatment for half a year, one and two years, the serum levels of T3, T4 in above two groups were markedly decreased than those of before treatment, the therapeutical effect of treated group was superior to that of control group. The activity of sodium pump in human erythrocyte in the GD patients was obviously higher than that of normal group and that of before treatment. After treatment for one and two years mainly by TCM or Western medicine, the erythrocyte sodium pump activity was obviously lower than that of before treatment and that of normal group. The decrease of erythrocyte sodium pump activity in group of combination therapy was markedly lower than that in group of Western medicine.. Combination therapy was much more effective on the functional remission of thyroid and energy metabolism in GD patients than that of using Tapazol therapy only.

Topics: Adolescent; Adult; Antithyroid Agents; Biological Transport, Active; Child; Drug Therapy, Combination; Drugs, Chinese Herbal; Erythrocytes; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Sodium; Thyroxine; Triiodothyronine

To obtain a simple standard regimen, suitable for general practice, and based upon the addition of antithyroid drug plus thyroxine for attaining euthyroidism in patients with Graves' disease.. Prospective, randomized trial of patients with Graves' disease followed for 3 months after the initiation of therapy with an antithyroid drug and combined with the later addition of triiodothyronine to keep the patient euthyroid. The patients were randomized, according to birth date, between methimazole and propylthiouracil. Three dose schemes were tested for each antithyroid drug.. The study was performed at the thyroid outpatient units of two general hospitals, with the patients having been referred from primary care.. Ninety-four patients with Graves' disease who were suitable for treatment with antithyroid drugs.. The patients were allocated into six groups. Three groups received methimazole (10 mg every 6th, 8th or 12th h) and three received propylthiouracil (100 mg every 6th, 8th or 12th h). Twenty micrograms of triiodothyronine was added when the patients were euthyroid to avoid hypothyroidism.. The lowest serum free thyroxine level within 3 months of the initiation of the antithyroid treatment.. Fourteen per cent of the patients on methimazole 10 mg every 12th h and 29% on propylthiouracil 100 mg every 12th h did not achieve euthyroidism within the 3-month observation period. All but one patient on methimazole 10 mg every 8th h or propylthiouracil 100 mg every 8th h reduced the free serum thyroxine levels to the normal or hypothyroid range within the observation period. All of the patients on methimazole 10 mg every 6th h and 56% on propylthiouracil 100 mg every 6th h reduced the serum T4 values into the hypothyroid range within the period.. A standard regimen, based upon the addition of methimazole 10 mg every 8th or 6th h or propylthiouracil 100 mg every 8th or 6th h and followed by the addition of thyroxine or triiodothyronine when euthyroid to avoid hypothyroidism, seems to be suitable for attaining euthyroidism within 3 months in patients with Graves' disease. A dose scheme based on methimazole 10 mg every 12th h or propylthiouracil 100 mg every 12th h were found to be unsuitable due to an unacceptably high incidence of failure to attain euthyroidism or hypothyroidism within 3 months.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Drug Administration Schedule; Drug Therapy, Combination; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Propylthiouracil; Prospective Studies; Thyroxine

Soluble class I major histocompatibility antigens (sHLA), beta 2-microglobulin (beta 2-M), and soluble interleukin-2 receptor (sIL-2R), are secreted by B and T lymphocytes upon activation, and have been used as markers of immune activation in several diseases. Thirty-two Graves' disease patients were randomly assigned to three methimazole (MMI) regimens of treatment: (1) low-dose, starting with 45 mg/day, and lowering the dose thereafter to maintain normal serum thyroid hormones; (2) MMI 60 mg/day + levothyroxine, and (3) MMI 30 mg/day + levothyroxine. Serum sHLA, beta 2-M, sIL-2R, TSH receptor antibodies (TSH-R Ab), T3, and free T4 (fT4) were measured at diagnosis and at weeks 4, 12, and 24 (end of treatment). Patients were followed-up after treatment for at least 24 weeks (24 to 89). At diagnosis, serum levels of sIL-2R, beta 2-M, sHLA, and TSH-R Ab were elevated. Serum sIL-2R, beta 2-M, sHLA, and TSH-R Ab decreased with treatment. No effect of the varying MMI regimens on these parameters was observed. Soluble IL-2R correlated positively with T3, fT4, beta 2-M, sHLA, and TSH-R Ab. Statistically significant, but weak, correlations (r < 0.35) were observed between beta 2-M, sHLA, and TSH-R Ab, between beta 2-M, T3, and fT4, and between TSH-R Ab and T3. Recurrence rates were not associated either with the MMI regimen or any of the parameters studied, with the exception of elevated initial TSH-R Ab levels. Serum sHLA, beta 2-M, and sIL-2R are increased in untreated Graves' disease, and decrease during treatment. No MMI dose-related differences were observed in these parameters, and in the recurrence rate. Unfortunately, sHLA, beta 2-M, and sIL-2R were not useful predictors of prolonged remission after MMI treatment.

Topics: Adolescent; Adult; Antithyroid Agents; beta 2-Microglobulin; Disease Progression; Dose-Response Relationship, Drug; Female; Graves Disease; Histocompatibility Antigens Class I; Humans; Male; Methimazole; Middle Aged; Receptors, Interleukin-2; Thyroid Function Tests; Thyroid Hormones

Medical treatment of Graves' disease involves use of antithyroid drugs with or without the addition of exogenous L-T4. There have been conflicting reports as to whether the addition of T4 reduces TSH receptor antibodies and improves remission rates more than antithyroid drugs alone. To further examine the effect of drug therapy on serum concentrations of TSH receptor antibodies. 70 patients with Graves' disease were treated with methimazole (Tapazole) alone until they were euthyroid. Then they were randomized to receive either: 1) methimazole alone in a dose sufficient to normalize TSH (0.3-5.4 mIU/L; Group 1); 2) 30 mg methimazole daily plus sufficient T4 (Synthroid) to maintain TSH in the high-normal range (2.0-5.4 mIU/L; Group 2); or 3) 30 mg methimazole daily plus sufficient T4 to suppress TSH to below 0.6 mIU/L (Group 3). The duration of treatment in all groups was 18 months. At baseline and after 6 and 18 months, TSH receptor antibodies were measured both by the ability of patients' sera to stimulate cAMP production by FRTL-5 cells (thyroid-stimulating Ig) and by the ability of patients' sera to inhibit binding of radiolabeled TSH to solubilized porcine thyroid membranes (TSH-binding, inhibiting Ig). Thyroid-stimulating Ig(TSI) and TSH-binding, inhibiting Ig(TBII) concentrations were similar among the three groups at baseline. Mean baseline TSI (expressed as the percent of normal control) for all patients combined was 306 +/- 21%. Mean baseline TBII (expressed as percent inhibition of TSH binding) was 38 +/- 2%. TSI was elevated in 85% and TBII was elevated in 75% of patients at baseline. After 18 months, TSI was elevated in 64% of patients, and TBII was elevated in 28%. Serum TSI decreased by 36 +/- 5% during the study, and there was no significant difference in the degree of reduction among the three groups (P = 0.99). Serum TBII decreased by 59 +/- 3%, and there also was no significant difference among the groups (P = 0.83). At baseline, serum TBII correlated with free T4 (r = 0.33, P < 0.01), total T3 (r = 0.55, P < 0.01), and thyroid size (r = 0.35, P < 0.01). There was no correlation between TSI and any of the baseline parameters or between TSI and TBII at any timepoint. In conclusion, we found that the addition of T4 to methimazole does not result in a greater decrease in TSH receptor antibody concentrations than treatment with methimazole alone. From these results, we would predict no difference in remission rates among these patients, but c

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Autoantibodies; Child; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Receptors, Thyrotropin; Thyrotropin; Thyroxine

Thirty-two cases of newly diagnosed Graves' disease with hyperthyroidism were recruited in this study on the changes of leucocyte glucocorticoid receptor (GCR), plasma ACTH, and cortisol levels befor and after treatment with methimazole (tapazole) alone (n = 16) and methimazole combined with Dexamethasone (Dex, TD group, n = 16). Twenty normals served as the control. Methimazole treatment was initiated with a dosage of 40 mg/d, tapered to 20 mg/d after two weeks and maintained until complete remission in both groups. Meanwhile, Dex 6 mg/d was added to the TD group along with methimazole from the commencement of therapy. The dosage of Dex was reduced to 4.5 mg/d on the 5th day and to 2.25 mg/d two weeks after treatment, and continued until remission. It was found that there was remarkable decrease in leucocyte GCR levels with a moderate elevation of plasma ACTH and a slight decline of plasma cortisol in untreated Graves' disease, suggestive of a compensation of the pituitary-adrenal axis function in hyperthyroidism. The levels of GCR, ACTH and cortisol returned to normal after complete remission by methimazole in the methimazole alone group. In the TD group, however, all GCR, ACTH and cortisol levels were significantly decreased after Dex therapy, implying down regulation of GCR by exogenous Dex and suppresion of the pituitary-adrenal axis. Thus the dosage of glucocorticoid should be appropriately adjusted to avoid adrenal insufficiency, especially in case of stress, due to the suppresion of pituitary adrenal function.

Topics: Adrenocorticotropic Hormone; Adult; Antithyroid Agents; Dexamethasone; Drug Therapy, Combination; Female; Glucocorticoids; Graves Disease; Humans; Hydrocortisone; Male; Methimazole; Middle Aged; Pituitary-Adrenal System; Receptors, Glucocorticoid

Sixty-nine cases of middle aged and senile female Graves' desease (GD) patients suffered from abnormal bone metabolism have been studied. They were divided randomly into group A and B, treated separately with antithyroid drugs (Tapazol and inderal, etc.) in group A, and added with Chinese herbal medicine for tonifying Kidney and promoting blood circulation in group B. Before treatment, patients of both groups showed obvious higher blood calcium (Ca) 24-hour urinary Ca, phosphorus (P) and serum clcitonin (CT) levels than that in normal subjects. These patients' serum Ca, moreover, had a parallel relationship with serum T3 levels (r = 0.6142, P < 0.01) and the serum Ca also a paralleled with serum CT levels (r = 0.5714, P < 0.05). After six months of treatment, the serum Ca, 24-hour urinary Ca, P and blood CT values were all reduced in various degree. The decrease of these bone metabolic parameters were more significant in group B than that in group A.

Topics: Aged; Antithyroid Agents; Bone and Bones; Calcium; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Graves Disease; Humans; Methimazole; Middle Aged; Postmenopause

A variety of regimens continue to be used in the treatment of Graves' disease with antithyroid drugs. We have investigated the factors which determine the initial response to methimazole (time until euthyroidism is achieved) in Graves' disease.. Five hundred and nine patients with Graves' disease in different European countries with normal and subnormal iodine supply. Patients were randomized to treatment with either 10 or 40 mg of methimazole per day for one year, with levothyroxine supplementation as required to maintain euthyroidism. Investigations were carried out before treatment and at 3 and 6 weeks and 3, 6, 9 and 12 months.. Response was assessed by serial measurements of serum thyroid hormones. TSH receptor antibodies, thyroid autoantibodies and urinary iodide excretion were measured centrally. Twenty-minute thyroid uptake was measured by standard techniques. Data were collected and analysed centrally. Standard techniques as well as a stepwise logistic regression model were used to examine the relations between methimazole dose, age, goitre size, presence of endocrine eye signs, thyroid hormone levels, urinary iodide excretion, thyroid uptake, index of disease severity (Crooks), presence of TSH receptor antibodies and duration of the hyperthyroid phase.. Within 3 weeks, 40.2% of patients responded to 10 mg of methimazole and 77.5% responded within 6 weeks. The corresponding figures for 40 mg of methimazole were 64.6 and 92.6%. Significant associations were found between duration of hyperthyroidism and the following variables: goitre size, urinary iodide excretion, methimazole dose, presence of TSH receptor antibodies (TBIAb), index of disease severity (Crooks) and pretreatment thyroid hormone levels. Response to methimazole was delayed in patients with large goitres, iodine excretion of > or = 100 micrograms/g creatinine, high pretreatment thyroid hormone levels, elevated levels of TBIAb and treatment with only 10 mg of methimazole. In the 10-mg group, 46% of patients were euthyroid within 3 weeks when urinary iodide was < 50 microgram/g of creatinine, and only 27% when iodide was above 100 micrograms/g. By stepwise logistic regression, the main factors for the response to methimazole were daily dose, pretreatment T3 levels, and goitre size.. Methimazole dose, pretreatment serum T3 levels, and goitre size are the main determinants of the therapeutic response to methimazole in Graves' disease, at least in areas comprising low, subnormal and normal iodine supply.

Topics: Adult; Antithyroid Agents; Drug Therapy, Combination; Female; Graves Disease; Humans; Iodides; Male; Methimazole; Thyroxine; Triiodothyronine

To compare the relapse rates in Graves' disease the first 2 years after methimazole 60 mg day-1 combined with thyroxine versus a titration regimen with methimazole alone, and to look for possible prognostic factors.. A randomized, open, prospective study. Methimazole was given for 6 months in both groups, and thyroid status evaluated every 3rd month during the first year, and every 6th month during the second year.. The study was performed at our outpatient clinic with patients referred from primary care.. Fifty-six patients were included. One became pregnant and one dropped out during the treatment period. Furthermore, nine patients in the high-dose and four in the low-dose group stopped the treatment because of side-effects. Thus, 19 patients in the high- and 22 in the low-dose group completed 6 months with methimazole.. In those tolerating the treatment, the relapse rates in the high- and low-dose groups were 26.3 vs. 59.1% (P < 0.05), 42.1 vs. 77.3% (P < 0.02); and 57.9 vs. 77.3% (NS) after 3, 12 and 24 months, respectively. The corresponding relapse rates calculated on an 'intention to treat' basis were: 51.7 vs. 66.7%; 62.1 vs. 81.5%: 72.4 vs. 81.5% (NS). The thyroid volume was significantly (P < 0.05) larger in those that relapsed (17.8 +/- 2.9 vs. 11.6 +/- 1.2 mL; mean +/- SEM).. In those tolerating the treatment, methimazole significantly reduced the relapse rate the 1st year when given in a high dose. However, the relapse rates in both groups, and the number of side-effects in the high-dose group, were unacceptably high.

Topics: Adult; Drug Administration Schedule; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Prognosis; Prospective Studies; Recurrence; Severity of Illness Index; Treatment Outcome

To better understand the clinical significance of changes in lymphocytes in thyroid disease this study analyzed the proportion of CD19+, CD3+, CD4+ and CD8+ cells among circulating lymphocytes in Graves' disease (GD, n = 34) and autoimmune hypothyroidism (AH, n = 28) vs healthy subjects (n = 15). In addition, the expression of CD25 and CD45 isoforms on CD4+ T cells as well as their modulation by methimazole in patients with GD was measured using three color flow cytometry. It was observed that, irrespective of age, both patients with GD (17.6 +/- 7.0% +/- SD) and those with AH (19.0 +/- 9.5%) had an increased percentage of the CD25+CD45RA+ (naive) subpopulation of helper cells vs healthy subjects (7.9 +/- 2.3%, p < 0.0001). In patients with AH peripheral memory cells and hence overall CD25+ cells were more frequent among helper cells (56.7 +/- 12.2%) than in healthy subjects (40.8 +/- 14.0%, p < 0.001). Patients with GD (46.2 +/- 13.4%) did not differ from normal subjects in this respect. Treatment of GD with MMI reduced the percentage of CD25+CD45RA+ cells among CD4+ cells toward values seen in healthy subjects. In addition, we confirm previous reports that CD8+ cells toward values seen in healthy subjects. In addition, we confirm previous reports that CD8+ cells are significantly reduced in AH (23.9 +/- 4.9%) and untreated Graves' disease (23.2 +/- 6.6%) vs healthy subjects (32.2 +/- 5.9%, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Antibodies, Monoclonal; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Female; Flow Cytometry; Graves Disease; Humans; Male; Methimazole; T-Lymphocyte Subsets; Thyroiditis, Autoimmune

Increased levels of antibodies to TSH receptors are thought to be a major cause of active Graves' disease or recurrence following therapy. It was recently reported that T4 administration during antithyroid drug treatment for Graves' disease resulted in a significant decrease of TSH receptor antibodies compared to drug therapy alone. It is known that these antibodies may remain elevated long after patients become euthyroid, so a large number of patients whose antibodies remained significantly elevated after 1 year of methimazole therapy were evaluated in the study. A total of 330 Graves' disease patients were treated with methimazole for 1 year. TSH receptor antibody titers remained persistently elevated in 195 patients. Thirty-five randomly selected patients were continued on maintenance doses of methimazole for a second year, and 160 patients were treated with a combination of methimazole and thyroxine for a second year. T4 doses needed ranged from 75-100 micrograms/day to maintain serum-free T4 and free T3 within the normal range. After 6 months of combined therapy, 35 patients were found to have suppressed serum TSH levels. The patients were divided after 18 months into three groups: A, B, and C. Group C, consisting of 35 randomly selected patients (8 males and 27 females) whose ages ranged from 12-62 years and who had been maintained on methimazole alone, served as controls. Group B, whose serum TSH levels were suppressed after 6 months of combined therapy, consisted of 9 males and 26 females whose ages were 15-66 years. Group A, 35 randomly selected patients with normal serum TSH levels after methimazole and thyroxine therapy for 6 months, consisted of 8 males and 27 females whose ages were 10-63 years. TSH receptor antibody titers gradually decreased in all three groups with drug therapy, and there was no significant difference in the titers at corresponding times, i.e. 0, 1.0, 1.5, and 2.0 years. After treatment for 2.0 years, all patients of the three groups were followed for a further 12 months. Rates of recurrence among the above three groups were not significantly different during the observation period. In the present study, T4 administration in combination with antithyroidal drugs had no effect on levels of antibodies to TSH receptors and no effect on rates of recurrence. The reason for the discrepant results in the present study from previous reports is not known.

Topics: Adolescent; Adult; Antibodies; Child; Drug Therapy, Combination; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Receptors, Thyrotropin; Recurrence; Thyroxine; Triiodothyronine

Thiourea drugs have been postulated to possess radioprotective property. We studied the effect of adjunctive antithyroid drugs (ATD) and L-thyroxine (L-T4) on the result of radioiodine (RAI) 131I therapy and determined the incidence of hypothyroidism and relapse of hyperthyroidism. One hundred and fifty-nine patients with Graves' disease were randomized prospectively to receive either RAI alone or adjunctive ATD in a form of block-replacement regimen of methimazole (MMI) plus L-T4 for 6 months. The patients were observed for a mean period of 4.6 (range 2-10) years. The incidence of permanent hypothyroidism was studied and the effect of ATD on iodine kinetics was analyzed. The cumulative incidence of hypothyroidism in the ATD group was significantly lower than the RAI group (p = 0.0009), and the difference is accounted by a reduction of early hypothyroidism within 12 months from 20.2 to 3.7% (p = 0.003). The incidence of late hypothyroidism was similar between the two groups. Treatment with ATD did not affect the one dose cure rate with RAI (61.2 vs 55.5%, p = NS), but the time to achieve euthyroidism was significantly earlier with adjunctive ATD (2 vs 8 weeks, p < 0.02). The incidence of relapse within the first year after one dose was also similar between the two groups (38.7 vs 44.5%, p = NS). Comparing the kinetics of the therapeutic dose with a tracer dose, patients receiving MMI were found to be underdosed by 22% (p = 0.003) and the biological half-life was significantly shortened. We conclude that ATD rendered euthyroidism earlier without compromising the one dose cure rate of RAI.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Dose-Response Relationship, Radiation; Drug Therapy, Combination; Female; Graves Disease; Humans; Hypothyroidism; Incidence; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Recurrence; Thyroxine

We previously reported the clinical characteristics of Graves' disease with undetectable TSH binding inhibitor immunoglobulins (TBII) at first visit, but a study of the prognosis of untreated TBII negative patients with anti-thyroid drug medication has never been undertaken. The aim of this paper is to study the difference between negative and positive TBII Graves' disease in relation to the effect of anti-thyroid drug treatment.. From January 1986 to April 1991, 1545 patients with untreated Graves' disease were referred to Kuma Hospital, Kobe, Japan. Of these, 94 TRAb negative patients were identified. Another 83 TRAb positive patients were randomly selected from the other Graves' disease patients and served as a comparison group. Fifty-six of the 94 patients in the TBII negative group and 52 of the 83 patients in the TBII positive group completed treatment with methimazole only.. The trial was conducted as a retrospective study with a maximum treatment period of 36 months and a follow-up period of a further 12 months. From the original pool of patients, we classified 56 TBII negative patients into two groups according to the clinical course taken; Group A in whom TBII remained undetectable throughout methimazole treatment (9 men and 34 women, age 37.2 +/- 2.2 years), and Group B who became TBII positive (4 men and 9 women, 31.2 +/- 4.4 years). Fifty-two TBII positive patients served as the comparison Group C (8 men and 44 women, age 38.1 +/- 2.0 years).. Serum free T4 and free T3 levels in groups A and B were significantly lower before treatment than those of Group C (P < 0.001). The thyroid volumes of Group A and B patients were significantly smaller than those of Group C (P < 0.01). The level of TBII in Groups A and B was significantly lower than that in Group C (8.3 +/- 0.7 and 8.8 +/- 1.1 vs 57.0 +/- 2.8%, respectively, P < 0.001). The level of thyroid stimulating antibody (TSAb) in Groups A and B was significantly lower than that in Group C (478 +/- 71.0 and 761 +/- 140.3 vs 2143 +/- 280%, respectively, P < 0.01), and there were no significant differences in TSAb activities between Groups A and B. The remission rates in Groups A, B and C were 77.4, 36.4 and 36.5%, respectively. These data indicate that Group A has a good prognosis, but Group B has the same prognosis as Group C.. We conclude that patients in whom TSH binding inhibitor immunoglobulins remained negative have a much better prognosis than TSH binding inhibitor immunoglobulins positive patients or those who become TSH binding inhibitor immunoglobulins positive, having been initially negative.

Topics: Adult; Antithyroid Agents; Autoantibodies; Female; Follow-Up Studies; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Prognosis; Receptors, Thyrotropin; Retrospective Studies

Graves' disease is an autoimmune disorder characterized by a course of remission and relapse. Several parameters have been evaluated for their abilities to predict the clinical course of Graves' disease in patients treated with antithyroid drugs. We recently demonstrated in patients with hyperthyroidism dependent by Graves' disease, an impaired Na+, K+ ATPase activity in red cells and a correlation between ATPase and free T3. With the aim to clarify the relationship between the course of hyperthyroidism and the Na+, K+ ATPase activity during and after discontinuing the antithyroid therapy, we followed up 24 patients for two years. In our previous work by restoring a normal level of free T3, we obtained a normalization of Na+, K+ ATPase activity in the red cells of all the patients. However, in eight subjects after a period of 150 days following the suspension of therapy, we observed a new reduction of ATPase activity in a clinical condition of euthyroidism. The same subjects, newly evaluated after 150 days, developed a clinical and biochemical relapse of hyperthyroidism. We believe that the determination of Na+, K+ ATPase activity is able to predict the recurrence of hyperthyroidism in patients with Graves' disease.

Topics: Adult; Antithyroid Agents; Enzyme Inhibitors; Erythrocytes; Female; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Ouabain; Prognosis; Receptors, Thyrotropin; Recurrence; Sodium-Potassium-Exchanging ATPase; Thyroid Function Tests

Tartrate-resistant acid phosphatase (TRAP) is one of the acid phosphatase isoenzymes. It is secreted by osteoclasts so it has been proposed as a marker of bone resorption. Bone turnover is high in hyperthyroidism due to an increase in both bone resorption and formation. The aim of the study was to measure serum TRAP as well as other markers of bone metabolism in 20 fertile age females affected by Graves-disease; 11 patients were also studied after euthyroid state was attained by means of a 6 month course of methimazole treatment. TRAP was measured with the colorimetric method using p-nitrophenylphosphate as substrate. Free thyroid hormones, TSH, serum calcium (corrected for albumin concentration), phosphate, osteocalcin, alkaline phosphatase, parathormone intact molecule, and urinary excretions of calcium, phosphate and hydroxyproline were measured, too. Twenty-eight healthy fertile women made up the control group. Untreated patients had a significant increase of TRAP, osteocalcin, serum calcium, alkaline phosphatase and urinary excretion of calcium and hydroxyproline. A significant fall in all these parameters but alkaline phosphatase was disclosed comparing patients before and after treatment, nevertheless only urinary calcium became not significantly different from the controls. TRAP showed a significant correlation with free T3 levels but not with hydroxyproline excretions. This survey on fertile age women with Graves' disease shows a significant increase in serum concentration of TRAP, which decreases, but doesn't get normalization, when euthyroidism is attained by a six month course of methimazole therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Adult; Biomarkers; Bone Remodeling; Female; Graves Disease; Humans; Methimazole; Middle Aged; Tartrates

Radioactive iodine-131 (RAI) has been reported to be associated with a high incidence of development or exacerbation of Graves' ophthalmopathy (GO). This is thought to be associated with a surge of autoantibodies after RAI therapy. The role of methimazole (MMI), which possesses immunomodulatory action, in the prevention of GO was explored by studying 114 patients with Graves' disease. They were assigned randomly to receive either RAI alone or adjunctive antithyroid drugs, which consisted of MMI and L-T4 as a block-replacement therapy for 12 months and were followed for 2 yr. Thirty-five patients (30.7%) had GO at presentation. Twenty-one (18%) patients developed new GO, and six had worsening of preexisting GO. The development of hypothyroidism (P < 0.01) and an elevation of TSH (P < 0.05) were associated with increased risk of development or exacerbation of GO. The chance of development or exacerbation of GO is higher in those with no ophthalmopathy than in those with preexisting GO at presentation (P = 0.002). The incidence of development or exacerbation of GO was similar in the two treatment groups (RAI, 22.8%; adjunctive antithyroid drugs, 23.7%; P = NS). MMI was able to suppress the surge of TSH receptor antibody (TRAB) after RAI, but a surge in TRAB was not of prognostic significance for the development of GO after RAI. Patients who developed or had exacerbation of GO actually had lower TRAB at presentation (P = 0.02). We conclude that hypothyroidism with elevated TSH is an important adverse factor for the development or exacerbation of GO, and MMI was unable to prevent the development or exacerbation of GO after RAI.

Topics: Adult; Aged; Autoantibodies; Eye Diseases; Female; Graves Disease; Humans; Hypothyroidism; Immunoglobulins, Thyroid-Stimulating; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Prognosis; Smoking; Thyrotropin; Thyroxine

Because of the previous controversial findings in studies of bone mineral density in patients with hyperthyroidism with older methodologies, we assessed bone mineral density in 15 Japanese patients with Graves' disease (8 males and 7 females) before and after treatment using dual energy X-ray absorptiometry (DEXA). Bone mineral density of the lumbar vertebrae and the femur, and thyroid function, and several metabolic parameters were measured before treatment and again after patients achieved a euthyroid state following treatment with methimazole for 4 to 20 months (mean 10.6 months). The bone mineral density of patients was calculated as the percentage of the mean value (%BMD) in an age- and sex-matched control group, and correlations between the changes in bone mineral density and metabolic parameters before and after treatment were investigated. The %BMD of vertebrae in patients with Graves' disease before treatment was 89.7% of that found in the normal population. When patients became euthyroid after treatment, %BMD increased significantly to 94.9%, although it still remained below the control level. TSH receptor antibody, osteocalcin, and alkaline phosphatase were elevated before treatment, but decreased significantly after treatment. The change between pre- and posttreatment TSH receptor antibody was negatively correlated with the change in bone mineral density. In conclusion, these findings suggest that bone mineral density is decreased in patients with Graves' disease and that successful treatment of hyperthyroidism results in a significant increase in bone mineral density within a short period of time. Furthermore, TSH receptor antibody is a useful marker of changes in bone metabolism in this group of patients.

Topics: Absorptiometry, Photon; Adolescent; Adult; Aged; Aged, 80 and over; Antibodies; Bone Density; Female; Femur Neck; Graves Disease; Humans; Male; Methimazole; Middle Aged; Osteocalcin; Receptors, Thyrotropin; Spine; Thyroid Hormones; Thyrotropin

Thyroid stimulating antibodies (TsAb) and thyrotropin releasing hormone (TRH) test were used as the indices for predicting relapse and remission in 58 patients. The variation of TsAb activities was observed before and after antithyroid drug (ATD) treatment. The findings showed that TsAb activities of untreated patients were significantly higher than those of patients treated by ATD, and TsAb activities were weak or negative after ATD treatment. When TsAb was positive or TRH test was abnormal at the time of cessation of ATD therapy, nearly 93% patients relapsed. Further analyses of relapsed patients indicated that there was no correlation between the two indicators, and the TsAb positive rate (84%) was significantly higher than the rate of abnormal TRH test (45%). The average ATD treatment duration in relapsed patients was shorter than that in remission patients. It is concluded that TsAb is more useful than TRH test when they are used for predicting the prognosis of Graves' disease. The duration of ATD treatment could affect relapse or remission. The immunosuppression effect of ATD was also identified.

Topics: Adult; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Methimazole; Middle Aged; Prognosis; Propylthiouracil; Recurrence; Thyrotropin; Thyrotropin-Releasing Hormone

The purpose of the present study was to investigate by a computed tomography (CT) the Hounsfield unit (H.U.) of the thyroid in hyperthyroid and euthyroid Graves' disease and destructive thyrotoxicosis. The mean thyroid CT number in 95 controls was 122 +/- 18 H.U. (+/- SD) and did not change significantly with advancing age. The mean thyroid CT number (+/- SD) of 85 +/- 22 H.U. in 60 patients with hyperthyroid Graves' disease was significantly (P < 0.001) lower than either in normal controls or 116 +/- 22 H.U. in 11 patients with euthyroid Graves' disease (P < 0.001). Comparison of thyroid hormones and TSH receptor Ab values of untreated patients with a normal and an abnormally low thyroid CT number showed that serum total and free T3 were significantly (P < 0.05) higher in the latter group than in the former group. With respect to the effect of methimazole (MMI) on the thyroid CT number, in the untreated 10 patients with a low thyroid CT number, the initial mean CT number was 65 +/- 11 H.U. and increased significantly (P < 0.05) to 76 +/- 14 H.U. after treatment with MMI. In contrast, in 6 patients with a normal thyroid CT number prior to therapy, the initial mean thyroid CT number was 102 +/- 11 H.U. and fell significantly (P < 0.05) to 84 +/- 16 H.U. after treatment with MMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Female; Graves Disease; Humans; Male; Methimazole; Reference Values; Thyrotoxicosis; Tomography, X-Ray Computed

Initial therapy of thyrotoxicosis usually includes beta-blockade for symptom relief and thionamides to block new thyroid hormone synthesis. In view of the increased enterohepatic circulation of thyroxine (T4) and triiodothyronine (T3) in thyrotoxicosis, we proposed that cholestyramine, an anion exchange resin which binds iodothyronines, when used adjunctively with thionamides and a beta-blocker, would lower serum iodothyronine levels faster than would standard therapy alone.. A double blind placebo-controlled cross-over design was used with patients randomly assigned to either the treatment or control groups. They received their initial treatment for two weeks (Phase 1) followed by a one-week washout period, and then crossed to the opposite treatment for two weeks (Phase 2). Standard therapy included atenolol 50 mg daily, individualized dosages of methimazole and either 4 g of cholestyramine or 4 g of placebo powder four times per day.. Fifteen patients with thyrotoxicosis (14 Graves' disease, 1 toxic adenoma) participated in this study.. Total and free thyroxine and triiodothyronine, as well as thyroid-stimulating immunoglobulin and thyrotrophin-binding inhibitory immunoglobulin, were measured weekly.. Seven patients received cholestyramine and eight patients received placebo during Phase 1. A more rapid decline in all thyroid hormone levels was seen in the cholestyramine-treated group (F = 4-7, P < 0.01) than in the placebo group (F = 2-3.1, P = 0.05). In Phase 2, the eight patients who received cholestyramine showed an additional decline in free thyroxine from weeks one to two, but the overall rate of decline in hormone levels was not different between the groups. Immunoglobulin levels remained unaffected regardless of group, treatment, or time.. We conclude that cholestyramine is a safe and effective adjunctive agent in the treatment of thyrotoxicosis and that its greatest efficacy may be during the first few weeks of treatment.

Topics: Adult; Atenolol; Chemotherapy, Adjuvant; Cholestyramine Resin; Double-Blind Method; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Thyroid Hormones; Thyrotoxicosis

Some studies have suggested that increasing the daily dose of anti-thyroid drugs might improve long-term remission rates of Graves' disease. Therefore, this question was addressed in a prospective multicenter trial involving 18 thyroid clinics in Europe, mostly in iodine-deficient or moderately iodine-sufficient regions. Five hundred and nine patients with Graves' hyperthyroidism were enrolled in a prospective randomized trial comparing the remission rates after treatment with methimazole (MMI) at two fixed dosages (10 vs. 40 mg) with levothyroxine supplementation. The treatment and follow-up periods lasted 12 months each. Sixty and seven-tenths percent of the recruited patients (total, 309; 153 in the 10 mg, 156 in the 40 mg group) were finally evaluated, and comparison of the two groups showed that they were well matched with respect to a wide range of variables, including parameters of thyroid function. With 10 mg MMI daily, 68.4% of the patients were euthyroid after 3 weeks, and 84.9% after 6 weeks, compared to 83.1% and 91.6%, respectively, with the use of 40 mg MMI daily. TSH receptor antibodies decreased similarly in the two groups, 25% of patients in the 10 mg group, and 30% in the 40 mg group still being TSH receptor antibodies positive after 12 months. One hundred and ninety six (63.4%) of the 309 patients achieved remission of Graves' disease. The two MMI doses were equally effective; 35.9% compared to 37.2% of patients treated with 10 and 40 mg MMI, respectively, had relapses. There was no difference in the length of the time interval between stopping treatment and recurrence between the two groups. However, the rate of adverse drug reactions increased from 39/251 (15.5%) in the 10 mg group to 67/258 (26.0%) in the 40 mg group (P < 0.01). Under conditions of iodine deficiency or borderline sufficient iodine supply, 40 mg MMI daily will render more patients with Graves' disease euthyroid within the first 6 weeks of treatment than 10 mg daily, but at the expense of an increased rate of adverse reactions. However, patients treated with 40 mg MMI daily for 1 yr have no higher chance of remission than patients treated with 10 mg. It does not appear justified at present to recommend MMI doses higher than required for the control of hyperthyroidism (with the goal of immunosuppression).

Topics: Adult; Dose-Response Relationship, Drug; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Prospective Studies; Remission Induction; Thyroxine

We studied 26 patients with Graves' disease, from a population with sufficient iodine supply, treated with high doses of methyl mercaptoimidazole (MMI) during eight moths. We evaluated: a) their evolution after treatment withdrawal; b) the correlation between evolution and TSH-receptor antibodies (TRAb), thyroid hormone levels, microsomal antibodies (MAb), T3/T4 index and clinical data; c) their prognosis. The patients were followed during 12-60 months, and blood samples were collected before treatment withdrawal. Out of 26 patients, 20 relapsed, with T3/T4 index and TRAb significantly higher than those under remission. The T3/T4 index correlated with TRAb. All the TRAb-positive patients, and only 57.1% of the negatives, relapsed. The relapses were significantly more frequent prior to the 6th month in the TRAb-positive patients than afterwards. The TRAb-negatives who relapsed during that period, showed TRAb and age means significantly higher than those under remission. The TRAb test, as a prognostic marker of evolution, showed a sensitivity of 60% and a specificity of 100%. No significant differences were found between evolution to relapse or to remission and the other parameters. It can be concluded that TRAb and T3/T4 index were different in the group that relapsed from that which remitted, and that a TRAb positive value, at the moment of treatment withdrawal, is a useful marker of relapse.

Topics: Adult; Autoantibodies; Autoimmune Diseases; Biomarkers; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Microsomes; Middle Aged; Prognosis; Receptors, Thyrotropin; Recurrence; Remission Induction; Thyroid Hormones; Treatment Outcome

Ophthalmopathy caused by Graves' disease may first appear or worsen during or after treatment for hyperthyroidism. It is not known, however, whether choosing to treat hyperthyroidism with antithyroid drugs, iodine-131, or surgery affects the development or aggravation of Graves' ophthalmopathy.. We studied 168 patients with hyperthyroidism caused by Graves' disease, stratified into two age groups--20 to 34 years (54 patients, group 1) and 35 to 55 years (114 patients, group 2). The patients in group 1 were randomly assigned to treatment with methimazole for 18 months or subtotal thyroidectomy, and those in group 2 to either of these two treatments or to iodine-131 therapy. All the patients received thyroxine to avert hypothyroidism, except those treated with iodine-131, who received thyroxine only if hypothyroidism developed. The duration of follow-up was at least 24 months.. Twenty-two patients (13 percent) had infiltrative Graves' ophthalmopathy at randomization. During follow-up, ophthalmopathy developed for the first time in 22 patients (13 percent) and worsened in 8 patients (5 percent). The frequency of the development or worsening of ophthalmopathy was similar among the patients in group 1 (medical therapy, 4 of 27 patients [15 percent]; and surgery, 3 of 27 patients [11 percent]). In group 2, ophthalmopathy developed or worsened in 4 of the 38 patients (10 percent) treated medically, 6 of the 37 patients (16 percent) treated surgically, and 13 of the 39 patients (33 percent) given iodine-131 (P = 0.02 for the comparison between the iodine-131 subgroup and the others combined). The risk of the development or worsening of ophthalmopathy increased as pretreatment serum triiodothyronine concentrations increased.. As compared with other forms of antithyroid therapy, iodine-131 is more likely to be followed by the development or exacerbation of Graves' ophthalmopathy.

Topics: Adult; Female; Follow-Up Studies; Graves Disease; Humans; Hypothyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Random Allocation; Thyroidectomy; Thyroxine

The relationship between the treatment of Graves' hyperthyroidism and the course of ophthalmopathy is rather unclear. Antithyroid drugs may improve eye manifestations, possibly by restoring normal thyroid function and reducing orbit-directed autoimmune reactions, whereas ophthalmopathy may worsen after radioiodine administration or thyroidectomy. This might occur because of a treatment-related release of thyroid antigens and activation of the autoimmune response that might involve the orbit. On the other hand, some authors suggest that complete thyroid ablation, either by radioiodine or surgery, might be beneficial for ophthalmopathy. However, reported effects of radioiodine and thyroidectomy on Graves' ophthalmopathy are conflicting. This may be due, at least in part, to the retrospective feature of most studies and the lack of precise evaluation of ocular involvement. Two prospective studies were performed in which patients with Graves' disease with mild or no ophthalmopathy were randomly assigned to treatment by radioiodine or subtotal thyroidectomy alone or in association with systemic glucocorticoids. Both treatments were followed by a progression of pre-existing mild ophthalmopathy in a substantial proportion of cases: glucocorticoids prevented such an exacerbation. Ophthalmopathy did not develop in patients without clinical evidence of eye disease prior to therapy. Therefore, it is recommended that a course of glucocorticoids be instituted concomitantly with radioiodine therapy or thyroidectomy in Graves' patients with some degree of ocular involvement.

Topics: Glucocorticoids; Graves Disease; Humans; Iodine Radioisotopes; Methimazole; Thyroidectomy

To evaluate the long-term efficacy of sodium ipodate (IPO) in the treatment of hyperthyroid Graves' disease, we studied 12 consecutive patients with Graves' hyperthyroidism treated only with 500 mg IPO po daily for several weeks to 22 months. Serum thyroid hormone concentrations markedly decreased and serum free T3 values normalized in all patients within 7 days of therapy. Five patients (42%, Group 1) were euthyroid after 6 weeks of IPO treatment and remained so until IPO was discontinued after 22 months. Recurrence of hyperthyroidism after drug withdrawal occurred in only one of these Group 1 patients, who was promptly responsive to a second course of IPO. In contrast, seven of 12 patients (58%, Group 2) relapsed with recurrent hyperthyroidism between 14 and 42 days of IPO therapy. After IPO was withdrawn, these Group 2 patients were treated with methimazole (20-30 mg/day, initial dose), but the therapeutic response was poor and delayed. Two patients were still hyperthyroid after 6 months of methimazole treatment. Elevated serum FT3 concentrations were observed in the Group 2 patients at 21 days following the early normalization of serum FT3 concentrations. No changes in serum thyroglobulin and thyroid microsomal and TSH-receptor autoantibody titers were observed in either groups during IPO therapy. In conclusion, the results of the present study demonstrate that IPO rapidly restores euthyroidism, but its prolonged administration is associated with a high rate of relapse of hyperthyroidism and a poor response to subsequent methimazole treatment and that long-term IPO administration does not affect humoral markers of thyroid autoimmunity.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Autoantibodies; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Ipodate; Longitudinal Studies; Male; Methimazole; Middle Aged; Recurrence; Thyroglobulin; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

We have carried out a prospective study to investigate whether orbital radiotherapy combined with high dose systemic glucocorticoids is more effective than orbital radiotherapy alone for Graves' ophthalmopathy. Thirty consecutive patients with relevant and active Graves' ophthalmopathy were randomly assigned to treatment either with orbital radiotherapy combined with systemic glucocorticoids (Group 1, n = 15) or with orbital radiotherapy alone (Group 2, n = 15). The final evaluation was made 6-9 months after beginning treatment. Two patients in each group were lost to follow-up. Ocular involvement and response to treatment were evaluated by the ophthalmopathy index and by clinical assessment. Mean ophthalmopathy index values were 5.85 in Group 1 and 5.46 in Group 2 (p = NS) before treatment, and 2.46 in Group 1 and 3.61 in Group 2 after treatment (p = 0.0001 and p = 0.003 vs initial value, respectively). The mean ophthalmopathy index decrease in Group 1 (-3.39) was significantly greater (p = 0.043) than that in Group 2 (-1.85). Favorable responses on clinical ground occurred in 9 patients (69%) in Group 1 and in 5 patients (38%) in Group 2. The difference was particularly evident on soft tissue changes and extraocular muscle involvement. Severe eye muscle restriction was substantially unaffected by either treatment. In conclusion, the association of orbital irradiation and high dose systemic glucocorticoids in the treatment of severe Graves' ophthalmopathy provides more favorable responses than orbital radiotherapy alone.

Topics: Adult; Combined Modality Therapy; Eye; Eye Diseases; Female; Glucocorticoids; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Orbit; Prospective Studies; Radiography; Thyroxine

Antibodies to thyroid-stimulating hormone (TSH) receptors that stimulate the thyroid gland cause hyperthyroidism in patients with Graves' disease, and their production during antithyroid drug treatment is an important determinant of the course of the disease. One factor that might contribute to the persistent production of antibodies to TSH receptors is stimulation of the release of thyroid antigens by TSH during antithyroid drug therapy. We therefore studied the effect of the suppression of TSH secretion by thyroxine on the levels of antibodies to TSH receptors after thyroid hormone secretion had been normalized by methimazole.. The levels of antibodies to TSH receptors were measured during treatment with methimazole, either alone or in combination with thyroxine, in 109 patients with hyperthyroidism due to Graves' disease. The patients first received 30 mg of methimazole daily for six months. All were euthyroid after six months, and their mean (+/- SD) level of antibodies to TSH receptors decreased from 64 +/- 9 percent to 25 +/- 15 percent (P less than 0.01; normal, 2.9 +/- 1.4 percent). Sixty patients then received 100 micrograms of thyroxine and 10 mg of methimazole and 49 received placebo and 10 mg of methimazole daily for one year. In the thyroxine-treated group, the mean serum thyroxine concentration increased from 108 +/- 16 nmol per liter to 145 +/- 11 nmol per liter (P less than 0.01), and the level of antibodies to TSH receptors decreased from 28 +/- 10 percent to 10 +/- 3 percent after one month of combination therapy. In the patients who received placebo and methimazole, the mean serum thyroxine concentration decreased and the level of antibodies to TSH receptors did not change. Methimazole, but not thyroxine or placebo, was discontinued in each group 1 1/2 years after the beginning of treatment. The level of antibodies to TSH receptors further decreased (from 6.6 +/- 3.2 percent at the time methimazole was discontinued to 2.1 +/- 1.2 percent one year later) in the patients who continued to receive thyroxine, but it increased (from 9.1 +/- 4.8 percent to 17.3 +/- 5.8 percent during the same period) in the patients who received placebo. One patient in the thyroxine-treated group (1.7 percent) and 17 patients in the placebo group (34.7 percent) had recurrences of hyperthyroidism within three years after the discontinuation of methimazole.. The administration of thyroxine during antithyroid drug treatment decreases both the production of antibodies to TSH receptors and the frequency of recurrence of hyperthyroidism.

Topics: Adolescent; Adult; Autoantibodies; Drug Therapy, Combination; Female; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Receptors, Thyrotropin; Recurrence; Risk; Thyrotropin; Thyroxine; Thyroxine-Binding Proteins

Topics: Adult; Aged; Graves Disease; Humans; Methimazole; Middle Aged; Thyroxine; Triiodothyronine

Little is known about the relationship between hypothyroidism and the parasympathetic nervous system. R-R interval variations revealed by electrocardiogram (ECG) are known to be a useful clinical indicator of abnormalities of parasympathetic nervous system activity. Studies were conducted in hypothyroid patients, and significant reductions in R-R interval variations were observed in patients with primary severe hypothyroidism due to Hashimoto's thyroiditis, and in patients with Graves' disease who became severely hypothyroid during antithyroid drug therapy. R-R interval variations were restored to normal levels in both groups of patients after treatment. The present investigation suggests that in marked hypothyroidism there are hypofunctional abnormalities in the parasympathetic nervous system in association with a reduction in the levels of serum T4 and T3.

Topics: Adult; Electrocardiography; Female; Graves Disease; Heart; Humans; Hypothyroidism; Male; Methimazole; Parasympathetic Nervous System; Thyroid Hormones; Thyroiditis, Autoimmune

Graves' disease is an autoimmune disease characterized by a course of remission and relapse. Since the introduction of antithyroid drug treatment, various parameters have been tested for their ability to predict the clinical course of a patient with Graves' disease after drug withdrawal. Nearly all these studies were retrospective [corrected] and often yielded conflicting results. In a prospective multicentre study with a total of 451 patients, we investigated the significance of a variety of routine laboratory and clinical parameters for predicting a patient's clinical course. Patients who had positive TSH receptor antibodies activity at the end of therapy showed a significantly higher relapse rate than those without (P less than 0.001). However, the individual clinical course cannot be predicted exactly (sensitivity 0.49, specificity 0.73, N = 391). The measurement of microsomal (P = 0.99, sensitivity 0.37, specificity 0.63, N = 275) or thyroglobulin antibodies (P = 0.76, sensitivity 0.18, specificity 0.84, N = 304) at the end of antithyroid drug therapy did not show a statistically significant difference in the antibody titre between the patients of the relapse and those of the remission group. Additionally, HLA-DR typing (HLA-DR3: P = 0.37, sensitivity 0.36, specificity 0.58, N = 253) was proven to be unsuitable for predicting a patient's clinical course. Patients with abnormal suppression or an abnormal TRH test at the end of antithyroid drug therapy relapse significantly more often (P less than 0.001) than patients with normal suppression or normal TRH test. Patients with a large goitre also have a significantly (P less than 0.001) higher relapse rate than those with only a small enlargement. The sensitivity and specificity values of all these parameters, however, were too low to be useful for daily clinical decisions in the treatment of an individual patient. This is also true for the combinations of different parameters. Though the highest sensitivity value (0.94) was found for a combination of the suppression and the TRH test at the end of therapy, the very low specificity value (0.13) for this combination reduced its clinical usefulness.

Topics: Follow-Up Studies; Graves Disease; HLA-DR Antigens; HLA-DR3 Antigen; Humans; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Methimazole; Multicenter Studies as Topic; Prospective Studies; Recurrence; Thyrotropin-Releasing Hormone; Thyroxine

A prospective randomized trial with the conventional divided doses (10 mg 3 times daily, N = 29) and a small single daily dose (15 mg once daily, N = 25) of methimazole for the treatment of Graves' hyperthyroidism was performed. Within 8 weeks, almost 80% of the patients in both groups became euthyroid. The mean time required to achieve the euthyroid state was 6.0 +/- 2.8 and 6.0 +/- 3.8 weeks, respectively. TSH binding inhibitor immunoglobulin was found in about 90% of the patients in both groups before methimazole treatment. However, a gradual fall of its levels was observed in nearly all patients after treatment. There was no difference in the mean levels of TSH binding inhibitor immunoglobulin between the two groups during therapy. We conclude that the single daily dose regimen of 15 mg of methimazole will control Graves' hyperthyroidism in most patients, and TSH binding inhibitor immunoglobulin levels decrease in this regimen in the same way as with the conventional divided dose regimen (10 mg 3 times daily).

Topics: Adult; Aged; Clinical Trials as Topic; Female; Graves Disease; Humans; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Prospective Studies; Random Allocation; Thyroxine

We have evaluated three regimens for the rapid control (10 days' therapy) of thyrotoxicosis in hyperthyroid Graves' disease: methimazole (MMI, 40 mg/day), MMI and sodium ipodate (MMI + Na Ipodate, 1 g/day and MMI and saturated solution of potassium iodide (MMI + SSKI, 6 drops twice daily). When serum T4 and T3 concentrations were analysed as the percent change from pre-treatment values, the following results were observed. Serum T4 concentration decreased in the three treatment groups and the decrease was similar in the MMI and MMI + SSKI groups but significantly lower than in the MMI + Na ipodate group. The serum T3 concentration decreased to the normal range in all seven MMI + Na Ipodate treated patients by the fourth day of treatment and the per cent decrease in serum T3 from pre-treatment values was significantly greater than in the MMI and MMI + SSKI treated patients. The decrease in serum T3 was similar in the latter two groups. Heart rate decreased in all three groups, but the decrease was significantly more in the MMI + Na Ipodate-treated patients. The present findings suggest that the rapid control of hyperthyroid Graves' disease is similar in patients treated with MMI and MMI + SSKI and that the combination of MMI + Na Ipodate is more efficacious since the decrease in serum T3 concentrations and heart rate was significantly greater in the MMI + Na ipodate-treated patients.

Topics: Adult; Blood Pressure; Drug Evaluation; Drug Therapy, Combination; Female; Graves Disease; Heart Rate; Humans; Ipodate; Male; Methimazole; Middle Aged; Potassium Iodide; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

In spite of the long-established use of antithyroid drugs, there are many unsettled questions connected with this treatment of Graves' disease. There is a lack of controlled prospective trials studying the results of antithyroid drug therapy while considering the many variables such as disease heterogeneity, regional differences, drug dosage and duration of treatment. Therefore, a multicenter study has been set up in order to compare the effects of two fixed doses of methimazole (10 vs 40 mg) with thyroid hormone supplementation on the clinical, biochemical and immunological course of Graves' disease and on remission rates. Experience accumulated so far suggests that treatment is safe using either 10 or 40 mg of methimazole. While there is a tendency for an advantage of the higher dose within the first weeks (higher effectiveness in controlling hyperthyroidism), this difference is not significant. The impact of dosage on remission rates remains to be shown.

Topics: Adult; Aged; Clinical Trials as Topic; Follow-Up Studies; Graves Disease; Humans; Methimazole; Middle Aged; Thyroid Gland; Thyroxine

We evaluated the efficacy of different doses of methimazole (MMI) as the initial therapy for Graves' disease. Fourteen patients were treated with 15 mg/die of the drug (group A) and 14 with 30 mg/die (group B). Blood samples for T3, T4, FT3 and FT4 were obtained before beginning therapy, every 48 h during the first 12 days and on the 45th day of treatment. All these hormonal parameters fell significantly from the 2nd day of therapy in both groups. All the patients, except for one in group B, had normal or subnormal levels of thyroidal hormones on the 45th day of treatment. The comparison between the two groups of regression coefficients over the first 12 days showed no significant differences. The absolute decrease of each examined parameter on day 12 was positively correlated with the relevant pretreatment value. These results demonstrate that doses of MMI (15 mg/die) much lower than those commonly recommended are able to rapidly control thyroidal overproduction as effectively as 30 mg/die.

Topics: Adult; Aged; Clinical Trials as Topic; Drug Administration Schedule; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Random Allocation; Thyroid Hormones

The effects of methimazole or betamethasone therapy on the TSH receptor antibody response to radioiodine therapy were compared in a prospective randomized study of 60 patients with hyperthyroidism due to Graves' disease. The patients were followed for 1 yr after treatment with 131I. Twenty-three patients received 131I alone, 17 were treated with methimazole for 2 months before and 3 months after 131I therapy, and 20 patients were treated with betamethasone for 3 weeks before and 4 weeks after 131I therapy. 131I induced a transient rise in the mean serum level of TSH receptor autoantibodies, measured as TSH binding inhibitory immunoglobulin (TBII), but in patients receiving methimazole treatment, no such rise occurred. In the betamethasone-treated patients, TBII increased similarly to that in patients treated with 131I alone. In addition, in patients given betamethasone, there was an early decrease in total serum immunoglobulin G, which persisted throughout the follow-up period. In the other 2 groups, no changes in total immunoglobulin G were found. The results demonstrate that in hyperthyroid Graves' disease, TBII production is influenced by therapy. Methimazole abolished the 131I-induced increase in TBII, whereas betamethasone did not have such an inhibitory effect.

Topics: Adult; Aged; Autoantibodies; Betamethasone; Female; Graves Disease; Humans; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Prospective Studies; Random Allocation; Receptors, Cell Surface; Receptors, Thyrotropin; Thyroxine; Triiodothyronine

The duration of action of methimazole (MMI) was studied in patients with hyperthyroidism due to Graves' disease. Perchlorate discharge tests performed 24 h after MMI administration revealed greater than 10% discharge in 77% of 53 patients who received a single dose of 15 mg MMI and in 74% of 23 patients who received 30 mg. The mean percent discharges were 41.5 +/- 26.4% (+/- SD) and 35.4 +/- 28.0, respectively. Based on these results, hyperthyroidism was treated with a single daily dose (SDD) of 15 mg in 43 patients and with 30 mg in 32 patients, and the results were compared with retrospective analysis of 50 patients who were treated with divided doses of MMI (10 mg, 3 times daily). Within 12 weeks, 93% of the patients treated with 15 mg SDD, 91% treated with 30 mg SDD, and 86% treated with divided doses were euthyroid. The mean times to achieve euthyroidism in these patients were 5.3 +/- 3.6 (+/- SD), 5.3 +/- 3.1, and 5.6 +/- 3.0 weeks, respectively. Side-effects occurred in 2 patients treated with 15 mg SDD and in 6 treated with 30 mg SDD. We conclude that a single daily dose of 15 mg MMI is not only effective in most patients with Graves' hyperthyroidism, but also less frequently causes adverse effects.

Topics: Adolescent; Adult; Aged; Child; Clinical Trials as Topic; Drug Administration Schedule; Drug Eruptions; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Perchlorates; Potassium; Potassium Compounds; Random Allocation; Thyroid Function Tests

Topics: Adult; Clinical Trials as Topic; Drug Administration Schedule; Drug Therapy, Combination; Female; Graves Disease; Humans; Lithium; Lithium Carbonate; Male; Methimazole; Middle Aged

We compared the effects of high and low dosages of antithyroid drugs in 113 patients with Graves' hyperthyroidism. The patients were randomly divided into 2 groups. In group A, 65 patients received either methimazole (MMI): 60 +/- 14.5 mg/day (mean +/- SD); range 40-100 mg/day, or propylthiouracil (PTU): 693 +/- 173 mg/day; range 500-1200 mg/day. These high doses were maintained throughout treatment with later addition of 50-75 micrograms T3 daily. Forty eight patients (group B) were treated with lower doses of MMI or PTU without thyroid hormone addition. The maintenance dose of MMI was 13.6 +/- 7 mg/day (range 5-25 mg/day) and that of PTU was 180 +/- 58 mg/day (range 100-300 mg/day). The treatment period was 15.1 +/- 4.2 (range 10-30) months for group A and 13.5 +/- 2.2 (range 12-20) months for group B. Remission occurred in 75.4% patients from group A and in 41.6% patients from group B (P less than 0.001). The mean follow-up was 42 +/- 14 months (17-81 months). The free T4 index (FT4I) in group A remained below the normal range during treatment. The mean FT4I, obtained during the course of treatment, of patients who went into remission from group A was significantly (P less than 0.001) lower than in relapsed patients (4.8 vs. 6.5). Moreover, there was an inverse correlation between mean FT4I and maintenance daily dose of either MMI (r = -0.567; P less than 0.001), or PTU (r = -0.379; P less than 0.01). A fall in microsomal antibody (MCHA) titer occurred mainly in remission patients, and was more significant (P less than 0.05) in group A patients. In contrast, 11 (7 from group B) of the 16 patients with an increase of microsomal antibody levels relapsed. The frequency of negative tests of thyroid-stimulating antibody was higher in group A patients (71%) than in group B (29%) at the end of therapy (P less than 0.01). No correlation was found between thyroid T3 suppressibility and either mean FT4I or thyroid-stimulatory antibody activity during treatment. Our findings show that patients treated with high doses of PTU or MMI throughout treatment have a higher remission rate when compared to those treated with a more conventional regimen. These results support the hypothesis that large antithyroid drug doses may have greater immunosuppressive effects than low dosage regimens. Furthermore, a high dosage regimen could permit the restoration of the immune surveillance mechanisms and, thus, lasting remission of Graves' disease.

Topics: Adolescent; Adult; Aged; Antibodies; Antithyroid Agents; Autoantibodies; Dose-Response Relationship, Drug; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Microsomes; Middle Aged; Propylthiouracil; Thyroglobulin; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

Microsomal antibodies and antibodies directed toward the receptor for thyroid-stimulating hormone (TSH) decreased in parallel while patients with Graves' disease were taking carbimazole, whereas no significant changes were observed during treatment with placebo or propranolol. The changes in autoantibody levels during carbimazole treatment were independent of changes in serum thyroxine and could have been due to a direct effect of the drug on autoantibody synthesis. Evidence for this suggestion was provided when low doses of methimazole (the active metabolite of carbimazole) were found to inhibit thyroid-autoantibody production in cultured lymphocytes. Since thyroid lymphocytes are probably a major site of thyroid-antibody synthesis in Graves' disease and methimazole is concentrated in the thyroid during treatment, a local action of the drug on antibody production seems likely. This possibility could be important in the use of carbimazole to control hyperthyroidism.

Topics: Antibody Formation; Autoantibodies; Carbimazole; Cells, Cultured; Graves Disease; Humans; Lymphocytes; Methimazole; Microsomes; Placebos; Propranolol; Receptors, Cell Surface; Thyroid Gland; Thyrotropin; Thyroxine

In 28 patients with Graves' disease showing a wide range of thyroid function between the extremes of hypothyroidism and hyperthyroidism, the following parameters of peripheral thyroid function were measured: serum thyroxine concentration, serum-free thyroxine concentration, serum triiodothyronine concentration, and serum-free triiodothyronine concentration. In 25 patients, thyroxine turnover was also measured. Thyroxine turnover was found to be highly correlated with serum-free thyroxine concentration (r equals 0.9405) and serum-free triiodothyronine concentration (r equals 0.9184). Serum-free thyroxine fraction correlated with serum-free triiodothyronine fraction (r equals 0.8445), suggesting that similar factors in serum controlled the intensity of protein binding for both thyroxine and triiodothyronine. Thyroxine turnover calculated by a noncompartmental method agreed closely with values calculated by the compartmental method, suggesting that the former simpler method has general utility.

Topics: Adult; Aged; Clinical Trials as Topic; Female; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Middle Aged; Propylthiouracil; Radioimmunoassay; Thyroid Function Tests; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine

Topics: Adult; Estrogens; Female; Graves Disease; Humans; Hyperthyroidism; Injections, Intravenous; Iodine Isotopes; Male; Methimazole; Middle Aged; Phenols; Phenytoin; Placebos; Thyroid Gland; Thyroxine; Thyroxine-Binding Proteins

Thyrotoxic periodic paralysis (TPP) is an acute complication of hyperthyroidism. Thyrotoxic periodic paralysis is treatable, and the management consists of potassium correction, beta-blockers, and antithyroid drug (ATD) therapy. While TPP is well described in the literature, we describe a case of TPP with urticarial dermographia (UD) that resolved with a short course of antihistamines while continuing ATD therapy. To the best of our knowledge, this is the first reported case of UD after methimazole (MMI) therapy in a TPP patient. A 25-year-old Cambodian active duty male with no significant past medical history presented to the emergency department with acute loss of lower extremity muscle tone with hypokalemia in the setting of previously undiagnosed Graves' disease (GD). He was started on MMI but within 2 weeks developed a rash consistent with UD. This was successfully treated with a second-generation antihistamine while continuing his MMI. Thyrotoxic periodic paralysis is primarily treated by controlling the underlying thyroid disease causing paralysis. Methimazole is commonly chosen as a treatment due to its rapid efficacy and long duration of action. However, adverse effects like UD can occur. Current recommendations are that minor cutaneous reactions can be treated with antihistamines for the management of Graves' disease. However, this case and others show that even moderate reactions can be managed in this manner. In a patient with TPP with UD after treatment with MMI, it is reasonable to attempt a trial of antihistamine before changing to another ATD.

Topics: Adult; Antithyroid Agents; Graves Disease; Humans; Male; Methimazole; Paralysis; Potassium; Thyrotoxicosis

Outcomes of childhood-onset Graves' disease (GD) and suggested duration of anti-thyroid drug (ATD) therapy have been controversial. This study aimed to determine long-term outcomes following ATD therapy, including remission and relapse rates.. A retrospective study of 265 paediatric patients with GD who were initially treated with ATD was conducted. Long-term outcomes were analysed.. Median (IQR) age at diagnosis was 11.5 (9.4, 13.7) years. Duration of ATD treatment was 4.3 (2.3, 6.7) years and time since diagnosis to the enrolment was 7.1 (3.8, 10.9) years. There were 77, 93 and 95 patients who underwent definitive treatment, had ATD discontinuation, and were still being treated with ATD, respectively. The remission rate was 21% (56 out of 265 patients) and relapse rate was 40% (37 out of 93 patients). Cumulative incidence of first remission increased with the duration of ATD treatment with maximum remission rate at 5.3 years following ATD therapy. Among patients who experienced relapse, approximately 50% had disease relapse which occurred within 1 year after ATD discontinuation. Patients with goitre size of less than 3.5 cm, thyroid-stimulating hormone receptor antibody of less than 10 IU/L, no ophthalmopathy at diagnosis and methimazole dose requirement of less than 0.25 mg/kg/day at 1 year after treatment were more likely to achieve remission.. Remission rate of childhood-onset GD was relatively low following ATD treatment. Longer-term ATD therapy was associated with increased remission rate. Approximately 50% of patients with relapse had disease relapse within 1 year following ATD discontinuation.

Topics: Antibodies; Antithyroid Agents; Child; Graves Disease; Humans; Methimazole; Recurrence; Remission Induction; Retrospective Studies; Thyrotropin; Treatment Outcome

Adults with hyperthyroidism have been found to have decreased bone mineral density (BMD) and higher fracture risk. The most typical cause of hyperthyroidism is Graves' disease. However, there are limited studies on how hyperthyroidism affects bone metabolism and fractures in children. We describe a unique instance of a patient who initially displayed a fragility fracture and was ultimately identified with Graves' disease after biochemical evaluations.. A 2-year-8-month-old female presented with fragility fractures three times in only 7 months. A series of examinations were performed to evaluate any possible malformations or abnormalities of bone metabolism. Graves' disease was found, and drug therapies were employed (methimazole, propranolol, calcium carbonate, vitamin D). Since children with Graves' disease and fragility fractures have been uncommonly described in the past, a stringent and thorough long-term follow-up was initiated.. Children with undiagnosed Graves' disease had a higher risk of fractures and osteoporosis. This case suggests that BMD measurement may be necessary for the initial evaluation of Graves' disease in children.

Topics: Adult; Child; Female; Graves Disease; Humans; Hyperthyroidism; Infant; Methimazole; Osteoporosis; Propranolol

The aim of this study was to compare long-term outcomes in terms of new onset or worsening of Graves orbitopathy (GO) in patients with Graves disease treated with different therapeutic modalities for hyperthyroidism.. A total of 1163 patients with Graves disease were enrolled in this study; 263 patients were treated with radioiodine and 808 patients received methimazole (MMI) therapy for a median of 18 months, of whom 178 patients continued MMI for a total of 96 months (long-term methimazole [LT-MMI]). The thyroid hormonal status and GO were evaluated regularly for a median of 159 months since enrollment.. The rates of relapse, euthyroidism, and hypothyroidism at the end of follow-up were as follows: radioiodine treatment group: 16%, 22%, and 62%, respectively; short-term MMI group: 59%, 36%, and 5%, respectively; and LT-MMI group: 18%, 80%, and 2%, respectively. During the first 18 months of therapy, worsening of GO (11.5% vs 5.7%) and de novo development of GO (12.5% vs 9.8%) were significantly more frequent after radioiodine treatment (P <.004). Overall worsening and de novo development of GO from >18 to 234 months occurred in 26 (9.9%) patients in the radioiodine group and 8 (4.5%) patients in the LT-MMI group (P <.037). No case of worsening or new onset of GO was observed in patients treated with LT-MMI from >60 to 234 months of follow-up.. Progression and development of GO were associated more with radioiodine treatment than with MMI treatment; GO may appear de novo or worsen years after radioiodine treatment but not after LT-MMI therapy.

Topics: Antithyroid Agents; Follow-Up Studies; Graves Disease; Graves Ophthalmopathy; Humans; Iodine Radioisotopes; Methimazole; Neoplasm Recurrence, Local; Thyroid Neoplasms

The effect of potassium iodide (KI) on radioiodine uptake (RAIU) before radioisotope therapy in Graves' disease (GD) patients was investigated. A total of 82 patients who had been treated with KI monotherapy before 24-hour RAIU (24 h RAIU) were evaluated and 354 of those who had been treated with thiamazole (MMI) monotherapy were extracted from the 1,130 GD patients who were identified as having had appropriate iodine restriction based on urinary iodine excretion. Urinary iodine excretion (UIE) <200 μg/day was confirmed in all subjects. Propensity score-matching was performed to identify the difference in 24 h RAIU between the KI group and the MMI group. In addition, multiple regression analysis was performed to evaluate related to 24 h RAIU. Propensity score-matching resulted in 57 matched patients in each group. After matching, 24 h RAIU was still significantly lower in the KI group than in the MMI group (median 53% (interquartile range 47-61%) vs. 63% (56-66%); p = 0.001). In addition, KI monotherapy was weakly negatively correlated with 24 h RAIU, whereas the female sex and FT3 were very weakly positively correlated on multiple regression analysis. The results suggest that KI monotherapy likely suppressed 24 h RAIU more than MMI monotherapy in GD patients with appropriate iodine restriction, given the difference in the mechanism of hormone suppression.

Topics: Female; Graves Disease; Humans; Iodine; Iodine Radioisotopes; Methimazole; Potassium Iodide

Immune thrombocytopenic purpura is a condition associated with an unusual, unexplained, and sometimes very severe reduction in the level of platelets in the blood. Though documented, its association with Graves' disease is not very common and can easily be missed or misdiagnosed, leading to excessive bleeding and mortality. Treatment with steroids and antithyroid medications has been shown to be beneficial in correcting thrombocytopenia in these patients, although the response is varied. We report on a patient with Graves' disease who presents with immune thrombocytopenic purpura.. A 37-year-old Ghanaian female presented to our hospital's emergency department with a complaint of palpitations, difficulty breathing, easy fatigue, and headaches. She had been referred from a peripheral hospital as a case of thrombocytopenia, severe anemia, and anterior neck swelling. She was diagnosed with Graves' disease 2 years ago, became euthyroid during treatment, but defaulted. On further examination and investigation, she was diagnosed with immune thrombocytopenic purpura and was also found to have elevated free T3 and T4, and suppressed thyroid stimulating hormone. She also had high thyroid autoantibodies. She was initially started on oral prednisolone but there was no stabilization of platelets until methimazole was introduced, which improved and normalized her platelet count.. The association of Graves' disease with immune thrombocytopenic purpura, though documented, is uncommon, and very few cases have been reported thus far. There have not been any reported cases in Ghana or Sub-Saharan Africa and hence, clinicians should be aware of this association when investigating immune thrombocytopenic purpura and should consider Graves' disease as a possible cause. From this study, we observed that there was no improvement in platelet count following the use of corticosteroid therapy until methimazole was started.

Topics: Adult; Female; Ghana; Graves Disease; Humans; Methimazole; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia

Methimazole (MMI) represents the conventional therapeutic agent for Graves' disease (GD) hyperthyroidism, but MMI efficacy is limited since it marginally affects the underlying autoimmune process. In a previous study, we randomly assigned 42 newly diagnosed GD patients with insufficient vitamin D (VitD) and selenium (Se) levels to treatment with MMI alone (standard) or combined with selenomethionine and cholecalciferol (intervention) and observed a prompter resolution of hyperthyroidism in the intervention group.. In the present study, we aimed to explore changes in peripheral T regulatory (Treg) and circulating natural killer (NK) cell frequency, circulating NK cell subset distribution and function, during treatment.. At baseline, circulating total CD3. This pilot study suggested that VitD and Se supplementation, in GD patients receiving MMI treatment, modulates Treg and NK cell frequency, favoring a more pronounced reduction of NK cells and the increase of Treg cells, compared to MMI alone. Even if further studies are needed, it is possible to speculate that this immunomodulatory action might have facilitated the prompter and better control of hyperthyroidism in the supplemented group observed in the previous study.

Topics: Antithyroid Agents; Dietary Supplements; Graves Disease; Humans; Hyperthyroidism; Methimazole; Pilot Projects; Selenium; Vitamin D; Vitamins

Topics: Antithyroid Agents; Erythema Nodosum; Graves Disease; Humans; Methimazole

Acute suppurative thyroiditis is an uncommon disorder caused by a bacterial infection, usually presenting with normal thyroid function. It is a serious condition that requires a prompt diagnosis and treatment with antibiotics and supportive measures. A 62 years-old female presented with a painful cervical induration and odynophagia a week after a fish bone had been removed from her pharynx. She was febrile, and tachycardic and, on physical examination, a painful thyroid mass was detected. High inflammatory parameters and thyrotoxicosis were confirmed: thyroid stimulating hormone (TSH) < 0.01 mIU/L (normal range [NR] 0.27-4.2); free thyroxine (FT4) 3.86 ng/dL (NR 0.9-1.7) and anti-TSH receptor antibodies (TRABs) 5.3 U/L (NR < 1.5). Thyroid scintigraphy showed a diffuse uptake of the thyroid parenchyma suggesting Graves disease. Cervical ultrasonography revealed an abscess of the left thyroid lobe of 36 × 36 mm and fine needle aspiration biopsy (FNAB) with partial drainage was performed.

Topics: Abscess; Acute Disease; Female; Graves Disease; Humans; Methimazole; Thyroiditis, Suppurative; Thyrotoxicosis

A common problem with antithyroid drugs (ATD) treatment in patients with Graves' disease (GD) is the high recurrence rate after drug withdrawal. Identifying risk factors for recurrence is crucial in clinical practice. We hereby prospectively analyze risk factors for the recurrence of GD in patients treated with ATD in southern China.. Patients who were newly diagnosed with GD and aged > 18 years were treated with ATD for 18 months and followed up for 1 year after ATD withdrawal. Recurrence of GD during follow-up was assessed. All data were analyzed by Cox regression with P values < 0.05 considered statistically significant.. A total of 127 Graves' hyperthyroidism patients were included. During an average follow-up of 25.7 (standard deviation = 8.7) months, 55 (43%) had a recurrence within 1 year after withdraw of anti-thyroid drugs. After adjustment for potential confounding factors, the significant association remained for the presence of insomnia (hazard ratio (HR) 2.94, 95% confidence interval (CI) 1.47-5.88), greater goiter size (HR 3.34, 95% CI 1.11-10.07), higher thyrotrophin receptor antibody (TRAb) titer (HR 2.66, 95% CI 1.12-6.31) and a higher maintenance dose of methimazole (MMI) (HR 2.14, 95% CI 1.14-4.00).. Besides conventional risk factors (i.e., goiter size, TRAb and maintenance MMI dose) for recurrent GD after ATD withdraw, insomnia was associated with a 3-fold risk of recurrence. Further clinical trials investigating the beneficial effect of improving sleep quality on prognosis of GD are warranted.

Topics: Antithyroid Agents; Graves Disease; Humans; Hyperthyroidism; Methimazole; Sleep Initiation and Maintenance Disorders

The use of iodinated contrast media (ICM) can lead to thyrotoxicosis, especially in patients with risk factors, such as Graves' disease, multinodular goiter, older age, and iodine deficiency. Although hyperthyroidism may have clinically relevant effects, whether high-risk patients should receive prophylactic treatment before they are administered ICM is still debated.. We aimed to demonstrate the safety and efficacy of prophylactic treatment with sodium perchlorate and/or methimazole to prevent ICM-induced hyperthyroidism (ICMIH) in a population of high-risk cardiac patients. We ran a cost analysis to ascertain the most cost-effective prophylactic treatment protocol. We also aimed to identify possible risk factors for the onset of ICMIH.. We performed a longitudinal retrospective study on 61 patients admitted to a tertiary-level cardiology unit for diagnostic and/or therapeutic ICM-procedures. We included patients with available records of thyroid function tests performed before and after ICM were administered, who were at high risk of developing ICMIH. Patients were given one of two different prophylactic treatments (methimazole alone or both methimazole and sodium perchlorate) or no prophylactic treatment. The difference between their thyroid function at the baseline and 11-30 days after the ICM-related procedure was considered the principal endpoint.. Twenty-three (38%) of the 61 patients were given a prophylactic treatment. Thyroid function deteriorated after the administration of ICM in 9/61 patients (15%). These cases were associated with higher plasma creatinine levels at admission, higher baseline TSH levels, lower baseline FT4 levels, and no use of prophylactic treatment. The type of prophylaxis provided did not influence any onset of ICMIH. A cost-benefit analysis showed that prophylactic treatment with methimazole alone was less costly per person than the combination protocol. On multivariate analysis, only the use of a prophylactic treatment was independently associated with a reduction in the risk of ICMIH. Patients not given any prophylactic treatment had a nearly five-fold higher relative risk of developing ICMIH.. Prophylactic treatment can prevent the onset of ICMIH in high-risk populations administered ICM. Prophylaxis is safe and effective in this setting, especially in cardiopathic patients. Prophylaxis with methimazole alone seems to be the most cost-effective option.

Topics: Contrast Media; Graves Disease; Humans; Hyperthyroidism; Methimazole; Retrospective Studies; Risk Factors

Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia and is characterized by the presence of insulin autoantibodies and fasting or late postprandial hypoglycemia. The number of reports on the association of long-term follow-up of IAS in China is limited. We herein report a case of drug-induced IAS in a 44-year-old Chinese woman. She had been taking methimazole for Graves' disease and had subsequently presented with recurrent hypoglycemic episodes. Laboratory assessments on admission revealed that her serum insulin level was significantly elevated (>1000 µIU/mL) and that she was positive for serum insulin autoantibody, leading to a diagnosis of IAS. Human leukocyte antigen DNA typing identified *04:06/*09:01:02, an immunogenetic determinant associated with IAS. After treatment with prednisone for 2 months, the hypoglycemic episodes disappeared, her serum insulin level gradually declined, and her insulin antibody levels became negative. Clinicians should be aware of the potential for methimazole to trigger autoimmune hypoglycemia in people with a genetic predisposition.

Topics: Adult; Autoimmune Diseases; Female; Follow-Up Studies; Graves Disease; Humans; Hyperinsulinism; Hypoglycemia; Hypoglycemic Agents; Insulin; Methimazole

The most common cause of hyperthyroidism is Graves' disease. Propylthiouracil (PTU) is one of the drugs used to treat this disease. Leukocytoclastic vasculitis is described among dermatologic adverse effects of PTU.. A 18-year-old woman, allergic to methimazole, developed a vasculitis associated to ANCAs with characteristics of leukocytoclastic vasculitis, associated to PTU treatment. She did not present systemic involvement. PTU treatment was suspended. Two months later, the skin lesions had almost completely resolved.. Leukocytoclastic vasculitis should be considered in the spectrum of complications caused by the consumption of propylthiouracil. The lesions can manifest over time, from a few weeks to years after taking the drug. When there is no systemic involvement, propylthiouracil suspension is sufficient to cure the disease.. La causa más frecuente de hipertiroidismo es la enfermedad de Graves. El propiltiouracilo es uno de los medicamentos más prescritos para esta enfermedad. Uno de los efectos adversos dermatológicos del propiltiouracilo es la vasculitis leucocitoclástica.. Paciente femenina de 18 años, alérgica al metamizol, con vasculitis asociada a ANCAs, con características de vasculitis leucocitoclástica provocada por el consumo de propiltiouracilo. No se observó afectación sistémica. Dos meses después de suspender el propiltiouracilo desaparecieron casi por completo las lesiones en la piel.. La vasculitis leucocitoclástica debe considerarse en el espectro de complicaciones provocadas por el consumo de propiltiouracilo. Las lesiones pueden manifestarse con el paso del tiempo, desde unas semanas hasta años después de consumir el fármaco. Cuando no existe afectación sistémica, la suspensión del propiltiouracilo es suficiente para detener la enfermedad.

Topics: Adolescent; Antithyroid Agents; Drug-Related Side Effects and Adverse Reactions; Female; Graves Disease; Humans; Methimazole; Propylthiouracil; Vasculitis, Leukocytoclastic, Cutaneous

Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia characterized by high levels of blood insulin autoantibodies. It has been documented that drugs containing sulfhydryl groups may result in IAS. In this study, we present two cases of IAS induced by methimazole, along with their corresponding treatments and a long-term follow-up after hospitalization.. We report two patients with Grave's disease (GD), carrying the HLA-DRB1 04:06 genotype, who experienced hypoglycemic episodes after taking methimazole. Inpatient treatments helped return their blood glucose levels to normal. Although no recurrences of hypoglycemia were present in the two cases studied, insulin autoantibodies remained positive for the previous follow-up sessions, which turned negative only three years after discharge.. GD patients who carry the HLA-DRB1 04:06 genotype are prone to IAS if they take drugs containing sulfhydryl groups. It may take time for the elimination of insulin autoantibodies after the recovery from the hypoglycemic episode in IAS patients.

Topics: Autoantibodies; Autoimmune Diseases; Follow-Up Studies; Graves Disease; HLA-DRB1 Chains; Humans; Hyperinsulinism; Hypoglycemia; Hypoglycemic Agents; Insulins; Methimazole; Patient Discharge; Sulfhydryl Compounds

2例女性格雷夫斯病患儿，分别为16岁和10岁。例1甲巯咪唑治疗3个月出现高肌酸激酶血症，无肌痛、肌无力等，甲巯咪唑减量1个月肌酸激酶恢复正常，后行甲状腺部分切除术。例2甲巯咪唑治疗1个月夜间出现烦躁、行为异常、意识障碍，指尖血糖1.6 mmol/L，胰岛素显著升高、胰岛素自身抗体阳性，停药后血糖恢复正常，后行碘131治疗，因甲状腺功能再次亢进口服丙硫氧嘧啶。随访至2023年2月，2例患儿甲状腺功能控制良好，未出现不良反应反复。.

Topics: Child; Graves Disease; Humans; Methimazole

This study aimed to evaluate the association between the initial dose of MMI and the clinical course, as well as adverse effects on young people with GD.. One hundred and sixty-one children and adolescents with newly diagnosed GD were enrolled for this study and categorized into four groups based on initial serum-free T3 and T4 levels and daily MMI doses: Group A (mild, 0.3-0.5 mg/kg/day, n = 78), Group B (moderate, 0.6-0.8 mg/kg/day, n = 37), Group C (severe, 0.6-0.8 mg/kg/day, n = 24), and Group D (severe, 0.8-1.0 mg/kg/day, n = 22). The thyroid function, blood cell analysis and liver function were examined before treatment and at 4, 8 and 12 weeks after treatment. Outcome of long-term follow-up were also observed.. After 12 weeks of treatment, 91.0% of the patients in group A and 90.9% of the patients in group D recovered to normalization of FT3, which was slightly higher than the other two groups; 70.8% of the patients in group C recovered to normalization of FT4, which was slightly lower than that in the other three groups. The incidence of minor adverse effects was 12.8% in group A, 13.5% in group B, 16.7% in group C and 40.9% in group D (P < 0.01). Remission was achieved in 38 patients (23.6%).. Lower doses of MMI (0.3-0.5 mg/kg/day) are suitable for mild GD, and higher doses of MMI (0.6-0.8 mg/kg/day) are advisable for moderate or severe GD. Much higher doses of MMI (0.8-1.0 mg/kg/day) are harmful for initial use in children and adolescents with GD patients.

Topics: Adolescent; Antithyroid Agents; Child; Graves Disease; Humans; Methimazole; Outpatients; Thyroxine

Graves' disease is one of the most common causes of hyperthyroidism. Guideline recommendations advocate the intake of thionamides for at least 1 year. If hyperthyroidism persists, subsequent radioiodine-131 treatment (RIT) is a therapeutic option. Thionamides are known to influence intra-thyroidal bio-kinetics of iodine and should therefore be discontinued at least 3 days prior to RIT if possible. However, the required therapeutic activity has to be calculated individually by pre-therapeutic measurement of the uptake prior to RIT [radioiodine-131 uptake test (RIUT)] in Germany according to national guidelines. Therefore, the aim of this study was to quantify the influence of thionamides on intra-therapeutic uptake. A cohort of 829 patients with Graves' disease undergoing RIUT and RIT was analysed. Patients were subdivided into three groups. Group A: patients with carbimazole medication (n = 312), group B: patients with methimazole medication (n = 252) and group C: patients without thionamides (n = 265). Group A and B were further subdivided depending on the reduction of dosage of thionamides. In order to analyse the influence of thionamides, the variance of the determined individual extrapolated maximum intra-thyroidal uptake (EMU) between RIUT and RIT within the single groups and within the subgroups was statistically evaluated. When administering an equal dose of thionamides or no thionamides in RIUT and RIT (groups A1, B1 and C) no significant differences were detected when comparing EMU in RIT to EMU in RIUT (p > 0.05). In the subgroups A2-A4 (reduced dosage of carbimazole prior to RIT) EMU was significantly increased in RIT compared to RIUT [21% for a reduction of 0 to < 10 mg/d (A2), 39% for a reduction of 10-15 mg/d (A3) and 80% for a reduction of > 15 mg/d (A4)]. In the subgroups B2-B4 (reduced dosage of methimazole prior to RIT) EMU was as well significantly increased in RIT compared to RIUT [26% for a reduction of 0 to < 10 mg/d (B2), 36% for a reduction of 10-15 mg/d (B3) and 59% for a reduction of > 15 mg/d (B4)]. A significant dose-dependent increase of EMU in RIT compared to EMU in RIUT in patients discontinuing or reducing thionamides was detected. Therefore, thionamides should be discontinued at least 2 days prior to RIUT in order to achieve the designated target dose more precisely and to minimize radiation exposure of organs at risk.

Topics: Carbimazole; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole

We report a Japanese boy with Graves' disease (GD) which developed during drug-free remission of juvenile dermatomyositis (JDM). He had been diagnosed with JDM at the age of 6 years by typical skin rashes, muscle weakness, elevated serum transaminase levels, and typical findings of both magnetic resonance imaging and muscle biopsy. Although anti-melanoma differentiation antigen 5 autoantibody was positive, there was no complication of interstitial lung disease. He showed good response to methylprednisolone pulse therapy followed by oral prednisolone in combination with weekly methotrexate (MTX) and achieved drug-free remission after 3.5 years of treatment. Nevertheless, serum levels of soluble interleukin-2 receptor (sIL-2R) gradually elevated to 3185 U/ml despite no signs of relapse or malignancy. Hyperactivity and attention deficit was also noted. One year and 3 months after the cessation of MTX, he presented with abdominal pain, tachycardia, and apparent goitre. Laboratory tests showed elevated free triiodothyronine, undetectable thyroid stimulating hormone (TSH), and positive anti-TSH receptor antibodies. 99mTc scintigraphy showed high levels of thyroid uptake. He was diagnosed with GD and treated with 15 mg/day of thiamazole. Although transient drug eruption was observed, his thyroid functions are currently well-controlled on 5 mg/day of thiamazole. In conclusion, to our knowledge, this is the first report in English literature describing complication of GD with JDM. Unexpected elevation of sIL-2R could be a clue to the diagnosis of GD during the follow-up of JDM.

Topics: Child; Dermatomyositis; Graves Disease; Humans; Male; Methimazole; Neoplasm Recurrence, Local; Thyroid Function Tests

A 28-year-old Japanese woman positive for TSH receptor antibody and anti-nuclear antibody complained of difficulty seeing nearby objects, severe throbbing retro-orbital pain, diplopia, blepharoptosis and upward gaze palsy when she became hypothyroid during treatment with 30 mg methylmercaptoimidazole for Graves' hyperthyroidism. Brain magnetic resonance imaging revealed slightly swollen bilateral inferior rectus muscles, suggesting the external ophthalmoplegia due to the muscle pathology commonly encountered in Graves' disease. The retro-orbital pain was associated with marked accommodation failure and the pupillary abnormalities. The left and/or right eye showed intermittent, asymmetric and fluctuating mydriasis, being unresponsive to ordinary light but slowly responsive to strong sunlight and slowly responsive in a dark room. During the 5-year period, mydriasis was observed 9 times on both sides, 11 times only on the right side and 4 times only on the left side. Internal ophthalmoplegia with tonic pupils and accommodation failure affecting both the pupillary sphincter muscle and ciliary muscle due to damage to the parasympathetic outflow to these muscles was suggested. Autoimmune mechanism and/or the mechanism underlying channelopathy affecting the ciliary ganglion or short ciliary nerves might be responsible for this fluctuating complication. This very rare panophthalmopathy affecting both external and internal muscles occurred when the patient was suffering from iatrogenic hypothyroidism during the 30 mg methylmercaptimidazole treatment for Graves' disease.

Topics: Adult; Female; Graves Disease; Graves Ophthalmopathy; Humans; Magnetic Resonance Imaging; Methimazole; Ophthalmoplegia

Thyroid hormone excess induces protein energy wasting, which in turn promotes muscle weakness and bone loss in patients with Graves' disease. Although most studies have confirmed a relationship between thyrotoxicosis and muscle dysfunction, few have measured changes in plasma metabolites and immune cells during the development and recovery from thyrotoxic myopathy. The aim of this study was to identify specific plasma metabolites and T-cell subsets that predict thyrotoxic myopathy recovery in patients with Graves' disease.. One hundred patients (mean age, 40.0 ± 14.2 years; 67.0% female), with newly diagnosed or relapsed Graves' disease were enrolled at the start of methimazole treatment. Handgrip strength and Five Times Sit to Stand Test performance time were measured at Weeks 0, 12, and 24. In an additional 35 patients (mean age, 38.9 ± 13.5 years; 65.7% female), plasma metabolites and immunophenotypes of peripheral blood were evaluated at Weeks 0 and 12, and the results of a short physical performance battery assessment were recorded at the same time.. In both patient groups, methimazole-induced euthyroidism was associated with improved handgrip strength and lower limb muscle function at 12 weeks. Elevated plasma metabolites including acylcarnitines were restored to normal levels at Week 12 regardless of gender, body mass index, or age (P trend <0.01). Senescent CD8. Restoring euthyroidism in Graves' disease patients was associated with improved skeletal muscle function and performance, while thyroid hormone-associated changes in plasma acylcarnitines levels correlated with muscle dysfunction recovery. T-cell senescence-related systemic inflammation correlated with plasma acylcarnitine levels and was also associated with small increases in handgrip strength.

Topics: Adult; CD8-Positive T-Lymphocytes; Female; Graves Disease; Hand Strength; Humans; Male; Methimazole; Middle Aged; Muscular Diseases

Hyperthyroidism, such as Basedow disease, causes fluid retention, although the common cause is volume overload due to congestive heart failure. In addition, hyperthyroidism and Basedow disease are known to cause pulmonary hypertension. Edematous thickening of the gallbladder wall is caused by venous blood congestion. The feature of edematous wall thickening of the gallbladder on abdominal computed tomography (CT) is subserosal edema and is often accompanied by a periportal collar sign.. A 30-year-old woman was referred to our hospital because of liver dysfunction, edematous gallbladder wall thickening, and fluid retention. In addition, the patient developed hyperthyroidism and heart failure. Enhanced abdominal CT revealed edematous wall thickening of the gallbladder and a periportal collar sign.. We suspected that fluid retention and congestion were caused by hyperthyroidism and Basedow disease.. On admission, we started thiamazole therapy for Basedow disease, and her thyroid hormone levels normalized.. Abdominal CT revealed disappearance of edematous wall thickening of the gallbladder, which was likely associated with an improvement in thyroid function. The patient was discharged 10 days after admission.. We encountered a case of hyperthyroidism and Basedow disease accompanied by edematous wall thickening of the gallbladder and various fluid retentions as the first symptoms. Such edematous wall thickening of the gallbladder and various fluid retentions were reduced, together with the improvement of hyperthyroidism.

Topics: Adult; Edema; Female; Gallbladder; Graves Disease; Heart Failure; Humans; Hyperthyroidism; Methimazole; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography

Liver injury related to Graves' Disease (GD) includes hepatotoxicity of thyroid hormone excess, drug-induced liver injury, and changes resulting from concomitant liver disease. Methimazole (MMI) has been shown to induce several patterns of liver injury. However, the diagnosis and treatment of autoimmune hepatitis (AIH) overlapping with either GD or chronic hepatitis B are challenging.. A 35-year-old man from China presented with a two-year history of GD and a 10-day history of progressive jaundice. He had taken MMI for two months and discontinuing treatment due to liver toxicity 1 year ago and for another 6 days 20 days prior to hospitalization. The patient was diagnosed with GD overlapping with chronic hepatitis B and MMI-induced liver injury with early stage of acute-on-chronic liver failure on admission. However, the elevated aminotransferase and bilirubin levels could not be controlled after correction of liver failure and effective control of HBV replication and hyperthyroidism by daily oral entecavir and one-time oral administration of 131-iodine. The patient underwent liver biopsy on the 43rd day of hospitalization, showing HBsAg expression on the membrane of hepatocytes and typical histopathological characteristics of AIH. He was finally diagnosed with GD overlapping with chronic hepatitis B and MMI-induced liver injury and AIH. The elevated aminotransferase and bilirubin completely returned to normal by 3-month glucocorticoid therapy and continuous entecavir treatment and there was no recurrence during a 6-month follow-up, suggesting that AIH in this patient is different from classical AIH or GD-associated AIH.. GD together with AIH is a complex and difficult subject. It needs to be clarified whether MMI or HBV can act as a trigger for AIH in this patient.

Topics: Adult; Chemical and Drug Induced Liver Injury, Chronic; Graves Disease; Hepatitis B, Chronic; Hepatitis, Autoimmune; Humans; Male; Methimazole

Idiopathic intracranial hypertension (IIH) is characterized by increased intracranial pressure without an evident cause. Obesity and the female sex have been recognized as risk factors for the development of this syndrome. Until now, Graves' disease has only been described in the literature as the probable cause of IIH in 7 patients. This report describes the case of a young girl with Graves' disease presenting with symptoms of intracranial hypertension (IH).. A 21-month-old girl presented with progressive symptoms of poor weight gain and bilateral exophthalmos. She also experienced difficulty sleeping, diarrhea multiple times per day, irritability, and heat intolerance. Laboratory investigation showed elevated free T4, fully suppressed TSH, and elevated anti-TSH antibodies, consistent with a diagnosis of new-onset Graves' disease. She was successfully treated with monotherapy thiamazole, titrated to the lowest possible dose of 1.25 mg once daily with normalization of thyroid function tests within 3 months of treatment initiation. After 18 months of treatment, her condition unexpectedly deteriorated as papilledema and slight esotropia were found at a routine checkup. An MRI and lumbar puncture showed increased intracranial pressure, but no underlying anatomical cause for the IH was found. Acetazolamide therapy was started, and papilledema in both eyes resolved within weeks. Unfortunately, papilledema has recurred several times over the following 2 years when attempts were made to decrease the acetazolamide dose.. This case report is the first to describe a very young patient who developed significant IIH in the chronic stage of Graves' disease. IIH development seemed to be related to the progression of the Graves' ophthalmopathy, rather than initiation of thiamazole therapy or fluctuations in serum fT4 levels.

Topics: Acetazolamide; Child, Preschool; Female; Graves Disease; Humans; Infant; Intracranial Hypertension; Methimazole; Papilledema; Pseudotumor Cerebri

We treated a 22-year-old woman suffering from Graves' disease and thymic hyperplasia. She was referred to our institution for a close investigation of thyrotoxicosis and thymic mass. Thyroid tests and magnetic resonance imaging resulted in a diagnosis of Graves' disease and thymic hyperplasia. The thyroid function and thyroid-stimulating hormone receptor antibody (TRAb) were normalized one and five months after thiamazole initiation, respectively. The thymic size began to decrease after 1 month and was further decreased after 5 months; it was normalized after 12 months. The correlation between TRAb titers and the thymic size (R

Topics: Adult; Autoantibodies; Female; Graves Disease; Humans; Methimazole; Receptors, Thyrotropin; Thymus Hyperplasia; Thyrotropin; Young Adult

The effectiveness of potassium iodide (KI) (100 mg/day) was evaluated in 504 untreated patients with Graves' hyperthyroidism (GD). Initial response to KI within 180 days, the effect of additional methylmercaptoimidazole (MMI) or radioactive iodine (RI) in resistant or escaped patients, and long-term prognosis were evaluated. Serum fT

Topics: Antithyroid Agents; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Iodides; Iodine Radioisotopes; Methimazole; Potassium Iodide; Thyroid Neoplasms; Thyrotropin

Immune dysfunction caused by environmental factors plays an important role in the development of Graves' disease (GD), and environmental factors are closely related to the intestinal flora. Our previous study showed significant changes in the intestinal flora in GD patients compared with healthy volunteers. This study analyzed the relationships between changes in the intestinal flora, thyroid function and relevant thyroid antibodies in GD patients before and after methimazole treatment. The subjects were divided into the UGD group (18 newly diagnosed GD patients), the TGD group (10 GD patients with normal or approximately normal thyroid function after methimazole treatment) and the NC group (11 healthy volunteers). Their fresh stool samples were sent for 16S rRNA gene amplification and Illumina platform sequencing. The correlations of the relative abundance of

Topics: Feces; Gastrointestinal Microbiome; Graves Disease; Humans; Methimazole; RNA, Ribosomal, 16S

We investigated longitudinal changes in circulating CD4. The study included 18 untreated hyperthyroid patients with Graves' disease and 18 age-matched controls. Before and after 12-week treatment with MMI, we used flow cytometry to measure circulating PD-1. The expression of PD-1 on circulating CD4

Topics: CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Death; Graves Disease; Humans; Methimazole; Programmed Cell Death 1 Receptor

Methimazole (MMI) is the first-line treatment for patients with Graves' disease (GD). While there are empirical recommendations for initial MMI doses, there is no clear guidance for subsequent MMI dose titrations. We aimed to (a) develop a mathematical model capturing the dynamics of free thyroxine (FT4) during MMI treatment (b), validate this model by use of numerical simulation in comparison with real-life patient data (c), develop the software application Digital Thyroid (DigiThy) serving either as a practice tool for treating virtual patients or as a decision support system with dosing recommendations for MMI, and (d) validate this software framework by comparing the efficacy of its MMI dosing recommendations with that from clinical endocrinologists.. Based on concepts of automatic control and by use of optimization techniques, we developed two first order ordinary differential equations for modeling FT4 dynamics during MMI treatment. Clinical data from patients with GD derived from the outpatient clinic of Endocrinology at the Medical University of Graz, Austria, were used to develop and validate this model. It was subsequently used to create the web-based software application DigiThy as a simulation environment for treating virtual patients and an autonomous computer-aided thyroid treatment (CATT) method providing MMI dosing recommendations.. Based on MMI doses, concentrations of FT4, thyroid-stimulating hormone (TSH), and TSH-receptor antibodies (TRAb), a mathematical model with 8 patient-specific constants was developed. Predicted FT4 concentrations were not significantly different compared to the available consecutively measured FT4 concentrations in 9 patients with GD (52 data pairs, p=0.607). Treatment success of MMI dosing recommendations in 41 virtually generated patients defined by achieved target FT4 concentrations preferably with low required MMI doses was similar between CATT and usual care. Statistically, CATT was significantly superior (p<0.001).. Our mathematical model produced valid FT4 predictions during MMI treatment in GD and provided the basis for the DigiThy application already serving as a training tool for treating virtual patients. Clinical trial data are required to evaluate whether DigiThy can be approved as a decision support system with automatically generated MMI dosing recommendations.

Topics: Antithyroid Agents; Computers; Graves Disease; Humans; Methimazole; Models, Theoretical; Thyroid Hormones; Thyroxine

Topics: Female; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Methimazole; Pregnancy; Pregnancy Complications; Pregnant Women; Thyroid Diseases; Thyroxine

We present the case of a 65 years old patient with Graves disease associated with hyperthyroidism and a medical history of bipolar disorder treated with lithium. Hyperthyroidism was initially treated with high-dose methimazole monotherapy and later the patient developed overt hypothyroidism (clinical and biochemical), but without remission of the underlying autoimmune disease. A "block and replace" therapeutic regimen was then started with reduced methimazole doses in combination with levothyroxine, which resulted in a short time in normalization of the hormonal profile and significant improvement of the clinical picture. Therefore, the "block and replace" regimen represents a valid therapeutic alternative to anti-thyroid drugs monotherapy in the treatment of hyperthyroidism due to Graves disease in selected cases.

Topics: Aged; Antithyroid Agents; Graves Disease; Humans; Hyperthyroidism; Methimazole; Sodium; Thyroxine

Hypoglycemia is an emergent condition with many causes, including underlying diabetes mellitus either with the use of insulin or oral anti-diabetic medications for glucose control, and organ (heart, hepatic, or renal) failure. Insulin autoimmune syndrome (IAS) can also cause hypoglycemia, however it is relatively difficult to diagnose as it is rare clinically. Although uncommon, IAS can be life threatening in patients with persistent hypoglycemia.. We report the case of a 27-year-old female with underlying Graves' disease who was treated with methimazole (MTZ). After 6 weeks of treatment, she developed hypoglycemia symptoms accompanied by dizziness and cold sweating. We excluded underlying diabetes mellitus, the use of insulin or oral anti-diabetic medications, and organ failure.. Laboratory data showed elevated insulin and C-peptide levels. Therefore, insulinoma and IAS were suspected. Abdominal computed tomography and magnetic resonance imaging ruled out insulinoma, and MTZ-induced IAS was finally diagnosed.. The hypoglycemia symptoms resolved after MTZ was switched to propylthiouracil, confirming the diagnosis of IAS.. This case emphasizes the significance of life-threatening MTZ-induced IAS. IAS should be suspected in patients who develop spontaneous hypoglycemia, especially in those with underlying Graves' disease receiving MTZ who present with hyperinsulinism.

Topics: Adult; Autoimmune Diseases; Diabetes Mellitus; Female; Graves Disease; Humans; Hyperinsulinism; Hypoglycemia; Insulin; Insulinoma; Methimazole; Pancreatic Neoplasms

Topics: Antithyroid Agents; Graves Disease; Humans; Methimazole; Myocarditis

The aim of this study was to compare the "time to euthyroidism" and "time spent in euthyroidism" following methimazole (MMI) and radioactive iodine (RAI) treatments.. Three hundred fifty-eight patients with hyperthyroidism, 178 who underwent long-term MMI treatment and 180 patients who underwent RAI treatment, were analyzed. The time to normalization of increased serum values of free thyroxine and triiodothyronine and suppressed serum thyroid-stimulating hormone (TSH) values as well as the percentage of time that the thyroid hormone levels remained within normal ranges during a mean follow-up time of 12 years were compared.. The mean time to euthyroidism was 4.59 ± 2.63 months (range, 2-16 months) in the MMI group and 15.39 ± 12.11 months (range, 2-61 months) in the RAI group (P < .001). During follow-up, the percentage of time spent in euthyroidism was 94.5% ± 7.3% and 82.5% + 11.0% in the MMI and RAI groups, respectively (P < .001). Serum TSH values above and below the normal range were observed in 5.3% and 0.2% of patients, respectively, in the MMI group and 9.8% and 7.7% of patients, respectively, in the RAI group (P < .001). The time to euthyroidism and the percentage of time spent in euthyroidism in 40 RAI-treated patients with euthyroidism were similar to those in the MMI group and significantly shorter than those in the RAI-treated hypothyroid and relapsed subgroups. In patients who continued MMI therapy for >10 years, the percentage of time spent in euthyroidism was >99%.. In our cohort of selected patients, MMI therapy was accompanied by faster achievement of the euthyroid state and more sustained normal serum TSH levels during long-term follow-up compared with RAI therapy.

Topics: Antithyroid Agents; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Thyroid Hormones; Thyroid Neoplasms; Thyrotropin; Thyroxine

A woman in her 30s presented to the emergency department with new-onset sore throat and fever. She had recently been diagnosed with Graves' disease 3 months prior. As a result, she was initiated on atenolol and methimazole for management. Her methimazole dosing had been stable at 15 mg daily for the month prior to presentation. Investigation revealed severe neutropenia and jaundice. She was found to have concomitant agranulocytosis and cholestatic jaundice secondary to methimazole.Methimazole was discontinued on admission and the patient received granulocyte colony-stimulating factor for an absolute neutrophil count (ANC) of zero. She was placed on broad-spectrum antibiotics and intravenous steroids for epiglottic and supraglottic oedema noted on bedside laryngoscopy. ANC and bilirubin improved over a 2-week hospital course. She was discharged on a temporary regimen of propranolol, dexamethasone and potassium iodide until she was able to undergo successful thyroidectomy for definitive management of Graves' disease outpatient.

Topics: Agranulocytosis; Antithyroid Agents; Female; Graves Disease; Humans; Jaundice, Obstructive; Methimazole; Neutropenia

Several case reports of Graves' disease (GD) occurrence after COVID-19 vaccination that are possibly related to the autoimmune syndrome induced by adjuvants (ASIA) were published recently.. The aim of our study was to evaluate possible distinctive features in the presentation and clinical course of patients with GD occurring early (within 4 weeks) after COVID-19 vaccination who attended our Endocrine Unit in 2021.. Patients with a first episode of GD attending a tertiary endocrine center between January 1, 2021, and December 31, 2021, were included.. Sixty-four patients with a first episode of GD were seen in 2021: 20 (31.2%) of them had onset within 4 weeks following vaccine administration. Compared with the other 44 patients, the 20 patients with postvaccine early-onset (PoVEO) GD were older (median age 51 years vs 35 years, P = .003) and more likely to be male (40.0% vs 13.6%, P = .018). At diagnosis, the biochemical and immune profiles were similar between the 2 groups. However, at 3 months after starting methimazole, patients with PoVEO GD had significantly lower thyrotropin receptor antibody titer and were taking lower doses of methimazole than the other patients with GD. None in the PoVEO group had sustained free triiodothyronine elevation.. This relatively large series suggests that in 2021 PoVEO GD may be a new nosologic entity representing one-third of patients evaluated for new-onset GD in our center. Distinctive features included older age at onset, higher male prevalence, and a better initial biochemical and immunologic response to treatment. Further studies are warranted to clinically and biochemically differentiate these cases from sporadically occurring GD.

Topics: COVID-19; COVID-19 Vaccines; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Vaccination

In children, Graves' disease (GD) is the most common cause of hyperthyroidism. Most pediatric patients with GD will not go into lasting remission, even following many years of antidrug therapy. Thus, most pediatric patients will require radioactive iodine (RAI) or surgery. When antithyroid drugs are used, methimazole is the drug of choice. When methimazole is used in children, up to 20% will have minor adverse reactions and serious adverse events occur in up to 1%. RAI is an effective form of therapy when the thyroid size is less than 80 g. Because of concerns of whole-body radiation exposure, it is recommended that RAI be avoided in children under 5 years of age, and dosages less than 10 mCi be used between 5 and 10 years of age. Surgery is an effective treatment in children if performed by a high-volume thyroid surgeon. Because of the scarcity of high-volume pediatric thyroid surgeons, a multidisciplinary approach using pediatric surgeons and endocrine surgeons can be considered. Whereas there is a trend toward long-term antithyroid drug therapy in adults, for several reasons, this approach may not be practical for children. Determining the optimal treatment for the pediatric patient with GD, requires consideration of the risks and benefits relating to age and likelihood of remission.

Topics: Adult; Antithyroid Agents; Child; Child, Preschool; Graves Disease; Humans; Iodine Radioisotopes; Methimazole; Thyroid Neoplasms

Hyperthyroidism is associated with a number of heart diseases, and it may aggravate previous cardiac problems or cause new ones, such as hyperthyroid cardiopathy. Cases of hyperthyroidism presenting with coronary vasospasm are rarely reported. Herein, we present a case of a 54-year male patient with recurrent left chest pain for 2 months. Coronary angiography showed no obvious coronary artery stenosis, and coronary vasospasm was suspected. After admission, the patient's thyroid function and TSH-receptor antibody (TRAb) were abnormal. However, there was no obvious palpitation, hyperhidrosis, or weight loss, and the diagnosis of Graves' disease was rendered, which seemed to be the cause of coronary vasospasm. The patient did not experience chest pain after treatment with methimazole. Patients with coronary vasospasm should be investigated for the possibility of hyperthyroidism. Key Words: Hyperthyroidism, Chest pain, Coronary angiography, Coronary vasospasm.

Topics: Antithyroid Agents; Chest Pain; Coronary Vasospasm; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole

An excess of thyroid hormones in Graves' disease (GD) has profound effects on systemic energy metabolism that are currently partially understood. In this study, we aimed to provide a comprehensive understanding of the metabolite changes that occur when patients with GD transition from hyperthyroidism to euthyroidism with methimazole treatment.. Eighteen patients (mean age, 38.6±14.7 years; 66.7% female) with newly diagnosed or relapsed GD attending the endocrinology outpatient clinics in a single institution were recruited between January 2019 and July 2020. All subjects were treated with methimazole to achieve euthyroidism. We explored metabolomics by performing liquid chromatography-mass spectrometry analysis of plasma samples of these patients and then performed multivariate statistical analysis of the metabolomics data.. Two hundred metabolites were measured before and after 12 weeks of methimazole treatment in patients with GD. The levels of 61 metabolites, including palmitic acid (C16:0) and oleic acid (C18:1), were elevated in methimazole-naïve patients with GD, and these levels were decreased by methimazole treatment. The levels of another 15 metabolites, including glycine and creatinine, were increased after recovery of euthyroidism upon methimazole treatment in patients with GD. Pathway analysis of metabolomics data showed that hyperthyroidism was closely related to aminoacyl-transfer ribonucleic acid biosynthesis and branched-chain amino acid biosynthesis pathways.. In this study, significant variations of plasma metabolomic patterns that occur during the transition from hyperthyroidism to euthyroidism were detected in patients with GD via untargeted metabolomics analysis.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Thyroid Hormones; Young Adult

Graves' disease (GD) is an autoimmune disorder that frequently results in hyperthyroidism and other symptoms. Here, we designed a 6-month study with patients divided into three treatment groups, namely, methimazole (MI, n = 8), MI + black bean (n = 9) and MI + probiotic Bifidobacterium longum (n = 9), to evaluate the curative effects of probiotics supplied with MI on thyroid function of patients with GD through clinical index determination and intestinal microbiota metagenomic sequencing. Unsurprisingly, MI intake significantly improved several thyroid indexes but not the most important thyrotropin receptor antibody (TRAb), which is an indicator of the GD recurrence rate. Furthermore, we observed a dramatic response of indigenous microbiota to MI intake, which was reflected in the ecological and evolutionary scale of the intestinal microbiota. In contrast, we did not observe any significant changes in the microbiome in the MI + black bean group. Similarly, the clinical thyroid indexes of patients with GD in the probiotic supplied with MI treatment group continued to improve. Dramatically, the concentration of TRAb recovered to the healthy level. Further mechanistic exploration implied that the consumed probiotic regulated the intestinal microbiota and metabolites. These metabolites impacted neurotransmitter and blood trace elements through the gut-brain axis and gut-thyroid axis, which finally improved the host's thyroid function.

Topics: Adult; Antithyroid Agents; Bifidobacterium longum; Brain-Gut Axis; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Probiotics; Thyroid Gland

Resistance to thyroid hormone is a rare autosomal dominant disorder characterized by reduced responsiveness to thyroid hormone and can cause syndrome of inappropriate secretion of thyroid stimulating hormone. Although Graves' disease is a common autoimmune thyroid disorder, the coexistence of these two diseases is extremely rare and makes the diagnosis and treatment complicated, leading to the delayed diagnosis of resistance to thyroid hormone. We describe the case of a Japanese man with resistance to thyroid hormone coexisting with Graves' disease, in which the correct diagnosis of resistance to thyroid hormone was delayed by masking of the signs of syndrome of inappropriate secretion of thyroid stimulating hormone, with final diagnosis 30 years after the initial treatment for Graves' disease.. A 30-year-old Japanese man presented with diffuse goiter and thyrotoxicosis. Anti-thyroid stimulating hormone receptor antibody was positive. He was diagnosed with Graves' disease. Anti-thyroid medication was chosen as the initial treatment for Graves' disease. However, this treatment failed to normalize the free triiodothyronine, free thyroxine, and thyroid stimulating hormone levels. His thyroid hormone levels indicated syndrome of inappropriate secretion of thyroid stimulating hormone. After cessation of methimazole treatment by remission of Graves' disease, his state of syndrome of inappropriate secretion of thyroid stimulating hormone persisted. Magnetic resonance imaging revealed no pituitary tumor lesions. The results of thyroid stimulating hormone-releasing hormone stimulation test showed a normal response of thyroid stimulating hormone. He was suspected to have resistance to thyroid hormone. Direct sequencing analysis of the thyroid hormone receptor β gene identified a heterozygous missense mutation, R282S. Coexistence of resistance to thyroid hormone with Graves' disease was confirmed. He has no signs of thyrotoxic symptoms, and is capable in activities of daily living at the present time.. We described a rare case of resistance to thyroid hormone simultaneously existing with Graves' disease. This case demonstrated that these diseases can coexist, and indicated some of the difficulties in diagnosis of resistance to thyroid hormone with coexisting Graves' disease. The diagnosis of resistance to thyroid hormone did not become apparent until after anti-hyperthyroidism treatment. Although rare, careful follow-up after the initial treatment of Graves' disease is necessary. The coexistence of these two diseases should be considered in patients showing occasional syndrome of inappropriate secretion of thyroid stimulating hormone.

Topics: Activities of Daily Living; Adult; Graves Disease; Humans; Male; Methimazole; Thyrotropin; Triiodothyronine

Graves's disease is the most common type of autoimmune hyperthyroidism. Numerous studies indicate different factors contributing to the onset of the disease. Despite years of research, the exact pathomechanism of Graves' disease still remains unresolved, especially in the context of immune response. B cells can play a dual role in autoimmune reactions, on the one hand, as a source of autoantibody mainly targeted in the thyroid hormone receptor (TSHR) and, on the other, by suppressing the activity of proinflammatory cells (as regulatory B cells). To date, data on the contribution of Bregs in Graves' pathomechanism, especially in children, are scarce. Here, we investigated the frequencies of Bregs before and during a methimazole therapy approach. We reported higher Foxp3+ and IL-10+ Breg levels with CD38- phenotype and reduced numbers of CD38 + Foxp3 + IL-10+ in pediatric Graves' patients. In addition, selected Breg subsets were found to correlate with TSH and TRAb levels significantly. Noteworthy, certain subpopulations of Bregs were demonstrated as prognostic factors for methimazole therapy outcome. Our data demonstrate the crucial role of Bregs and their potential use as a biomarker in Graves' disease management.

Topics: Adolescent; ADP-ribosyl Cyclase 1; Autoantibodies; B-Lymphocytes, Regulatory; Case-Control Studies; Child; Female; Forkhead Transcription Factors; Graves Disease; Humans; Interleukin-10; Male; Membrane Glycoproteins; Methimazole; Receptors, Thyrotropin; Thyrotropin

Here, we report a case of an increase in serum creatine kinase (CK) concentration in an 11-year-old girl being treated for Graves' disease with antithyroid drugs (ATDs). The patient complained of myalgia two weeks after methimazole treatment. Triiodothyronine (T3) and free thyroxine (FT4) levels were normal, but the serum CK level was significantly elevated. After switching to propylthiouracil, the serum CK level decreased to normal, and the myalgia was resolved. The development of myopathy during the treatment of hyperthyroidism may be considered as an adverse reaction of MMI. In this report, we present a rare pediatric case, along with a discussion on the possible causes of myopathy that occurred during the treatment of Graves' disease. A careful follow-up (serum CK levels and thyroid function) and treatment reassessment should always be considered after antithyroid treatment.

Topics: Antithyroid Agents; Child; Female; Graves Disease; Humans; Methimazole; Myalgia; Thyroxine; Triiodothyronine

Topics: Adult; Antithyroid Agents; Computed Tomography Angiography; Conservative Treatment; Echocardiography, Transesophageal; Electrocardiography; Female; Graves Disease; Heart Failure; Humans; Hypertension, Pulmonary; Image Processing, Computer-Assisted; Methimazole; Propylthiouracil; Scimitar Syndrome; Thyroid Function Tests; Treatment Outcome; Tricuspid Valve Insufficiency; Vena Cava, Inferior

Not required for Clinical Vignette.

Topics: Adolescent; Graves Disease; Humans; Hyperthyroidism; Intracranial Thrombosis; Ischemic Stroke; Magnetic Resonance Imaging; Male; Methimazole; Precipitating Factors; Sinus Thrombosis, Intracranial; Treatment Outcome; Venous Thrombosis

Graves' disease, a typical metabolism disorder, causes diffuse goiter accompanied by ocular abnormalities and ocular dysfunction. Although methimazole (MI) is a commonly used drug for the treatment of GD, the efficacy of methimazole is only limited to the control of clinical indicators, and the side effects of MI should be seriously considered. Here, we designed a 6-month clinical trial that divided the patients into two groups: a methimazole group (

Topics: Berberine; Biomarkers; Disease Management; Drug Therapy, Combination; Dysbiosis; Gastrointestinal Microbiome; Graves Disease; Humans; Metabolic Networks and Pathways; Metagenome; Metagenomics; Methimazole; Models, Biological; Prebiotics; Thyroid Function Tests; Treatment Outcome

Immune checkpoint blockade therapy may lead to thyroid dysfunction in 3-7% of treated patients. Alemtuzumab is a CD52 inhibitor leading to thyroid dysfunction in approximately 40% of patients. A female patient was affected by multiple sclerosis (MS) and subclinical hyperthyroidism due to an autonomously functioning thyroid nodule (AFTN). After alemtuzumab treatment, she developed aggressive clinical hyperthyroidism consistent with Marine-Lenhart syndrome.. A 36-year-old woman presented in July 2019 with symptoms of hyperthyroidism and eye complaints. Three years earlier, she was diagnosed with MS. Subclinical hyperthyroidism was diagnosed in April 2017. Thyroid scintigraphy showed an intranodular distribution of. We present a case of Graves' disease with active, moderate-to-severe Graves' ophthalmopathy in a patient with pre-existing AFTN presenting with a coexisting, rare case of Marine-Lenhart syndrome associated with immune reconstitution after alemtuzumab treatment.

Topics: Adult; Alemtuzumab; Antineoplastic Agents, Immunological; Antithyroid Agents; Female; Graves Disease; Graves Ophthalmopathy; Humans; Methimazole; Methionine; Multiple Sclerosis; Organoselenium Compounds

We report the case of a 42-year-old male patient with acute onset of asymmetrical polyarthritis of the medium and large joints as well as fever and elevated serological inflammation markers. The symptoms began shortly after initiation of thiamazole treatment for newly diagnosed Graves' disease. Antithyroid arthritis syndrome (AAS) is a rare but serious adverse side effect of antithyroid treatment with thioamides such as thiamazole. Clinically, AAS may present with myalgia, arthralgia, fever, exanthema and polyarthritis. In the case of suspected AAS, when possible the thionamide medication should be rapidly discontinued or modified in consultation with the endocrinologist. In some cases anti-inflammatory therapy with NSAID or corticosteroids may be required for symptom control.. Wir berichten über den Fall eines 42-jährigen Patienten mit akuter asymmetrischer Polyarthritis der großen und mittelgroßen Gelenke sowie Fieber und erhöhten serologischen Entzündungszeichen. Die Symptomatik begann kurz nach Beginn einer Thiamazol-Therapie bei neu diagnostiziertem Morbus Basedow. Eine durch Thionamide ausgelöste Arthritis wird auch als „antithyroid arthritis syndrome“ (AAS) bezeichnet und ist eine seltene unerwünschte medikamentöse Nebenwirkung. Klinisch kann sich das Krankheitsbild mit Myalgien, Arthralgien, Fieber, Hautausschlag und Polyarthritis präsentieren. Bei Verdacht auf ein AAS sollte die Thionamid-Medikation in Rücksprache mit dem Endokrinologen nach Möglichkeit zeitnah abgesetzt oder umgestellt werden. In einigen Fällen ist eine antiinflammatorische Therapie mit NSAR oder Glukokortikoiden zur Symptomkontrolle nötig.

Topics: Adult; Antithyroid Agents; Arthralgia; Arthritis; Graves Disease; Humans; Male; Methimazole

The imbalance of gut microbiota has been linked to manifold endocrine diseases, but the association with Graves' disease (GD) is still unclear. The purpose of this study was to investigate the correlation between human gut microbiota and clinical characteristics and thyroidal functional status of GD.. 14 healthy volunteers (CG) and 15 patients with primary GD (HG) were recruited as subjects. 16SrDNA high-throughput sequencing was performed on IlluminaMiSeq platform to analyze the characteristics of gut microbiota in patients with GD. Among them, the thyroid function of 13 patients basically recovered after treatment with anti-thyroid drugs (oral administration of Methimazole for 3-5 months). The fecal samples of patients after treatment (TG) were sequenced again, to further explore and investigate the potential relationship between dysbacteriosis and GD.. In terms of alpha diversity index, the observed OTUs, Simpson and Shannon indices of gut microbiota in patients with GD were significantly lower than those in healthy volunteers (P < 0.05).The difference of bacteria species was mainly reflected in the genus level, in which the relative abundance of Lactobacillus, Veillonella and Streptococcus increased significantly in GD. After the improvement of thyroid function, a significant reduction at the genus level were Blautia, Corynebacter, Ruminococcus and Streptococcus, while Phascolarctobacterium increased significantly (P < 0.05). According to Spearman correlation analysis, the correlation between the level of thyrotropin receptor antibody (TRAb) and the relative abundance of Lactobacillus and Ruminococcus was positive, while Synergistetes and Phascolarctobacterium showed a negative correlation with TRAb. Besides, there were highly significant negative correlation between Synergistetes and clinical variables of TRAb, TPOAb and TGAb (P < 0.05, R <  - 0.6).. This study revealed that functional status and TRAb level in GD were associated with composition and biological function in the gut microbiota, with Synergistetes and Phascolarctobacterium protecting the thyroid probably, while Ruminococcus and Lactobacillus may be novel biomarkers of GD.

Topics: Adult; Antithyroid Agents; Asian People; Feces; Female; Gastrointestinal Microbiome; Graves Disease; Healthy Volunteers; High-Throughput Nucleotide Sequencing; Humans; Lactobacillus; Male; Methimazole; Receptors, Thyrotropin; Ruminococcus; Thyroid Function Tests; Young Adult

Upside-down reversal of vision (UDRV) is a rare form of metamorphopsia, or visual illusions that can distort the size, shape or inclination of objects. This phenomenon is paroxysmal and transient in nature, with patients reporting a sudden inversion of vision in the coronal plane, which typically remains for seconds or minutes, though occasionally persists for hours or days, before returning to normal. Distorted egocentric orientation (ie, the patient perceives the body to be tilted away from the vertical plane) is even more rare as a co-occurring phenomenon. To the best of our knowledge, this is the first reported case of a veteran who presented with UDRV and distorted egocentric orientation during hospitalisation on an inpatient physical medicine and rehabilitation setting following an elective hip surgery. This case serves not only to document the presence of rare visual illusions, but also illustrates the importance and value of an interdisciplinary team approach.

Topics: Aged; Antithyroid Agents; Arthroplasty, Replacement, Hip; Casts, Surgical; Endocrinology; Graves Disease; Hip Dislocation; Hospitals, Veterans; Humans; Illusions; Male; Methimazole; Neuropsychology; Patient Care Team; Perceptual Disorders; Postoperative Complications; Psychiatry; Reoperation; Veterans; Vision Disorders

Serum thyroglobulin levels are often elevated in Graves' disease (GD) and in most cases decrease during treatment. Its relation to Graves' orbitopathy (GO) has not been clarified. Previously, a risk of GO has been linked to smoking, TSH receptor stimulation, high TSH-receptor antibodies (TRAb), low thyroid peroxidase and thyroglobulin antibodies (TPOAb, TgAb).. We examined Tg levels in 30 consecutive patients with GD were given drug therapy (methimazole + thyroxine) for up to 24 months. GO was identified by clinical signs and symptoms. 17 patients had GO, 11 of whom had it at diagnosis while 6 developed GO during treatment. During the study, 5 subjects were referred to radioiodine treatment, 3 to surgery. The remaining 22 subjects (GO n = 12, non-GO n = 10) completed the drug regimen.. At diagnosis, Tg levels in GO patients (n = 11) were higher (84, 30-555 µg/L, median, range) than in non-GO patients (n = 19) (38, 3.5-287 µg/L), p = 0.042. Adding the 6 subjects who developed eye symptoms during treatment to the GO group (n = 17), yielded p = 0.001 vs. non-GO (n = 13). TRAb tended to be higher, while TPOAb and TgAb tended to be lower in the GO group. For the 22 patients who completed the drug regimen, Tg levels were higher in GO (n = 12) vs. non-GO (n = 10), p = 0.004, whereas TRAb levels did not differ.. The data may suggest that evaluation of thyroglobulin levels in GD could contribute to identify patients at increased risk of developing GO. Possibly, thyroidal release of Tg in GD reflects a disturbance that also impacts retroorbital tissues.

Topics: Adult; Aged; Antithyroid Agents; Biomarkers; Female; Graves Disease; Graves Ophthalmopathy; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Orbit; Prognosis; Thyroglobulin; Thyroid Hormones; Thyroxine; Tobacco Smoking

Graves' disease (GD) is hyperthyroidism associated with organ-specific autoimmune inflammation. GD occurs more frequently in adults than in children; however, pediatric patients are a therapeutic challenge due to cycles of remissions and relapses requiring constant monitoring at every stage of treatment administered. Dendritic cells (DCs) are considered to be a link between innate and adaptive immunity. DCs, as antigen-presenting cells (APCs), are involved in antigen presentation to T lymphocytes, thereby initiating a shift towards effector cells. In accordance, DCs also participate in the modulation of tolerance to specific antigens. To date, the data on DCs' role in Graves' pathological processes are scarce. Therefore, here, we evaluated the frequencies and role of circulating DCs in GD pediatric patients treated with methimazole. Flow cytometric analysis was implemented to evaluate three subsets of dendritic cells and their correlation with clinical GD-related parameters. We found significantly higher levels of DC subsets in patients at diagnosis. Furthermore, methimazole treatment seemed to effectively reduce subsets of DCs, which, in addition, were found to differentially correlate with thyroid function. Our study shed new light on DCs' role in the pediatric GD pathomechanism. Further studies are required for the mechanistic assessment of DCs' exact role in disease progression and influence on thyroid function.

Topics: Age Factors; Antithyroid Agents; Case-Control Studies; Cell Count; Dendritic Cells; Disease Susceptibility; Graves Disease; Humans; Immunophenotyping; Methimazole; Treatment Outcome

Mitral valve prolapse is a common finding in Graves' disease. However, severe mitral regurgitation (MR) is a relatively uncommon manifestation of Graves' disease. We report a case of a 32-year-old woman with toxic Graves' disease and MR. The echocardiogram was suggestive of severe MR with biventricular failure, severe enough to be considered for mitral valve replacement. With medical control of the thyrotoxic state, a repeat echocardiogram revealed only trace MR, with normal left ventricular function. The timely management of the thyrotoxic state in this patient with Graves' disease and moderate to severe MR possibly related to myxomatous degeneration, averted the need for mitral valve replacement.

Topics: Adrenergic beta-Antagonists; Adult; Antithyroid Agents; Echocardiography; Fatigue; Female; Graves Disease; Humans; Hyperthyroidism; Methimazole; Mitral Valve Insufficiency; Propranolol

A 23-year-old woman was diagnosed with Graves' disease 5 months ago with decompensated thyroid function, for which she is taking thiamazole and propranolol. She developed progressive respiratory dyspnoea [New York Heart Association (NYHA) class III] and frequent palpitations. On emergency admission, the patient was tachypnoeic, hypotensive (77/54 mm Hg) and tachycardic (120 beats per minute), with an oxygen saturation of 94%. She also presented with cold, swollen and shaky extremities, with extended capillary filling time, and a significant reduction in heart sounds. Echocardiogram showed massive pericardial effusion compatible with cardiac tamponade. Pericardiocentesis was performed, with a drainage of 1420 mL serosanguinolent fluid, with prompt haemodynamic recovery. Analysis of the pericardial fluid showed exudates. A diagnosis of pericardial effusion secondary to Graves' disease was determined and corticotherapy, lithium carbonate, cholestyramine and phenobarbital were prescribed. An oral iodine-131 was performed and the patient showed reasonable control of the clinical manifestations of hyperthyroidism. After 3 months, the patient showed no symptoms of hyperthyroidism and a new echocardiogram revealed a significant reduction in pericardial effusion.

Topics: Adult; Cardiac Tamponade; Female; Graves Disease; Humans; Methimazole; Pericardial Effusion; Pericardiocentesis; Young Adult

Contrary to large multinodular goiters, reports on

Topics: Adult; Aged; Dose-Response Relationship, Radiation; Female; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Remission Induction; Retrospective Studies; Tomography, X-Ray Computed

Chromosome 22q11.2 deletion syndrome is a multisystem genetic disorder that presents with hypocalcemia due to congenital hypoparathyroidism; cardiovascular, renal, and facial anomalies; and skeletal defects. This syndrome is also associated with an increased risk of autoimmune disease. We report here on a 33-year-old Japanese woman with 22q11.2 deletion syndrome complicated by Graves' disease. The patient had facial abnormalities and a history of a surgical procedure for a submucous cleft palate at age 3 years. At age 33, the patient was diagnosed with Graves' disease because both hyperthyroidism and thyroid stimulating hormone receptor antibody were present. The patient's serum calcium level was within the normal range, but symptomatic hypocalcemia developed 1 month after treatment with methimazole was started for thyrotoxicosis. Methimazole was discontinued because it caused liver dysfunction, so the patient underwent total thyroidectomy to treat her Graves' disease. We examined longitudinal changes in the number of subsets of CD4 and CD8 lymphocytes, including regulatory T (T reg) cells and PD-1

Topics: Adult; Antithyroid Agents; B-Lymphocytes; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; DiGeorge Syndrome; Female; Flow Cytometry; Graves Disease; Humans; Hypocalcemia; Longitudinal Studies; Methimazole; Programmed Cell Death 1 Receptor; T-Lymphocytes, Regulatory; Thyroidectomy

Triiodothyronine (T3)-predominant Graves' disease is characterized by increased serum free T3 (FT3) levels after free thyroxine (FT4) levels become normal or even low during antithyroid drug treatment. We encountered a 34-year-old pregnant woman, gravida 5 para 4, who was complicated by T3-predominant Graves' disease. She was diagnosed with Graves' disease at 20 years old, and had received methimazole. Methimazole was changed to potassium iodide to reduce the risk of congenital anomalies during the first trimester. The dose of antithyroid drugs was adjusted based on maternal FT4 levels, so that maternal Graves' disease deteriorated and fetal goitrous hyperthyroidism appeared during the second trimester. Since the fetus presented goiter and tachycardia at 27-28 gestational weeks, doses of methimazole and potassium iodide were increased. A male newborn weighing 2604 g was delivered by a cesarean section at 35 gestational weeks. The newborn was diagnosed with neonatal hyperthyroidism, and received methimazole for six months. He developed normally with normal thyroid function at 1 year old. In pregnancies complicated by T3-predominant Graves' disease, the kinds and doses of antithyroid drugs have to be carefully selected to maintain maternal levels of FT4 as well as FT3 within the normal range, considering trimesters of pregnancy, teratogenicity of medication, and maternal levels of thyroid-stimulating hormone receptor antibody.

Topics: Adult; Antithyroid Agents; Female; Goiter; Graves Disease; Humans; Infant, Newborn; Male; Maternal-Fetal Exchange; Methimazole; Potassium Iodide; Pregnancy; Pregnancy Complications; Pregnant Women; Thyroxine; Treatment Outcome; Triiodothyronine; Ultrasonography, Prenatal

To determine the relationship between the positivity of third-generation TSH receptor antibody (TRAb) at the time of diagnosis and the cumulative methimazole dose used until remission in patients with Graves' disease.. Cross-sectional, descriptive study.. Department of Endocrinology and Metabolic Diseases, University of Health Sciences, Kartal Dr. Lütfi Kırdar City Hospital, Turkey from 2016 to 2018.. Newly diagnosed Graves' patients were included in the study. The patients were divided into two groups according to whether they entered remission (n: 21) or not (n: 20), in the 18th month of methimazole treatment. In addition, the patients were further divided into two categories, according to TRAb status at the time of diagnosis as negative (n: 17) or positive (n: 24). The TRAb positivity and the cumulative methimazole dose they used until the month of remission were compared in these groups.. The mean time to reach remission in 41 patients was 20.5 ± 3.1 months. TSH receptor antibody positivity rate was 58.5%. When the TRAb positivity of the groups was compared according to the state of having remission in the 18th month of the treatment, the positivity rate in the non-remission group was statistically significantly higher (p = 0.023).The time to go into remission was longer and the cumulative methimazole dose requirement was higher in the TRAb positive group (p <0.001).. Graves' disease patients with positive third-generation TRAb were found to have a lower rate of remission in the 18-month period compared to negative patients. Key Words: Graves' disease, TSH receptor antibody, Cumulative, Methimazole.

Topics: Antithyroid Agents; Autoantibodies; Cross-Sectional Studies; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Methimazole; Receptors, Thyrotropin; Turkey

Graves' disease is associated with thyrotropin (TSH) receptor stimulating antibody, for which there is no therapeutic agent. This disease is currently treated through inhibition of thyroid hormone synthesis or destruction of the thyroid gland. Recurrence after antithyroid drug (ATD) treatment is common. Recent studies have shown that the longer is the duration of use of ATD, the higher is the remission rate. Considering the relationship between clinical outcomes and iodine intake, recurrence of Graves' disease is more common in iodine-deficient areas than in iodine-sufficient areas. Iodine restriction in an iodine-excessive area does not improve the effectiveness of ATD or increase remission rates. Recently, Danish and Korean nationwide studies noted significantly higher prevalence of birth defects in newborns exposed to ATD during the first trimester compared to that of those who did not have such exposure. The prevalence of birth defects was lowest when propylthiouracil (PTU) was used and decreased by only 0.15% when methimazole was changed to PTU in the first trimester. Therefore, it is best not to use ATD in the first trimester or to change to PTU before pregnancy.

Topics: Antithyroid Agents; Female; Graves Disease; Humans; Infant, Newborn; Methimazole; Pregnancy; Propylthiouracil; Thyrotropin

Mature cystic teratoma is the most common kind of ovarian germ tumor. However, malignant transformation is uncommon, differentiated thyroid carcinoma is even rare. Hyperthyroidism due to coexistence of Graves' disease (GD) and struma ovarii has been reported. Functional teratoma with papillary thyroid carcinoma (PTC) in GD case has never been reported in literature.. A 48-year-old woman with GD for 4 years, who visited our hospital with complaints of severe abdominal pain for 1 day. Computed tomography of the abdominal revealed a large fat-containing lesion with dense calcification, measured 8.6 × 7.2 cm in size. Laparotomy right total oophorectomy was performed, and a huge gangrenous right ovary was noted during exploration. The final pathological diagnosis was teratoma with PTC change at right ovary. We performed thyroglobulin, TTF-1 and CK19 staining in the teratoma, the results were positive, suggesting the thyroid-hormone secretion in the PTC tissue.. After resection of the ovarian lesion, euthyroidism was achieved. Adjuvant thyroidectomy is not performed for no evidence of thyroid lesion or distant metastases. No GD recurrence in the 2 years after operation. The patient also does not manifest any gynecological disease symptoms, whereas the other ovary, in the follow-up ultrasound examinations, shows normal size and echo structure.. PTC can arise within ovarian teratoma and may have thyroid hormone production. Surgeries of unilateral oophorectomy or cystectomy are a reasonable treatment, and follow-up of thyroid image and data is necessary.

Topics: Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Methimazole; Middle Aged; Neoplasms, Multiple Primary; Ovarian Neoplasms; Ovariectomy; Teratoma; Thyroid Cancer, Papillary; Tomography, X-Ray Computed; Ultrasonography

Graves' disease (GD) is the most common cause of thyrotoxicosis in children and adolescents. There is some debate regarding the optimal treatment and predicting factors of remission or relapse in children and adolescents with GD. In this study, we report a retrospective study of 195 children and adolescents with GD treated at a single tertiary institution in Korea.. This study included children and adolescents with GD diagnosed before 19 years of age from January of 2000 to October of 2020. The diagnosis of GD was based on clinical features, high thyroxine (FT4), suppressed thyroid-stimulating hormone, and a positive titer of thyrotropin receptor antibodies. Remission was defined as maintenance of euthyroid status for more than six months after discontinuing antithyroid drug (ATD).. A total of 195 patients with GD were included in this study. The mean age at diagnosis was 12.9 ± 3.2 years, and 162 patients (83.1%) were female. Among all 195 patients, five underwent thyroidectomy and three underwent radioactive iodine therapy. The mean duration of follow-up and ATD treatment were 5.9 ± 3.8 years and 4.7 ± 3.4 years, respectively. The cumulative remission rates were 3.3%, 19.6%, 34.1%, 43.5%, and 50.6% within 1, 3, 5, 7, and 10 years of starting ATD, respectively. FT4 level at diagnosis (P = 0.001) was predicting factors for remission [HR, 0.717 (95% CI, 0.591 - 0.870), P = 0.001]. Methimazole (MMI)-related adverse events (AEs) occurred in 11.3% of patients, the most common of which were rash and hematologic abnormalities. Of a total of 26 AEs, 19 (73.1%) occurred within the first month of taking MMI.. In this study, the cumulative remission rate increased according to the ATD treatment duration. Long-term MMI treatment is a useful treatment option before definite treatment in children and adolescents with GD.

Topics: Adolescent; Antithyroid Agents; Child; Female; Goiter; Graves Disease; Humans; Male; Methimazole; Propylthiouracil; Remission Induction; Retrospective Studies; Treatment Outcome

Topics: Adrenergic beta-Antagonists; Adult; Antithyroid Agents; Drug Therapy, Combination; Electrocardiography; Graves Disease; Humans; Hypokalemia; Male; Methimazole; Muscle Weakness; Propranolol; Tachycardia; Thyroidectomy

As thyroid-stimulating immunoglobulins (TSI) are a sign of Graves' disease (GD), measuring TSI titers is becoming increasingly important for GD diagnosis. This study evaluated the diagnostic accuracy of a new fully automated TSI immunoassay (Immulite™ TSI assay) in GD patients and compared it to the third generation thyroid-stimulating hormone receptor antibody (TRAb) electrochemiluminescence assay (Elecsys Anti-TSHR assay). Additionally, clinical characteristics associated with responsiveness to methimazole in patients with newly diagnosed GD were preliminarily explored.. This study involved 324 subjects, comprising patients with untreated GD (GD-UT), Graves' ophthalmopathy (GO) patients, GD patients who had been treated for > 12 months (GD-T), autoimmune thyroiditis (AIT) patients, and healthy subjects (HS). The Immulite™ TSI and Elecsys Anti-TSHR assay were performed on all samples. According to their responsiveness to methimazole, the GD-UT patients were divided into rapid and slow responder groups, and their clinical characteristics were compared.. A receiver operating characteristic (ROC) curve analysis of GD-UT patients showed that the optimal TSI cut-off value was 0.57 IU/L. Logistic regression revealed that age and initial FT4 and TSI levels in the middle-dose methimazole group were related to a rapid response, while the initial FT4 level, but not TSI, in the high-dose group was also associated with a rapid response.. The clinical diagnostic performance of the Immulite™ TSI assay for diagnosing GD was comparable to that of the Elecsys Anti-TSHR assay. The initial FT4 and TSI levels can be used as predictors of the responsiveness to methimazole in patients with newly diagnosed GD.

Topics: Adult; Aged; Case-Control Studies; Female; Graves Disease; Graves Ophthalmopathy; Humans; Immunoassay; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Thyroid Function Tests; Treatment Outcome; Young Adult

We report a case of a 47-year-old woman with hypercalcemia 6 months after discontinuation of denosumab. She underwent right mastectomy for breast cancer and had received aromatase inhibitor and denosumab therapy for 5 years. Thirst, appetite loss, and bilateral ankle pain began few months after cessation of denosumab. She was admitted to the hospital for hypercalcemia and hyperthyroidism 6 months after the last dose of denosumab. Laboratory investigations revealed hypercalcemia, normophosphatemia, normal renal function, and elevated levels of fibroblast growth factor 23 (FGF-23). Serum tartrate-resistant acid phosphatase 5b and urine N-terminal cross-linked telopeptide of type I collagen were both elevated, and bone scintigraphy revealed increase of whole bone uptake. Radiological examinations showed no recurrence of breast cancer or tumors that secrete intact PTH or FGF-23. Hypercalcemia, which lasted for 1 month, was refractory to discontinuation of the aromatase inhibitor, normalization of thyroid hormone levels, saline hydration, and calcitonin administration, but was effectively treated with zoledronic acid. Abnormal uptake on bone scintigraphy and ankle pain both resolved a few months after treatment, and hypercalcemia has not recurred in the ensuing 2 years. In conclusion, we found elevated levels of circulating FGF-23 with hypercalcemia following the discontinuation of denosumab. FGF-23 might be a surrogate marker for massive bone resorption triggered by discontinuation of long-term denosumab treatment.

Topics: Ankle; Anorexia; Antithyroid Agents; Aromatase Inhibitors; Arthralgia; Bone Density Conservation Agents; Bone Neoplasms; Bone Resorption; Breast Neoplasms; Collagen Type I; Denosumab; Deprescriptions; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Graves Disease; Humans; Hypercalcemia; Methimazole; Middle Aged; Parathyroid Hormone; Peptides; Potassium Iodide; Radionuclide Imaging; Tartrate-Resistant Acid Phosphatase; Thirst; Zoledronic Acid

The "block-and-replace" (BR) method involves the use of a high dose of antithyroid drugs (ATD) with levothyroxine (L-T4). Its use in the management of Graves' disease (GD) is still debated mainly because the frequency of side effects of ATD is dose dependent. We retrospectively studied the effect of medium dose of ATD with L-T4 versus monotherapy with ATD in pediatric patients with unstable GD.. 28 pediatric patients with GD with unstable response to ATD were treated with L-T4 and medium dose of ATD. We compared the rate of euthyroidism, hypothyroidism and hyperthyroidism episodes observed during treatment with methimazole alone with those observed during the BR approach. We evaluated the occurrence of side effects and the rate of remission in patients treated with ATD + L-T4 therapy and the efficacy of combination therapy to postpone a definitive treatment (radioiodine and thyroidectomy).. Patients showed a better control of thyroid function during the BR therapy, presenting fewer episodes of hyperthyroidism and hypothyroidism. No serious side effects during the BR approach were observed. Only one patient went into remission with the ATD + L-T4 therapy. Fifteen patients required a definitive therapy (4 radioiodine, 11 thyroidectomy). The use of BR method has delayed radioiodine treatment for 4.9 years and surgery for 2.9 years.. The BR method does not increase the remission rates. It may be useful to combine L-T4 with a medium dose of methimazole when GD is difficult to manage with methimazole alone. It may represent a therapeutic option to postpone definitive treatments to a suitable age.

Topics: Adolescent; Antithyroid Agents; Child; Child, Preschool; Combined Modality Therapy; Drug Therapy, Combination; Graves Disease; Humans; Iodine Radioisotopes; Methimazole; Recurrence; Retrospective Studies; Thyroidectomy; Thyroxine; Treatment Outcome

Methimazole (MMI), the first-line anti-thyroid agent used in clinical practice is known to induce hepatotoxicity in patients with Grave's disease (GD), although its exact mechanism remains largely unclear. This cohort study aimed to examine the mechanism of MMI-induced hepatotoxicity using metabolomic approach. A total of 40 GD patients with MMI-induced hepatotoxicity (responders) and 80 GD patients without MMI-induced hepatotoxicity (non-responders) were included in this study and their plasma metabolomics was profiled with targeted gas chromatography-tandem mass spectrometry (GC-MS/MS). The plasma levels of 42 metabolites, including glucuronic acid, some amino acids, fatty acids, ethanolamine and octopamine were found to be significantly different between responders and non-responders. In agreement with our previous genotyping data, the genetic polymorphism of uridine 5'-diphospho-glucuronosyltransferase (UGT)1A1*6, which affects the glucuronidation activity and circulating glucuronic acid level was identified as one of the determinants of MMI-induced hepatotoxicity. Plasma level of ethanolamine has a significant correlation with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. The pathway analyses further revealed that monoamine oxidase (MAO) inhibition, reactive oxygen species (ROS) production, mitochondria dysfunction, and DNA disruption might contribute to MMI-induced hepatotoxicity. Interestingly, the metabolomic data further suggested the responders had a higher risk of developing osteoporosis and fatty liver disease in comparison to the non-responders. This mechanistic study sheds light on the pathogenesis of MMI-induced hepatotoxicity and prompts personalized prescription of MMI based on UGT1A1*6 genotype in the management of GD.

Topics: Adult; Alanine Transaminase; Antithyroid Agents; Aspartate Aminotransferases; Blood; Chemical and Drug Induced Liver Injury; Female; Gas Chromatography-Mass Spectrometry; Glucuronosyltransferase; Graves Disease; Humans; Male; Metabolomics; Methimazole; Treatment Outcome

Although type 1 diabetes mellitus is largely associated with autoimmune thyroid disease and this entity has been recently referred to as autoimmune polyglandular syndrome type 3 variant, the autoimmune polyglandular syndrome type 3 variant in patients with rheumatoid arthritis has not been reported so far. We herein describe the first case of rheumatoid arthritis that was associated with autoimmune polyglandular syndrome type 3 variant.. A 77-year-old woman with a 15-year history of rheumatoid arthritis (RA) and a 10-year history of type 2 diabetes mellitus (T2D) presented with polyarthralgia and hyperglycaemia. Methotrexate 16 mg/week had been started from the onset and was continued, and adalimumab 40 mg/day was started for RA. Insulin treatment was also started for the diabetes. Laboratory examinations revealed high levels of C-reactive protein (CRP), rheumatoid factor, anti-cyclic citrullinated peptide antibody, and matrix metalloprotease 3. She was admitted multiple times as the symptoms recurred after treatment. Subsequently, based on the clinical course and investigations, she was diagnosed with type 1 diabetes mellitus and Graves' disease occurring during the course of RA and T2D. Her clinical course improved after reinforcement of insulin therapy and the addition of thiamazole therapy.. In patients with rheumatoid arthritis, the autoimmune polyglandular syndrome type 3 variant should be considered as the cause of the deterioration.

Topics: Aged; Antirheumatic Agents; Antithyroid Agents; Arthritis, Rheumatoid; Diabetes Mellitus, Type 1; Female; Graves Disease; Humans; Hypoglycemic Agents; Insulin; Methimazole; Polyendocrinopathies, Autoimmune

Topics: Anti-Arrhythmia Agents; Antithyroid Agents; Graves Disease; Humans; Hyperthyroidism; Hypokalemia; Male; Methimazole; Periodicity; Potassium; Propranolol; Quadriplegia; Young Adult

Topics: Adult; Antithyroid Agents; Drug Substitution; Female; Graves Disease; Humans; Methimazole; Potassium Iodide; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Thyroid Hormones; Treatment Outcome

Although simple febrile seizures are relatively common and benign in toddlers, it is important to rule out any underlying critical disease that necessitates further intervention and treatment. Thyroid storm, the extreme manifestation of hyperthyroidism, is relatively rare and not often considered in the differential diagnosis of a febrile seizure despite its high mortality rate. Here, we report 1 of the youngest patients with thyroid storm, who initially presented with a febrile seizure. After reevaluation, the 2-year-9-month-old patient was discovered to have thyromegaly, which led to recognition that her persistent tachycardia and widened pulse pressure were likely signs of thyrotoxicosis. Laboratory results were consistent with primary hyperthyroidism due to Graves' disease. Thyroid storm was then diagnosed on the basis of clinical features including gastrointestinal and central nervous system disturbances. Treatment with methimazole, propranolol, hydrocortisone, and Lugol's iodine solution was used. This medication regimen was safe and effective with restoration of a euthyroid state after 2 months and no recurrence of seizures. Improved awareness of hyperthyroidism and thyroid storm can lead to prompt diagnosis and treatment of this endocrine emergency, thus reducing mortality and morbidity. Pediatricians should consider this diagnosis in children with febrile seizures and suggestive vital signs and physical examination findings.

Topics: Child, Preschool; Female; Graves Disease; Humans; Hydrocortisone; Hypertension; Iodides; Methimazole; Propranolol; Seizures, Febrile; Tachycardia; Thyroid Crisis

Topics: Aged; Aged, 80 and over; Antithyroid Agents; Cardiovascular Diseases; Case-Control Studies; Cross-Over Studies; Diabetes Mellitus; Female; Gallstones; Graves Disease; Humans; Liver Diseases, Alcoholic; Male; Methimazole; Middle Aged; Pancreatitis; Prognosis; Risk Factors

A 62-year-old woman with a history of partially treated Graves disease and hypertension presented with approximately 3 weeks of worsening fatigue, lower extremity myalgias, and shortness of breath. Her medical history included a thyroid radiofrequency ablation several years earlier. Following the ablation, she was found to have some residual thyroid activity, negating the need for therapy. She was lost to follow-up after months of normal thyroid-stimulating hormone values. On this presentation, the patient was noted to be in atrial fibrillation with a rapid ventricular rate, and although she presented alert and oriented initially, she developed progressive inattentiveness and confusion while in the ED. The patient was transferred to the medical ICU for further management of her rapid heart rate and progressive delirium.

Topics: Anti-Arrhythmia Agents; Anti-Inflammatory Agents; Anticoagulants; Antithyroid Agents; Atrial Fibrillation; Delirium; Disseminated Intravascular Coagulation; Dyspnea; Fatal Outcome; Fatigue; Female; Femoral Artery; Graves Disease; Heparin; Humans; Hydrocortisone; Ischemia; Lower Extremity; Methimazole; Middle Aged; Myalgia; Pneumoperitoneum; Popliteal Artery; Potassium Iodide; Propranolol; Radiofrequency Ablation; Thrombosis; Thyroid Crisis; Tibial Arteries; Venous Thrombosis

The incidence of Hashimoto's thyroiditis among patients who have Turner syndrome (TS) has increased, but Graves' disease (GD) in patients with TS is rarely reported. Here we report a rare case of TS with GD accompanied by hypogonadotropic hypogonadism.. We report the case of a 16-year-old girl who complained nervousness, fatigue, marasmus, heat intolerance, sweating, palpitation, and tremor lasting for more than a month. She had no medical history.. TS was diagnosed of the results of karyotyping demonstrated a gene karyotype of 46, X, i (X)(q10). GD was also diagnosed in this patient following the detection of thyroid function analysis.. Methimazole was administered after identification of GD. Due to the absence of secondary sex characteristics, the patient was given a conjugated estrogen preparation for 1 year, followed by the addition of estradiol cyproterone tablets for the onset of menstruation.. The hyperthyroidism symptoms of the patient had improved both clinically and laboratory tests after methimazole therapy. She was treated with estrogen and estradiol cyproterone, and the uterus and secondary sexual characteristics of the patient developed during 1 year follow-up.. TS generally presents as hypergonadotropic hypogonadism. However, hypogonadotropic hypogonadism cannot completely exclude TS. The diagnosis of this disease depends on chromosomal examination. The disease should be detected and treated as early as possible to improve life quality of the patient.

Topics: Adolescent; Antithyroid Agents; Diagnosis, Differential; Fatigue; Female; Graves Disease; Humans; Karyotyping; Methimazole; Tremor; Turner Syndrome

The treatment of Graves' hyperthyroidism (GD) complicated with malignancy is challenging, as anti-thyroid thionamide drugs (ATDs) and anti-cancer chemotherapy are both associated with a risk of neutropenia. Treatment with conventional ATDs, radioactive iodine (RAI) or potassium iodide (KI) was attempted in 8 patients with malignancy (34-80 years of age; 2 males and 6 females) in whom GD had been fortuitously diagnosed during a detailed systematic examination. Three patients requiring surgery were initially treated conventionally with methylmercaptoimidazole (MMI), MMI and KI or RAI (group A; one patient each). The patients became euthyroid on days 17-31 and underwent surgery on days 25-47. RAI therapy was administered to one patient after surgery. The patients were then treated with KI during chemotherapy. Five other patients who did not require surgery were initially treated with 100 mg KI monotherapy (group B). The serum free T

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Antithyroid Agents; Female; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Neoplasms; Neutropenia; Potassium Iodide; Risk Factors; Thyroidectomy

Paediatric hyperthyroidism cases are mostly caused by Grave's disease. Thyroid storm is a life-threatening condition seen rarely, in severe thyrotoxicosis, occurring in about 1%-2% of patients with hyperthyroidism. Antithyroid medications and beta-blockers are typically the first-line management of thyroid storm. We report a challenging case of a 15-year-old girl who presented with thyroid storm in the setting of septic shock and methimazole-induced agranulocytosis. Since the first-line agents were contraindicated, plasmapheresis was used to control the thyroid storm and as a bridging therapy to the definitive therapy of early thyroidectomy. This is the first paediatric case report that outlines the use of plasmapheresis in the management of complicated thyrotoxicosis in a setting of septic shock.

Topics: Adolescent; Agranulocytosis; Antithyroid Agents; Female; Graves Disease; Humans; Methimazole; Sepsis; Thyroid Crisis

Topics: Adrenergic beta-Antagonists; Antibodies; Antithyroid Agents; Betacoronavirus; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Testing; Female; Graves Disease; Humans; Lung; Methimazole; Middle Aged; Pandemics; Pneumonia, Viral; Propranolol; Receptors, Thyrotropin; SARS-CoV-2; Thyroglobulin; Thyroid Function Tests; Treatment Outcome; Ultrasonography

Immune checkpoint inhibitors (ICIs) can induce immune-related adverse events (irAEs) including thyroid dysfunction. There are only a few reports on Graves' disease induced by ICIs. We report a case of new-onset Graves' disease after the initiation of nivolumab therapy in a patient receiving gastric cancer treatment.. The patient was a 66-year-old Japanese man, who was administered nivolumab (240 mg every 3 weeks) as a third-line therapy for stage IVb gastric cancer. His thyroid function was normal before the initiation of nivolumab therapy. However, he developed thyrotoxicosis before the third administration of nivolumab. Elevated, bilateral, and diffuse uptake of radioactive tracer was observed in the. This is the first complete report of a case of new-onset Graves' disease after starting nivolumab therapy, confirmed by diffusely increased thyroid uptake in scintigraphy and the positive conversion of antibodies against thyroid-stimulating hormone receptor. It is important to perform thyroid scintigraphy and ultrasonography to accurately diagnose and treat ICI-induced thyrotoxicosis, because there are various cases in which Graves' disease is developed with negative and positive TRAb titres.

Topics: Adenocarcinoma; Aged; Graves Disease; Humans; Japan; Male; Methimazole; Nivolumab; Potassium Iodide; Remission Induction; Stomach Neoplasms; Thyroid Gland

Stickler syndrome is a connective tissue disorder with predominantly autosomal dominant inheritance, with ocular, auditory and joint involvement. Thyroid dysfunction was not described as part of alterations in Stickler syndrome and in particular, the association between Stickler's syndrome and Graves' disease has never been previously reported in literature. Moreover, the presence of Graves' disease is uncommon in the pediatric age (especially in children younger than 6 years old).. We report the case of a 5-years old child affected by Stickler syndrome who received the diagnosis of Graves's disease, in absence of suggestive symptoms, during health supervision.. This is the first evidence of thyroid dysfunction and autoimmune pattern for Sticker syndrome. Further clinical reports are expected before suggesting the implementation of new clinical skills for Stickler syndrome, but this paper may contribute to improve personalized management of this rare disorder.

Topics: Antithyroid Agents; Arthritis; Child, Preschool; Connective Tissue Diseases; Female; Graves Disease; Hearing Loss, Sensorineural; Humans; Methimazole; Precision Medicine; Retinal Detachment

Thionamides (such as thiamazole/methimazole) are a common first line treatment for Graves' disease. Common side effects include rash, urticaria, and arthralgia. However, thionamide treatment has also been associated with a variety of auto-immune syndromes. Here, we describe a patient presenting with mild arthritis after starting thiamazole. Although severe presentation warrants acute withdrawal of the causative agent, our case suggests that milder forms can be successfully treated with anti-inflammatory drugs alone. Recognition of the syndrome is key to warrant timely and effective treatment.

Topics: Antithyroid Agents; Arthralgia; Graves Disease; Humans; Methimazole; Treatment Outcome

Iodine 131 (I-131) radioactive iodine (RAI) therapy has been the preferred treatment for Graves disease in the United States; however, trends show a shift toward antithyroid drug (ATD) therapy as first-line therapy. Consequently, this would favor RAI as second-line therapy, presumably for ATD refractory disease. Outcomes of RAI treatment after first-line ATD therapy are unclear. The purpose of this study was to investigate treatment failure rates and potential risk factors for treatment failure, including ATD use prior to RAI treatment.. A retrospective case control study of Graves disease patients (n = 200) after I-131 RAI therapy was conducted. Treatment failure was defined as recurrence or persistence of hyperthyroidism in the follow-up time after therapy (mean 2.3 years). Multivariable regression models were used to evaluate potential risk factors associated with treatment failure.. RAI treatment failure rate was 16.5%. A majority of patients (70.5%) used ATD prior to RAI therapy, predominantly methimazole (MMI) (91.9%), and approximately two-thirds of patients used MMI for >3 months prior to RAI therapy. Use of ATD prior to RAI therapy (P = .003) and higher 6-hour I-123 thyroid uptake prior to I-131 RAI therapy (P<.001) were associated with treatment failure. MMI use >3 months was also associated with treatment failure (P = .002).. More patients may be presenting for RAI therapy after failing first-line ATD therapy. MMI use >3 months was associated with RAI treatment failure. Further studies are needed to investigate the association between long-term first-line ATD use and RAI treatment failure.

Topics: Antithyroid Agents; Case-Control Studies; Graves Disease; Humans; Iodine Radioisotopes; Methimazole; Neoplasm Recurrence, Local; Retrospective Studies; Thyroid Neoplasms; Treatment Failure

Nephritis has been rarely associated with methimazole, primarily in the development of nephrotic syndrome. We describe a case of acute kidney injury without evidence of nephrotic syndrome following methimazole initiation.. We present the relevant history, laboratory data, and nuclear medicine data and review relevant documentation from the literature.. A 72-year-old male recently diagnosed with new-onset atrial fibrillation was found to have suppressed thyroid-stimulating hormone (TSH) levels; elevated free T. Acute kidney injury with or without the presence of nephrotic syndrome may occur during treatment with methimazole. Renal function should be closely monitored after the initiation of methimazole to prevent progressive renal dysfunction.

Topics: Acute Kidney Injury; Aged; Antithyroid Agents; Graves Disease; Humans; Male; Methimazole; Nephrotic Syndrome; Propylthiouracil

Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated condition that can affect almost any organ. We investigated the association between IgG4-RD and the main characteristics of Graves' disease (GD) at the time of diagnosis. Additionally, we evaluated whether serum IgG4 levels change during treatment.. Twenty-eight patients with newly diagnosed GD were enrolled into this longitudinal follow-up study. Serum IgG4 levels and thyroid function were measured in all the participants at the time of diagnosis. Further, the serum IgG4 levels of nine of 28 patients with untreated GD were measured after the achievement of euthyroid state (through the use of methimazole).. Two (7.1%) of 28 patients with untreated GD had elevated serum IgG4 levels of >135 mg/dL. There was no significant difference in the average IgG4 levels before and after the achievement of euthyroid state (66.2±74.0 mg/dL vs. 50.5±47.3 mg/dL). In two patients, the elevated serum IgG4 levels returned to normal after treatment. However, one patient had an elevated serum IgG4 level of 136.6 mg/dL after treatment.. This study showed that serum IgG4 levels varied with treatment in patients with GD, independent of thyroid function, suggesting that IgG4 might be indirectly related to GD.

Topics: Adult; Aged; Antithyroid Agents; Female; Graves Disease; Humans; Immunoglobulin G; Longitudinal Studies; Male; Methimazole; Middle Aged; Treatment Outcome

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alanine Transaminase; Antithyroid Agents; Bilirubin; Chemical and Drug Induced Liver Injury; Child; Female; Graves Disease; Humans; Japan; Male; Methimazole; Middle Aged; Prevalence; Propylthiouracil; Retrospective Studies; Severity of Illness Index; Young Adult

To assess the predictive value of some clinical and biochemical parameters, and of the +49 A/G polymorphism of the CTLA-4 gene, for long-term remission following the withdrawal of antithyroid drugs before starting antithyroid drug therapy.. Observational, prospective and longitudinal study.. Seventy-two patients (11 of whom were men) with newly diagnosed Graves' hyperthyroidism who had been attended consecutively at a University Clinic in a population with sufficient iodine intake were included in the study.. patients under the age of 18, pregnant women and non-Caucasian patients. All subjects were treated following a well-defined protocol. Long-term remission was calculated at 12 and 36 months following withdrawal of the antithyroid drug.. Thirty-six of the 72 study subjects experienced a remission of at least 12 months following withdrawal of methimazole, with no differences according to their age or sex. A comparison made between the remission rates seen in both groups yielded significant differences regarding the presence of Graves' orbitopathy, the duration of the treatment with methimazole and the absence of the CTLA-4 G/G genotype. In the univariate and multivariate analyses performed, only lower frequencies of Graves' orbitopathy and an absence of the CTLA-4 G/G genotype were considered independent predictors of long-term remission.. The absence of Graves' orbitopathy and of the CTLA-4 G/G genotype are independent predictors of long-term remission following a first course of antithyroid drugs.

Topics: Adult; Antithyroid Agents; Biomarkers; CTLA-4 Antigen; Female; Genetic Predisposition to Disease; Genotype; Graves Disease; Graves Ophthalmopathy; Humans; Hyperthyroidism; Longitudinal Studies; Male; Methimazole; Middle Aged; Polymorphism, Single Nucleotide; Predictive Value of Tests; Prognosis; Remission Induction; Time Factors; Treatment Outcome; Withholding Treatment

A 76-year-old Japanese woman was diagnosed with Graves' disease and was administered methimazole (MMI) 10 mg and potassium iodide 50 mg. After 19 days of the drug regime, she developed high-grade fever and nausea and was admitted to our hospital. Blood test results showed elevated pancreatic enzymes and C-reactive protein levels. Abdominal computed tomography showed swollen pancreas, and she was diagnosed with acute pancreatitis. These abnormalities improved after discontinuation of MMI. Five similar cases have been reported, but this is the first case report without abdominal pain. When acute pancreatitis is observed after the initiation of MMI, drug-induced pancreatitis should be considered as the possible etiology.

Topics: Aged; Antithyroid Agents; Female; Graves Disease; Humans; Methimazole; Pancreatitis

Serum TSH receptor autoantibody (TSH-R-Ab) is a biomarker of Graves disease (GD). Studies have shown that the levels of this TSH-R-Ab have clinical significance.. To differentiate between thyroidal GD only and Graves orbitopathy (GD + GO).. Controlled, follow-up study.. Academic tertiary referral center for GD + GO.. Sixty patients with GD, GD + GO, and controls.. Serial serum dilution analyses with six automated, ELISA, and cell-based assays for TSH-R-Ab.. Differentiation among GD phenotypes.. All undiluted samples of hyperthyroid-untreated GD patients were positive with the six assays but became negative at dilution 1:9 in four of six assays. In contrast, all undiluted samples of hyperthyroid-untreated GD + GO patients remained positive up to dilution 1:81, P < 0.001. At high dilutions 1:243, 1:729, 1:2187, and 1:6561, the rate of stimulating TSH-R-Ab positivity in the bioassay for GD + GO patients was 75%, 35%, 5%, and 0%, respectively (all P < 0.001). The five ELISA and/or automated assays confirmed this marked difference of anti-TSH-R-Ab detection between GD-only and GD + GO. In comparison, the baseline-undiluted samples of GD vs GD + GO showed an overlap in the ranges of TSH-R-Ab levels. Subsequent to 12-month methimazole treatment, samples from euthyroid GD + GO patients were still TSH-R-Ab positive at the high dilution of 1:243. In contrast, all GD samples were negative already at dilution 1:3. A GD patient with TSH-R-Ab positivity at dilution 1:729 developed de novo GO.. TSH-R-Ab titers, as determined by dilution analysis, significantly differentiate between GD and GD + GO.

Topics: Adult; Aged; Antithyroid Agents; Autoantibodies; Diagnosis, Differential; Female; Follow-Up Studies; Graves Disease; Graves Ophthalmopathy; Humans; Male; Methimazole; Middle Aged; Prognosis; Receptors, Thyrotropin; Young Adult

Topics: Adolescent; Antithyroid Agents; Biopsy; Female; Graves Disease; Humans; Kidney; Methimazole; Proteinuria

Topics: Adolescent; Antithyroid Agents; Biopsy; Diagnosis, Differential; Female; Glomerular Basement Membrane; Glomerulonephritis, IGA; Glomerulonephritis, Membranoproliferative; Glomerulonephritis, Membranous; Graves Disease; Humans; Methimazole; Nephrosis, Lipoid; Proteinuria; Rituximab; Treatment Outcome

We report two women who were diagnosed with hypothyroidism due to what was thought to be Hashimoto's thyroiditis 18 and 16 years ago, respectively. They had been euthyroid on stable doses of levothyroxine for many years, and they presented to our clinic with clinically and biochemically overt hyperthyroidism that persisted even after stopping levothyroxine. Immunological and imaging workups were consistent with Graves' disease. Both patients were treated medically and then received definitive treatment. To our knowledge, the intervals for these two conversions are among the longest conversion intervals reported in the medical literature.

Topics: Adrenergic beta-Antagonists; Antithyroid Agents; Female; Graves Disease; Hashimoto Disease; Humans; Hyperthyroidism; Hypothyroidism; Methimazole; Middle Aged; Propranolol; Thyroidectomy; Thyroxine; Treatment Outcome

Topics: Antithyroid Agents; Child, Preschool; Choanal Atresia; Female; Graves Disease; Hearing Loss; Humans; Male; Methimazole; Pregnancy; Pregnancy Complications

Immune checkpoint inhibitors act to restore T cell-mediated antitumor immunity. By this nature, these cancer immunotherapy drugs are associated with various immune-related adverse events such as thyroid dysfunction. We describe a case of thyrotoxicosis secondary to a programmed cell death 1 (PD-1) immune checkpoint inhibitor, pembrolizumab. A 30-year-old female was started on pembrolizumab immunotherapy for stage III small cell carcinoma of the ovary, hypercalcemic type. Thirteen days after her second cycle of therapy, she presented with symptoms consistent with thyrotoxicosis. A thyroiditis was diagnosed by thyroid function tests and ultrasonography. She was originally treated with prednisone and metoprolol for possible Grave's disease. Pertechnetate thyroid scan was more consistent with thyroiditis secondary to pembrolizumab. She underwent a total thyroidectomy 10 days after initial presentation for refractory thyrotoxicosis despite maximal medical therapy. Her symptoms resolved and thyroid function tests significantly improved. Pathology was consistent with severe thyroiditis. Immune microenvironment may play a role in the expression of programmed cell death protein 1 ligand 1 (PD-L1). Chronic inflammation surrounding tumor upregulates PD-L1 expression on tumor cells by the release of cytokines, which acts to inhibit tumor destruction. We suggest that our patient had an undetected chronic inflammation of the thyroid, specifically Hashimoto's thyroidits, which predisposed her to thyroid destruction when taking pembrolizumab. Understanding that an inflammatory environment impacts thyroid toxicity to PD-1 inhibitor therapy is novel and should be further studied.

Topics: Adult; Antibodies, Monoclonal, Humanized; Antithyroid Agents; Carcinoma, Small Cell; Female; Graves Disease; Humans; Methimazole; Ovarian Neoplasms; Thyroid Gland; Thyroidectomy; Thyroiditis

Methimazole (MMI) has been used for the treatment of Graves' Disease (GD) for more than half a century. The MMI treatment has been reported to be associated with hepatotoxicity. Previous studies have demonstrated that human leukocyte antigen (HLA) genetic polymorphisms were associated with many drugs-induced liver injuries. To investigate HLA genetic susceptibility to MMI-induced liver injury (MMI-DILI), we characterized both HLA class I and class Ⅱ in a well-characterized phenotypic cohort with 40 MMI-DILI cases and 118 MMI-tolerant controls. Among the 40 MMI-DILI cases, 57.5% were women and 50% were cholestatic liver damage with occurring time from days to months after MMI dosing. The frequency of HLA-C*03:02 was 6.7% (5/75) in the MMI-DILI case patients and 6.4% (4/62) in MMI-induced cholestatic/mixed liver damage, which were significantly different from the percentage of 0.4% (1/231) in the MMI-tolerant patients (odds ratio (OR) = 15.4, 95% confidence interval (CI) = 1.77-133.9, adjusted P = 0.0292; OR=14.9, 95% CI=2.38-182.9, adjusted P = 0.0323; respectively). HLA-A*02:01 was also found to be associated with MMI-induced cholestatic/mixed liver injury (OR = 3.13, 95%CI=1.45-6.91, adjusted P = 0.0464). The present study demonstrated that individuals carrying HLA-C*03:02 allele are at increased risk of developing MMI-induced DILI. These results may assist doctors to prevent the occurrence of hepatotoxicity in GD patients receiving MMI.

Topics: Adult; Alleles; Chemical and Drug Induced Liver Injury; Female; Genetic Predisposition to Disease; Graves Disease; HLA-C Antigens; Humans; Liver; Male; Methimazole; Polymorphism, Genetic; Retrospective Studies

Methimazole (MMI) has been used in the therapy of Grave's disease (GD) since 1954, and drug-induced liver injury (DILI) is one of the most deleterious side effects. Genetic polymorphisms of drug-metabolizing enzymes and drug transporters have been associated with drug-induced hepatotoxicity in many cases. The aim of this study was to investigate genetic susceptibility of the drug-metabolizing enzymes and drug transporters to the MMI-DILI. A total of 44 GD patients with MMI-DILI and 118 GD patients without MMI-DILI development were included in the study. Thirty-three single nucleotide polymorphisms (SNPs) in twenty candidate genes were genotyped. We found that rs12422149 of SLCO2B1, rs2032582_AT of ABCB1, rs2306283 of SLCO1B1 and rs4148323 of UGT1A1 exhibited a significant association with MMI-DILI; however, no significant difference existed after Bonferroni correction. Haplotype analysis showed that the frequency of SLCO1B1*1a (388A521T) was significantly higher in MMI-DILI cases than that in the control group (OR = 2.21, 95% CI = 1.11-4.39, P = 0.023), while the frequency of SLCO1B1*1b (388G521T) was significantly higher in the control group (OR = 0.52, 95% CI = 0.29-0.93, P = 0.028). These results suggested that genetic polymorphisms of SLCO1B1 were associated with susceptibility to MMI-DILI. The genetic polymorphism of SLCO1B1 may be important predisposing factors for MMI-induced hepatotoxicity.

Topics: Adult; Aged; Aged, 80 and over; Alleles; ATP Binding Cassette Transporter, Subfamily B; Chemical and Drug Induced Liver Injury; Female; Genetic Predisposition to Disease; Genotype; Glucuronosyltransferase; Graves Disease; Haplotypes; Humans; Liver-Specific Organic Anion Transporter 1; Male; Methimazole; Middle Aged; Multidrug Resistance-Associated Proteins; Oxygenases; Polymorphism, Genetic

Graves' is disease an autoimmune disorder of the thyroid gland caused by circulating anti-thyroid receptor antibodies (TRAb) in the serum. TRAb mimics the action of thyroid stimulating hormone (TSH) and stimulates the thyroid hormone receptor (TSHR), which results in hyperthyroidism (overactive thyroid gland) and goiter. Methimazole (MMI) is used for hyperthyroidism treatment for patients with Graves' disease.. We have developed a model using a system of ordinary differential equations for hyperthyroidism treatment with MMI. The model has four state variables, namely concentration of MMI (in mg/L), concentration of free thyroxine - FT4 (in pg/mL), and concentration of TRAb (in U/mL) and the functional size of the thyroid gland (in mL) with thirteen parameters. With a treatment parameter, we simulate the time-course of patients' progression from hyperthyroidism to euthyroidism (normal condition). We validated the model predictions with data from four patients.. When there is no MMI treatment, there is a unique asymptotically stable hyperthyroid state. After the initiation of MMI treatment, the hyperthyroid state moves towards subclinical hyperthyroidism and then euthyroidism.. We can use the model to describe or test and predict patient treatment schedules. More specifically, we can fit the model to individual patients' data including loading and maintenance doses and describe the mechanism, hyperthyroidism→euthyroidism. The model can be used to predict when to discontinue the treatment based on FT4 levels within the physiological range, which in turn help maintain the remittance of euthyroidism and avoid relapses of hyperthyroidism. Basically, the model can guide with decision-making on oral intake of MMI based on FT4 levels.

Topics: Antithyroid Agents; Graves Disease; Humans; Hyperthyroidism; Methimazole; Models, Biological; Thyroid Gland; Thyrotropin; Thyroxine; Treatment Outcome

Dysregulated DNA methylation in lymphocytes has been linked to autoimmune disorders. The aims of this study were to identify global DNA methylation patterns in patients with autoimmune thyroid diseases and to observe methylation changes after treatment for these conditions.. A cross-sectional study was conducted, including the following patients: 51 with newly diagnosed Graves' disease (GD), 28 with autoimmune hypothyroidism (AIT), 29 with positive thyroid autoantibodies, and 39 matched healthy volunteers. Forty GD patients treated with radioiodine or antithyroid drugs and 28 AIT patients treated with L-thyroxine were followed for three months. Serum free triiodothyronine, free thyroxine, thyrotropin, thyroid peroxidase antibodies, thyroglobulin antibodies, and thyrotropin receptor antibodies were assayed using electrochemiluminescent immunoassays. CD3. Hypomethylation and down-regulated DNMT1 expression in T and B lymphocytes were observed in the newly diagnosed GD patients. Neither the AIT patients nor the positive thyroid autoantibodies patients exhibited differences in their global DNA methylation status or DNMT mRNA levels compared with healthy controls. Antithyroid drugs restored global methylation and DNMT1 expression in both T and B lymphocytes, whereas radioiodine therapy affected only T cells. L-thyroxine replacement did not alter the methylation or DNMT expression levels in lymphocytes. The global methylation levels of B cells were negatively correlated with the serum thyroid peroxidase antibodies in patients with autoimmune thyroid diseases.. Hyperthyroid patients with newly diagnosed GD had global hypomethylation and lower DNMT1 expression in T and B lymphocytes. The results provide the first demonstration that antithyroid drugs or radioiodine treatment restore global DNA methylation and DNMT1 expression with concurrent relief of hyperthyroidism.

Topics: Adult; B-Lymphocytes; Cross-Sectional Studies; DNA (Cytosine-5-)-Methyltransferase 1; DNA Methylation; Female; Graves Disease; Hashimoto Disease; Humans; Hypothyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; T-Lymphocytes; Thyroiditis, Autoimmune; Thyroxine; Triiodothyronine

Immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients after initiating antiretroviral therapy usually involves worsening manifestations of overt infectious disease. Here, we describe a sporadic case of a late-diagnosed HIV-positive man who developed Graves' disease as the first noninfectious IRIS followed by immune thrombocytopenic purpura as the second noninfectious IRIS.

Topics: Aged; AIDS-Related Opportunistic Infections; Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Graves Disease; HIV; HIV Infections; Humans; Immune Reconstitution Inflammatory Syndrome; Immunocompromised Host; Male; Methimazole; Purpura, Thrombocytopenic, Idiopathic; Treatment Outcome

A 27-year-old male patient who presented to the emergency room with complaints of sweating, palpitations, heat intolerance, insomnia and weight loss for the last 3 months. His medical history was significant for hypertension. On examination, he was tachycardic, hypertensive, had tremors of the upper extremities and a smooth goitre with a thyroid bruit. Laboratory assessment revealed a suppressed thyroid-stimulating hormone, high free thyroxine and positive thyroid receptor antibodies. Complete blood count showed pancytopenia. As part of the work-up for pancytopenia, haptoglobin, ferritin, Coombs test, reticulocyte count hepatitis B and C antibodies were done, all of which were normal. Patient was started on methimazole, propranolol and hydrocortisone. His symptoms improved through the hospital course and he was subsequently discharged. Thyroidectomy was done once the patient's hyperthyroidism was controlled. Levothyroxine was started for the control of postsurgical hypothyroidism. Six months after thyroidectomy, the patient was euthyroid and the pancytopenia resolved.

Topics: Adult; Antithyroid Agents; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Pancytopenia; Thyroidectomy; Thyrotropin; Thyroxine; Treatment Outcome

Subacute thyroiditis is a common inflammatory disorder of the thyroid gland, possibly of viral etiology, that typically presents with neck pain, fever and tenderness on palpation of the thyroid gland. Graves' disease is an autoimmune thyroid disorder caused by stimulation of the thyroid gland by thyrotropin receptor antibodies (TRAb). The development of Graves´ disease and subacute thyroiditis simultaneously is an uncommon condition and only a few cases have been reported. In this article we present a case of a 46-year old woman diagnosed with Graves´ disease who was started on thiamazole and weeks later developed high fever. Several differential diagnoses were considered such as infection, lymphoma and vasculitis due to thiamazole. Finally, the fine needle aspiration of the thyroid gland displayed histopathological features of subacute thyroiditis. Remarkably, our patient did not have neck pain or tenderness on palpation of the thyroid gland and overall the clinical presentation of subacute thyroiditis was atypical. Thus, subacute thyroiditis may be considered as a potential cause of fever of unknown origin.

Topics: Anti-Inflammatory Agents; Antithyroid Agents; Diagnosis, Differential; Female; Graves Disease; Humans; Methimazole; Middle Aged; Prednisolone; Thyroiditis, Subacute

Anti-N-methyl-D-aspartic acid-receptor (NMDA-R) encephalitis is a novel disease discovered within the past 10 years. It is an autoimmune disease (AD) that has been associated with other ADs, such as Graves' disease. However, association with autoimmune polyglandular syndromes (APS) has not been previously described. A 58-year-old woman presented with altered mental status and an 8-month history of weight loss, apathy and somnolence. Laboratory evaluation confirmed Graves' disease with thyrotoxicosis and type 1 diabetes mellitus. Despite treatment, she continued to have a fluctuating mental status. Further diagnostic evaluation included an abdominal MRI that showed a cystic lobular left adnexal mass. Serum anti-NMDA-R antibodies were positive, raising concern for NMDA-R encephalitis. Bilateral salpingo-oophorectomy was performed, with pathology consistent with cystadenofibroma. She had a favourable recovery with marked clinical improvement. Anti-NMDA-R antibodies were negative 2 months following surgery. The concomitant occurrence of APS and anti-NMDA-R encephalitis suggests a shared mechanism of autoimmune pathophysiology.

Topics: Abdomen; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Antibodies; Antithyroid Agents; Cystadenofibroma; Diabetes Mellitus, Type 1; Female; Graves Disease; Humans; Magnetic Resonance Imaging; Methimazole; Middle Aged; Ovarian Neoplasms; Polyendocrinopathies, Autoimmune; Receptors, N-Methyl-D-Aspartate

Thiamazole might trigger the onset of type 1 diabetes.

Topics: Antithyroid Agents; Diabetes Mellitus, Type 1; Female; Graves Disease; Humans; Methimazole; Middle Aged

Thyrotropin-secreting adenoma (TSHoma) is rare. Even though the thyrotoxicosis is mild in patients with TSHoma, it is still a rare cause of arrhythmia, ignore of mild disfunction of thyroid function of TSHoma can lead to the delayed diagnosis of pituitary tumor or leading to recurring of complications. Graves' disease is an auto-immue endocrinological disorder. Association of TSHoma and Graves's disease is extremely rare. Coexistence of these two diseases made the diagnosis and treatment complicated.. This patient was a 55-year-old man who had been referred to the department of endocrinology and metabolism of the West China Hospital due to recurrent atrial fibrillation (AF) and thyroxicosis.. Examinations revealed pituitary thyrotropin-secreting macroadenoma with Graves' disease.. We conducted transsphenoidal surgery. Thyrozol was used to treat the recurrence of Graves' disease after pituitary surgery.. The TSHoma was successfully cured, and recurrent Graves' disease was controlled very well.. The association of TSHoma and Graves' disease is extremely rare. Even though the clinical features of thyrotoxicosis are milder in patients with TSHoma, thyroid function tests are still important clinical assessment of patients with AF, which is an arrhythmia associated with hyperthyroidism. TSHoma is a rare cause of thyrotoxicosis; however, ignoring of the mild disfunction caused by TSHoma can lead to the delayed diagnosis of pituitary tumors or to recurring of complications of TSHoma.

Topics: Antithyroid Agents; Atrial Fibrillation; Catheter Ablation; China; Graves Disease; Humans; Magnetic Resonance Imaging; Male; Methimazole; Middle Aged; Neurosurgical Procedures; Pituitary Gland; Pituitary Neoplasms; Recurrence; Thyrotoxicosis; Thyrotropin

A 39-year-old multigravida woman presented 3 weeks postpartum with worsening generalised pruritus without primary rash. Workup was significant for cholestasis and undiagnosed Graves' disease. She began to have symptomatic relief after starting methimazole, and liver function tests normalised as she became euthyroid.

Topics: Antithyroid Agents; Female; Graves Disease; Humans; Liver Function Tests; Methimazole; Postpartum Period; Pruritus; Treatment Outcome; Young Adult

Concurrent presentation of acute hepatitis A virus (HAV) infection and Graves' disease has not been reported in literature worldwide. Although there is no well-established mechanism that explains the induction of Graves' disease by HAV to date, our case suggests that HAV infection may be responsible for inducing Graves' disease. A healthy 27-year-old female presented fever, palpitation, and diarrhea, and she was subsequently diagnosed as acute HAV infection. Concurrently, she showed hyperthyroidism, and the diagnosis was made as Graves' disease. She had never had symptoms that suggested hyperthyroidism, and previous thyroid function test was normal. Acute HAV infection was recovered by conservative management, however, thyroid dysfunction was maintained even after normalization of liver enzymes. Methimazole was used to treat Graves' disease. We report a case of concurrent acute HAV infection and Graves' disease in a patient without preexisting thyroid disease. This suggests that HAV infection may be a trigger for an autoimmune thyroid disease in susceptible individuals.

Topics: Adult; Alanine Transaminase; Antithyroid Agents; Bilirubin; Female; Graves Disease; Hepatitis A; Humans; Hyperthyroidism; Liver; Methimazole; Thyroid Function Tests

Graves' disease (GD) is the most common cause of hyperthyroidism. Anti-thyroid drugs, including methimazole, are the most commonly selected treatment option for this condition. But for decades, no additional drug option has been added. Anemarrhena Bunge has been used in many herbal decoctions for patients who had hyperthyroidism-like symptoms, such as sweating, heat intolerance, and anxiety. In this case study, a patient with GD who had once achieved therapeutic goals with methimazole but then re-developed hyperthyroidism was treated with only herbal decoctions, and achieved euthyroidism, normalization of T3, T4 levels for 13 months and maintenance of thyroid stimulating hormone (TSH) levels for 8 months and TSH binding inhibitory immunoglobulins (TBII)-negative status for 13 months (TSH and TBII level before treatment: 0.01 μIU/mL, 10.94 IU/L; TSH level normalization after 14 months from the initiation of the treatment: 0.75 μIU/mL, TBII level normalization after 9 months from the initiation of the treatment: 0.8 IU/L). The patient did not report any adverse effects related to this treatment. A herbal decoction with Anemarrhena Bunge might be effective in patients who are resistant to methimazole treatments, a finding which needs further investigation in future.

Topics: Adult; Anemarrhena; Drug Resistance; Female; Graves Disease; Humans; Methimazole; Plant Extracts

Topics: Adrenergic beta-Antagonists; Antithyroid Agents; Female; Graves Disease; Humans; Methimazole; Middle Aged; Propranolol; Vomiting

Antithyroid drugs (ATDs) are known to cause various adverse drug reactions (ADRs) that can lead to treatment complexity and unpredictable risks. With the aim of ensuring safer drug use, we assessed whether thyrotropin receptor antibody (TRAb) titers are associated with ATD-induced cutaneous reactions and/or hepatotoxicity, and examined potential genetic predisposition factors.. We compared TRAb titers of 37 Graves' disease (GD) patients who had experienced carbimazole/methimazole-induced cutaneous reactions and/or hepatotoxicity with those of 40 normal individuals, or 78 GD patients without the aforementioned ATD-induced ADRs. We performed a genome-wide association study and/or human leukocyte antigen genotyping on GD patients [first stage (chart reviews): 24 cases with ADRs and 423 controls; second stage (actively recruited): 45 cases with ADRs and 137 controls].. For patients with Graves' hyperthyroidism, individuals with higher TRAb titers showed a predisposition to carbimazole/methimazole-induced cutaneous reactions and/or hepatotoxicity, with an estimated odds ratio of 5.19 (cut-off value: 64%). Potential associations with the rs144542704 and rs61893841 on chromosomes 17 and 11, respectively, warrant further genetic association analysis.. Our findings support the use of carbimazole/methimazole in patients with low TRAb titers to ensure safer drug use. The identified genetic associations warrant further research.

Topics: Adolescent; Adult; Aged; Antibodies; Antithyroid Agents; Carbimazole; Case-Control Studies; Chemical and Drug Induced Liver Injury; Drug Eruptions; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Graves Disease; Humans; Male; Methimazole; Middle Aged; Receptors, Thyrotropin; Young Adult

A 71-year-old male with no previous medical history was admitted to our hospital for paralysis of the right upper extremity. Although DWI of the brain revealed high-intensity signals in the bilateral frontal and left parietal lobes, CT revealed a hyperdense spot in the anterior superior sagittal sinus (SSS). Because CT venography revealed SSS occlusion, he was diagnosed with cerebral venous thrombosis (CVT). In addition, laboratory findings, including free triiodothyronine, 8.85 pg/ml; thyroxine, 3.39 pg/dl, thyroid-stimulating hormone (TSH), < 0.02 μU/ml; and anti-TSH receptor antibody, 5.7 IU/l, led to the diagnosis of hyperthyroidism for the first time. Moreover, factor VIII procoagulant protein levels exhibited a marked increase (187.5%). Based on these findings, the patient was diagnosed with CVT due to Graves' disease.

Topics: Aged; Antithyroid Agents; Autoantibodies; Factor VIII; Graves Disease; Heparin; Humans; Intracranial Thrombosis; Levetiracetam; Magnetic Resonance Imaging; Male; Methimazole; Phlebography; Receptors, Thyrotropin; Tomography, X-Ray Computed; Treatment Outcome

Insulin autoimmune syndrome (IAS) is a rare endocrine disease characterized by repeated fasting hypoglycemia or episodes of hypoglycemia late after meals, elevated serum insulin, and positivity for insulin autoantibody (IAA) or insulin receptor antibody (IRA). We summarize the clinical manifestations and treatment experiences of 3 patients with IAS.. One patient with >20-year history of type 2 diabetes mellitus had irregular episodes of hypoglycemia 2 years of after treatment with insulin. Another patient with a 6-year history of type 2 diabetes mellitus presented irregular episodes of hypoglycemia after 6 months of treatment with insulin. One patient with a history of Graves' disease showed hypoglycemia after administration of thiamazole.. Serum islet cell antibody (ICA) and glutamic acid decarboxylase antibody (GADA) were negative, while antibody insulin autoantibodies were positive in all the 3 patients. Two patients demonstrated diabetes mellitus after an oral glucose tolerance test, while one had normal glucose tolerance. Furthermore, serum insulin levels significantly elevated and did not matched C peptide levels. No abnormalities were found on enhanced MRI of the pancreas, and all 3 patients were clinically diagnosed with IAS.. In case one, insulin aspart 30 injection was withdrawn after admission. In addition, the patient was prescribed sublingual acarbose 3 times daily. Two weeks after admission, prednisone acetate was administered orally once daily at night. In case 2, insulin aspart 30 injection was withdrawn after admission, the patient was prescribed sublingual acarbose 3 times daily with a meal. Five days after admission, oral prednisone acetate was administered once daily at night. In case 3, oral propylthiouracil was prescribed and thiamazole withdrawn after admission, and the patient consumed an extra meal before sleeping.. At the 3-month follow-up visit, the hypoglycemic episodes had disappeared, serum insulin levels were significantly decreased, and insulin antibody (IA) levels were no longer detectable in all 3 patients.. For those patients with high-insulin hypoglycemia, IAA should be evaluated if serum insulin concentrations are inconsistent with C peptide levels. Therapeutically, a lower dose of glucocorticoids with more appropriate medication timing can be used to achieve good results.

Topics: Adult; Aged; Antithyroid Agents; Autoantibodies; Autoimmune Diseases; Diabetes Mellitus, Type 2; Female; Graves Disease; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Male; Methimazole; Middle Aged; Syndrome

Topics: Antithyroid Agents; Female; Graves Disease; Humans; Infant; Methimazole; Thyrotropin; Thyroxine; Triiodothyronine

Agranulocytosis is a rare and serious adverse effect of antithyroid drugs, with unknown etiology. The present study aimed to uncover genetic susceptibility and underlying mechanisms of antithyroid drug-induced agranulocytosis (ATDAC). We studied two independent families with familial Graves' disease, of which several members developed ATDAC. In addition, six sporadic ATDAC patients with Graves' disease were investigated. Whole exome sequencing analysis of affected and unaffected family members was performed to identify genetic susceptibility variants for ATDAC, followed by functional characterization of primary granulocytes from patients and unrelated healthy controls. Whole exome sequencing, cosegregation analysis, and stringent selection criteria of candidate gene variants identified NOX3 as a genetic factor related to ATDAC. Functional studies revealed increased apoptosis of methimazole-treated granulocytes from patients carrying NOX3 variants. In conclusion, genetic variants in NOX3 may confer susceptibility to antithyroid drug-induced apoptosis of granulocytes. These findings contribute to the understanding of the mechanisms underlying ATDAC.

Topics: Agranulocytosis; Antithyroid Agents; Apoptosis; Case-Control Studies; Exome; Female; Genetic Predisposition to Disease; Granulocytes; Graves Disease; Humans; Male; Methimazole; NADPH Oxidases; Pedigree

We herein report the case of a Japanese woman with familial dysalbuminemic hyperthyroxinemia (FDH) who was initially diagnosed with Graves' disease. Direct genomic sequencing revealed a guanine to cytosine transition in the second nucleotide of codon 218 in exon 7 of the albumin gene, which then caused a proline to arginine substitution. She was finally diagnosed with FDH, which did not require treatment. FDH is - superficially - an uncommon cause of syndrome of inappropriate secretion of thyrotropin (SITSH) in Japan. A misdiagnosis of pseudo-hyperthyroidism will lead to inappropriate treatment. Thus, physicians should strongly note the possibility of FDH as a differential diagnosis of SITSH.

Topics: Adult; Antithyroid Agents; Codon; Diagnosis, Differential; Female; Graves Disease; Humans; Hyperpituitarism; Hyperthyroxinemia, Familial Dysalbuminemic; Methimazole; Mutation; Serum Albumin; Thyroid Gland; Thyrotropin; Ultrasonography

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Child; Female; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Propranolol; Thyrotropin

A 46-year-old woman with a history of Graves' disease presented with the chief complaints of appetite loss, weight loss, fatigue, nausea, and sweating. She was diagnosed with diabetic ketoacidosis (DKA), thyroid storm, and influenza A. She was treated with an intravenous insulin drip, intravenous fluid therapy, intravenous hydrocortisone, oral potassium iodine, and oral methimazole. As methimazole-induced neutropenia was suspected, the patient underwent thyroidectomy. It is important to maintain awareness that thyroid storm and DKA can coexist. Furthermore, even patients who have relatively preserved insulin secretion can develop DKA if thyroid storm and infection develop simultaneously.

Topics: Administration, Oral; Antithyroid Agents; Diabetic Ketoacidosis; Diagnosis, Differential; Female; Fluid Therapy; Graves Disease; Humans; Influenza, Human; Infusions, Intravenous; Insulin; Methimazole; Middle Aged; Thyroid Crisis; Thyroidectomy

Although Graves' disease and systemic sclerosis are both autoimmune disorders, their relationship is rarely reported. We present the case of a Filipino woman with goitre and thyrotoxic signs and symptoms. Diagnosed with Graves' disease at the outpatient clinic, she took antithyroid medications and underwent radioactive iodine ablation with resultant hypothyroidism after 6 months, during which she began to experience skin tightness over the face, neck and fingers. Workup revealed limited cutaneous systemic sclerosis, and the patient improved with methotrexate. This case highlights the increased prevalence of coincident autoimmune disorders in Graves' disease.

Topics: Adult; Antithyroid Agents; Facial Dermatoses; Female; Graves Disease; Hormone Replacement Therapy; Humans; Hypothyroidism; Immunosuppressive Agents; Iodine Radioisotopes; Methimazole; Methotrexate; Neck; Scleroderma, Limited; Thyroxine

Graves' disease is an autoimmune thyroid disorder characterized by hyperthyroidism, and patients exhibit thyroid-stimulating hormone receptor antibody. The major methods of measuring circulating thyroid-stimulating hormone receptor antibody include the thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Although the diagnostic accuracy of these assays has been improved, a minority of patients with Graves' disease test negative even on second-generation and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulins. We report a rare case of a thyroid-stimulating hormone-binding inhibitory immunoglobulin-positive patient with Graves' disease who showed rapid lowering of thyroid-stimulating hormone-binding inhibitory immunoglobulin levels following administration of the anti-thyroid drug thiamazole, but still experienced Graves' hyperthyroidism.. A 45-year-old Japanese man presented with severe hyperthyroidism (serum free triiodothyronine >25.0 pg/mL; reference range 1.7 to 3.7 pg/mL) and tested weakly positive for thyroid-stimulating hormone-binding inhibitory immunoglobulins on second-generation tests (2.1 IU/L; reference range <1.0 IU/L). Within 9 months of treatment with oral thiamazole (30 mg/day), his thyroid-stimulating hormone-binding inhibitory immunoglobulin titers had normalized, but he experienced sustained hyperthyroidism for more than 8 years, requiring 15 mg/day of thiamazole to correct. During that period, he tested negative on all first-generation, second-generation, and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, but thyroid scintigraphy revealed diffuse and increased uptake, and thyroid ultrasound and color flow Doppler imaging showed typical findings of Graves' hyperthyroidism.. The possible explanations for serial changes in the thyroid-stimulating hormone-binding inhibitory immunoglobulin results in our patient include the presence of thyroid-stimulating hormone receptor antibody, which is bioactive but less reactive on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, or the effect of reduced levels of circulating thyroid-stimulating hormone receptor antibody upon improvement of thyroid autoimmunity with thiamazole treatment. Physicians should keep in mind that patients with Graves' disease may show thyroid-stimulating hormone-binding inhibitory immunoglobulin assay results that do not reflect the severity of Graves' disease or indicate the outcome of the disease, and that active Graves' disease may persist even after negative results on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Timely performance of thyroid function tests in combination with sensitive imaging tests, including thyroid ultrasound and scintigraphy, are necessary to evaluate the severity of Graves' disease and treatment efficacy.

Topics: Antithyroid Agents; Autoantibodies; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Radionuclide Imaging; Receptors, Thyrotropin; Thyroid Function Tests; Thyroid Gland; Thyroxine; Treatment Outcome

Pediatric Graves' disease is rare in young children, more frequent in children with other autoimmune diseases or with family history of autoimmune thyroid disease.. The 2.5 year old girl was admitted to the hospital with tachycardia and subfebrile temperature. The girl presented symptoms of atopic dermatitis. Child's mother was diagnosed with Hashimoto disease two months after the child's diagnosis. In physical examination of the child, enlarged thyroid was found. At the admission, the laboratory tests revealed decreased TSH (0.001 uIU/ml), increased both FT3 (>30 pg/ml) and FT4 (3.43 ng/dl), but normal levels of anti-thyreoglobulin antibodies (ATG - 0.64 IU/ml) and anti-thyroid peroxidase antibodies (ATPO - 0 IU/ml); thyrotropin receptor antibodies (TRAb) were not identified. The Graves' disease was diagnosed. The girl started treatment with methimazole (2x5mg) and propranolol (due to tachycardia, 2x5mg). The thyroid function (TSH, FT4 and FT3) normalized 1 year after diagnosis and hormone levels remained within normal reference values, but she received methimazole for 18 months. At presen, the patient is 8 years old. She is not receiving any treatment and her thyroid function is correct. The girl still presents symptoms of atopy.. In case of symptoms of tachycardia in children, the hyperthyroidism should be taken into consideration. Numerous methods of treatment provide a therapy appropriate to the age and condition of patients. Long remission after treatment with antithyroid drugs could also be achieved in younger (prepubertal) children.. Wstęp. Dziecięca postać choroby Gravesa występuje rzadko u małych pacjentów, częściej u dzieci z chorobami autoimmunologicznymi albo z rodzinnym występowaniem chorób autoimmunologicznych. Opis przypadku. 2,5-letnia dziewczynka została przyjęta do szpitala z tachykardią i stanem podgorączkowym. W wywiadzie: atopowe zapalenie skóry u dziecka, choroba Hashimoto u matki (zdiagnozowana 2 miesiące po postawieniu diagnozy u dziecka). W badaniu fizykalnym zaobserwowano powiększony gruczoł tarczowy. W badaniach laboratoryjnych przy przyjęciu stwierdzono nieprawidłowości wskazujące na nadczynność tarczycy: TSH – 0,001 uIU/ml, FT3 >30 pg/ml, FT4 3,43 ng/dl oraz prawidłowy poziom przeciwciał ATG i ATPO. Rozpoznano chorobę Gravesa i rozpoczęto leczenie metimazolem (2x5 mg) oraz propranololem (ze względu na tachykardię 2x5 mg). Po rocznym leczeniu uzyskano stabilizację funkcji tarczycy, jakkolwiek pacjentka otrzymywała leczenie metimazolem przez 18 miesięcy. Obecnie pacjentka ma 8 lat i nie otrzymuje żadnego leczenia, funkcja tarczycy pozostaje prawidłowa, natomiast wciąż prezentuje objawy atopii. Podsumowanie. Przy występowaniu tachykardii u małego dziecka należy rozważyć rozpoznanie nadczynności tarczycy. Wybór terapii powinien zależeć od wieku i stanu dziecka. Długotrwała remisja nadczynności tarczycy niewymagająca leczenia jest również możliwa u młodszych (przed okresem dojrzewania) dzieci.

Topics: Antithyroid Agents; Child; Child, Preschool; Female; Graves Disease; Humans; Methimazole; Rare Diseases; Treatment Outcome

Management of Graves' disease (GD) in Europe was published in 1987. Aim of this survey was to provide an update on clinical practice in Europe, and to compare it with a 2011 American survey.. Members of the European Thyroid Association (ETA) were asked to participate in a survey on management of GD, using the same questionnaire of a recent American survey.. A total of 147 ETA members participated. In addition to serum TSH and free T4 assays, most respondents would request TSH-receptor autoantibody (TRAb) measurement (85·6%) and thyroid ultrasound (70·6%) to confirm aetiology, while isotopic studies were selected by 37·7%. Antithyroid drug (ATD) therapy was the preferred first-line treatment (83·8%). Compared to the previous European survey, Europeans currently more frequently use TRAb measurement and thyroid ultrasound for diagnosis and evaluation, but first-line treatment remains ATDs in a similar percentage of respondents. Current clinical practice patterns differ from those in North America, where isotopic studies are more frequently used, and radioiodine (RAI) still is first-line treatment. When RAI treatment is selected in the presence of mild Graves' orbitopathy and/or associated risk factors for its occurrence/exacerbation, steroid prophylaxis is frequently used. The preferred ATD in pregnancy is propylthiouracil in the first trimester and methimazole in the second and third trimesters, similar to North America.. Significant changes in clinical practice patterns in Europe were noted compared to the previous European survey, as well as persisting differences in diagnosis and therapy between Europe and North America.

Topics: Antithyroid Agents; Autoantibodies; Europe; Female; Graves Disease; Humans; Methimazole; North America; Practice Patterns, Physicians'; Pregnancy; Pregnancy Complications; Propylthiouracil; Receptors, Thyrotropin; Surveys and Questionnaires; Thyrotropin; Thyroxine

Graves' disease (GD) is an autoimmune disease characterized by the presence of circulating autoantibodies against thyroid-stimulating hormone (TSH) receptor. Despite extensive research, the pathogenic mechanisms remain unclear. Immune responses associated with the disease may lead to cell activation/apoptosis and the release of microvesicles (MVs) into the circulation. MVs can display biological activities which may aggravate GD further. We studied immune mechanisms in GD by investigating the numbers and phenotype of circulating MVs in patients before and after antithyroid therapy with thiamazole.. Samples were obtained from 15 patients with GD in the acute phase of hyperthyroidism and following 17-26 months treatment and 14 healthy controls. MVs from platelets, endothelial cells and monocytes exposing inflammation/activation markers (P-selectin, CD40 ligand, E-selectin and HMGB1) and MVs containing nuclear molecules were measured with flow cytometry.. Patients had elevated baseline values of MVs (P < 0·001 for all types of MVs), while the levels decreased during thiamazole treatment (P < 0·05 for all types of MVs). The majority of MV populations remained, however, significantly higher in patients after treatment compared to levels in controls.. GD patients have elevated levels of MVs that carry molecules with potential biological activities. MVs are significantly reduced after antithyroid treatment with thiamazole but still higher compared to levels in healthy controls. Assessment of MV levels and pattern may therefore provide additional information on underlying immune disturbances not obtained by measurements of hormone levels alone.

Topics: Adult; Antithyroid Agents; Blood Platelets; CD40 Ligand; Cell-Derived Microparticles; E-Selectin; Endothelial Cells; Extracellular Vesicles; Female; Flow Cytometry; Graves Disease; HMGB1 Protein; Humans; Male; Methimazole; Middle Aged; Monocytes; P-Selectin; Time Factors; Treatment Outcome

Both therapies for Graves' disease (GD), radioactive iodine (RAI) and antithyroid drugs (ATD), were reported to have specific immune effects. We aimed at investigating the effects of RAI therapy on cellular subsets involved in immune regulation. We conducted a thirty day follow-up prospective cohort study of adult patients. Patients eligible for RAI therapy at our centre were approached. Twenty seven patients with GD were recruited, among whom 11 were treated with ATD. Twenty-two healthy subjects (HS) were also studied. Over time, frequency of regulatory T cells (Treg) and of invariant natural killer T cells (iNKT), along with Treg cell-mediated suppression and underlying mechanisms, were monitored in the peripheral blood. Variance in frequency of Treg and iNKT after RAI therapy was higher in GD patients than in HS over time (p < 0.0001). Reduced Treg suppressive function was observed after RAI therapy in GD patients (p = 0.002). ATD medication prior to RAI dampened these outcomes: less variation of Treg frequency (p = 0.0394), a trend toward less impaired Treg function, and prevention of reduced levels of suppressive cytokines (p < 0.05). Shortly after RAI therapy, alterations in immunoregulatory cells in patients with GD were observed and partially prevented by an ATD pretreatment. Worsening of autoimmunity after RAI was explained in previous studies by enhanced immune activity. This study adds new highlights on immune regulation deficiencies after therapeutic interventions in thyroid autoimmunity.

Topics: Adult; Aged; Antithyroid Agents; Autoimmunity; Cells, Cultured; Cytoprotection; Female; Graves Disease; Humans; Iodine Radioisotopes; Killer Cells, Natural; Male; Methimazole; Middle Aged; Radiation Injuries; T-Lymphocytes, Regulatory; Young Adult

Genotyping increases the accuracy of a clinical score (based on pretreatment age, goiter size, FT4, TBII) for predicting recurrence of Graves' hyperthyroidism after a course of antithyroid drugs: a prospective study.

Topics: Adult; Antithyroid Agents; Autoantibodies; Female; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Prospective Studies; Recurrence; Risk Factors; Thyroxine

Thyrotoxicosis after total thyroidectomy is mostly iatrogenic. Rarely, a hyperfunctional thyroid remnant or ectopic tissue may be the cause. There are few cases of Graves' disease arising from thyroid tissue located in the mediastinum and none in which Graves' disease was diagnosed only after surgery. We report the case of a patient with Graves's disease in a mediastinal thyroid mass presenting 7 years after total thyroidectomy for nontoxic goiter.. A 67-year-old Caucasian woman presented with palpitations, fatigue and weight loss. She had a history of total thyroidectomy for nontoxic multinodular goiter at the age of 60 without any signs of malignancy on microscopic examination. She had been medicated with levothyroxine 100 μg/day since the surgery without follow-up. She was tachycardic, had no cervical mass or eye involvement. Her thyroid-stimulating hormone levels were suppressed (0.000 μU/mL) and her free thyroxine (3.22 ng/dL) and free triiodothyronine (8.46 pg/mL) levels increased. Neither mediastinal enlargement nor trachea deviation was found on chest roentgenogram. Levothyroxine treatment was stopped but our patient showed no improvement on free thyroxine or free triiodothyronine 10 days later. Thyroglobulin was increased to 294 mg/mL. A cervical ultrasound scan revealed no thyroid remnant. Her anti-thyroid-stimulating hormone receptor antibodies were high (19.7 U/L). Corporal scintigraphy demonstrated increased intrathoracic radioiodine uptake. A computed tomography scan confirmed a 60 × 40 mm mediastinal mass. Methimazole 10 mg/day was started. Three months later, her thyroid function was normal and she underwent surgical resection. Microscopic examination showed thyroid tissue with no signs of malignancy.. Although thyrotoxicosis after total thyroidectomy is mostly due to excessive supplementation, true hyperthyroidism may rarely be the cause, which should be kept in mind. The presence of thyroid tissue after total thyroidectomy in our patient may correspond to a remnant or ectopic thyroid tissue that became hyperfunctional in the presence of anti- thyroid-stimulating hormone receptor antibodies.

Topics: Aged; Antithyroid Agents; Fatigue; Female; Goiter; Graves Disease; Humans; Mediastinal Diseases; Methimazole; Thyroidectomy; Thyrotoxicosis; Thyroxine; Tomography, Emission-Computed; Treatment Outcome; Weight Loss

The older of a pair of sisters experienced hypoglycemia after the start of thiamazole (MMI) treatment. Based on a high insulin antibody level, she was diagnosed with insulin autoimmune syndrome (IAS). HLA-DNA typing identified DRB1*04:06. Although a 75-g oral glucose tolerance test (OGTT) showed biphasic insulin secretion, the secretion pattern became monophasic after discontinuation of the MMI. The younger sister was diagnosed with IAS after the start of MMI treatment. HLA-DNA typing identified DRB1*04:06. The 75-g OGTT showed biphasic insulin secretion, but it became monophasic after discontinuation of the MMI. According to the similar insulin secretion kinetics in the two sisters with IAS, we suspect that a genetic predisposition may be associated with the features of anti-insulin antibodies.

Topics: Adult; Antithyroid Agents; Autoimmune Diseases; Female; Genetic Predisposition to Disease; Glucose Tolerance Test; Graves Disease; HLA-DRB1 Chains; Humans; Hyperinsulinism; Hypoglycemia; Insulin; Insulin Antibodies; Insulin Secretion; Methimazole; Siblings

Amiodarone-induced thyrotoxicosis (AIT) type I describes inducement of clinical hyperthyroidism by excessive thyroidal iodine in the setting of latent Graves disease, and therapy differs from that used for AIT type II. A 65-year-old man previously on amiodarone for atrial fibrillation developed clinical hyperthyroidism. Diagnosis of AIT was made, but the type was not clear. Tc sestamibi thyroid scan showed diffusely increased uptake and retention in an enlarged thyroid gland, a pattern consistent with AIT type I. Methimazole was initiated and controlled the thyrotoxicosis. I iodide thyroid scan and uptake study performed later was consistent with Graves disease.

Topics: Aged; Amiodarone; Antithyroid Agents; Graves Disease; Humans; Male; Methimazole; Potassium Channel Blockers; Radionuclide Imaging; Technetium Tc 99m Sestamibi; Thyrotoxicosis

Management options are limited for the treatment of Graves' disease, and there is controversy regarding optimal treatment. We describe the demographic and biochemical characteristics of children with Graves' disease and the outcomes of its management.. This is a retrospective study reviewing medical records from 2001 to 2011 at a tertiary-care paediatric hospital. Diagnostic criteria included elevated free T4 and total T3, suppressed TSH, and either positive thyroid-stimulating immunoglobulin or thyroid receptor antibodies or clinical signs suggestive of Graves' disease, for example exophthalmos. Patients were treated with antithyroid drugs (ATD), radioactive iodine, or thyroidectomy. The main outcome measures were remission after medical therapy for at least 6 months and subsequent relapse.. A total of 291 children met diagnostic criteria. A total of 62 were male (21%); 117 (40%) were Hispanic, 90 (31%) Caucasian, and 59 (20%) African American. Mean age (±standard deviation) at diagnosis was 12·3 ± 3·8 (range 3-18·5) years. At diagnosis, 268 patients were started on an antithyroid drug and 23 underwent thyroid ablation or thyroidectomy. Fifty-seven (21%) children achieved remission and 16 (28%) of these patients relapsed, almost all within 16 months. Gender and ethnicity did not affect rates of remission or relapse. Of 251 patients treated with methimazole, 53 (21%) had an adverse reaction, including rash, arthralgias, elevated transaminases, or neutropenia.. Most children with Graves' disease treated with ATD do not experience remission, but most remissions do not end in relapse. Adverse reactions to methimazole are common but generally mild.

Topics: Adolescent; Antithyroid Agents; Child; Child, Preschool; Female; Graves Disease; Humans; Male; Methimazole; Racial Groups; Remission Induction; Retrospective Studies; Time Factors; Treatment Outcome

Topics: Adult; Aged; Antithyroid Agents; Drug Utilization; Female; Graves Disease; Health Care Surveys; Humans; Male; Methimazole; Middle Aged; United States

We reported a case of an 11-year-old girl admitted to our hospital for goiter, tachycardia, sweating, and visible and palpable thyroid. Thyroid function tests revealed a low thyrotropin level (<0.004 mIU/L) and elevated free thyroxine level (3.4 ng/ dL) diagnosed with Graves' disease and treated with methimazole. This anti-thyroid drug is recommended as first-line treatment in children with Graves' disease because it produces minor adverse effects with respect to propylthiouracil. She developed a lateralized exanthem mimicking figurate inflammatory dermatosis of infancy after methimazole therapy. The symptoms resolved after discontinuation of methimazole and treatment with an antihistamine and a corticosteroid. Furthermore, the treatment was changed to propylthiouracil without any adverse effects. According to current literature this is the first case of cutaneous figurate erythema related to methimazole, different from other well-known reactions such as skin eruption or urticaria.

Topics: Child; Exanthema; Female; Graves Disease; Humans; Inflammation; Methimazole; Skin Diseases; Thyroid Gland

Topics: Adult; Antithyroid Agents; Biomarkers; Electrocardiography; Graves Disease; Humans; Hypokalemic Periodic Paralysis; Male; Methimazole; Potassium Chloride; Thyrotoxicosis; Treatment Outcome; Turkey

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Japan; Male; Methimazole; Middle Aged; Organ Size; Severity of Illness Index; Thyroid Gland; Thyroxine; Treatment Outcome; Ultrasonography

Understanding the roles of circulating microRNAs (miRNAs) can provide important and novel information regarding disease pathogenesis and a patient's clinical condition. Circulating miRNAs, such as exosomal miRNA, may regulate various bioactivities related to intercellular communication. However, the circulation of miRNAs in Graves' disease (GD) in relation to disease activity has never been elucidated. This study aimed to identify circulating miRNAs in GD in relation to disease activity and whether their exosomes play a role in the pathogenesis of GD.. Circulating miRNAs were measured in serum obtained from seven intractable GD patients, seven GD patients in remission, and seven healthy controls using the miScript miRNA PCR Array. Altered miRNAs selected from array data were validated in 65 subjects. To investigate exosome biology, peripheral blood mononuclear cells (PBMCs) were incubated with exosomes isolated from the subjects' sera. mRNAs were quantified for cytokines using quantitative real-time polymerase chain reaction.. Circulating miR-23b-5p and miR-92a-39 were increased in GD patients in remission compared with intractable GD patients (p < 0.05). On the other hand, let-7g-3p and miR-339-5p were decreased in GD patients in remission compared with intractable GD patients (p < 0.05). Exosomes from intractable GD patients stimulated mRNA expression for IL-1β and TNF-α compared with GD patients in remission or healthy controls.. This study demonstrates that different levels of circulating miRNAs are associated with intractable GD. Moreover, serum exosomes of patients with intractable GD may activate immune cells, which may play an important role in GD pathogenesis.

Topics: Adult; Antithyroid Agents; Biomarkers; Cells, Cultured; Drug Resistance; Exosomes; Female; Graves Disease; Humans; Leukocytes, Mononuclear; Male; Methimazole; MicroRNAs; Middle Aged; Remission Induction; Severity of Illness Index

Resistin, belongs to cysteine-rich secretory protein, is mainly produced by circulating leukocytes, such as neutrophils monocytes and macrophages in humans. To date, few but controversial studies have reported about resistin concentrations in hyperthyroid patients, especially in Graves' disease (GD). We undertaked a controlled, prospective study to explore the serum resistin concentration in GD patients before and after -MMI treatment. In addition, we also investigated the main influencing factor on serum resistin level and discuessed the potential role of serum resistin plays in GD patients. 39 untreated GD (uGD) patients, including 8 males and 31 females, were enrolled in our investigation. All of these patients were prescribed with MMI treatment, in addition to 25 healthy controls. Anthropometric parameters and hormone assessment were measured. Enzyme-linked immunosorbent assay was used to detect serum resistin concentration in different stages of GD patients. Furthermore, neutrophil cell line NB4 with or without T3 treatment to detect the effect of thyroid hormones on resistin expression. The serum resistin level and neutrophil counts in untreated GD patients were significantly declined. And all of these parameters were recovered to normal after MMI treatment in ethyroid GD (eGD) and TRAb-negative conversion (nGD) patients. Resistin concentration exhibited a negative correlation with FT3 and FT4, but a positive correlation with absolute number of neutrophiles in uGD patients, whereas did not correlate with thyroid autoimmune antibodies and BMI. Neutrophile cell line, NB4, produced decreased expression of resistin when stimulated with T3. Our study showed a decrease of serum resistin level in GD patients and we suggested that the serum resistin might primarily secreted from circulating neutrophils and down-regulated by excessive thyroid hormones in GD patients.

Topics: Antithyroid Agents; Biomarkers; Case-Control Studies; Cell Line; Down-Regulation; Enzyme-Linked Immunosorbent Assay; Female; Graves Disease; Humans; Leukocytes; Male; Methimazole; Neutrophils; Prospective Studies; Resistin; Thyroxine; Triiodothyronine

Introduction and aims: The most recent hypothesis postulated that early restoration of euthyroid state in patients with Graves' disease changes the course of the disease and leads to better disease control. Therefore, we analyzed the efficacy of methimazole therapy and the course of disease in patients with restored euthyroidism and in patients with active disease on first control visit.. We included 63 patients with total T4 level >190 nmol/L or T3 >7 nmol/L and diffuse goiter with no previous episodes of hyperthyroidism. All patients received initially high doses of methimazole (60-80 mg) followed by a rapid dose reduction.. Ten percent of patients were excluded from the study due to side effects. Two different groups emerged after 5 weeks of treatment with same dose of methimazole: group 1 with active disease (48%) and group 2 with restored euthyroidism. Further controls on 12th, 24th and 68th weeks of treatment showed no difference in remission rates, number of iatrogenic hypothyroid episodes, and number of exacerbations between the two groups, regardless of methimazole dose. There was no association between age, gender, thyroid hormone levels, and remission and exacerbation rates.. Initially, higher methimazole doses with rapid progressive decrease to maintenance dose result in similar remission rates and are followed by similar incidence of adverse side-effect as fixed low dose therapy. Our results indicate that neither an early restoration of euthyroidism nor the difference in methimazole doses influence the course of Graves' disease.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Drug Administration Schedule; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Remission Induction; Thyroxine; Treatment Outcome; Triiodothyronine; Young Adult

Topics: Antithyroid Agents; Diagnosis, Differential; Female; Goiter; Graves Disease; Humans; Methimazole; Middle Aged; Neck; Thermography

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Hyperthyroidism; Liver Failure, Acute; Liver Transplantation; Methimazole; Propylthiouracil

Antithyroid drug (ATD)-induced severe hepatotoxicity is a rare but serious complication of ATD therapy. The characteristics of severe hepatotoxicity have been reported in only a small number of patients.. Ninety patients with ATD-induced severe hepatotoxicity presenting during a 13 year period (2000-2013) who were about to undergo nuclear medicine therapy with (131)I from a sample of 8864 patients with hyperthyroidism were studied, and the outcomes were evaluated.. The mean age of the patients with ATD-induced severe hepatotoxicity was 41.6±12.5 years (mean±standard deviation), and the female to male ratio was 2.2:1. The methimazole (MMI) dose given at the onset was 19.1±7.4 mg/day. The propylthiouracil (PTU) dose given at the onset was 212.8±105.0 mg/day. ATD-induced severe hepatotoxicity occurred in 63.3%, 75.6%, and 81.1% of patients within 4, 8, and 12 weeks of the onset of ATD therapy, respectively. The types of severe hepatotoxicity did not differ significantly between the MMI and PTU groups (p=0.188). The frequency of the cholestatic type in the MMI group (35.3%, 18/51) was higher than that in the PTU group (17.9%, 7/39), but these frequencies were not significantly different (p=0.069). The patients who were treated with (131)I received an average dose of 279.1±86.1 MBq (n=84). Therapy was successful in 60 of the 67 patients (89.6%). The success rate was equivalent (p=0.696) between the groups receiving MMI (91.7%, 33/36) and PTU (87.1%, 27/31).. Severe hepatotoxicity tends to occur within the first three months after the onset of ATD therapy. The type of ATD-induced severe hepatotoxicity did not differ between the MMI and PTU groups. (131)I therapy is an effective treatment approach for patients with ATD-induced severe hepatotoxicity.

Topics: Adult; Aged; Antithyroid Agents; Chemical and Drug Induced Liver Injury; China; Female; Graves Disease; Humans; Hyperthyroidism; Liver; Male; Methimazole; Middle Aged; Propylthiouracil; Retrospective Studies; Thyroxine; Treatment Outcome; Triiodothyronine; Young Adult

Topics: Adult; Antithyroid Agents; Chemical and Drug Induced Liver Injury; Diagnosis, Differential; Female; Graves Disease; Hepatitis, Autoimmune; Humans; Methimazole

Neonatal immune hyperthyroidism is a rare but potentially fatal condition. It occurs in 1-5% of infants born to women with Graves' disease (GD). In most of the cases it is due to maternal antibodies transferred from the mother into the fetal compartment, stimulating the fetal thyroid by binding thyrotropin (thyroid-stimulating hormone, TSH) receptor. We present a case of neonatal thyrotoxicosis due to maternal GD detected at 25 days of age and discuss the potential pitfalls in the diagnosis.

Topics: Antithyroid Agents; Female; Graves Disease; Humans; Infant, Newborn; Iodides; Male; Methimazole; Pregnancy; Pregnancy Complications; Propranolol; Thyrotoxicosis

To report a rare case of erythrocytosis that occurred in close association with Graves' hyperthyroidism. In order to explore the role of altered erythropoiesis in hyperthyroidism, factors related to erythropoiesis were studied in 30 patients with Graves' hyperthyroidism.. The relationship between thyroid hormone level and erythrocytosis was studied in a patient with Graves' hyperthyroidism and erythrocytosis. Later, 30 consecutive patients with proven untreated Graves' hyperthyroidism and 30 age- and sex-matched healthy controls were recruited. All patients received methimazole therapy. Erythrocyte indices, thyroid function, serum erythropoietin (EPO), and hypoxia-inducible factor-1α (HIF-1α) concentrations were measured before and after eight weeks of therapy.. In our case study, erythrocytosis relapsed with elevation of thyroid hormones. Methimazole or subsequent radioiodine therapy reduced the conditions of erythrocytosis and thyroid function returned to normal. In the clinical study, erythrocyte counts, serum erythropoietin, and HIF-1α levels in the hyperthyroid group were significantly higher than those in the control subjects. All subjects were grouped together for correlation analyses and HIF-1α was shown to correlate with total triiodothyronine (TT(3)), total thyroxine (TT(4)), and EPO levels. The correlation between EPO and TT(3) or TT(4) approached significance. After eight weeks of anti-thyroid drug therapy, a small but statistically significant increase in hemoglobin and erythrocyte count with a significant decrease in HIF-1α and EPO level was seen in hyperthyroid subjects.. Erythrocytosis may appear in patients with hyperthyroidism, and one possible mechanism is thyroid hormone-induced augmentation of HIF-1α, resulting in increased EPO levels.

Topics: Adolescent; Adult; Antithyroid Agents; Erythropoietin; Female; Graves Disease; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Methimazole; Middle Aged; Polycythemia; Young Adult

A 42-year-old woman visited our hospital with palpitations, excessive sweating, and finger tremors in March 2011. She was diagnosed with Graves' disease based on the following test results: thyroid stimulating hormone < 0.01 μU/ml, free thyroxine 6.15 ng/ml, and thyrotropin receptor antibody 7.8 U/ml. Treatment with methimazole 30 mg and propranolol 30 mg was started, and her thyroid function showed improvement. However, significant manic symptoms, irritability, hallucinations, and delusions were noted, and she was hospitalized for her own protection in May 2011. Although treatment with aripiprazole 24 mg and lithium 400 mg was started, the hallucinatory and delusional symptoms persisted, necessitating adjustment of the antipsychotics. Her psychiatric symptoms showed amelioration in July 2011 after improvement in her thyroid function, and she was discharged from our hospital. After discharge, her thyroid function remained normal with methimazole 10 mg, and administration of the antipsychotics was discontinued. Affective psychotic symptoms such as altered mood and activity are frequently observed in cases with Graves' disease, but there have been few reports describing cases with full-blown psychiatric disorders manifesting with features such as hallucinations and delusions as the chief symptoms requiring hospitalized treatment, as in the present case. In symptomatic psychosis associated with Graves' disease, prolonged psychiatric symptoms might develop, and close cooperation with psychiatrists is thus important.

Topics: Adult; Affective Disorders, Psychotic; Antipsychotic Agents; Antithyroid Agents; Aripiprazole; Bipolar Disorder; Delusions; Female; Graves Disease; Hallucinations; Humans; Lithium Compounds; Methimazole; Piperazines; Propranolol; Quinolones; Treatment Outcome

Topics: Adolescent; Affective Disorders, Psychotic; Antipsychotic Agents; Antithyroid Agents; Benzodiazepines; Bipolar Disorder; Delirium; Diagnosis, Differential; Female; Graves Disease; Humans; Methimazole; Olanzapine; Psychotic Disorders; Radionuclide Imaging; Thyroid Gland; Thyroidectomy

Control of thyroid function in hyperthyroid women during pregnancy is based on antithyroid drugs (ATD) [propylthiouracil (PTU) and methimazole (MMI)]. While a teratogenic effect has been suggested for MMI and, more recently, for PTU, a clear demonstration is still lacking. Aim of this study was to assess the safety of ATD during pregnancy.. A total of 379 pregnancies were retrospectively recruited in eight Italian Departments of Endocrinology and divided in five groups: (1) MMI-treated and euthyroid throughout pregnancy (n = 89); (2) MMI-treated and hyperthyroid on at least two occasions (n = 35); (3) PTU-treated women and euthyroid throughout pregnancy (n = 32); (4) PTU-treated women and hyperthyroid on at least two occasions (n = 20); and (5) non-ATD-treated (n = 203). Data on maternal thyroid function, miscarriages, type of delivery, neonatal weight, length and TSH, perinatal complications and congenital malformation were analyzed.. The gestational age at delivery, the rate of vaginal delivery, neonatal weight, length and neonatal TSH did not significantly differ among groups. In all groups, the rates of spontaneous miscarriage and of major congenital malformations were not higher than in the general population. No newborns were born with a phenotype similar to those described in the "MMI embryopathy".. While a clear demonstration of a teratogenic effect of MMI is currently lacking, it seems reasonable to follow the current guidelines and advice for PTU treatment in hyperthyroid women during the first trimester of pregnancy. Further, large and prospective worldwide studies will be needed to fully clarify the issue of ATD safety during pregnancy.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Hyperthyroidism; Infant, Newborn; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Propylthiouracil; Prospective Studies; Retrospective Studies

Topics: Adult; Antipsychotic Agents; Antithyroid Agents; Benzodiazepines; Female; Graves Disease; Humans; Methimazole; Olanzapine; Periventricular Nodular Heterotopia; Psychotic Disorders

Thyrotoxic periodic paralysis is an acute endocrine emergency characterized by hyperthyroidism, profound muscle weakness and/or paralysis, and hypokalemia that is not due to potassium deficiency. Typically described in young males of Asian descent, it is becoming increasingly recognized outside of this demographic group and is believed to be an underrecognized cause of symptomatic hypokalemia. Thyrotoxic periodic paralysis usually manifests as acute onset of symmetrical distal extremity weakness and is treated with careful potassium replacement and nonselective β-blockers. In this case, a 43-year-old African American woman with thyrotoxic periodic paralysis had recurrent lower extremity myopathy and acute respiratory failure precipitated by noncompliance with treatment for Graves disease.

Topics: Adrenergic beta-Antagonists; Adult; Antithyroid Agents; Black or African American; Female; Graves Disease; Humans; Hyperthyroidism; Hypokalemia; Methimazole; Muscle Weakness; Paralysis; Potassium; Propranolol; Respiratory Insufficiency

Graves' disease is the most prevalent cause of hyperthyroidism in children. The treatment commonly involves antithyroid therapy using a thionamide. We present a case of a 13-year-old girl with the antithyroid arthritis syndrome, presenting as a migratory polyarthritis, after the initiation of thionamide treatment for Graves' disease. Antithyroid arthritis syndrome warranted immediate cessation of thionamide. Improvement of the arthritis was seen in subsequent days. As there are no other reversible treatment modalities for Graves' disease in children, definitive treatment with radioactive iodine was needed to control the hyperthyroidism in this child. Antithyroid arthritis syndrome presenting as a migratory polyarthritis is a severe adverse effect of a common pediatric disease and should therefore be recognized by pediatricians.

Topics: Adolescent; Antithyroid Agents; Arthritis; Female; Graves Disease; Humans; Methimazole

Aim of this commentary is to summarize the salient literature news on the relationships between autoimmune thyroid diseases (ATDs) and either Down syndrome (DS) or Turner syndrome (TS).According to literature reports both Hashimoto's thyroiditis (HT) and Graves' disease (GD) are more frequent in children with DS or TS than in those without these chromosomopathies.An up-regulation of proinflammatory cytokines might be responsible for the enhanced susceptibility of TS children to ATDs, whereas a dysregulation of immune system may favor the development of ATDs in DS.In TS children biochemical presentation of HT is less severe than in peer controls. In both DS and TS GD picture at the time of diagnosis is not significantly different than in the pediatric general population.The evolution over time of GD in DS and TS does not differ from that observed in the pediatric general population, whereas the evolution of HT in both TS and DS is more severe than in girls without these chromosomopathies.. The association with TS or DS is able to affect both epidemiology and course of ATDs by conditioning: a) an increased susceptibility to these disorders; b) a less severe biochemical presentation and a more severe evolutive pattern of HT in TS girls; c) a more severe biochemical presentation and evolution of HT in DS patients.

Topics: Antithyroid Agents; Child; Comorbidity; Down Syndrome; Genetic Predisposition to Disease; Graves Disease; Hashimoto Disease; Humans; Methimazole; Turner Syndrome

Topics: Adolescent; Anaphylaxis; Antithyroid Agents; Drug Hypersensitivity; Female; Graves Disease; Humans; Hypersensitivity, Delayed; Methimazole; Skin Tests

To control hyperthyroidism due to Graves' disease, antithyroid drugs should be administered. Several studies have shown that exposure to methimazole (MMI) during the first trimester of pregnancy increases the incidence of specific congenital anomalies that are collectively referred to as MMI embryopathy. Congenital anomalies associated with exposure to propylthiouracil (PTU) have also recently been reported.. This study investigated whether substituting potassium iodide (KI) for MMI in the first trimester would result in a lower incidence of major congenital anomalies than continuing treatment with MMI alone. The cases of 283 women with Graves' disease (GD) were reviewed whose treatment was switched from MMI to KI in the first trimester (iodine group), as well as the cases of 1333 patients treated with MMI alone (MMI group) for comparison. Another major outcome of interest was the incidence of neonatal thyroid dysfunction. The subjects of the analysis of major congenital anomalies and neonatal thyroid dysfunction were live-born infants.. The incidence of major anomalies was 4/260 (1.53%) in the iodine group, which was significantly lower than the incidence of 47/1134 (4.14%) in the MMI group. Two neonates in the iodine group had anomalies consistent with MMI embryopathy (0.8%), as opposed to 18 neonates in the MMI group (1.6%). None of the neonates exposed to KI had thyroid dysfunction or goiter.. Substituting KI for MMI as a means of controlling hyperthyroidism in GD patients during the first trimester may reduce the incidence of congenital anomalies, at least in iodine-sufficient regions.

Topics: Abnormalities, Drug-Induced; Adult; Antithyroid Agents; Drug Substitution; Female; Graves Disease; Humans; Incidence; Japan; Methimazole; Potassium Iodide; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Retrospective Studies; Thyrotropin; Thyroxine; Treatment Outcome; Triiodothyronine

Antithyroid medications such as methimazole and propylthiouracil are commonly used to treat hyperthyroid disorders. Thionamide-induced agranulocytosis is a rare but life-threatening potential side effect of these medicines. In addition to routine monitoring of blood counts, healthcare workers caring for patients on such medication need to be mindful of atypical presentations of acute agranulocytosis throughout the treatment course. The manifestations of underlying infectious aetiologies can be mistaken for more common illness and result in delayed diagnosis. We present a case of a 41-year-old woman receiving methimazole for Grave's disease, who presented to outpatient care with high fever, pharyngitis, lymphadenopathy and jaundice. After failing to respond to empiric antibiotics, a diagnosis of neutropenia was made and the patient was admitted for inpatient care with eventual recovery following a course of granulocyte colony-stimulating factor. A diagnosis of atypical Bartonella henselae was eventually made and treated appropriately. The patient was later discharged and underwent radioactive iodine ablation.

Topics: Adult; Agranulocytosis; Anti-Bacterial Agents; Antithyroid Agents; Bartonella henselae; Doxycycline; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Immunologic Factors; Insect Bites and Stings; Methimazole; Treatment Outcome

Low doses of antithyroid drugs (ATD) for extended periods may be an alternative for Graves' disease (GD) patients who relapse after a course of ATD.. Patients with GD relapse (n = 238) after discontinuation of ATD therapy for 12-24 months were retrospectively analyzed in a nonrandomized study. Radioiodine (RAI) treatment and L-thyroxine replacement was used in 114 patients, and a low dose of methimazole (MMI; 2.5-7 mg/daily) was used in 124 patients. Thyroid dysfunction, Graves' ophthalmopathy (GO) evolution, quality of life (QoL), and body weight were evaluated during the follow-up.. The mean follow-up was 80.8 ± 35.3 months for the RAI group, and 71.3 ± 40.3 months for the low-dose MMI group. No notable side effects were observed in either group. Thyroid dysfunction was predominant in the RAI group (p < 0.001), and euthyroidism was more common in the MMI group (p < 0.001). GO deterioration was mainly evaluated by clinical activity score (CAS)--it was higher in the RAI group (p < 0.0005) over all periods of follow-up. Multivariate logistic analysis showed that RAI treatment was associated with no improvement in CAS during follow-up (24 months: OR = 3.51 [CI 1.02-12.03], p < 0.05; 36 months: OR = 8.46 [CI 1.47-48.58], p < 0.05; 48 months: OR = 19.52 [CI 1.70-223.10], p < 0.05; 60 months: OR = 21.1 [CI 1.5-298], p < 0.05). Kaplan-Meier survival analysis confirmed this finding (p < 0.0003). Assessment of QoL using the Short Form Health Survey's 36 parameters in stable euthyroid patients (at least six months) was similar in both groups. The RAI group patients gained more weight (p < 0.005), particularly after 24 months of follow-up.. The use of low doses of MMI is efficient and safe, and offers better outcomes for GO than RAI treatment. Prolonged low doses of MMI may be an alternative choice for relapsed GD patients, particularly for GO patients or for patients who refuse a definitive treatment.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Graves Ophthalmopathy; Hormone Replacement Therapy; Humans; Iodine Radioisotopes; Maintenance Chemotherapy; Male; Methimazole; Middle Aged; Recurrence; Retrospective Studies; Thyroxine; Treatment Outcome

Therapeutic plasma exchange (TPE) is one possible treatment for patients resistant to conventional antithyroid drugs or requiring urgent attention for thyrotoxicosis. We report a 35-yr-old man with thyrotoxicosis, ultimately attributed to Graves' disease in whom antithyroid drug used initially was soon discontinued, due to abnormal liver function, and replaced by Lugol's solution. Three weeks later, an escape phenomenon (to Lugol's solution) was apparent, so we performed TPE to control the thyrotoxicosis. Two courses of TPE by a centrifugal type machine resulted in diminished levels of thyroid hormone levels, which then rebounded after another two courses of membrane filtration type TPE. However, the patient could be treated with radioactive iodine therapy without any complications at present.

Topics: Adult; Antithyroid Agents; Cetirizine; Graves Disease; Hepatitis B, Chronic; Humans; Iodides; Iodine Radioisotopes; Male; Methimazole; Plasmapheresis; Thyroid Gland; Thyrotoxicosis

Antithyroid drug treatment (ATDT) effectively achieves euthyroidism in patients with Graves' disease (GD). However, apparently successful treatment may be followed by relapse. We investigated the outcome of ATDT in Chinese patients with GD to identify predictive features of relapse.. In total, 133 patients with mild to moderate goiter were included in this analysis. All patients received methimazole for 12 to 40 months and were subsequently followed up for at least 1 year. Lasting remission was defined as the presence of clinical and laboratory features of euthyroidism for ≥ 1 year after stopping methimazole.. Most patients (118 of 133, 88.7%) remained in remission after the follow-up period; 15 patients (11.3%) developed relapse. A history of GD, larger goiter at the time of drug withdrawal, a positive thyroid-stimulating antibody titer and restauration of low thyroid-stimulating hormone levels during the maintenance period were related to a subsequent risk of relapse according to stepwise logistic regression analysis results. However, other clinical and biological features (age, sex, initial goiter, ophthalmopathy, thyroxine and triiodothyronine levels and thyroglobulin antibody and thyroid microsomal antibody titers) did not reach statistical significance.. Regular, individualized ATDT achieved an 88.7% remission rate in Chinese patients with GD. The features associated with probable relapse were a history of GD, larger goiter at the time of drug withdrawal, a positive thyroid-stimulating antibody titer at the time of drug withdrawal and redevelopment of low thyroid-stimulating hormone levels during the maintenance period.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Autoantibodies; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Prospective Studies; Recurrence; Thyrotropin; Thyroxine; Treatment Outcome; Triiodothyronine

Coexisting of Graves' disease and functioning struma ovarii is a rare condition. Although the histology of struma ovarii predominantly composed of thyrocytes, the majority of the patients did not have thyrotoxicosis. The mechanism underlying the functioning status of the tumor is still unclear but the presence of thyroid stimulating hormone receptor (TSHR) is thought to play a role. Here we describe the patient presentation and report the TSHR expression of the tumor.. A 56-year old Asian woman presented with long standing thyrotoxicosis for 23 years. She was diagnosed with Graves' disease and thyroid nodules. She had bilateral exophthalmos and had high titer of plasma TSHR antibody. Total thyroidectomy was performed and the histologic findings confirmed the clinical diagnosis. The patient had persistent thyrotoxicosis postoperatively. Thyroid uptake demonstrated the adequacy of the thyroid surgery and the whole body scan confirmed the presence of functioning thyroid tissue at pelvic area. The surgery was scheduled and the patient had hypothyroidism after the surgery. The pathological diagnosis was struma ovarii at right ovary. We performed TSHR staining in both the patient's struma ovarii and in 3 cases of non-functioning struma ovarii. The staining results were all positive and the intensity of the TSHR staining of functioning struma ovarii was the same as that in other cases of non-functioning tumors, suggesting that the determinant of functioning struma ovarii might be the presence of TSHR stimuli rather than the intensity of the TSHR in the ovarian tissue.. In patients with Graves' disease with persistent or recurrent thyrotoxicosis after adequate ablative treatment, the possibility of ectopic thyroid hormone production should be considered. TSHR expression is found in patients with functioning and non-functioning struma ovarii and cannot solely be used to determine the functioning status of the tumor.

Topics: Antithyroid Agents; Female; Graves Disease; Humans; Hysterectomy; Methimazole; Middle Aged; Ovarian Neoplasms; Ovariectomy; Salpingectomy; Struma Ovarii; Thyroidectomy; Thyrotoxicosis; Treatment Outcome

It is known that Hashimoto's thyroiditis (HT) may progress to Graves' disease (GD) and that this phenomenon may be more frequent in the patients with Down syndrome (DS).. To shed light on the relationships between Down syndrome (DS) and metamorphic thyroid autoimmunity.. We reconstructed the conversion process from HT to GD in 12 DS children. All the data recorded at HT diagnosis and throughout the time interval from entry to GD presentation were retrospectively taken from patients' files, as well as those recorded at GD diagnosis and during the subsequent evolution. From GD diagnosis all patients underwent methimazole treatment, at a dose that was adjusted on the basis of clinical findings and thyroid tests.. Time interval between HT and GD was not different in the seven patients who received during that time a L-thyroxine (L-T4) treatment than in those who were not treated. After methimazole onset all patients exhibited a prolonged remission of hyperthyroidism. In 8/12 patients this treatment is still being continued 2-7 years after its initiation. The mean methimazole dosage needed to maintain euthyroidism in these eight patients was 0.12 ± 0.02 mg/kg/day. In the remaining four patients methimazole was withdrawn from 1.9 to 7 years after its initiation and no relapses were recorded 2.0-2.1 years after its withdrawal. These patients developed, 0.1-0.3 years after methimazole withdrawal, a picture of overt hypothyroidism and needed treatment with L-T4, that is now being continued. No patients needed non-pharmacological therapies.. 1) DS children might be incline to manifest over time a phenotypic metamorphosis from HT to GD and to subsequently fluctuate from hyperthyroidism to hypothyroidism; 2) in DS GD may have a mild biochemical and clinical course.

Topics: Adolescent; Antithyroid Agents; Autoimmunity; Child; Child, Preschool; Down Syndrome; Female; Graves Disease; Hashimoto Disease; Humans; Male; Methimazole; Retrospective Studies; Thyroid Gland; Young Adult

To observe the improvement of thyroid function and changes of Akt, p-Akt, mammalian target of rapamycin (mTOR), and para-mTOR (p-mTOR) expression in Graves' disease (GD) mice after intervened by Jiakangning Capsule (JC), and to explore possible mechanism for JC in treating GD.. GD model was established by immunizing female BALB/c mice with thyroid stimulating hormone receptor A subunit (Ad-TSHRα-289). Totally 70 successfully modeled mice were divided into the model group (n =20), the JC intervened group (n =25), the Methimazole Tablet intervened group (n =25) according to random digit table. A normal control group (n =15) and a vehicle control group (n =20, injected with Ad-null) were also set up. Mice in the JC intervened group were administered with JC suspension at the daily dose of 1. 5 g/kg by gastrogavag. Mice in the Methimazole intervened group were administered with Methimazole suspension at the daily dose of 2. 5 g/kg by gastrogavage. Equal volume of normal saline was administered to mice in the rest 3 groups by gastrogavage. All intervention lasted for 5 weeks. Six mice were selected from each group to observe pathological changes of thyroid tissues. Serum levels of thyroxine (T4), triiodothyronine (T3), thyroid stimulating hormone (TSH), and thyrotropin receptor antibody (TRAb) were analyzed by radioimmunoassay. Expression levels of Akt, p-Akt, mTOR, and p-mTOR in thyroid tissues were etermined by Western blot.. (1) The thyroid gland in the GD model group showed proliferative changes, with enlarged follicles of various sizes. Interstitial stroma was filled with blood vessels. Structures of thyroid tissues in the JC intervened group and the Methimazole intervened group were significantly restored, and follicular hyperplasia was relieved. (2) Compared with the normal control group and the vehicle control group, levels of TRAb, T4, and T3 increased; ratios of P-Akt/β-actin, p-Akt/Akt, p-mTOR/β-actin, and p-mTOR/mTOR also increased in the model group (all P <0. 01). Compared with the model group, levels of TRAb, T4, and T3 decreased in the JC intervened group and the Methimazole intervened group (P <0. 01); ratios of p-mTOR/β-actin and pmTOR/mTOR decreased in the JC intervened group (P <0.01); ratios of P-Akt/β-actin, p-Akt/Akt, p-mTOR/β-actin, and p-mTOR/mTOR decreased in the Methimazole intervened group (P <0. 05, P <0. 01). Conclusion JC could reduce thyroid hormonc levels of GD mice and lower expression levels of mTOR, and its mechanism for improving thyroid function of GD mice might be associated with this influence.

Topics: Actins; Animals; Capsules; Disease Models, Animal; Drugs, Chinese Herbal; Female; Graves Disease; Methimazole; Mice; Mice, Inbred BALB C; Receptors, Thyrotropin; Signal Transduction; Thyrotropin; Thyroxine; TOR Serine-Threonine Kinases; Triiodothyronine

Topics: Adult; Antithyroid Agents; Breast Neoplasms; Carcinoma, Ductal, Breast; Comorbidity; Female; Graves Disease; Humans; Methimazole; Remission Induction; Thyroxine; Triiodothyronine

The management of Graves' disease (GD) in children is associated with a dilemma. Although the established initial treatment for GD in children is antithyroid drug (ATD) treatment, the remission rate in children is said to be lower than in adults, and severe propylthiouracil-induced adverse events (AEs) are an issue. Definitive treatments are effective, but they often result in permanent hypothyroidism and the need for lifelong T4 supplementation.. The objective of this study was to investigate the outcome of ATD treatment, identify significant predictors of a remission, and evaluate the AEs of ATDs in a large pediatric population of GD patients.. We retrospectively assessed the reports of 1138 children up to 18 years of age who had been newly diagnosed with GD at our institution between 1982 and 2006. Their median age at diagnosis was 16 years (range: 3-18 years), and there were 995 females and 143 males. All patients were initially treated with an ATD. Remission was defined as maintenance of euthyroidism for more than 12 months after discontinuing ATD treatment and the absence of any relapses during the follow-up period.. Of the 1138 patients, 723 continued on ATD treatment, 271 underwent surgery or radioactive iodine therapy, and 144 dropped out. Of the 723 patients who continued on ATD treatment, ATD treatment was subsequently ongoing in 84 and was discontinued in 639 (median duration of treatment: 3.8 years; range: 0.3-24.8 years). Of the 639 patients who discontinued ATD treatment, 334 (46.2%) achieved a remission, 247 (34.2%) experienced a relapse, and 58 (8.0%) dropped out. The cumulative remission rate increased with the duration of ATD treatment up until five years. No significant predictors of a remission were identified. The overall incidences of AEs associated with methimazole and propylthiouracil were 21.4% and 18.8% respectively. There were no fatal AEs in our population. While most AEs (91.6%) occurred within the first three months of ATD treatment, 2.7% developed more than two years after the start of ATD treatment. Seven of the eight late-onset AEs were induced by propylthiouracil.. Long-term ATD treatment is a useful treatment option for GD in children.

Topics: Adolescent; Antithyroid Agents; Child; Child, Preschool; Female; Graves Disease; Humans; Male; Methimazole; Propylthiouracil; Recurrence; Remission Induction; Retrospective Studies; Treatment Outcome

Graves' disease is the most common reason of hyperthyroidism in children. Graves' disease with accompanying functioning nodules is defined as Marine-Lenhart syndrome. This syndrome has not been described in children before. Here, a 15-year-old girl with Graves' disease and a coexisting cold nodule is presented. A thyroid scan showed diffuse uptake of Tc-99m pertechnatate in both lobes and decreased uptake in accordance with the left lobe nodule. The nodule was histologically diagnosed as benign. The patient was diagnosed with type 1 diabetes mellitus and polyglandular autoimmune syndrome during clinical follow-up. The differential diagnoses of Graves' disease with coexisting nodules should include the Marine-Lenhart syndrome. Treatment options should be determined taking this rare condition into account.

Topics: Adolescent; Antithyroid Agents; Diabetes Mellitus, Type 1; Female; Graves Disease; Humans; Iodine Radioisotopes; Methimazole; Polyendocrinopathies, Autoimmune; Syndrome

Agranulocytosis is a serious adverse effect of antithyroid drugs (ATDs) and mainly develops within three months after the start of uninterrupted ATD treatment. Agranulocytosis can also develop for the first time after interruption and subsequent resumption of the same ATD treatment. However, little is known with regard to agranulocytosis that develops after resumption of the same ATD treatment.. We investigated the characteristics of patients who developed agranulocytosis during their second or later course of ATD treatment.. A total of 81 patients at our hospital were diagnosed with ATD-induced agranulocytosis. In 14 of the cases (methimazole (MMI), n=10; propylthiouracil (PTU), n=4), the agranulocytosis developed for the first time in the context of the second or later course of treatment with the same ATD; those patients were designated the "resumed group." The 35 patients (MMI, n=28; PTU, n=7) who developed agranulocytosis during their first uninterrupted course of ATD therapy were designated the "first group.". The median total duration of ATD treatment before the diagnosis of agranulocytosis was 559 days (range 86-1775 days), and the median interval between the final day of the previous course and the first day of the course in which agranulocytosis was diagnosed was 916.5 days (range 153-8110 days). There were no cases in which agranulocytosis developed when treatment with the same ATD was resumed after discontinuation for less than five months. The difference between the start of ATD treatment in the course in which agranulocytosis was diagnosed and the time interval at which agranulocytosis was diagnosed was similar when comparing the first group and the resumed group (39 (20-98) days in the first group vs. 32.5 (21-95) days in the resumed group; n.s.). There were no significant differences between the groups in terms of granulocyte count at the time agranulocytosis was diagnosed, mortality rate, or the interval between the diagnosis of agranulocytosis and recovery.. When ATD treatment is resumed, patient follow-up is essential in order to monitor for the development of agranulocytosis.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Antithyroid Agents; Drug Monitoring; Electronic Health Records; Female; Granulocytes; Graves Disease; Hospitals, Urban; Humans; Japan; Leukopoiesis; Male; Methimazole; Middle Aged; Propylthiouracil; Time Factors; Young Adult

The role of T helper 17 (Th17) and T regulatory cells (Treg) in the pathogenesis of Graves' disease (GD) remains uncertain. The influence of methimazole (MMI) on the human immune system is still poorly understood. The aim of the present research was to assess changes in the frequencies of peripheral blood Th17 and Treg cells during GD treatment in the group of teenagers. The frequencies of Th17 and Treg were measured by flow cytometry in 60 adolescents at the time of GD diagnosis and after achieving MMI-induced euthyreosis. The control group consisted of 20 healthy volunteers. Lower percentages and absolute counts of Treg cells were found in the study group before the treatment in comparison with healthy controls (p = 0.032 and p = 0.006, respectively). Treatment with MMI caused an increase in the percentages and absolute counts of Treg lymphocytes (p = 0.037 and p = 0.007). After the treatment, no clinically significant differences in Treg cells between GD patients and controls were found. Higher absolute counts of Th17 lymphocytes were found in hyperthyroid adolescents before the treatment initiation and after achieving euthyreosis than in healthy individuals (p = 0.0001 and p = 0.047). Treatment with MMI caused a significant decrease in the percentages and absolute counts of Th17 lymphocytes (p = 0.047 and p = 0.043). The present study demonstrates that both Th17 and Treg cells might play a role in the pathogenesis of GD. Increased percentage of Treg after MMI therapy seems a predictor of response to anti-hypertensive treatment as it is associated with the normalization of thyroid hormone levels.

Topics: Adolescent; Antigens, Surface; Antithyroid Agents; Child; Female; Graves Disease; Humans; Immunophenotyping; Lymphocyte Count; Male; Methimazole; Recurrence; T-Lymphocytes, Regulatory; Th17 Cells; Treatment Outcome

Iodine is beneficial against Graves' thyrotoxicosis, though its effects are short-lived. However, its long-term effectiveness as an initial therapy has not been fully elucidated. Here, we compared the effects of potassium iodine (KI) and methimazole (MMI) in Graves' thyrotoxicosis and on thyrotropin receptor antibody (TRAb) levels. Between 2008 and 2011, 293 patients with untreated Graves' disease visited the outpatient clinic of Juntendo University. Of these, 227 patients were treated with MMI and 30 treated with KI as the initial therapy. To compare the effects of KI and MMI, we identified patients with similar probabilities of receiving MMI or KI using propensity score (PS) analysis based on the observed clinical features. PS matching created 20 matched pairs of patients with Graves' disease treated with MMI and KI. The baseline characteristics of post-matched patients treated with MMI were comparable to those treated with KI (FT3; 7.16 ± 2.30, 6.56 ± 1.85 pg/ml, FT4; 2.57 ± 0.79, 2.49 ± 0.70 ng/dl, respectively). The initial dose of MMI was 14.0 ± 8.2 mg/day and that of KI was 53.6 ± 11.7 mg/day. Three patients of the KI group did not respond to the monotherapy, requiring the inclusion of antithyroid drugs. One patient on MMI developed moderate skin eruption, but continued the treatment. Patients who continued the initial treatment showed significant and comparable reductions in FT4, FT3 and TRAb by MMI as well as by KI at the end of 12-month treatment. Although patients were limited to mild untreated Graves' disease thyrotoxicosis, KI offers a possible alternative initial treatment for this condition.

Topics: Adult; Aged; Antithyroid Agents; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Potassium Iodide; Treatment Outcome; Young Adult

Epidemiological studies on the association between Turner syndrome (TS) and Graves' disease (GD) are sparse and no studies are available on the clinical course of GD in TS.. To retrospectively investigate the GD prevalence in children and young adults with TS and to compare the GD course in patients with or without TS who were followed up for 4.1 ± 0.6 and 4.5 ± 3.7 years, respectively.. The prevalence of GD in 408 TS patients was evaluated; presentation and evolution of GD under therapy were evaluated both in 7 patients with TS (group A) and in 89 patients without TS (group B).. (a) The prevalence of GD in TS patients was 1.7%; (b) GD in TS was not associated with a specific karyotype; (c) with respect to group B patients, those of group A exhibited at presentation more advanced age, a lower fT4 level and more frequent association with other autoimmune diseases, and (d) the clinical course under methimazole therapy was not different in the two groups.. The prevalence of GD in children and young adults with TS is 1.7% and in TS patients, GD presents later and its clinical course is not different than in those without TS.

Topics: Adolescent; Adult; Antithyroid Agents; Child; Child, Preschool; Comorbidity; Female; Graves Disease; Humans; Infant; Methimazole; Prevalence; Retrospective Studies; Turner Syndrome; Young Adult

To evaluate clinical and biochemical features of 115 children (98 female, mean age 11.3 ± 3.5 years) with Graves disease to identify possible determinants of remission.. We defined as positive outcome the improvement of clinical features and restoration of euthyroidism or induction of hypothyroidism after antithyroid drug (ATD) therapy and as negative outcome hyperthyroidism persistent over 2 years of ATD therapy or relapsed after ATD withdrawal.. Thirty-eight children (33%) had remission after 2 years of ATD therapy. The absence of goiter at diagnosis was correlated with a better outcome. Median thyroid-stimulating hormone receptor antibody (TRAb) values at diagnosis were significantly lower in patients with a positive outcome (P = .031). We found a significant relationship between the time required for TRAb normalization and the patient outcome; TRAb normalization within 1 year from time of Graves disease diagnosis was significantly more common among patients with a positive outcome (P < .0001), and the mean time for TRAb normalization was significantly shorter in patients with a positive outcome (1.3 ± 0.8 years) compared with that observed in patients with a negative outcome (2.5 ± 2.7 years, P = .026).. Although no clinical variable investigated is constantly associated with a definite outcome, the absence of goiter at the diagnosis may be associated with a better outcome. The most relevant predictor of Graves disease outcome was serum level; TRAb at time of Graves disease diagnosis less than 2.5 times the upper reference limit, TRAb normalization during ATD, and TRAb normalization timing each may predict positive outcomes. These results may have a role in the empiric clinical management of pediatric patients with Graves disease.

Topics: Adolescent; Antithyroid Agents; Biomarkers; Child; Drug Administration Schedule; Drug Monitoring; Female; Follow-Up Studies; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Logistic Models; Male; Methimazole; Radioimmunoassay; Recurrence; Remission Induction; Retrospective Studies; Treatment Outcome

Topics: Adolescent; Antithyroid Agents; Chronic Disease; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Vomiting

Graves hyperthyroidism is commonly seen in clinical practice and Takotsubo stress cardiomyopathy is an increasingly recognized cardiac complication of physical or emotional stress. We report the rare case of a patient with Graves hyperthyroidism that was complicated by severe biventricular takotsubo cardiomyopathy, which was demonstrated on heart catheterization. After appropriate pharmacologic treatment of her hyperthyroidism, she had complete resolution of her cardiomyopathy.

Topics: Adult; Carbazoles; Carvedilol; Drug Therapy, Combination; Electrocardiography; Female; Graves Disease; Humans; Hyperthyroidism; Lisinopril; Methimazole; Propanolamines; Takotsubo Cardiomyopathy; Thyroid Function Tests; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Dysfunction, Right

Topics: Adult; Apgar Score; Eyelids; Female; Fetal Growth Retardation; Graves Disease; Heart Rate, Fetal; Humans; Infant, Newborn; Male; Methimazole; Potassium Iodide; Pregnancy; Propranolol; Thyrotoxicosis; Thyroxine; Ultrasonography; Weight Loss

A 26-year-old Hispanic man with no significant medical history presented to our emergency room with gradual onset weakness of his lower extremities. He was haemodynamically stable and examination revealed loss of motor function in his lower limbs up to the level of hips. Laboratory data revealed hypokalaemia. The patient was started on potassium supplementation and he recovered his muscle strength. Differential diagnosis included familial hypokalaemic periodic paralysis and thyrotoxic periodic paralysis (TPP). Further investigations revealed a low thyroid-stimulating hormone and high free thyroxine levels. Radio iodine 123 scan revealed an enhanced homogeneous uptake in the thyroid suggesting Graves' disease. Thyroid stimulating antibodies were also found to be elevated. The patient was started on methimazole and propranolol and he never had another attack of TPP even at 1 year follow-up.

Topics: Adult; Diagnosis, Differential; Graves Disease; Hispanic or Latino; Humans; Hypokalemia; Hypokalemic Periodic Paralysis; Immunoglobulins, Thyroid-Stimulating; Iodine Radioisotopes; Male; Methimazole; Muscle Strength; Muscle Weakness; Potassium; Propranolol; Thyroid Gland; Thyrotoxicosis; Thyrotropin; Thyroxine

The aim of this study was to evaluate clinical manifestations, laboratory findings, and effects of antithyroid drugs in younger children with Graves' disease (GD).. A retrospective and collaborative study.. Nine facilities in Chiba prefecture, Japan.. We analyzed 132 children and adolescents with GD. The subjects were divided according to the median age into a group of young children (group I, 4.1-12.4 years, n=66) and an adolescent group (group II, 12.5-15.9 years, n=66).. Clinical manifestations, laboratory findings, incidence of adverse effects, and remission rates 5 years after initial therapy were assessed.. The mean height SD score of group I (1.0) was higher than that of group II (0.3, p<0.001). The mean BMI SD score of group I (-0.7) was lower than that of group II (-0.3, p<0.05). The most common presentations were goiter, sweating, and hyperactivity in group I, whereas the most common presentations were goiter, sweating, and easy fatigability in group II. Hyperactivity was more frequent in group I (56.7%) than in group II (37.9%, p<0.05). Liver dysfunction appeared more often in group I (14.3%) than in group II (1.9%, p<0.05). There was no difference in the appearance of adverse effects between the two groups. The remission rate was slightly lower in group I (23.1%) than in group II (31.3%), but was not significant.. Thyrotoxicosis had more influence on the growth and liver function in younger children.

Topics: Adolescent; Antithyroid Agents; Child; Child, Preschool; Female; Graves Disease; Growth; Humans; Japan; Liver; Male; Methimazole; Propylthiouracil; Retrospective Studies; Thyrotoxicosis; Treatment Outcome

Acute pericarditis is either dry, fibrinous or effusive, independent of its aetiology. A case is presented involving a 44-year-old man with acute pericarditis. The cause was established to be an aggravation of Graves' disease due to non-compliance with treatment. Pericarditis is an uncommon cardiac complication of Graves' disease and is associated with more recurrent episodes when not detected. Pharmacological treatment should include anti-inflammatory drugs in combination with treatment for hyperthyroidism. The specific pathophysiological link between the two conditions is still to be elucidated.

Topics: Adult; Antithyroid Agents; Electrocardiography; Graves Disease; Humans; Male; Medication Adherence; Methimazole; Pericarditis

Antithyroid drugs are usually considered first-line therapy for management of pediatric Graves' disease because they avoid permanent hypothyroidism, provide a chance for remission, and are less invasive than the alternatives of thyroidectomy or radioactive iodine. Methimazole (MMI) is the only antithyroid drug recommended in pediatrics due to the risk of propylthiouracil-induced liver toxicity. Allergic reactions with MMI occur in up to 10% of patients and, when mild, can be managed with concurrent antihistamine therapy. Guidelines recommend discontinuation of MMI with serious allergic reactions. We present the case of an adolescent girl with Graves' disease and a serious allergic reaction after starting MMI whose family refused radioactive iodine and was reluctant to proceed to surgery. Antihistamine therapy was successfully used to allow continued treatment with MMI. This case demonstrates extension of management guidelines for minor cutaneous allergic reactions to MMI, through the use of antihistamines for a serious allergic reaction, allowing us to continue MMI and provide treatment consistent with the family's preferences and values.

Topics: Adolescent; Antithyroid Agents; Diphenhydramine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Hypersensitivity; Female; Graves Disease; Histamine H1 Antagonists; Humans; Methimazole; Treatment Outcome

Myopathy is a known complication of hypothyroidism, commonly characterized by an elevation in Creatine Kinase (CPK) due to increase capillary permeability proportional to the hypothyroid state. Thyroid hormone is important for the expression of fast myofibrillar proteins in the muscle. In hypothyroidism the expression of these proteins are deficient and there is an increase accumulation of slow myofibrillar proteins. A rapid or abrupt descend in thyroid hormones caused by radioiodine therapy after prolonged hyperthyroidism can lead to local hypothyroid state within the muscle tissue, resulting in CPK elevation and hypothyroid myopathy. Hormone replacement leads to resolution of symptoms and normalization of muscle enzymes serum levels.

Topics: Diagnosis, Differential; Edema; Electromyography; Emergencies; Female; Graves Disease; Hormone Replacement Therapy; Humans; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Magnetic Resonance Imaging; Methimazole; Muscle Cramp; Muscle Weakness; Propranolol; Reflex, Abnormal; Thyroid Hormones; Thyroxine; Young Adult

Almost all cases of hyperthyroidism in children result from Graves' disease (GD). Recent studies have confirmed a significant role of T regulatory cells (Tregs) in the development of autoimmune diseases. However, the interactions between T cell responses and Treg proliferation in GD are still poorly understood. The aim of this study was to assess the proliferation of Treg cells (Tregs) and CD3+ T lymphocytes isolated from 50 children with GD before and after treatment with the thyreostatic drug methimazole (MMI). The proliferation rates, measured by methyl-3H-thymidyne incorporation, of CD3+ cells and Tregs stimulated with mitogen phorbol 12-myristate 13-acetate (PMA) were compared with those of unstimulated cells. The proliferation rates of both PMA-stimulated and unstimulated CD3+ cells prior to treatment with MMI were significantly higher than after treatment. Simultaneously, the proliferation rates of both PMA-stimulated and unstimulated Tregs were significantly lower before MMI treatment. Moreover, we observed higher cell proliferation rates of unstimulated and PMA-stimulated Tregs before the initiation of MMI therapy and after treatment in patients who had no relapse of hyperthyroidism. There was a positive correlation between the CD3+ cells proliferation rate before MMI treatment and fT3, as well as fT4 concentration in peripheral blood. The proliferation rates of CD3+ T cells before and after MMI treatment positively correlated with the TSI index. Thus, children suffering from Graves' disease presented lower Tregs proliferative potential compared with CD3+ T cells. Cocultures of CD3+ T cells and Tregs showed that Tregs were not capable of efficiently inhibiting the proliferation of CD3+ T cells in GD patients. Conclusions. MMI treatment reduced the proliferative activity of CD3+ T cells in pediatric GD patients and increased the proliferation rate of Tregs. We suggest that Treg cells that are partly dysfunctional in GD disease are probably suppressed by CD3+ T cells and that methimazole exerts some immunomodulatory effects.

Topics: Adolescent; Antithyroid Agents; Case-Control Studies; CD3 Complex; Cell Proliferation; Cells, Cultured; Child; Female; Graves Disease; Humans; Lymphocyte Count; Methimazole; T-Lymphocytes; T-Lymphocytes, Regulatory

Brown adipose tissue (BAT) is important for energy expenditure through thermogenesis, although its regulatory factors are not well known in humans. There is evidence suggesting that thyroid hormones affect BAT functions in some mammals, but the effects of thyroid hormones on BAT activity in humans are still unclear. The aim of this study was to investigate the effects of thyroid hormones on glucose metabolism of BAT and other organs in humans.. Nine Graves' disease-caused hyperthyroid patients who were newly diagnosed and untreated were studied. Putative brown adipose tissue activity was determined by the integrated ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron-emission tomography and computed tomography (PET-CT). All hyperthyroid patients were treated with methimazole and had been monitored until their symptoms disappeared and thyroid hormone levels returned to normal. At the end, a second PET-CT scan was performed. The average follow-up period was 77 days. Meanwhile, compared with a group of seventy-five brown adipose tissue-negative controls, thyroid hormones of seventy-five BAT-positive healthy subjects were measured.. Active brown adipose tissue was not present in any of the hyperthyroid patients. However, one patient with normalized thyroid function showed active BAT after therapy. The free T3 levels and free T4 levels were significantly lower in the 75 BAT-positive subjects than in the BAT-negative subjects. All hyperthyroid patients showed symmetrically increased uptake of fluorodeoxyglucose in skeletal muscles before treatment, whereas, the standardized uptake value was substantially decreased after treatment.. Abnormally high circulating thyroid hormone levels may not increase brown adipose tissue activity, which may be limited by the increased obligatory thermogenesis of muscle in adult humans.

Topics: Adipose Tissue, Brown; Adiposity; Adult; Antithyroid Agents; Energy Metabolism; Female; Fluorodeoxyglucose F18; Follow-Up Studies; Glucose; Graves Disease; Humans; Male; Methimazole; Middle Aged; Muscle, Skeletal; Positron-Emission Tomography; Thyroid Hormones; Tomography, X-Ray Computed; Whole Body Imaging; Young Adult

We report a 40-year-old woman with onset of oligoarthritis shortly after initiating treatment with methimazole for Graves disease. Over the course of 7 years, her arthritis became progressively severe, leading to a diagnosis of seronegative rheumatoid arthritis. Treatment with disease-modifying antirheumatic agents and surgical intervention was contemplated. Ultrasound and magnetic resonance imaging revealed exuberant synovitis, involving right elbow and knees. Upon withdrawal of methimazole, prompt resolution of all signs and symptoms of arthritis was observed within several weeks. Following a MEDLINE search of available literature concerning antithyroid drug-induced arthritis, it is evident that this case represents the lengthiest duration of inflammatory arthropathy ever described in a patient that nonetheless was rapidly reversible with discontinuation of methimazole.

Topics: Adult; Antithyroid Agents; Arthritis, Rheumatoid; Chronic Disease; Diagnosis, Differential; Female; Graves Disease; Humans; Methimazole

Methimazole (MMI)-induced acute pancreatitis is very rare but severe adverse reaction. A 51-yr-old male developed a high fever, chills, and abdominal pain, two weeks after commencement on MMI for the treatment of Graves' disease. There was no evidence of agranulocytosis, and fever subsided soon after stopping MMI treatment. However, 5 hr after taking an additional dose of MMI, abdominal pain and fever developed again. His symptoms, biochemical, and imaging studies were compatible with acute pancreatitis. After withdrawal of MMI, he showed clinical improvement. This is the first case of MMI-induced acute pancreatitis in Korea. Clinicians should be aware of the rare but possible MMI-induced pancreatitis in patients complaining of fever and abdominal pain.

Topics: Abdominal Pain; Acute Disease; Diagnosis, Differential; Fever of Unknown Origin; Graves Disease; Humans; Male; Methimazole; Middle Aged; Pancreatitis; Treatment Outcome

Thionamides have various side effects.. The effectiveness of potassium iodide (KI) was evaluated in hyperthyroid patients who experienced side effects to thionamides.. An observational study was conducted at an academic medical center.. Among 1388 patients with Graves' hyperthyroidism treated with thionamides, 204 (14.7%) exhibited side effects, and 44 were treated with KI and followed for 17.6 (median; range, 8.6-28.4) years.. The primary endpoint was the initial response to KI, and the secondary endpoint was the long-term prognosis.. The conditions of 29 (65.9%) of the 44 patients were well controlled with KI alone (10-400 mg/d) (A group), and 17 (38.6%) patients went into remission after 7.4 (1.9-23.0) years. The conditions of 15 (34.1%) patients were not controlled with KI alone (B group), even at a high dose (100-750 mg/d), but seven patients (15.9%) were controlled with a combination of KI and low-dose thionamides, resulting in remission after 7.2 (2.8-10.8) years. The initial parameters did not predict the response to KI or long-term prognosis. However, remission occurred in 70.8% of the patients treated with less than 200 mg of KI, compared with 35.0% of the patients who required 200 mg or more of KI (P < .05).. Among hyperthyroid patients with thionamide-associated side effects, KI therapy was effective in two-thirds of cases, and about 40% of the patients experienced remission after KI therapy alone. The chance of remission was small among the patients refractory to KI.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Drug Administration Schedule; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Potassium Iodide; Propylthiouracil; Remission Induction; Retreatment; Treatment Outcome; Young Adult

Topics: Child; Cross-Sectional Studies; Female; Graves Disease; Hashimoto Disease; Humans; Male; Methimazole; Nursing Diagnosis; Thyroid Function Tests; Thyroiditis, Autoimmune; Thyroxine

The main clinical manifestations of autoimmune thyroid diseases are Graves' disease (GD) and Hashimoto's thyroiditis (HT). Graves' disease is the cause of most cases of hyperthyroidism in childhood. Indications for radical therapy (surgery or 131I treatment) in children are still a matter of discussion, as sustained (sometimes very long) remission of GD is possible, while the radical therapy almost always leads to hypothyroidism. Spontaneous evolution from GD with hyperthyroidism to HT with hypothyroidism may also be observed.. The aim of the study was to analyze the clinical course of 6 cases of hyperthyroid girls with GD in whom a normalization of previously increased autoantibodies against thyrotropin (TSH) receptor (anti-TSHR) was observed together with a significant increase in autoantibodies against thyroid peroxidase (anti-TPO) and thyroglobulin (anti-Tg), with concomitant hypo- or euthyroidism but no recurrence of hyperthyroidism.. Patients' age at diagnosis ranged from 5.0 to 16.5 years. Two (2) patients had Turner syndrome, another one (1), diabetic, was on insulin therapy.. In all the girls, antithyroid drugs were administered and euthyroid state was achieved during the first 2.0-3.5 months of the treatment. Mild side effects were observed in only one case. The therapy was continued up to 1.5-4.0 years. Relapses during the therapy were observed in 2 cases. Up to now, no relapses have been observed for 0.5-7.5 years since the therapy withdrawal in 5 patients (1 patient was lost to follow-up), 2 patients are currently treated with levothyroxine due to hypothyroidism.. It seems that the prolonged pharmacotherapy with antithyroid drugs, followed by observation after remission of hyperthyroidism, may be an appropriate therapeutic option at least in some children with GD as they can be cured without radical therapy and the potential risks of such treatment.

Topics: Adolescent; Antithyroid Agents; Autoantibodies; Child; Child, Preschool; Female; Graves Disease; Hashimoto Disease; Humans; Hypothyroidism; Male; Methimazole; Propylthiouracil; Receptors, Thyrotropin; Remission Induction; Thyrotropin

Agranulocytosis is a serious complication of antithyroid drugs (ATD) treatment of thyrotoxicosis. The aim of our work was to assess the occurrence of agranulocytosis in Graves disease (GD) patients admitted for radioactive iodine 131I (RAI) treatment to our thyroid unit.. We analyzed retrospectively a cohort of 603 GD patients (500 women and 103 men; mean age 51.5 ± 12.7 years) who received RAI between 1999 and 2012. Of them, 327 (54 %) patients were originally treated with carbimazole (CBZ), 215 (36 %) with methimazole (MMI) and 61 (10 %) with propylthiouracil (PTU).. Agranulocytosis due to ATD was the cause of RAI treatment in 7 patients of 603. All of them were women (mean age 48.7 years; range 23-78). In 4 patients, agranulocytosis occurred on MMI treatment, and in 3 patients on CBZ. After recalculation of CBZ to the equipotent dose of MMI, the mean ATD dose was 22.4 mg MMI/day (range 9-40). No agranulocytosis due to PTU was found in our cohort. The time from beginning ATD treatment to agranulocytosis was 20-41 days. In 5 patients there was a development of fever, while in 2 patients the complication was diagnosed from routine blood count. The mean duration of agranulocytosis was 5.9 days (range 4-8).. Agranulocytosis incidence in our cohort of patients was 1.2 %, while in most reports the prevalence ranged from 0.2 to 0.5 %. In all patients, agranulocytosis occurred early, and in one third it was asymptomatic when found. The aim of our report is to bring attention to a relatively rare, but potentially serious, complication of ATD treatment.

Topics: Adult; Aged; Agranulocytosis; Antithyroid Agents; Carbimazole; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Retrospective Studies

Prenatal ultrasonography of a pregnant woman with a past history of total thyroidectomy for Graves' disease detected fetal tachycardia, fetal growth restriction and oligohydramnios at 30 weeks gestation. Because a high titer of thyroid-stimulating hormone receptor antibody was noted in maternal serum and the fetal goiter was detected on ultrasonography, fetal hyperthyroidism was strongly suspected and subsequently confirmed with cordocentesis at 31 weeks gestation. After treatment of fetal hyperthyroidism through oral maternal administration of methimazole (MMI) starting at 33 weeks gestation, fetal heart rate and amniotic fluid volume returned to normal ranges. Complete resolution of the fetal goiter was observed at 35 weeks gestation. A male infant was born at 35 weeks 6 days gestation via cesarean section in the absence of thyrotoxic findings; however, cord blood chemical analysis at birth indicated iatrogenic fetal hypothyroidism. In the present report, maternal therapy using MMI to resolve symptoms of fetal thyrotoxicosis, including fetal tachycardia and oligohydramnios, was successfully conducted.

Topics: Antithyroid Agents; Cordocentesis; Female; Fetal Diseases; Goiter; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Middle Aged; Neck; Oligohydramnios; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Tachycardia; Thyroidectomy; Thyroxine; Ultrasonography, Doppler, Color; Ultrasonography, Prenatal

Topics: Adult; Antithyroid Agents; Elephantiasis; Graves Disease; Humans; Iodine Radioisotopes; Leg; Male; Methimazole; Thyroxine

Topics: Adult; Antithyroid Agents; Diagnosis, Differential; Female; Graves Disease; Humans; Methimazole

The data in the literature suggests that Methimazole (MMI)/Carbimazole (CMZ) embryopathy is rare. This study examined the incidence of CMZ embryopathy in the Hong Kong Chinese population and the factors associated with its development.. Of the 145 pregnant women with hyperthyroidism managed from 2008 to 2010, 29 (20%) had taken CMZ during pregnancy. The presence and details of birth defects, the dosage of CMZ, and the period of exposure during pregnancy were examined in these 29 pregnancies. All cases of CMZ embryopathy in the English literature were reviewed in the same way.. Of the 27 babies (93.1%) with known outcome, 3 had aplasia cutis and 1 had an omphalocele in addition, and 1 affected baby had a sibling with aplasia cutis and patent vitellointestinal duct. The incidence of CMZ embryopathy in our study group is 11.1%. Amongst the 21 cases of CMZ embryopathy in the literature, 85% were exposed to a CMZ dosage of ≥20 mg/day, and the minimum duration of exposure being 7 weeks from last menstrual period. The most common abnormality is ectodermal anomaly (62%), followed by oro-nasal anomaly (48%), facial dysmorphism (38%), gastrointestinal anomaly (33%) and abdominal wall defect (19%). There was no relationship between the type of abnormality and the dosage or duration of exposure to CMZ.. The incidence of CMZ embryopathy in our study group is 11.1%. Critical factors for its development are exposure to a CMZ dosage of ≥20 mg/day before 7 weeks of gestation. Genetic susceptibility may also play a role.

Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Asian People; Female; Fetal Diseases; Gestational Age; Graves Disease; Hong Kong; Humans; Incidence; Infant, Newborn; Male; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Outcome

Topics: Graves Disease; Humans; Hypokalemic Periodic Paralysis; Intracellular Fluid; Ion Transport; Male; Methimazole; Middle Aged; Potassium; Radionuclide Imaging; Recurrence; Thyrotoxicosis

The aim of this research was to assess plasma magnesium (Mg) concentration, the frequencies of activated T CD4+ and T CD8+ lymphocytes and B lymphocytes in adolescents with hyperthyroidism due to Graves' disease (GD), and to assess changes in the above-mentioned parameters during methimazole (MMI) treatment. The frequencies of activated T and B cells were measured by flow cytometry method and plasma Mg concentration was determined by spectrophotometry method in 60 adolescents at the time of GD diagnosis and after receiving the normalisation of the thyroid hormones levels. The control group consisted of 20 healthy volunteers. We observed lower plasma Mg concentration, and higher frequencies of activated T and B lymphocytes in the study group before the treatment in comparison with healthy controls, and with study group in MMI-induced euthyreosis (p < 0.01).Statistically significant negative correlations between the percentages of activated T CD3+, T CD4+, T CD8+ and B CD19+ lymphocytes, and plasma Mg concentration before the treatment were found (r < -0.335, p < 0.002). After the treatment no vital differences in plasma Mg concentration, and in percentages of activated cells between GD patients and controls were found, except CD8+CD25+ cells (p = 0.03). The present study demonstrates that both activated T and B cells might play an important role in the pathogenesis of GD, and activation is related to Mg plasma level. The use of MMI in treatment of hyperthyroidism due to GD leads to decrease the frequencies of activated lymphocytes and normalisation of Mg levels.

Topics: Adolescent; Antithyroid Agents; Graves Disease; Humans; Lymphocyte Activation; Magnesium; Methimazole

Localized myxoedema is a rare dermopathy in patients with Graves' disease. The pretibial area is the most commonly affected region but herein we present a case of myxoedema of the big toe.. A 44-year-old male with Graves' disease ongoing for seven years presented bilateral ophthalmopathy and myxoedema of the big toes. The myxoedema was treated successfully with intralesional steroids.. The physiopathology of myxoedema involves fibroblast activation and glycosaminoglycan production. This activation could result from stimulation of TSH receptors at their surface by TSH receptor antibodies (TRAK) or from an inflammatory process. The pretibial topography may be related to the high frequency in this area of microtrauma, with modulation of the cytokine microenvironment.. The atypical localization seems to correlate with a Koebner phenomenon. Treatment of Graves' disease is generally insufficient to resolve the cutaneous problems. Topical corticosteroid therapy generally results in rapid improvement of recent lesions.

Topics: Adult; Biopsy; Carbimazole; Decompression, Surgical; Fibroblasts; Foot Dermatoses; Glycosaminoglycans; Graves Disease; Graves Ophthalmopathy; Hormone Replacement Therapy; Humans; Immunoglobulins, Thyroid-Stimulating; Immunosuppressive Agents; Injections, Intralesional; Male; Methimazole; Myxedema; Receptors, Thyrotropin; Thyroidectomy; Thyroxine; Toes; Triamcinolone

Chemokine (C-X-C motif) ligand (CXCL)9 and CXCL11 play an important role in the initial phases of autoimmune thyroiditis (AT); however, their serum levels in patients with Graves' disease (GD) have never been evaluated in relation to thyroid function and treatment.. To evaluate CXCL9 and CXCL11 serum levels in GD and to relate these parameters to the clinical phenotype, we measured CXCL9 and CXCL11 serum levels in 91 GD patients; 91 AT, 34 nontoxic multinodular goiters (MNGs), 31 toxic nodular goiters (TNGs), respectively; and 91 healthy controls (age- and sex-matched).. Mean CXCL9 and CXCL11 levels were higher in GD in comparison with controls, euthyroid AT, MNG, or TNG (p < 0.05, ANOVA; CXCL9: 274 ± 265, 76 ± 33, 132 ± 78, 87 ± 48, and 112 ± 56  pg/mL; CXCL11: 140 ± 92, 64 ± 20, 108 ± 48, 76 ± 33, 91 ± 41 pg/mL, respectively). Hyperthyroid GD patients had significantly higher CXCL9 or CXCL11 than euthyroid or hypothyroid GD patients. GD patients with untreated hyperthyroidism had higher CXCL9 or CXCL11 than hyperthyroid or euthyroid GD patients under methimazole (MMI) treatment. Comparable CXCL9 and CXCL11 levels were observed in newly diagnosed untreated hyperthyroid GD versus untreated patients with relapse of hyperthyroidism after a previous MMI course.. Serum CXCL9 and CXCL11 levels are associated with the active phase of GD both in newly diagnosed and relapsing hyperthyroid patients. The reduction of serum CXCL9 and CXCL11 levels in treated patients with GD may be related to the immunomodulatory effects of MMI.

Topics: Adult; Aged; Antithyroid Agents; Case-Control Studies; Chemokine CCL2; Chemokine CXCL11; Chemokine CXCL9; Female; Goiter; Graves Disease; Humans; Hyperthyroidism; Immunologic Factors; Interferon-gamma; Male; Methimazole; Middle Aged; Phenotype; Recurrence; Thyroid Gland

Therapeutic plasma exchange (TPE) is an alternative treatment for hyperthyroidism, resulting in a rapid decline in plasma thyroid hormones and anti-thyroid antibodies. TPE has also been used both in primary liver disease and in drug-induced cholestasis. Data on thyrotoxic patients with severe hepatic complications are scarce. Cholestasis induced by imidazol-derived anti-thyroid drugs is extremely rare. The use of TPE for treating this complication was not previously reported. We report the experience of one such patient with a favorable response to TPE. A 45-year-old male patient with Graves' disease, presented with severe jaundice and extremely high serum bilirubin levels due to hepatotoxicity induced by tiamazol. Through extensive investigation primary liver disease, including viral, metabolic, neoplastic and autoimmune disease, as a cause of cholestasis were all ruled out. The patient underwent total of 6 TPEs which in combination with low dose of glucocorticoids and standard supportive measures, resulted in normalization of thyroid hormones and normal liver function tests. TPE provided a safe, rapid and effective treatment of severe drug-induced cholestasis and auto immune hyperthyroidism. From this case we conclude that TPE should be considered as a valuable alternative therapeutic option in thyrotoxic patients with severe complications. Guidelines and indication criteria for TPE treatment in patients with hyperthyroidism are still lacking.

Topics: Antithyroid Agents; Bilirubin; Graves Disease; Humans; Jaundice, Obstructive; Male; Methimazole; Middle Aged; Plasma Exchange

Topics: Adult; Antithyroid Agents; Asian People; Autoimmune Diseases; Female; Graves Disease; Humans; Insulin; Methimazole

An HIV-infected patient who experienced immune reconstitution after highly active antiretroviral therapy (HAART) (increase in CD4 T-cell count from 84/mm3 to 310/mm3) presented with severe Graves' disease twice, after commencing and recommencing HAART. At the first episode of Graves' disease, 21 months after the introduction of HAART, the symptoms of thyroid dysfunction vanished without any specific treatment, but were associated with termination of taking HAART. At the second episode, 5 years after recommencing HAART, the patient continued taking HAART and commenced antithyroid therapy with thiamazole. Graves' disease developed after a long period, while the patient was in good condition and when complications resulting from HAART were not expected. No features of any autoimmune disease were diagnosed before HAART initiation.

Topics: Antiretroviral Therapy, Highly Active; Antithyroid Agents; CD4 Lymphocyte Count; Female; Graves Disease; HIV Infections; Humans; Immune Reconstitution Inflammatory Syndrome; Immunocompromised Host; Methimazole; Middle Aged; Recurrence; Treatment Outcome

Optimal treatment of Graves' disease (GD) remains controversial. The authors retrospectively reviewed the surgical cases of GD at a single academic tertiary center.. Demographic, clinical, and surgical data were analyzed for all patients with GD undergoing thyroidectomy over 25 years, in 3 periods: 1985 to 1993 (n = 32), 1994 to 2002 (n = 91), and 2003 to 2010 (n = 177).. There were 300 patients with GD (85.7% women; mean age, 39.3 years; median length of follow-up, 24.6 months). Overall, perioperative morbidity occurred in 36 patients (12.0%), and there was no mortality. Thyroidectomy-specific morbidity was very low, and the incidental malignancy rate was 10.3%.. Surgical treatment of GD has a very high safety profile, with low perioperative and thyroidectomy-specific morbidity, even in patients with overt hyperthyroidism. Incidental malignancy in patients with GD is not uncommon.

Topics: Ablation Techniques; Adult; Antithyroid Agents; Drainage; Female; Graves Disease; Humans; Incidental Findings; Iodine Radioisotopes; Length of Stay; Male; Massachusetts; Methimazole; Operative Time; Postoperative Complications; Preoperative Care; Propylthiouracil; Retrospective Studies; Thyroid Neoplasms; Thyroidectomy

Agranulocytosis is a rare but serious complication of antithyroid drug (ATD) therapy. Characteristics of agranulocytosis have been reported in only a small number of patients.. We studied 754 cases of ATD-induced agranulocytosis reported over 30 years. The age distribution and sex ratio were compared with those in 12 503 untreated Graves' patients at Kuma Hospital. The annual number of new Graves' patients in Japan was estimated from the Japan Medical Data Center Data Mart-Pharmacovigilance health insurance receipt database.. Agranulocytosis developed within 90 days after starting ATD therapy in most patients (84.5%). The methimazole dose given at onset was 25.2 ± 12.8 mg/d (mean ± SD). The mean age was 43.4 ± 15.2 years, and the male to female ratio was 1:6.3. When compared with patients at Kuma Hospital, patients with agranulocytosis were older (P < .001) and more females (P < .0001). Of 211 patients with more than 1 granulocyte measurement before onset, 131 (62%) showed normal counts (>1000/μL) within 2 weeks before onset, demonstrating real sudden onset of agranulocytosis. In contrast, some of the 20 patients with more than 4 measurements showed gradual decreases in granulocyte counts. Analysis of physician reports for 30 fatal cases revealed that some deaths might have been prevented. The number of new Graves' patients treated with ATD was estimated at about 35 000 per year, and the incidence rate of agranulocytosis was 0.1% to 0.15% in Japan.. This is the largest study of agranulocytosis. Agranulocytosis tends to occur abruptly within 3 months after initiation of ATD therapy, although it develops gradually in some patients. Providing every patient with sufficient information on agranulocytosis is critical.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Agranulocytosis; Anemia, Aplastic; Antithyroid Agents; Drug Therapy, Combination; Female; Graves Disease; Hospitals, Urban; Humans; Incidence; Japan; Leukopoiesis; Male; Methimazole; Middle Aged; Pancytopenia; Pharmacovigilance; Propylthiouracil; Sex Distribution

Both Graves disease and Guillain-Barre syndrome (GBS) are autoimmune disorders caused by impaired self-tolerance mechanisms and triggered by interactions between genetic and environmental factors. GBS in patients who suffer from other autoimmune diseases is rarely reported, and the development of postinfectious GBS in a patient with Graves disease has not been previously reported in the literature. Herein, we report a patient with Graves disease who developed postinfectious GBS during a course of methimazole-induced agranulocytosis.

Topics: Agranulocytosis; Antithyroid Agents; Female; Graves Disease; Guillain-Barre Syndrome; Humans; Immunoglobulins, Intravenous; Methimazole; Middle Aged; Opportunistic Infections; Thyroidectomy; Treatment Outcome

The protein product of the proto-oncogene Bcl-2 is a physiological inhibitor of programmed cell death. The results obtained in our previous researches suggest that apoptosis may be involved in the regulation of an immune response in hyperthyroidism. The most common cause of hyperthyroidism is Graves' disease. The aim of this study was evaluation of expression of Bcl-2 protein in peripheral blood T lymphocytes in hyperthyroid children due to Graves' disease (GD) before and after therapy with methimazole (MMI), in comparison with healthy controls.. Thirty-two children with newly diagnosed hyperthyreosis due to GD before and after 4-6 weeks treatment with MMI, and 20 healthy controls were included into the study. The staining with monoclonal antibodies against CD8 and Bcl-2 was performed within 2 hours after collection, and followed with flow cytometry acquisition and analysis.. Our study revealed that the expression of Bcl-2 protein in circulating CD8+ T lymphocytes of patients with hyperthyreosis was significantly lower than in healthy controls (p<0.03). The expression of Bcl-2 after 4-6 week therapy with MMI returned to normal level. The difference in Bcl-2 expression between patients after treatment and control group was insignificant.. The use of MMI in the treatment of hyperthyroidism due to GD leads to the normalization of the Bcl-2 expression on the CD8+ lymphocytes in peripheral blood. Our findings suggest that the changes in the expression of Bcl-2 on the CD8+ cells indicate the involvement of these cells and Bcl-2-regulated apoptotic pathway in the pathogenesis of GD.

Topics: Adolescent; Antithyroid Agents; Case-Control Studies; CD8-Positive T-Lymphocytes; Child; Female; Gene Expression Regulation; Graves Disease; Humans; Male; Methimazole; Proto-Oncogene Mas; Proto-Oncogene Proteins c-bcl-2

In many countries, methimazole (MMI) therapy is the first-line treatment in children with Graves' disease (GD). The rate of side effects of antithyroid drugs (ATDs) in children has been reported to range between 6% and 35%. Of these side effects, polyarthritis is uncommon but serious, and can also develop as a part of the antineutrophil cytoplasmic antibody-associated vasculitis that is induced by ATDs. Here, we describe two GD girl patients aged 15 years and 11 years who developed polyarthritis. The onset of polyarthritis in these patients was 24 days and 28 days after the initiation of MMI therapy, respectively. MMI was suspected of causing the polyarthritis in the two patients and was withdrawn. The symptoms of polyarthritis disappeared rapidly following cessation of treatment. Subsequently, one patient was treated with 131I therapy and the other patient was subjected to thyroidectomy. Although it rarely occurs in pediatric GD patients, severe polyarthritis is a serious side effect of MMI and is an indication for prompt cessation of treatment.

Topics: Adolescent; Antithyroid Agents; Arthritis; Child; Female; Graves Disease; Humans; Methimazole

Topics: Aged, 80 and over; Antithyroid Agents; Autoantibodies; Autoimmune Diseases; Diabetes Mellitus, Type 2; Female; Graves Disease; Graves Ophthalmopathy; Humans; Hypoglycemia; Hypoglycemic Agents; Immunosuppressive Agents; Insulin, Regular, Human; Methimazole; Prednisone; Recombinant Proteins; Treatment Outcome

Antithyroid medications are the preferred therapy for the treatment of Graves' disease during pregnancy. Propylthiouracil (PTU) is favored over methimazole (MMI) due to potential teratogenic concerns with MMI. This study was to determine the teratogenic potential of MMI and PTU using a validated Xenopus tropicalis embryo model. Embryos were exposed to 1 mM PTU (EC(50)=0.88 mM), 1 mM MMI, or vehicle control (water) from stages 2 to 45. Treated embryos were examined for gross morphological defects, ciliary function, and gene expression by in situ hybridization. Exposure to PTU, but not MMI, led to cardiac and gut looping defects and shortening along the anterior-posterior axis. PTU exposure during gastrulation (stage 8-12.5) was identified as the critical period of exposure leading to left-right (LR) patterning defects. Abnormal cilia polarization, abnormal cilia-driven leftward flow at the gastrocoel roof plate (GRP), and aberrant expression of both Coco and Pitx2c were associated with abnormal LR symmetry observed following PTU exposure. PTU is teratogenic during late blastula, gastrulation, and neurulation; whereas MMI is not. PTU alters ciliary-driven flow and disrupts the normal genetic program involved in LR axis determination. These studies have important implications for women taking PTU during early pregnancy.

Topics: Animals; Antithyroid Agents; Body Patterning; Cilia; Digestive System Abnormalities; Female; Gene Expression Regulation, Developmental; Graves Disease; Heart Defects, Congenital; Humans; Methimazole; Models, Animal; Pregnancy; Pregnancy Complications; Propylthiouracil; Teratogens; Time Factors; Triiodothyronine; Xenopus

Propylthiouracil (PTU) is recommended as a first-line antithyroid drug (ATD) during first trimester organogenesis in pregnancy because recent evidence suggests that methimazole (MMI) may be associated with congenital anomalies. However, PTU more commonly causes myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, which usually occurs during prolonged treatment, compared with MMI. We report a case of MPO-ANCA-associated vasculitis in a 35-year-old woman with Graves'disease. Although her thyroid function could be maintained euthyroid by MMI, her ATD was switched to PTU because she wished to become pregnant. The patient presented with flu-like symptoms 8 days after starting PTU and developed hemoptysis and dyspnea at 22 days. Her MPO-ANCA titer was 21 ELISA units (EUs) before PTU treatment but increased to 259 EUs at 22 days after PTU treatment. Her clinical condition improved with the discontinuation of PTU and with immunosuppressive therapy. This case indicated that MPO-ANCA vasculitis occurred within several weeks after the initiation of PTU and that this side effect could be caused by the change from MMI to PTU. Thus, our clinical observation suggests that patients treated with PTU should be carefully monitored for MPO-ANCA titers and variable manifestations of MPO-ANCA-associated vasculitis regardless of the period of administration.

Topics: Abnormalities, Drug-Induced; Adult; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Graves Disease; Humans; Methimazole; Peroxidase; Pregnancy; Pregnancy Complications; Propylthiouracil

We previously reported that serum interleukin-18 (IL-18) levels were significantly increased in hyperthyroid Graves' disease patients. The development of insulin resistance in hyperthyroidism has been documented. We investigated the relationship between IL-18 and insulin resistance in patients with hyperthyroid Graves' disease and in experimental hyperthyroid mice. Then, we examined whether IL-18 induces insulin resistance in mice injected with IL-18 for a week. A significant positive correlation was observed between serum IL-18 levels and parameters such as thyroid functions and homeostasis model assessment for insulin resistance in hyperthyroid Graves' disease. In experimental hyperthyroid mice, IL-18 was significantly elevated. Insulin resistance increased in experimental hyperthyroid mice and IL-18-injected mice. These findings suggest IL-18 to be an important factor inducing insulin resistance in hyperthyroidism.

Topics: Adolescent; Adult; Animals; Antithyroid Agents; Blood Glucose; Female; Graves Disease; Humans; Hyperthyroidism; Injections, Intraperitoneal; Insulin; Insulin Resistance; Interleukin-18; Male; Methimazole; Mice; Mice, Inbred C57BL; Middle Aged; Recombinant Proteins; Young Adult

A 78 year old white male on methimazole due to Grave's thyroiditis presented with acute renal failure after a short term history of progressive shortness of breath, malaise, myalgias, arthralgias, and bilateral lower limb swelling. The abdomen was remarkable for splenomegaly and lower extremities for erythema nodosum. No peripheral lymphadenopathy was detected. Serum albumin was 1.7 g/dl and very high erythrocyte sedimentation rate. Urine sediment was very active with dysmorphic red blood cells and casts and significant proteinuria (6.6 grams/day). Serum complements were abnormally low and antinuclear and anti-DNA antibodies were positive. Renal histopathology revealed membranoproliferative glomerulonephritis, along with a full house pattern on IFF consistent with lupus nephritis. Bone marrow aspiration revealed a 40% infiltration by a lymphocyte population of small cells consistent with a B cell non-Hodgkin lymphoma. The patient was treated with methylprednisolone, cyclophosphamide and rituximab and acute dialysis. Over the following weeks the patient became dialysis independent and returned to his baseline GFR.

Topics: Aged; Antibodies, Monoclonal, Murine-Derived; Antithyroid Agents; Biopsy, Needle; Bone Marrow Examination; Cyclophosphamide; Drug Therapy, Combination; Graves Disease; Humans; Immunosuppressive Agents; Lupus Nephritis; Lymphoma, B-Cell; Male; Methimazole; Methylprednisolone; Renal Dialysis; Risk Factors; Rituximab; Treatment Outcome

11β hydroxylase deficiency (OHD) is one of the main causes of congenital adrenal hyperplasia. There have been only a few reported cases of nonclassic 11β OHD, a milder form of the disease. It is difficult to detect occult nonclassic 11β OHD because patients present with no or mild symptoms. We herein present a case of thyrotoxic periodic paralysis (TPP) with Graves' disease leading to the discovery of a hidden nonclassic 11β OHD. In this case, increased levels of thyroid hormone seem to have induced symptoms of occult nonclassic 11β OHD and aggravated TPP.

Topics: Adrenal Hyperplasia, Congenital; Diagnosis, Differential; Drug Therapy, Combination; Graves Disease; Humans; Hypokalemic Periodic Paralysis; Male; Methimazole; Mutation; Polymerase Chain Reaction; Polymorphism, Genetic; Potassium; Propranolol; Risk Assessment; Severity of Illness Index; Steroid 11-beta-Hydroxylase; Thyrotoxicosis; Tomography, X-Ray Computed; Treatment Outcome; Young Adult

A 15-year-old girl presented with chorea as a first sign of Graves' hyperthyroidism. Chorea abated with antithyroid drug treatment and reappeared when hyperthyroidism recurred but not when thyrotropin receptor antibodies increased after administration of (131)I. Therefore, chorea in this patient is associated with hyperthyroxinemia and not with autoantibodies.

Topics: Adolescent; Anemia, Sickle Cell; Antithyroid Agents; Bone Marrow Transplantation; Chorea; Comorbidity; Diagnosis, Differential; Drug Therapy, Combination; Female; Follow-Up Studies; Graves Disease; Humans; Hyperthyroxinemia; Methimazole; Neurologic Examination; Thyroid Function Tests; Thyroxine; Transplantation Conditioning

This study is to explore the role of IL-23/IL-17 axis in subjects with Graves' disease, while IL-23/IL-17 axis plays an important role in a number of autoimmune diseases, but it's not clear in Graves' disease. Thirty-three patients with Graves' disease as a GD group, 15 patients with euthyroid GD as eGD group and 22 healthy volunteers as a control group whose age- and sex-matched. Peripheral blood was collected and peripheral blood mononuclear cells (PBMCs) were isolated in the both groups, then PBMCs were cultured in the presence or absence of IL-23 in vitro. The expression of retinoid-related orphan receptor gamma t (RORγt) and IL-17 mRNA were examined by Semi-quantitative RT-PCR, and the levels of IL-17 protein were measured by enzyme-linked immunosorbent assay. The expression of RORγt, IL-17 mRNA and IL-17 protein levels were markedly higher in GD and euthyroid GD group as compared with the control group. IL-17 levels were still higher in euthyroid GD patients. When PBMCs derived from the three groups were cultured in vitro with or without IL-23, the expression of RORγt in GD group with IL-23 dramatically increased as compared with that in GD group without IL-23 and in control group with IL-23. RORγt expression of PBMCs from eGD group cultured with IL-23 was increased compared with that cultured without IL-23. The levels of IL-17 mRNA and the protein were also significantly higher than that of GD and eGD cultured without IL-23 and control group. There was no difference of the expression of RORγt mRNA and IL-17 protein levels between GD and eGD group cultured with or without IL-23. Our studies demonstrated that IL-23/IL-17 axis is associated with the pathogenesis of Graves' disease in it activated term. This effect is not dependent on thyroid function, but may be associated to the immunity.

Topics: Adult; Antithyroid Agents; Autoantibodies; Cells, Cultured; Female; Graves Disease; Humans; Interleukin-17; Interleukin-23 Subunit p19; Leukocytes, Mononuclear; Male; Methimazole; Middle Aged; Nuclear Receptor Subfamily 1, Group F, Member 3; RNA, Messenger; Th17 Cells; Thyroid Gland; Up-Regulation; Young Adult

Methimazole (MMI) is used as a first-line antithyroid drug in children and adolescents with Graves' disease (GD). The aim of this study was to evaluate the correlation between the initial dose of MMI and the clinical course of GD after treatment.. Retrospective and collaborative study.. Nine facilities in Chiba prefecture, Japan.. Sixty-four children and adolescents with GD were analyzed. The subjects were divided into three groups by the initial daily dose of MMI: group A, 0.4±0.1 mg/kg (mean±SD, n=11); group B, 0.7±0.2 (n=37); group C, 0.9±0.2 (n=16).. The duration of time required for normalization of serum free T4 on initial treatment and the incidence of adverse effects for 1 year after the start of MMI were compared. Outcomes were compared among patients who were followed more than 3 years (group A, n=7; group B, n=24; group C, n=12).. Mean duration of times for normalization of T4 was 1.9±1.5 months in group A, 1.6±0.9 in group B and 1.9±1.5 in group C (NS). No major adverse reactions were observed. Minor adverse effects occurred in 9.1% of cases in group A, 13.5% in group B and 62.0% in group C (p<0.01). Remission rates did not differ among the three groups.. Higher doses of MMI are harmful for initial use in children and adolescents with GD.

Topics: Adolescent; Antithyroid Agents; Child; Female; Graves Disease; Humans; Male; Methimazole; Retrospective Studies; Thyroxine

Maternal thyrotoxicosis, predominantly secondary to Graves' disease, affects 0.2% of all pregnancies. The Endocrine Society guidelines recommend the use of propylthiouracil as a first-line drug for thyrotoxicosis in pregnancy because of associations between carbimazole or methimazole and congenital anomalies. However, recent studies have highlighted the risk of severe liver injury with propylthiouracil. Here, we report another case with multiple congenital anomalies following in utero exposure to carbimazole and review the literature to consider the risks and benefits of available pharmacological treatments for thyrotoxicosis in pregnancy.

Topics: Antithyroid Agents; Carbimazole; Ectodermal Dysplasia; Face; Female; Graves Disease; Humans; Infant; Lacrimal Apparatus Diseases; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyrotoxicosis; Thyroxine

Although antithyroid drug (ATD)-induced hematopoietic damage is a significant concern, it has not been comprehensively investigated.. Our objective was to describe the clinical features of ATD-induced hematopoietic damage.. This was a retrospective cohort study in Tokyo, Japan.. Between January 1983 and December 2002, 50,385 patients at Ito Hospital were diagnosed with Graves' disease. We retrospectively reviewed their medical, pathological, and laboratory records between January 1983 and December 2010.. Incidence and clinical features of ATD-induced agranulocytosis and pancytopenia were evaluated.. Of 55 patients with documented hematopoietic damage, 50 had agranulocytosis and 5 had pancytopenia. All of them received ATD, either methimazole (n = 51) or propylthiouracil (n = 4). Median intervals between initiation of ATD therapy and the onset of agranulocytosis and pancytopenia were 69 d (range, 11-233 d) and 41 d (range, 32-97 d), respectively. Either anemia or thrombocytopenia was also documented in seven of the 50 patients with agranulocytosis. Agranulocytosis was the first manifestation of hematopoietic damage in four of the five patents with pancytopenia. Hematopoietic damage recovered with supportive measures including granulocyte colony-stimulating factor (n = 37), steroids (n = 10), and other supportive measures (n = 8) in 54 patients, whereas the remaining patient died of complications from infection. This study failed to identify the risk factors for ATD-induced hematopoietic damage.. This study showed that ATD cause hematopoietic changes, which are occasionally severe and potentially fatal. The pathogenesis of agranulocytosis and pancytopenia might overlap, and additional studies are warranted to clarify this and to establish an optimal treatment strategy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Agranulocytosis; Antithyroid Agents; Child; Cohort Studies; Female; Graves Disease; Hematopoiesis; Humans; Japan; Male; Methimazole; Middle Aged; Pancytopenia; Propylthiouracil; Retrospective Studies; Tokyo; Young Adult

Antithyroid drugs such as methimazole (MMI), the mainstay of pharmacologic therapy for Graves' disease, can provoke a variety of adverse effects. MMI-induced acute pancreatitis is very rare, being described in only a few patients and never after more than two exposures as reported here. Here, we report an 18-year-old girl with Graves' disease who developed acute pancreatitis each time she received MMI.. The patient was an 18-year-old girl with Graves' disease who took MMI on four occasions. Each time she promptly developed similar features consisting of high fever and left upper quadrant abdominal pain. On three occasions, serum lipase and amylase values were measured. Serum lipase was elevated on all three occasions and serum amylase was elevated once. Features resolved after MMI was stopped. We considered these episodes to be most consistent with pancreatitis, and to be induced by MMI administration.. MMI-induced acute pancreatitis is rare and easily misdiagnosed. Based on very limited experience, it should resolve after MMI is stopped. The pathogenesis of MMI-induced pancreatitis is not known. Clinicians should be aware of this entity so that MMI is promptly stopped if the features described here develop after MMI is started, and measures are taken to avoid future MMI treatment.

Topics: Acute Disease; Adolescent; Antithyroid Agents; Female; Graves Disease; Humans; Methimazole; Pancreatitis

Topics: Antithyroid Agents; Child; Female; Graves Disease; Humans; Male; Methimazole; Organ Size; Thymus Gland; Thyroid Gland; Tomography, X-Ray Computed; Ultrasonography; Young Adult

Hyperthyroidism has been associated with liver function abnormalities; however, cholestasis as the presenting feature of adolescent Graves' disease has not been previously reported.. The patient was a 17-year-old girl who presented with severe cholestasis and was found to have Graves' disease. She also had a positive hepatitis A immunoglobulin M antibody but her clinical course, the liver histopathology, and her mildly elevated transaminases indicated that the acute hepatitis A infection was not dominant at the time of presentation with severe cholestasis. Other causes of cholestasis, including congestive heart failure, autoimmune hepatitis, and viral infection, were excluded. Treatment with methimazole resolved the hyperthyroidism, and the cholestasis improved, as well.. Severe cholestasis is a rare presenting feature of Graves' disease. With careful monitoring, methimazole can be used to treat the hyperthyroidism in the setting of cholestasis.

Topics: Adolescent; Adrenergic beta-Antagonists; Antithyroid Agents; Bilirubin; Cholestasis; Female; Graves Disease; Hepatitis A; Hepatitis A Antibodies; Humans; Immunoglobulin M; Liver Function Tests; Methimazole; Propranolol; Thyroid Function Tests

Several reports have suggested that propylthiouracil (PTU) may be safer than methimazole (MMI) for treating thyrotoxicosis during pregnancy because congenital malformations have been associated with the use of MMI during pregnancy.. We investigated whether in utero exposure to antithyroid drugs resulted in a higher rate of major malformations than among the infants born to a control group of pregnant women.. We reviewed the cases of women with Graves' disease who became pregnant. The pregnancy outcomes of 6744 women were known, and there were 5967 live births. MMI alone had been used to treat 1426 of the women, and 1578 women had been treated with PTU alone. The 2065 women who had received no medication for the treatment of Graves' disease during the first trimester served as the control group. The remaining women had been treated with potassium iodide, levothyroxine, or more than one drug during the first trimester. The antithyroid drugs were evaluated for associations with congenital malformations.. The overall rate of major anomalies in the MMI group was 4.1% (50 of 1231), and it was significantly higher than the 2.1% (40 of 1906) in the control group (P = 0.002), but there was no increase in the overall rate of major anomalies in the PTU group in comparison with the control group (1.9%; 21 of 1399; P = 0.709). Seven of the 1231 newborns in the MMI group had aplasia cutis congenita, six had an omphalocele, seven had a symptomatic omphalomesenteric duct anomaly, and one had esophageal atresia. Hyperthyroidism in the first trimester of pregnancy did not increase the rate of congenital malformation.. In utero exposure to MMI during the first trimester of pregnancy increased the rate of congenital malformations, and it significantly increased the rate of aplasia cutis congenita, omphalocele, and a symptomatic omphalomesenteric duct anomaly.

Topics: Abnormalities, Drug-Induced; Adult; Antithyroid Agents; Case-Control Studies; Female; Graves Disease; Humans; Infant, Newborn; Live Birth; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnancy Trimester, First; Prenatal Exposure Delayed Effects; Prevalence; Propylthiouracil; Young Adult

With the increased survival of HIV-infected patients receiving antiretroviral therapy (ART), unexpected complications due to the untoward effect of antiretroviral agents or immunologic changes have been observed. Here, we report two cases of Graves' disease (GD) presenting with classic symptoms of hyperthyroidism occurring 44 and 47 months after ART initiation. Both patients had severe immune suppression prior to ART initiation (CD4 cell count≤50 cells/μL), with an increase on CD4 cell count to 354 and 329 cells/μL, respectively, at the time of GD diagnosis. Administration of methimazole (MMI) resulted in dramatic improvements in symptoms and thyroid function. In addition, CD4 cell count unexpectedly increased to >500 cells/μL within three months on MMI. Hyperthyroidism caused by GD has been increasingly reported following the initiation of ART and may be related to immune reconstitution. The mechanisms underlying the increases in CD4 cell count after successful treatment of GD with MMI require further investigation, but may be due to improved immune recovery with the correction of hyperthyroidism or a specific effect of MMI on immune function.

Topics: Adult; Antiretroviral Therapy, Highly Active; Antithyroid Agents; CD4 Lymphocyte Count; Graves Disease; HIV Infections; Humans; Male; Methimazole

We developed an ultrasensitive enzyme immunoassay (ICT-EIA) for insulin autoantibody (IAA) measurements to better understand the pathophysiology of diabetes.. We developed ICT-EIA for IAA and measured IAA in 24 patients with type 1 diabetes, 30 patients with type 2 diabetes, 30 patients with methimazole-treated Graves' disease, 20 patients with Hashimoto's disease, 9 patients with hyperinsulinemia, and 73 healthy control subjects.. The conventional ELISA identified 3 patients with type 1 diabetes and 2 patients with type 2 diabetes as IAA positive, whereas 15 patients with type 1 diabetes, 7 patients with type 2 diabetes, and 4 patients with methimazole-treated Graves' disease were identified as IAA positive using ICT-EIA.. The ICT-EIA is an ultrasensitive and specific assay for IAA, and its use may provide a better understanding of the role of IAA in diabetes onset and progression.

Topics: Autoantibodies; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Disease Progression; Graves Disease; Hashimoto Disease; Humans; Hyperinsulinism; Immunoenzyme Techniques; Insulin; Insulin Antibodies; Methimazole; Sensitivity and Specificity

Insulin autoimmune syndrome (IAS) or Hirata's disease is a rare disorder characterized by hypoglycemia secondary to insulin autoantibodies (IAb). Over 200 patients have been described from Japan with significantly less numbers being reported from outside the Orient. IAS is more common in patients older than 40 yr of age with reports in the pediatric age group being notably rarer. Exposure to sulfhydryl group containing medications is implicated in the pathogenesis of this syndrome. In this report, we describe a case of IAS in an African-American adolescent. A 16-yr-old healthy African-American male was diagnosed with Graves' disease and started on Methimazole. Four weeks later, he was found unconscious and hypoglycemic (blood sugar 1.5 mmol/L). Evaluation was negative for insulinoma. Insulin antibodies were positive. Oral glucose tolerance test revealed elevated free insulin concentrations with disproportionately elevated total insulin levels. The patient was started on prednisone, diazoxide, and propranolol for management of IAS and hyperthyroidism. Thyroid radio-ablation was subsequently undertaken. The doses of prednisone and diazoxide were tapered and these medications discontinued after 9 months. The insulin antibody levels decreased gradually and became undetectable in 6 months with resolution of the hypoglycemia.

Topics: Adolescent; Antithyroid Agents; Autoantibodies; Autoimmune Diseases; Black or African American; Diazoxide; Graves Disease; Humans; Hypoglycemia; Insulin; Male; Methimazole; Prednisone; Propranolol

The aryl hydrocarbon receptor (AhR) is a transcription factor that is activated by xenobiotic substances such as dioxin. After activation, it binds to dioxin response elements of DNA, thereby inducing transcription of a variety of xenobiotic metabolizing enzymes. To investigate whether AhR-activating substances accumulate in patients with endocrine disorders, we tested serum samples for AhR-stimulating activity.. Serum AhR-stimulating activity was evaluated by exposing the HepG2 cells transiently transfected with an AhR-responsive reporter plasmid to serum samples. On the basis of preliminary findings that implicated methimazole (MMI), wild-type and AhR-null mice were treated with MMI, and their plasma AhR-stimulating activities and thyroxine levels were quantified.. In 28 randomly chosen patients, 7 out of 10 Graves' disease patients exhibited increased serum AhR-stimulating activity. The increased activity did not correlate with thyroid hormone status. However, we hypothesized that it might be caused by MMI. Subsequent analyses revealed that in 25 of 26 MMI-treated Graves' patients, serum samples collected after the MMI treatment had significantly higher AhR-stimulating activity compared to samples obtained when the same patients were not on MMI. By contrast, serum AhR-stimulating activity was unchanged in samples from the seven patients on propylthiouracil (PTU) compared to serum taken before the PTU treatment. In vitro experiments demonstrated that an MMI metabolite 3-methyl-2-thiohydantoin, but not MMI, activated AhR. MMI increased plasma AhR-stimulating activities and reduced plasma thyroxine concentrations, in both wild-type and AhR-deficient mice.. Graves' patients taking MMI have increased serum AhR-stimulating activity, which is unrelated to thyroid hormone status, but correlates with MMI treatment. The AhR activation is likely caused by 3-methyl-2-thiohydantoin. Further studies are required to determine the potency of 3-methyl-2-thiohydantoin as an AhR activator and the significance of the differences between MMI and PTU observed in this study.

Topics: Adult; Aged; Aged, 80 and over; Animals; Female; Graves Disease; Hep G2 Cells; Humans; Male; Methimazole; Mice; Middle Aged; Propylthiouracil; Receptors, Aryl Hydrocarbon; Thiohydantoins

Bullous systemic lupus erythematosus (SLE) is a kind of LE-non-specific bullous skin disease that is rarely induced by a medication. We describe the first case of bullous SLE to develop after administration of methimazole. A 31-yr-old woman presented with generalized erythematous patches, multiple bullae, arthralgia, fever, conjunctivitis, and hemolytic anemia. Biopsy of her bulla showed linear deposition of lgG, lgA, C3, fibrinogen, and C1q at dermo-epidermal junction. She was diagnosed as bullous SLE and treated with prednisolone, dapsone, hydroxychloroquine, and methotrexate. Our experience suggests that SLE should be considered as a differential diagnosis when bullous skin lesions develop in patients being treated for hyperthyroidism.

Topics: Adult; Anti-Inflammatory Agents; Antirheumatic Agents; Antithyroid Agents; Blister; Drug Therapy, Combination; Female; Graves Disease; Humans; Hydroxychloroquine; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lupus Nephritis; Methimazole; Mycophenolic Acid; Prednisolone; Skin

Propylthiouracil (PTU) and methimazole (MMI) are drugs that are widely used to treat Graves' disease. Although both exert an antithyroid effect primarily by blocking thyroid peroxidase activity, their molecular structure and other actions are different. We hypothesized that PTU and MMI may have differential effects on thyroid-specific gene expression and function.. The effects of PTU and MMI on thyroid-specific gene expression and function were examined in rat thyroid FRTL-5 cells using DNA microarray, reverse transcriptase (RT)-polymerase chain reaction (PCR), real-time PCR, Western blot, immunohistochemistry, and radioiodine uptake studies.. DNA microarray analysis showed a marked increase in sodium/iodide symporter (NIS) gene expression after PTU treatment, whereas MMI had no effect. RT-PCR and real-time PCR analysis revealed that PTU-induced NIS mRNA levels were comparable to those elicited by thyroid-stimulating hormone (TSH). PTU increased 5'-1880-bp and 5'-1052-bp activity of the rat NIS promoter. While PTU treatment also increased NIS protein levels, the size of the induced protein was smaller than that induced by TSH, and the protein localized predominantly in the cytoplasm rather than the plasma membrane. Accumulation of (125)I in FRTL-5 cells was increased by PTU stimulation, but this effect was weaker than that produced by TSH.. We found that PTU induces NIS expression and iodide uptake in rat thyroid FRTL-5 cells in the absence of TSH. Although PTU and MMI share similar antithyroid activity, their effects on other thyroid functions appear to be quite different, which could affect their therapeutic effectiveness.

Topics: Animals; Graves Disease; Iodides; Methimazole; Propylthiouracil; Rats; Real-Time Polymerase Chain Reaction; RNA, Messenger; Symporters; Thyroid Gland; Thyrotropin

Agranulocytosis is a rare adverse effect of methimazole. The usual duration of treatment prior to the onset of agranulocytosis is approximately 1 to 4 months, and can be as long as 1 year. Agranulocytosis together with hepatotoxicity is an extremely rare idiosyncratic side effect of methimazole treatment. We present an unprecedented case of a Grave's disease patient who showed a strong reaction to methimazole with obvious agranulocytosis and hepatotoxicity which developed only six days after administration. This case, along with a literature review, is offered with the aim to increase the awareness of physicians of sudden onset agranulocytosis and hepatotoxicity from methimazole.

Topics: Adult; Agranulocytosis; Antithyroid Agents; Bone Marrow; Drug-Related Side Effects and Adverse Reactions; Female; Graves Disease; Humans; Liver; Methimazole; Time Factors

To evaluate weight change during hyperthyroidism treatment, and to correlate it with IL-6 and TNF-alpha concentrations.. Forty two patients were included. Body weight (BW), body mass index (BMI), clinical and laboratory characteristics were recorded. IL-6 and TNF-alpha were determined before treatment with methimazole (MMI) and in euthyroidism.. BW was 59.62 ± 11.5 kg in hyperthyroidism, and 69.91 ± 14.4 kg in euthyroidism (p < 0.001). BMI increased from 23.1 ± 3.8 kg/m(2) to 27 kg/m(2) ± 4.7 during treatment (p < 0.0001). Before treatment, 66.6% subjects had BMI < 25 kg/m(2) and 33.3%, BMI > 25 kg/m(2). In euthyroidism, 38% of patients had BMI < 25 kg/m(2) and 62%, BMI > 25 kg/m(2) (p = 0.01). In euthyroidism, we found a significant reduction in IL-6 and TNF-alpha concentrations, but no correlation between IL-6 and TNF-alpha, and BW or BMI.. An important increase in BW and BMI was observed during hyperthyroidism treatment, and IL-6 and TNF-alpha alterations were only related with return to euthyroidism.

Topics: Adult; Antithyroid Agents; Body Mass Index; Body Weight; Female; Graves Disease; Humans; Hyperthyroidism; Interleukin-6; Male; Methimazole; Thyroid Gland; Thyroid Hormones; Tumor Necrosis Factor-alpha; Weight Gain

Thyrotoxic periodic paralysis (TPP) is an uncommon but potentially lethal manifestation of hyperthyroidism characterized by muscle paralysis and hypokalemia. We have reported 3 cases of TPP in male patients, which manifested with morning muscle weakness evolved into paralysis. In all patients were found severe hypokalemia, abnormalities on electrocardiogram, and Graves' hyperthyroidism. Intravenous potassium administration led to normalization of potassium levels, and resolution of neurological symptoms. In addition, beta blockers and methimazole were started. Two patients required total thyroidectomy for poor control of hyperthyroidism with antithyroid drug. In patients presenting with periodic paralysis or diffuse muscle weakness thyroid function should be investigated in order to find out the cases secondary to unknown hyperthyroidism and to start an early appropriate combined therapy. The correct management of TPP can prevent serious cardiopulmonary complications.

Topics: Adrenergic beta-Antagonists; Adult; Antithyroid Agents; Drug Therapy, Combination; Electrocardiography; Graves Disease; Humans; Hypokalemic Periodic Paralysis; Injections, Intravenous; Male; Methimazole; Potassium; Thyroidectomy; Treatment Outcome

The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital disorder characterized by aplasia of the uterus and the upper part of the vagina in an XX individual with normal development of secondary sexual characteristics. Individuals with this syndrome may also present with renal and skeletal abnormalities. We report a case of a 16-year-old girl presenting with thyrotoxicosis and primary amenorrhea. After being diagnosed with Graves disease, this patient was placed on antithyroid medication. Although her thyroid function normalized, she did not start to menstruate. Therefore, we assessed her primary amenorrhea and diagnosed the patient with MRKH syndrome through pelvic imaging. To our knowledge, an association between Graves disease and MRKH syndrome has not yet been reported.

Topics: 46, XX Disorders of Sex Development; Abnormalities, Multiple; Adolescent; Amenorrhea; Antithyroid Agents; Congenital Abnormalities; Diagnosis, Differential; Female; Graves Disease; Humans; Kidney; Methimazole; Mullerian Ducts; Pelvis; Somites; Spine; Thyrotoxicosis; Tomography, X-Ray Computed; Uterus; Vagina

Cytokines are involved in the pathogenesis of Graves' disease (GD), but ambiguous serum cytokine results have been described.. We studied the changes in serum interleukin (IL)-1β, soluble IL-2 receptor (sIL-2R), IL-5, IL-6 and tumor necrosis factor (TNF)-α concentrations in 29 untreated GD patients before and after restoration of euthyroidism with methimazole (MMI) treatment compared to 25 control subjects. Eleven out of 29 GD patients had active Graves' ophthalmopathy (GO).. Compared to controls, untreated GD patients had significantly higher median levels of serum IL-1β (18.7 vs. 34.0 pg/ml), sIL-2R (292.5 vs. 1,585.0 pg/ml), IL-5 (1.0 vs. 9.0 pg/ml), IL-6 (3.0 vs. 5.0 pg/ml) and TNF-α (8.1 vs. 16.0 pg/ml). In euthyroidism following MMI treatment, concentrations of IL-1β (25.0 pg/ml), sIL-2R (362.0 pg/ml), IL-5 (3.0 pg/ml), IL-6 (3.0 pg/ml) and TNF-α (5.0 pg/ml) declined significantly and were similar to controls. The greatest reductions were noted in sIL-2R (76.9%), TNF-α (68.8%) and IL-5 (66.6%) levels. Serum sIL-2R, IL-5 and TNF-α levels in active GO patients were significantly elevated, but no significant differences were observed in GD patients without GO. Using a multiple linear regression analysis, serum IL-1β was significantly associated with free thyroxine, sIL-2R with triiodothyronine and serum thyrotropin receptor antibody (TRAb) and TNF-α with TRAb.. These results support the notion that serum cytokines could be used as a marker of GD activity, and the decrease in cytokine levels might be related to the achievement of euthyroidism and the immunomodulatory effects of MMI treatment.

Topics: Adolescent; Adult; Antithyroid Agents; Cytokines; Female; Graves Disease; Graves Ophthalmopathy; Humans; Male; Methimazole; Middle Aged; Thyroid Function Tests; Young Adult

To study the possible pharmacokinetic and pharmacodynamic interactions between irinotecan and methimazole.. A patient treated for colorectal cancer with single agent irinotecan received methimazole co-medication for Graves' disease. Irinotecan pharmacokinetics and side effects were followed during a total of four courses (two courses with and two courses without methimazole).. Plasma concentrations of the active irinotecan metabolite SN-38 and its inactive metabolite SN-38-Glucuronide were both higher (a mean increase of 14 and 67%, respectively) with methimazole co-medication, compared to irinotecan monotherapy. As a result, the mean SN-38 glucuronidation rate increased with 47% during concurrent treatment. Other possible confounding factors did not change over time. Specific adverse events due to methimazole co-treatment were not seen.. Additional in vitro experiments suggest that these results can be explained by induction of UGT1A1 by methimazole, leading to higher SN-38G concentrations. The prescribed combination of these drugs may lead to highly toxic intestinal SN-38 levels. We therefore advise physicians to be very careful in combining methimazole with regular irinotecan doses, especially in patients who are prone to irinotecan toxicity.

Topics: Antineoplastic Agents, Phytogenic; Antithyroid Agents; Camptothecin; Colorectal Neoplasms; Drug Interactions; Glucuronides; Glucuronosyltransferase; Graves Disease; Humans; Irinotecan; Male; Methimazole; Middle Aged

3,5,3'-triiodothyronine-predominant Graves' disease (T(3)-P-GD) is characterized by a persistently high serum T(3) level and normal or even lower serum thyroxine (T(4)) level during antithyroid drug therapy. The source of this high serum T(3) level has not been clarified. Our objective was to evaluate the contribution of type 1 and type 2 iodothyronine deiodinase (D1 (or DIO1) and D2 (or DIO2) respectively) in the thyroid gland to the high serum T(3) level in T(3)-P-GD.. We measured the activity and mRNA level of both D1 and D2 in the thyroid tissues of patients with T(3)-P-GD (n=13) and common-type GD (CT-GD) (n=18) who had been treated with methimazole up until thyroidectomy.. Thyroidal D1 activity in patients with T(3)-P-GD (492.7±201.3 pmol/mg prot per h) was significantly higher (P<0.05) than that in patients with CT-GD (320.7±151.9 pmol/mg prot per h). On the other hand, thyroidal D2 activity in patients with T(3)-P-GD (823.9±596.4 fmol/mg prot per h) was markedly higher (P<0.005) than that in patients with CT-GD (194.8±131.6 fmol/mg prot per h). There was a significant correlation between the thyroidal D1 activity in patients with T(3)-P-GD and CT-GD and the serum FT(3)-to-FT(4) ratio (r=0.370, P<0.05). Moreover, there was a strong correlation between the thyroidal D2 activity in those patients and the serum FT(3)-to-FT(4) ratio (r=0.676, P<0.001).. Our results suggest that the increment of thyroidal deiodinase activity, namely D1 and especially D2 activities, may be responsible for the higher serum FT(3)-to-FT(4) ratio in T(3)-P-GD.

Topics: Adult; Aged; Antithyroid Agents; Biomarkers; Female; Graves Disease; Humans; Iodide Peroxidase; Iodothyronine Deiodinase Type II; Male; Methimazole; Middle Aged; Polymerase Chain Reaction; RNA, Messenger; Thyroid Gland; Thyroidectomy; Thyroxine; Triiodothyronine

Treatment of Graves' disease during pregnancy with antithyroid drugs (ATDs) poses a risk of inducing hypothyroidism and, thus, development of a goiter to the fetus.. We report two patients referred to our department after discovery of a fetal goiter by ultrasound examination in the second trimester of pregnancy. The women receiving 400 mg/day propylthiouracil and 10 mg/day thiamizole, respectively, had thyrotropin and total thyroxine values within the normal reference range but a lowered free thyroxine level. Fetal blood sampling by cordocentesis revealed severe fetal hypothyroidism as the cause of goiter development. Reduction of maternal ATD dose and injection of levothyroxine intra-amniotically quickly reduced the goiter size, and both babies were born euthyroid and without goiters.. Two pregnant women with Graves' disease were overtreated with ATDs inducing iatrogenic goiter in the fetuses. Successful treatment with intra-amniotic levothyroxine injections rendered the babies euthyroid and nongoitrous at birth.. Correct interpretation of thyroid function tests during pregnancy in general--and during ATD therapy of Graves' disease in particular--is difficult. Awareness of pregnancy-related changes in maternal thyroid status, and a close teamwork among endocrinologists, obstetricians, and experts in fetal medicine, is pivotal in ensuring normal growth and development of the unborn child of these patients.

Topics: Adult; Antithyroid Agents; Female; Fetal Diseases; Goiter; Graves Disease; Humans; Hypothyroidism; Infant, Newborn; Male; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Second; Propylthiouracil; Thyrotropin; Thyroxine

According to the guideline issued by the Japan Thyroid Association in 2006 for treatment of Graves' disease, discontinuing antithyroid drug (ATD) therapy is recommended when serum free thyroxine (FT4) and thyroid stimulating hormone (TSH) concentrations have been maintained within the reference range for a certain period after treatment with one ATD tablet every other day (minimum maintenance dose therapy, MMDT). In this retrospective study, the relationship between MMDT duration and remission rate was investigated. The participants were 107 consecutive patients with Graves' disease whose ATD therapy was stopped according to the guideline. Serum FT4, TSH, and TSH receptor antibody (TRAb) levels were measured when ATD was discontinued and every 3 months thereafter. The percentage of patients in remission was 86.9% at 6 months, 73.8% at 1 year, and 68.2% at 2 years after ATD discontinuation. The remission rate increased with MMDT duration, being significantly higher in patients with MMDT durations of 19 months or more than those with MMDT durations of 6 months or less. In patients with MMDT durations of 6 months or less, the remission rate was significantly lower in TRAb-positive patients than in TRAb-negative patients at the time of withdrawal of ATD; however, this was not observed in patients with MMDT durations of 7 months or more. These findings suggest that in patients who discontinue ATD after a certain MMDT duration, the remission rate increases as the MMDT duration increases, and ATD should not be discontinued in TRAb-positive patients with MMDT durations of 6 months or less.

Topics: Adolescent; Aged; Antithyroid Agents; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Japan; Male; Methimazole; Middle Aged; Propylthiouracil; Recurrence; Remission Induction; Retrospective Studies; Thyroid Gland; Thyrotropin; Thyroxine; Time Factors; Treatment Outcome

Agranulocytosis/granulocytopenia is a rare side effect of thyreostatics. Earlier publications state that for thiamazole this side effect occurs during the first few months of treatment. In two patients this thiamazole-induced agranulocytosis/granulocytopenia only occurred after years of treatment. A 53-year-old man presented with fever after a visit to Suriname. He had used thiamazole for 12 years for Graves' hyperthyroidism. The second patient, a 31-year-old woman, presented at the emergency department with fever and sore throat after 13 years of intermittent treatment with thiamazole. Both patients had an agranulocytosis/granulocytopenia and leukopenia. This was thought to be a side effect of thiamazole and blood values normalised after cessation of therapy. Both patients were treated empirically with broad-spectrum antibiotics during the agranylocytic period. They then received radioactive sodium iodide. To our knowledge this case report is the first to describe agranulocytosis/granulocytopenia following long-term treatment with thiamazole.

Topics: Adult; Agranulocytosis; Anti-Bacterial Agents; Antithyroid Agents; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Time Factors; Treatment Outcome

Agranulocytosis is an uncommon but serious complication of Graves' disease under thionamide therapy. In some patients removal of circulating thyroid hormones and thyroid antibodies by plasmapheresis is an effective adjunctive therapeutic option. In perioperative settings, however, plasmapheresis may cause excess bleeding intraoperatively due to coagulation factor depletion unless fresh frozen plasma (FFP) products are used in the replacement fluid mix. Double filtration plasmapheresis (DFPP) in which only a small amount of albumin supplementation is used may be a potential alternative to conventional apheresis interventions where clotting factor depletion is problematic. We report a case of a patient with Graves' disease complicated with intravenous immunoglobulin responsive methimazole-induced agranulocytosis/hemophagocytosis who underwent successful preoperative DFPP treatment in preparation for thyriodectomy. In addition to conventional apheresis using FFP replacement, DFPP may offer an effective adjunct option in the management of hyperthyroid patients needing emergent surgical interventions.

Topics: Adult; Agranulocytosis; Female; Graves Disease; Humans; Lymphohistiocytosis, Hemophagocytic; Methimazole; Plasmapheresis; Preoperative Care; Treatment Outcome

Right-sided heart failure with clinical manifestation is only occasionally seen in patients with Graves' disease (GD). Recent studies revealed that pulmonary hypertension (PHT) detected by echocardiography was not rare in patients with GD. We performed this study to investigate the prevalence of PHT in patients with GD before and after antithyroid treatment, and to assess potential mechanisms from the relationship with clinical and echocardiographic features.. Serial echocardiographic examinations were performed in 64 patients with newly diagnosed GD before and after antithyroid treatment to measure cardiac factors, such as pulmonary artery systolic pressure (PAPs), cardiac output, total vascular resistance, left ventricular filling pressure and right ventricular (RV) function. PHT was defined as PAPs of at least 35 mmHg.. The prevalence of PHT in untreated GD patients was 44% (28 out of 64 patients). The presence of systemic hypertension was associated with PHT, especially with pulmonary venous hypertension. GD patients with PHT showed reduced RV function represented by higher RV myocardial performance index without difference of pulmonary vascular resistance, RV wall thickness and peak systolic velocity of free wall side of tricuspid annulus. Follow-up echocardiography was performed in 20 out of 28 GD patients with PHT, and PHT disappeared in all except one patient.. PHT is a frequent and reversible complication in patients with GD. Our study suggests that PHT in GD may not be related to underlying autoimmune process and increased pulmonary blood flow from thyrotoxicosis might contributes to the pathogenesis of PHT related to GD.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Echocardiography; Female; Graves Disease; Humans; Hypertension, Pulmonary; Male; Methimazole; Middle Aged; Thyroid Hormones; Young Adult

Topics: Antithyroid Agents; Arthritis; Child; Female; Graves Disease; Humans; Methimazole; Severity of Illness Index

Topics: Adolescent; Amino Acid Substitution; Antithyroid Agents; Drug Monitoring; Graves Disease; Humans; Male; Methimazole; Mutation, Missense; Thyroid Hormone Receptors beta; Thyroid Hormone Resistance Syndrome; Thyrotropin; Treatment Outcome

During pregnancy, changes in maternal physiology influence thyroid status. In addition, maternal thyroid disease can have substantial adverse effects on the fetus. Therefore, evaluating and treating women with thyroid disease during pregnancy requires careful observation and management to ensure favorable pregnancy outcomes. To evaluate thyroid hormone levels during gestation, gestational age-specific values should be used. When hyperthyroidism is treated, the goals of therapy are to achieve a subclinical hyperthyroid state and monitor fetal development. Care must be taken so as not to induce a state of maternal hypothyroidism during pregnancy, since such a diagnosis is also associated with adverse outcomes for both mother and infant.. Consideration should be given to routine screening of pregnant women and all women of childbearing age for thyroid disease.

Topics: Female; Fetus; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Infant, Newborn, Diseases; Methimazole; Pregnancy; Pregnancy Complications; Thyroid Diseases; Thyroid Gland; Thyrotoxicosis; United States

Topics: Adult; Ectodermal Dysplasia; Female; Graves Disease; Humans; Infant, Newborn; Male; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Prenatal Exposure Delayed Effects

To ascertain the prevalence of Graves' disease (GD) in 1,323 Caucasian children with type 1 diabetes mellitus (T1DM), and to compare the course of GD in T1DM patients with the one observed in 109 Caucasian peer patients with GD but without T1DM (group B).. Only 7 patients (0.53%) of the T1DM series also presented with GD (group A)which was diagnosed many years after diabetes presentation. At GD diagnosis, the prevalence of preclinical hyperthyroidism was higher in group A (p = 0.0001), whereas serum TSH receptor antibodies (TRABs) were higher in group B (p = 0.04). The subsequent course with methimazole therapy and after its withdrawal was very similar in both groups.. GD prevalence in T1DM patients was 0.53%, i.e. almost identical to the one reported in the general population. GD was diagnosed many years after T1DM presentation. At GD diagnosis, the clinical picture was milder and TRAB serum levels were lower in diabetic patients. Preclinical diagnosis and early treatment of GD were not associated with better responsiveness to therapy. Screening programs based on periodical TRAB assessments are not useful in T1DM.

Topics: Adolescent; Child; Child, Preschool; Diabetes Mellitus, Type 1; Disease Progression; Female; Graves Disease; Humans; Hyperthyroidism; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Prevalence; Prognosis; Receptors, Thyrotropin; Retrospective Studies; Thyroiditis, Autoimmune

A 15-year-old female presented to a pediatric emergency department with glycosuria, ketonuria, and hyperglycemia and was admitted with a presumed diagnosis of diabetes mellitus. The patient required no insulin therapy and only minor dietary modification to maintain euglycemia. Clinical examination and laboratory findings revealed a primary diagnosis of Graves' hyperthyroidism with associated impaired glucose tolerance. Here, we review the mechanisms of thyrotoxicosis resulting in impaired glucose metabolism.

Topics: Adolescent; Adrenergic beta-Antagonists; Antithyroid Agents; Blood Glucose; Female; Graves Disease; Humans; Hyperglycemia; Iodine Radioisotopes; Methimazole; Propranolol; Thyrotoxicosis; Thyroxine

Patients with severe Graves' orbitopathy often have hyperthyroidism that is difficult to treat and a high proportion of patients experience relapse of hyperthyroidism after a course of antithyroid drug (ATD) therapy of fixed duration. The aim of the study was to evaluate the feasibility of prolonged low-dose ATD therapy for attaining stable euthyroidism in patients with severe Graves' orbitopathy and hyperthyroidism.. We performed retrospective analyses of data collected during observation of a cohort of patients (n = 108) treated for severe Graves' orbitopathy and for hyperthyroidism using partial block with low-dose thionamide + replacement with levothyroxine (L-T4) for >2 years. The study was performed at a university hospital referral center for patients with severe Graves' orbitopathy.. The median duration of thionamide therapy was 80 months (25-75 percentiles: 55-115 months); 101 patients received methimazole (median: 5 mg/day) without side effects during prolonged therapy, and 7 propylthiouracil (median: 200 mg/day); median L-T4 dose was 0.1 mg/day. Ninety percent of patients remained euthyroid throughout the period of therapy, and 65% of them had thyroid stimulating hormone (TSH) receptor antibodies in serum within the assay reference interval at the last observation. Only four (3.7%) developed episodes of hyperthyroidism during stable therapy, and 94% had serum TSH within 0.1-4.0 mU/L at the last observation. One patient developed reversible cutaneous vasculitis after 6 years of propylthiouracil therapy.. Prolonged partial block plus replacement therapy with low-dose ATD + L-T4 keeps the majority of patients with severe Graves' orbitopathy and hyperthyroidism stable and euthyroid.

Topics: Adult; Antithyroid Agents; Biomarkers; Denmark; Drug Administration Schedule; Feasibility Studies; Female; Graves Disease; Graves Ophthalmopathy; Hormone Replacement Therapy; Hospitals, University; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Propylthiouracil; Recurrence; Retrospective Studies; Severity of Illness Index; Thyroxine; Time Factors; Treatment Outcome

Little information is available about changes in body weight and body mass index in children before, during, and after treatment for Graves' disease (GD).. Our objective was to examine changes in body weight after treatment for GD in children as related to clinical features.. The medical records of 43 pediatric patients with GD [35 girls and eight boys, aged 4.0-18.5 (mean 10.9) yr] were examined. Patients were included if clinical data were available for 1 yr before and after the diagnosis of GD.. Weight, height, body mass index (BMI) z-scores, and thyroid hormone levels were assessed.. Overall, patients presented with an average BMI z-score of -0.02 ± 1.05 that was not different from the normal population (P = 0.921) or their premorbid values (P = 0.07). However, in the subset of patients who were initially overweight or obese in the premorbid state, the BMI decreased significantly during the development of hyperthyroidism (P < 0.05). After initiation of treatment, patients gained significant amounts of weight over the first 6 months leading to elevated BMI z-scores (P < 0.0001), and elevations in BMI persisted in about 25% of the patients.. Excessive weight gain within 6 months of treatment is seen in children treated for GD, and the gain in weight can persist.

Topics: Adolescent; Aging; Antithyroid Agents; Body Mass Index; Body Weight; Child; Child, Preschool; Cohort Studies; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Propylthiouracil; Sex Characteristics; Thyroid Function Tests; Thyroid Hormones; Thyroidectomy; Weight Gain

Resistance to thyroid hormone (RTH) is characterized by elevated serum levels of thyroid hormones and normal or slightly increased serum thyrotropin (TSH) levels. Recently it has been suggested that chronic TSH stimulation in RTH activates intrathyroidal lymphocytes, leading to thyroid damage and autoimmune thyroid disease (AITD). Therefore, individuals with RTH have an increased likelihood of AITD compared to unaffected relatives. We here report a 33-year-old woman in whom we diagnosed Graves' disease and treated her with thiamazole (MMI). For two years, her TSH levels were suppressed when thyroid hormones were elevated and conversely they were increased when thyroid hormones levels were decreased. These findings were common for a clinical course during treatment for Graves' disease with anti-thyroid drug. However, three years after the initiation of MMI therapy, she had a normal or gradually elevated serum TSH level even though the level of thyroid hormones never decreased, indicating inappropriate secretion of TSH. We concluded she had RTH clinically, and we demonstrated by direct sequence analysis a mutation of the TRβ gene, causing replacement of a glycine (G) with arginine (R) at codon 251. The finding of an elevated TSH level without decreased thyroid hormones should suggest the presence of RTH during therapy of Graves' disease.

Topics: Adult; Antithyroid Agents; Comorbidity; Female; Genes, erbA; Graves Disease; Humans; Methimazole; Mutation; Thyroid Hormone Resistance Syndrome; Thyrotropin

Interferon-induced thyroiditis (IIT) is a major clinical problem for patients receiving interferon-alpha (IFN-α) therapy. But, destructive thyroiditis followed by Graves' disease associated with IFN-α therapy is very rarely reported. Herein, we report a rare case of pegylated IFN-α (pegIFN-α) induced destructive thyroiditis followed by Graves' disease in a patient with HCV infection. A 31-yr-old woman suffered from chronic active hepatitis C and was treated with pegIFN-α and ribavirin for 12 months. Results of a thyroid function test and autoantibody levels were normal before IFN-α therapy was initiated. Destructive thyrotoxicosis appeared seven months after the initiation of IFN-α therapy, followed by Graves' thyrotoxicosis two months after the cessation of therapy. The diagnoses of destructive thyroiditis and Graves' disease were confirmed by the presence of TSH receptor antibodies in addition to Tc-99m scintigraphy findings. The patient's antithyroglobulin antibody titer increased gradually during IFN-α therapy and remained weakly positive after IFN-α therapy was discontinued.

Topics: Adult; Antiviral Agents; Female; Graves Disease; Hepatitis C, Chronic; Humans; Interferon-alpha; Methimazole; Propranolol; Thyroiditis

We report on a 9-year-old boy who suffered from hyperthyroidism and a new appearance of enuresis. Bedwetting ceased and prepulse inhibition (PPI) - measured as a parameter of central control - increased during the course of therapy.. The increase in PPI is an indication that enuresis in hyperthyroidism could be as a result of a temporary loss of central control on brainstem reflexes. The case conveys new insights into the correlation between thyroid hormones and micturition patterns and the aetiology of enuresis.

Topics: Antithyroid Agents; Brain Stem; Child; Graves Disease; Humans; Male; Methimazole; Neural Inhibition; Nocturnal Enuresis; Reflex, Startle

To compare the presentation and clinical course of Graves' disease (GD) in two pediatric populations consisting of 28 patients with Down's syndrome (DS) and 109 controls without DS respectively.. The evolution over time of GD was determined in both groups according to the clinical changes and the variations in TSH, free thyroxine, and TSH receptor autoantibodies serum levels during the entire follow-up.. Female prevalence (50 vs 81.6%; chi(2)=12.0, P<0.0005) and average age at GD presentation (9.9+/-4.4 vs 11.5+/-3.5 years, P<0.05) were significantly lower in DS group than in controls. Clinical responsiveness to methimazole therapy was significantly better in DS patients, as demonstrated by both the lower relapse rates after the first cycle withdrawal (7.1 vs 31.2%; chi(2)=7.4, P<0.005) and the higher persistent remission rates after definitive therapy withdrawal (46.4 vs 26.7%; chi(2)=4.1, P<0.05). Moreover, in DS group, no patients needed surgery or radioiodine ablation, whereas non-pharmacological treatment was necessary in 11% of controls (chi(2)=3.8, P<0.05). Antecedents of Hashimoto's thyroiditis (HT) were documented in 21.4% of DS patients and in 3.7% of controls (chi(2)=10.4, P<0.005). Association with other autoimmune diseases was detected in 32.1% of DS cases and in 12.8% of controls (chi(2)=5.94, P<0.025).. GD in DS children and adolescents is characterized by several peculiarities: i) earlier presentation; ii) no gender predominance; iii) less severe clinical course; iv) higher frequency of documented HT antecedents; v) more frequent association with other autoimmune diseases.

Topics: Adolescent; Age of Onset; Antithyroid Agents; Chi-Square Distribution; Child; Disease Progression; Down Syndrome; Female; Graves Disease; Humans; Kaplan-Meier Estimate; Male; Methimazole; Patient Selection; Prevalence; Severity of Illness Index; Sex Factors; Statistics, Nonparametric

Methimazole (MeimzH) is an anti-thyroid drug and the first choice for patients with Grave's disease. Two new copper(II) complexes of this drug: [Cu(MeimzH)(2)(NO(3))(2)]*0.5H(2)O and [Cu(MeimzH)(2)(H(2)O)(2)](NO(3))(2)*H(2)O were synthesized and characterized by elemental analysis, dissolution behavior, thermogravimetric analysis and UV-vis, diffuse reflectance, FTIR and EPR spectroscopies. As it is known that copper(II) cation can act as an inhibitor of alkaline phosphatase (ALP), the inhibitory effect of methimazole and its copper(II) complexes on ALP activity has also been investigated.

Topics: Alkaline Phosphatase; Animals; Antithyroid Agents; Copper; Electron Spin Resonance Spectroscopy; Graves Disease; Humans; Methimazole; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared

It is well known that iodide exacerbates thyroid function in subclinical hypothyroid patients with autoimmune thyroiditis. To investigate the immunological mechanism of iodine-induced thyroid dysfunction, we studied the effect of iodide in cultured human thyroid follicles, which respond to physiological concentrations of human thyrotropin (TSH) (0.3-10 microU/mL) and maintain the Wolff-Chaikoff effect.. Thyroid follicles obtained from Graves' patients at subtotal thyroidectomy were precultured in medium containing 0.5% fetal calf serum and 10(-8) M iodide for 5 days, and then cultured with the medium containing bovine TSH (30 microU/mL) and low (10(-8)M) or high (10(-5)M) concentrations of iodide. After 3-72 hours of culture, the effect of iodide on thyroid cell mRNA expression was analyzed by microarray and reverse transcriptase-polymerase chain reaction.. After 48 hours of culture, iodide nearly doubled the mRNA expression levels of the immunity-associated genes (intercellular adhesion molecule-1, transforming growth factor beta 1-induced protein, early growth response gene 1, guanylate-binding protein 1, and annexin A1) and decreased the mRNA expression of sodium-iodide symporter to less than 20%. Further, the mRNA expression levels of chemokines (CCL2, CXCL8, and CXCL14) increased nearly twofold, whereas their receptors did not show any significant response. Real-time polymerase chain reaction analyses confirmed that iodide increased the mRNA expression levels of these genes in a time- and concentration-dependent manner. Immunohistochemical studies revealed that the chemokines were expressed mainly in the thyroid follicular cells in addition to the immune cells. The iodide-induced increase in CCL2 was greater in thyroid follicles obtained from thyroid gland that had been moderately infiltrated with the immunocompetent cells.. We have demonstrated that iodide stimulates thyroid follicular cells to produce chemokines, particularly CCL2, CXCL8, and CXCL14. These chemokines and intercellular adhesion molecule-1 would attract immunocompetent cells into thyroid gland. These in vitro findings suggest that iodide at high concentrations may induce thyroid dysfunction through not only biochemical but also immunological mechanisms, particularly in patients with autoimmune thyroid disorders.

Topics: Antithyroid Agents; Chemokines; Dose-Response Relationship, Drug; Down-Regulation; Graves Disease; Humans; Immunogenetic Phenomena; Immunohistochemistry; Iodides; Methimazole; Oligonucleotide Array Sequence Analysis; Protein Isoforms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Symporters; Thyroid Gland; Thyrotropin; Time Factors; Tissue Culture Techniques; Up-Regulation

Immunoglobulins stimulating the TSH receptor (TSI) influence thyroid function and likely mediate extrathyroidal manifestations of Graves' disease (GD).. The aim of this study was to assess the clinical relevance of TSI in GD patients with or without Graves' orbitopathy (GO), to correlate the TSI levels with activity/severity of GO, and to compare the sensitivity/specificity of a novel TSI bioassay with TSH receptor (TSH-R) binding methods (TRAb).. TSI were tested in two reporter cell lines designed to measure Igs binding the TSH-R and transmitting signals for cAMP/CREB/cAMP regulatory element complex-dependent activation of luciferase gene expression. Responsiveness to TSI of the novel chimeric (Mc4) TSH-R (amino acid residues 262-335 of human TSH-R replaced by rat LH-R) was compared with the wild-type (wt) TSH-R.. All hyperthyroid GD/GO patients were TSI-positive. TSI were detected in 150 of 155 (97%, Mc4) and 148 of 155 (95%, wt) GO patients, in six of 45 (13%, Mc4) and 20 of 45 (44%, wt) mostly treated GD subjects, and in 0 of 40 (Mc4) and one of 40 (wt) controls. Serum TSI titers were 3- and 8-fold higher in GO vs. GD and control, respectively. All patients with diplopia and optic neuropathy and smokers were TSI-positive. TSI strongly correlated with GO activity (r = 0.87 and r = 0.7; both P < 0.001) and severity (r = 0.87 and r = 0.72; both P < 0.001) in the Mc4 and wt bioassays, respectively. Clinical sensitivity (97 vs. 77%; P < 0.001) and specificity (89 vs. 43%; P < 0.001) of the Mc4/TSI were greater than TRAb in GO. All 11 of 200 (5.5%) TSI-positive/TRAb-negative patients had GO, whereas all seven of 200 (3.5%) TSI-negative/TRAb-positive subjects had GD only.. The novel Mc4/TSI is a functional indicator of GO activity and severity.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Antithyroid Agents; Female; Graves Disease; Graves Ophthalmopathy; Humans; Hyperthyroidism; Immunoglobulins, Thyroid-Stimulating; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Rats; Receptors, Thyrotropin; Reference Values; Severity of Illness Index; Thyroidectomy; Young Adult

Hyperthyroidism is mainly caused by Graves' disease and toxic adenoma or multinodular goiter. In Europe, treatment of both disorders is usually started with antithyroidal drugs such as methimazole. Complications include agranulocytosis and the risk is dose-dependent. The starting dose of methimazole should not exceed 15-20 mg/d. Propylthiouracil can cause severe liver failure, leading to liver transplantation or death. Propylthiouracil, therefore, should not be used as first line agent and is only recommended when an antithyroid drug is to be started during the first trimester of pregnancy or in individuals who have experienced adverse responses to methimazole. Toxic adenoma is finally treated with radioioidine. To reduce the risk of treatment failure, antithyroidal drugs should be stopped at least one week prior to radioiodine. For Graves' disease, remission is unlikely if antibodies against the TSH-receptor remain above 10 mU/l after 6 months of antithyroidal treatment and radioiodine or thyroidectomy can be recommended. Thyroidectomy should be performed as (near) total thyreoidectomy.

Topics: Adenoma; Agranulocytosis; Antithyroid Agents; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Neoplasms; Thyroidectomy

A 34-year-old Japanese woman was referred to the hospital because of general fatigue and palpitations. She was diagnosed as having resistance to thyroid hormone (RTH) and Hashimoto's thyroiditis at the age of 28. She felt general fatigue, palpitations, heat intolerance, and sweating for 6 months. Thyroid function tests demonstrated elevated levels of free triidothyronine (T3) and free thyroxine (T4) that were above detectable ranges and a completely suppressed level of TSH that was below the detectable range. Titers of anti-TSH receptor antibody (TRAb) and thyroid-stimulating antibody (TSAb) were positive. A 20-minute Technetium-m99 pertechnetate thyroid uptake imaging study showed an elevated value of 39.53% and a normal-shaped thyroid gland. These results indicated that Graves' disease (GD) caused primary hyperthyroidism. Pituitary and peripheral tissues responded to the presence of excess thyroid hormone in the patient. Oral administration of methimazole was started and continued for 1 year 10 months, after which it was ceased. Two years after the cessation of methimazole treatment, level of free T4 was elevated compared to reference range, but levels of TSH and free T3 were within normal reference ranges. Titers of TRAb and TSAb remained negative for 2 years. These findings indicated that the patient's GD was in remission. In conclusion, it is difficult to make a differential diagnosis between GD with RTH and GD alone if RTH is not diagnosed before the onset of GD. An antithyroid drug is able to cause the remission of GD with RTH.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Hashimoto Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Methimazole; Radionuclide Imaging; Remission Induction; Sodium Pertechnetate Tc 99m; Thyroid Gland; Thyroid Hormone Resistance Syndrome; Thyrotropin; Thyroxine; Triiodothyronine

A major problem with antithyroid drug (ATD) therapy in Graves' disease is the high relapse rate. Therefore, clinicians have sought prognostic indicators of permanent remission. Suppression of serum thyrotropin (TSH) when ATD therapy is stopped carries a poor prognosis, but little is known regarding the significance of elevated serum TSH concentrations in the course of ATD therapy. The objective of this study was to determine if elevated serum TSH concentrations during methimazole (MMI) therapy is associated with a favorable long-term prognosis.. We retrospectively studied patients with Graves' disease who were initially on MMI, in whom this drug was stopped because they had undetectable thyroid-stimulating antibodies (TSAbs) or were euthyroid after at least 24 months on MMI treatment. A strategy of high MMI doses plus T4 was not used in these patients. We identified 40 patients with elevated serum TSH concentration (>10 microIU/mL) during MMI therapy (H-TSH group). Eighty-five percent of the H-TSH group had negative tests for TSAb. The H-TSH group was sex- and age-matched with 37 patients who had similar selection criteria, but did not have elevated serum TSH concentration during MMI therapy (N-TSH group). The H-TSH and N-TSH groups were similar in gross thyroid size, percentage of patients with exophthalmos, serum free thyroxine, duration of MMI treatment, TSAb status, duration that their TSAb tests remained negative, and thyroid peroxidase antibody titers. The patients were followed for 24 months after stopping MMI.. In the H-TSH group, MMI-associated hypothyroidism typically occurred after 7-8 months of treatment with daily doses of 10-15 mg MMI. No patient had severe symptoms of hypothyroidism. The percentage of patients in remission at 6, 12, and 24 months after discontinuation of MMI was 90.0, 87.5, and 85.0, respectively, in the H-TSH group and 70.3, 67.6, and 54.1, respectively, in the N-TSH group (p  <  0.05 for the comparison of groups at 6 and 12 months and p  <  0.001 for comparison of the groups at 24 months).. In patients with Graves' disease who are treated with MMI for at least 2 years and become euthyroid, the occurrence of elevated serum TSH concentrations during MMI treatment is a favorable indicator for long-term remission and is independent of multiple other factors including TSAb status, duration of MMI treatment, and gross parameters of goiter size.

Topics: Adult; Antithyroid Agents; Autoantibodies; Exophthalmos; Female; Goiter; Graves Disease; Humans; Hypothyroidism; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Prognosis; Retrospective Studies; Thyrotropin; Thyroxine

Topics: Antithyroid Agents; Coronary Artery Bypass; Coronary Stenosis; Drug Therapy, Combination; Female; Graves Disease; Humans; Hydrocortisone; Hyperthyroidism; Methimazole; Middle Aged; Potassium Iodide; Severity of Illness Index; Thyroid Crisis; Treatment Outcome

Thymic hyperplasia is associated with Graves' disease, particularly in young patients. The degree of thymic transformation is minimal in most but not all patients. In the latter group radiological measurements of thyroid size and their change with treatment have rarely been reported. We present two patients with Graves' disease and relatively rapid resolution of thymic enlargement after successful treatment of their hyperthyroidism.. Three patients with thyrotoxicosis secondary to Graves' disease and marked thymic enlargement were seen at our institution during a 2-year period. On computed tomography (CT) studies their volumes were 67, 81, and 54 cm(3). Thymic hyperplasia in the setting of Graves' disease was the diagnosis of exclusion. Two of the patients returned for follow-up after successful treatment of thyrotoxicosis as requested. On repeat CT their thymic volumes had decreased by 72% and 78%, respectively. Two types of histological modifications of the thymus have been described in association with Graves' disease, namely, thymic parenchyma hyperplasia and medullary lymphoid hyperplasia. The mechanisms underlying thymic transformation in patients with Graves' hyperthyroidism are not completely elucidated, but autoimmune processes underlying Graves' disease are presumed to play a role. The clinical course of our patients is consistent with earlier literature, indicating that thymic enlargement may occur in conjunction with Graves' hyperthyroidism, and that it usually resolves as hyperthyroidism is treated, but there is little quantitative pre- and posttreatment of hyperthyroidism data.. Although every patient must be individually considered, it appears that thymic hyperplasia can be diagnosed in most Graves' hyperthyroid patients by considering the clinical context and appropriate radiologic studies such as CT. Raising awareness of the association of thymic hyperplasia in patients with Graves' hyperthyroidism and its resolution with the reversibility of the hyperthyroid state should prevent unnecessary thymic evaluation and surgery with its attendant risks.

Topics: Adrenergic beta-Antagonists; Adult; Anti-Inflammatory Agents; Antithyroid Agents; Calcium Channel Blockers; Diltiazem; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Organ Size; Prednisone; Propanolamines; Propranolol; Radiography; Thymus Gland; Thymus Hyperplasia; Thyroidectomy; Thyrotoxicosis; Thyrotropin; Thyroxine; Treatment Outcome; Triiodothyronine; Young Adult

A 56-year-old woman with Graves' disease presented with the complaints of diarrhea and palpitations. Physical examination and laboratory data revealed hypothermia and signs of mild hyperthyroidism, heart failure, hepatic dysfunction with jaundice, hypoglycemia, and lactic acidosis. The patient was diagnosed as having developed the complication of thyroid storm in the absence of marked elevation of the thyroid hormone levels, because of the potential hepatic and cardiac dysfunctions caused by heavy alcohol drinking. A year later, after successful treatment, the patient remains well without any clinical evidence of heart failure or hepatic dysfunction. Thyroid storm associated with lactic acidosis and hypothermia is a serious condition and has rarely been reported. Prompt treatment is essential even if the serum thyroid hormone levels are not markedly elevated. We present a report about this patient, as her life could eventually be saved.

Topics: Acidosis, Lactic; Alcoholism; Diarrhea; Echocardiography; Female; Graves Disease; Humans; Hypothermia; Methimazole; Middle Aged; Thyroid Crisis; Thyroid Hormones; Tomography, X-Ray Computed; Treatment Outcome

A 45-year-old man was hospitalized because of weight loss, finger tremor, thirst, polydipsia and increased urinary frequency. He was diagnosed with Graves' disease (GD) and central diabetes insipidus (CDI). Magnetic resonance imaging revealed the enlarged posterior pituitary with thickened stalk. Histological examination obtained from biopsy of the pituitary revealed lymphocytic infundibulo-neurohypophysitis. He received treatment with thiamazole (MMI) for GD and desmopressin acetate (DDAVP) for CDI. However, DDAVP administration could be discontinued as GD was gradually improved. This course indicates that not only the recovered renal response to arginine-vasopressin but also the immunomodulative effects of MMI might attribute to the improvement of polyuria.

Topics: Arginine Vasopressin; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Fibrosis; Graves Disease; Humans; Inflammation; Lymphocytes; Male; Methimazole; Middle Aged; Osmolar Concentration; Pituitary Gland, Posterior; Polyuria; Remission Induction; Saline Solution, Hypertonic; Thyroxine; Urine

A 55-year-old Filipina with Grave's disease, diabetes, hypertension, bronchial asthma, Parkinson's disease and a history of adverse drug reaction to penicillin consulted due to high-grade fever and sore throat. Patient was diagnosed with aplastic anaemia secondary to methimazole and was treated with high-dose granulocyte colony stimulating factor, thrombopoietin and mesterolone. Antibiotics used included levofloxacin, clindamycin, amikacin and fluconazole. Due to bleeding and slow recovery of blood parameters, 30 units of platelets and 7 units of packed red blood cells were transfused during her 22-day admission. This case presents a life-threatening adverse drug reaction in a patient with co-morbid conditions that complicate recovery and limit one's therapeutic options.

Topics: Anemia, Aplastic; Antithyroid Agents; Diabetes Complications; Female; Graves Disease; Humans; Methimazole; Middle Aged; Remission Induction; Severity of Illness Index

The prevalence and titer of glutamic acid decarboxylase antibody (GADAb) in type 1 diabetes mellitus (T1DM) has been reported to be higher in patients with autoimmune thyroid diseases (AITD) than those without them. However, we have no data about the influence of GADAb on AITD. We therefore studied the clinical characteristics of Graves' disease (GD) with GADAb in order to clarify the influence of GADAb on GD. Twelve GD patients with GADAb were enrolled and were compared to 40 GD patients without DM. The male to female ratio and age of onset of GD showed no statistical difference. The titer of TSH receptor antibody (TRAb) at the onset of GD was similar in both groups. Initial treatment with methimazole (MMI) was started in all patients with GADAb but radioactive iodine (RI) therapy was carried out in five patients because of adverse effects of MMI or poor control of hyperthyroidism. The initial titer of TRAb was significantly lower in patients treated with MMI alone compared to that in RI treated patients but none of the patients treated with MMI alone went into remission after more than 3-years of follow up. We also compared these GADAb-positive patients with 14 patients with diabetes mellitus who had matched clinical features. The number of diabetic patients who remained in possible remission was significantly higher than that of GADAb-positive patients (5 in 14 vs 0 in 12). Moreover, the rate of remission in the diabetic patients was no different from that of 21 control patients without diabetes followed for more than 7 years (5 in 14 vs 7 in 21). These data suggested that GADAb-positive patients are unlikely to go into remission with antithyroid agents. Therefore, definitive therapies might be preferable for the initial treatment of GADAb-positive patients.

Topics: Adult; Aged; Antithyroid Agents; Diabetes Mellitus, Type 1; Female; Glutamate Decarboxylase; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Iodine Radioisotopes; Male; Methimazole; Middle Aged

mu-Crystallin is an NADPH-dependent cytosolic T3-binding protein. A knockout study in mice showed that mu-crystallin has a physiological function as a reservoir of T3 in the cytoplasm in vivo. Patients with nonsyndromic deafness were reported to have point mutations in the mu-crystallin gene. The expression of mu-crystallin is regulated by multiple factors. The present study was performed to determine whether thyroid function is related to the expression of mu-crystallin mRNA in peripheral mononuclear cells. We examined 23 normal healthy male and female subjects and 15 patients with Graves' disease. mu-Crystallin protein expression was determined immunohistochemically in peripheral mononuclear cells. The expression of mu-crystallin mRNA was assessed by reverse transcription of total RNA from peripheral mononuclear cells followed by quantitative PCR. mu-Crystallin protein was detected in peripheral mononuclear cells. The mRNA expression was negatively correlated with age in normal female subjects. The values in female subjects were significantly higher than those in males. The values were positively correlated with serum TSH concentration. The values of the thyrotoxic patients with Graves' disease were lower than those in healthy subjects. A transient increase in mu-crystallin expression was observed within 14-42 days after the initial treatment with antithyroid medication. Thyroid hormone inversely relates to the expression of mu-crystallin mRNA in euthyroid mononuclear cells. Abrupt suppression of thyroid function leads to overexpression of mu-crystallin mRNA in thyrotoxic mononuclear cells. Thyroid hormone-regulated mu-crystallin expression may control thyroid hormone action via the intracytoplasmic T (3) capacity.

Topics: Adult; Age Factors; Antithyroid Agents; Cells, Cultured; Crystallins; Female; Gene Expression; Graves Disease; Humans; Leukocytes, Mononuclear; Male; Methimazole; Middle Aged; mu-Crystallins; RNA, Messenger; Sex Factors; Thyroid Function Tests; Thyroid Hormones

Antithyroid drugs (ATDs) are prescribed as the initial therapy for the majority of patients with Graves' disease in many areas of the world. Although, it is well known that agranulocytosis is one of the most serious side effects of ATDs, there has not yet been any conclusive evidence that the prevalence of agranulocytosis induced by ATDs is dose related. This study was performed to determine if the prevalence of agranulocytosis is different depending on the starting dosage of ATDs in patients with Graves' disease.. Until 1996, we had typically prescribed 30 mg/d of methimazole (MMI) as the initial dosage for the treatment of Graves' disease at our institution. We changed the initial MMI dosage to 15 mg/d as a general rule in 1997. As a consequence, we acquired two groups of patients with Graves' disease who received different dosages of MMI. We retrospectively compared the prevalence of MMI-induced agranulocytosis in patients who received 15 mg/d of MMI to those who received 30 mg/d of MMI.. There were 2087 subjects treated with 30 mg/d of MMI and 2739 treated with 15 mg/d of MMI. The prevalence of agranulocytosis in the 30 mg/d group was significantly higher than in the 15 mg/d group (0.814% vs. 0.219%, respectively, p < 0.01). The prevalence of agranulocytosis plus neutropenia in the 30 mg/d group was also significantly higher than in the 15 mg/d group (1.581% vs. 0.474%, respectively, p < 0.001).. It is very likely that MMI-induced agranulocytosis occurs with a larger dosage of MMI and is dose related. Considering both the effectiveness and the risk of serious side effects, we recommend 15 mg/d of MMI as the starting dosage for the treatment of Graves' disease.

Topics: Adolescent; Adult; Agranulocytosis; Antithyroid Agents; Dose-Response Relationship, Drug; Female; Graves Disease; Humans; Leukocyte Count; Male; Methimazole; Middle Aged; Neutropenia; Neutrophils; Retrospective Studies; Young Adult

We report on a case of diffuse alveolar haemorrhage in a Chinese woman due to methimazole-induced antineutrophil cytoplasmic antibodies. A literature search for anti-thyroid drugs associated with antineutrophil cytoplasmic antibody-induced diffuse alveolar haemorrhages is reviewed. Diffuse alveolar haemorrhage is a rare complication of thiourea agents and the treatment often requires corticosteroids or other immunosuppressants, together with withdrawal of the causative agent.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Comorbidity; Female; Graves Disease; Hemorrhage; Humans; Lung Diseases; Methimazole; Pulmonary Alveoli; Vasculitis

Topics: Adult; Antithyroid Agents; Female; Goiter; Graves Disease; Humans; Methimazole; Tomography, X-Ray Computed

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Liver Failure; Methimazole; Pregnancy; Propylthiouracil; Societies, Medical; United States; United States Food and Drug Administration

Benign thymic hyperplasia (TH) is a known feature of hyperthyroidism. In most cases, thymic enlargement is minimal; however, this syndrome may occasionally appear as an appreciable anterior mediastinal mass. Recognition of the benign nature of TH and its regression following treatment of the hyperthyroidism is important to prevent unnecessary surgical procedures. We present a case of TH associated with hyperthyroidism due to Graves' disease.

Topics: Animals; Antithyroid Agents; Diagnosis, Differential; Female; Graves Disease; Humans; Hyperplasia; Immunoglobulins, Thyroid-Stimulating; Indium Radioisotopes; Magnetic Resonance Imaging; Mediastinal Neoplasms; Methimazole; Radionuclide Imaging; Receptors, Thyrotropin; Somatostatin; Thymic Factor, Circulating; Thymoma; Thymus Gland; Thymus Neoplasms; Young Adult

We present 4 patients with Graves' disease who developed spontaneous hypothyroidism during follow-up. The two most plausible physiopathologic mechanisms for this development were progressive autoimmune-mediated destruction of the thyroid follicular epithelium and a predominance of blocking antibodies to the thyroid-stimulating hormone (TSH) receptor at the expense of stimulating antibodies in the same patient. Description of these patients not only illustrates the heterogeneous nature of this disease, but also the interrelation among its distinct clinical forms.

Topics: Adult; Aged; Autoantibodies; Disease Progression; Female; Goiter; Graves Disease; Humans; Hypothyroidism; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Receptors, Thyrotropin; Thyroid Hormones; Thyrotoxicosis; Thyroxine

Topics: Adult; Anti-Arrhythmia Agents; Antithyroid Agents; Anxiety; Arrhythmias, Cardiac; Dyspnea; Graves Disease; Humans; Hypokalemic Periodic Paralysis; Malaysia; Male; Methimazole; Muscle Weakness; Neurologic Examination; Potassium; Propranolol; Propylthiouracil; Sleep Initiation and Maintenance Disorders; Tremor; Weight Loss

Topics: Adult; Antihypertensive Agents; Antithyroid Agents; Emergencies; Follow-Up Studies; Genetic Predisposition to Disease; Graves Disease; Humans; Hypokalemic Periodic Paralysis; Jews; Male; Methimazole; Potassium; Prevalence; Propranolol; Recurrence; Thyrotoxicosis; Time Factors; Treatment Outcome

Topics: Adult; Antithyroid Agents; Female; Fever; Filgrastim; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Injections, Subcutaneous; Methimazole; Neutropenia; Recombinant Proteins

Topics: Antithyroid Agents; Female; Graves Disease; Humans; Methimazole; Middle Aged; Radionuclide Imaging; Ultrasonography; Venous Thrombosis

Graves' disease (GD) is caused by autoantibodies to the thyrotropin receptor (TRAb). In a controlled study using the B-lymphocyte depleting agent rituximab (RTX), an RTX-specific effect was found on long-term remission following methimazole (MMI) therapy. However, benefits were limited to patients with low baseline TRAb levels, and the decrease in TRAb levels observed after treatment with RTX in combination with MMI was no greater than that observed after treatment with MMI alone. Considering its price and adverse effect profile, RTX therapy does not seem to be a relevant treatment option in uncomplicated GD. The potential use of other immunomodulatory agents in GD is discussed.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antithyroid Agents; Autoantibodies; B-Lymphocytes; Drug Therapy, Combination; Graves Disease; Humans; Immunologic Factors; Methimazole; Rituximab; Treatment Outcome

The Bcl-2 family proteins that control homeostasis of cells play an important role in apoptosis. This group consists of antiapoptotic (Bcl-2, Bcl-XL) and proapoptotic (Bcl-2 associated protein X, Bax; B-cell homologous antagonist/killer, Bak) molecules. In the thyroid, abnormal apoptotic activity may be involved in a variety of diseases such as autoimmune thyroid diseases. The aim of the current study was to estimate the expression of pro- and antiapoptotic proteins in thyroid tissues from young patients with Graves' disease (GD), nontoxic nodular goiter and toxic nodular goiter using Western Blot and immunohistochemistry. Identification of the antiapoptotic Bcl-2 and Bcl-XL molecules in the thyrocytes revealed higher expression of both proteins in patients with GD (assessed as +++/++ and ++/+, respectively). In adolescents with toxic and nontoxic nodular goiter, this expression was lower (Bcl-2 ++/+ , ++/+; Bcl-XL +, +). The tissue material was additionally subjected to Western Blot analysis, which in GD patients showed the presence of Bcl-2 and Bcl-XL in one band p26 kDa. In patients with toxic and nontoxic nodular goiter, the intensity of expression for these two antiapoptotic proteins was lower (referred to band 26 kDa for Bcl-2 and Bcl-XL). Identification of the proapoptotic proteins Bax and Bak revealed their predominance in thyrocytes of GD patients (+, ++/+, respectively) as compared to patients with toxic and nontoxic nodular goiter (0/+, 0/+ for Bax and 0/+, 0/+ for Bak). In GD patients, Western Blot analysis showed Bax expression in one band 21 kDa and Bak in two bands p50, p24 kDa. In patients with nodular goiter, the degree of expression of both proapoptotic proteins was lower and referred to band 21 kDa for Bax (toxic and nontoxic goiter) and 24 kDa for Bak (toxic goiter only). Patients with GD showed a statistically significant correlation between Bcl-2 expression and antibodies against receptor for thyroid stimulating hormone (R = 0.47, p < 0.03); however, such a correlation was not observed in patients with nodular goiter. In conclusion, our findings suggest that the changes in the expression of regulatory proteins of the Bcl-2 family in the thyroid follicular cells indicate the involvement of apoptosis in the pathogenesis of GD.

Topics: Adolescent; Adult; Antithyroid Agents; Apoptosis; Blotting, Western; Child; Female; Goiter, Nodular; Graves Disease; Humans; Immunohistochemistry; Male; Methimazole; Proto-Oncogene Proteins c-bcl-2; Thyrotropin; Thyroxine; Triiodothyronine

This study was performed to analyse the impact of the choice of antithyroid drugs (ATD) on the outcome of ablative radioiodine therapy (RIT) in patients with Graves' disease.. A total of 571 consecutive patients were observed for 12 months after RIT between July 2001 and June 2004. Inclusion criteria were the confirmed diagnosis of Graves' disease, compensation of hyperthyroidism and withdrawal of ATD two days before preliminary radioiodine-testing and RIT. The intended dose of 250 Gy was calculated from the results of the radioiodine test and the therapeutically achieved dose was measured by serial uptake measurements. The end-point measure was thyroid function 12 months after RIT; success was defined as elimination of hyperthyroidism. The pretreatment ATD was retrospectively correlated with the results achieved.. Relief from hyperthyroidism was achieved in 96% of patients. 472 patients were treated with carbimazole or methimazole (CMI) and 61 with propylthiouracil (PTU). 38 patients had no thyrostatic drugs (ND) prior to RIT. The success rate was equal in all groups (CMI 451/472; PTU 61/61; ND 37/38; p = 0.22).. Thyrostatic treatment with PTU achieves excellent results in ablative RIT, using an accurate dosimetric approach with an achieved post-therapeutic dose of more than 200 Gy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antithyroid Agents; Carbimazole; Combined Modality Therapy; Dose-Response Relationship, Radiation; Female; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Recurrence; Retrospective Studies; Treatment Outcome

Graves' disease (GD), a prototypical autoimmune disorder, is associated with other autoimmune diseases, including vasculitis. Antithyroid drugs, despite their postulated immunosuppressive effects, may cause several autoimmune disorders. Here we describe the first patient with central nervous system (CNS) vasculitis that developed shortly after the start of methimazole (MMI) treatment for GD.. CNS vasculitis was suspected on the basis of the clinical features and neurologic examination, showing a reinforcement of deep reflexes, especially of the left knee and Achilles reflexes. The diagnosis was confirmed by a brain magnetic resonance imaging (MRI), which showed some hyperintensive spots in the subcortical substantia alba and in the parietal area bilaterally, and by a single-photon emission computed tomography (SPECT) imaging, which showed a nonhomogenous distribution of the blood flow in the brain, with a reduced perfusion on the left side of the frontotemporal and parietal regions, and on the right side of the frontotemporal area. MMI was stopped before total thyroidectomy, and symptoms resolved in the next 5 weeks. Six months after MMI was stopped, the brain MRI and SPECT had become normal.. To our knowledge, this is the first report of CNS vasculitis related to MMI therapy.

Topics: Adult; Antithyroid Agents; Brain; Female; Graves Disease; Humans; Immunosuppressive Agents; Magnetic Resonance Imaging; Methimazole; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Vasculitis, Central Nervous System

Resistance to the conventional treatment of hyperthyroidism with antithyroid drugs is not commonly found in clinical practice, and only few other treatment options have been reported on in detail. For example, surgery or radioiodine ablation are well-accepted interventions that must be always considered. The euthyroid state is strongly recommended before both of these as this might reduce complications. There are few studies indicating that bile acid sequestrants, when added to antithyroid drugs, produce a more rapid decline in serum thyroid hormone levels and that this effect is maintained for at least 4 weeks. Complete normalization of serum thyroid hormone levels is generally not expected, however.. We report a patient whose thyrotoxicosis failed to respond to conventional treatment. The patient remained persistently hyperthyroid, both clinically and biochemically, despite several months of methimazole and propranolol and the addition of iodine. Cholestyramine, a bile acid sequestrant, was then added, and a dramatic improvement was observed.. We report a patient who was resistant to conventional antithyroid drugs in whom thyroid hormone levels completely normalized after 1 week of additional treatment with cholestyramine.

Topics: Adult; Antithyroid Agents; Cholestyramine Resin; Drug Resistance; Drug Therapy, Combination; Ehlers-Danlos Syndrome; Female; Graves Disease; Humans; Iodine; Methimazole; Propranolol; Treatment Outcome

Antithyroid drugs have been used for more than 50 years for the management of hyperthyroidism. Most patients tolerate treatment well but some may develop life threatening side effects such as agranulocytosis and aplastic anemia (AA). We review all cases of antithyroid drug induced AA and describe, as illustrative cases, two women with Graves' disease who developed AA after 8 and 24 weeks of carbimazole (CBM) and methimazole (MMI) treatment respectively.. To date, at least 34 cases of aplastic anemia (AA) due to antithyroid drugs [(1 with CMZ, 31 with MMI, and 2 with propylthiouracil (PTU)] have been published, not including the two patients described here. In addition, at least another 14 patients in whom AA developed after treatment with antithyroid drugs (11 with CMZ, and 3 with MMI) have been reported in Yellow Card Scheme data analysis. Patients with AA usually exhibit sudden onset of symptoms after a relative short time of exposure to the drugs, and all have concomitant agranulocytosis. Most have a rapid recovery following discontinuation of the drug and supportive treatment. Although only two antithyroid drug induced AA deaths have been published, the mortality rate was higher in the Yellow Card Scheme data analysis.. Aplastic anemia associated with antithyroid drug treatment is rarer than antithyroid drug associated agranulocytosis. The prognosis of patients with antithyroid drug induced AA is good overall, but may not be as favorable as that of antithyroid drug induced isolated agranulocytosis.

Topics: Adult; Agranulocytosis; Anemia, Aplastic; Antithyroid Agents; Carbimazole; Female; Graves Disease; Humans; Kaplan-Meier Estimate; Methimazole; Middle Aged

Fas gene, which is related to apoptosis, influences the clinical remission of Graves' disease (GD). This study was performed to determine whether the Fas gene promoter polymorphism at position-670 is associated with different efficacy in GD patients treated with methimazole (MMI). Serum levels of thyroid hormone, sFas and thyrotropic-stimulating hormone receptor antibodies (TRAb) were evaluated as therapeutic efficacy parameters before and after 18-month treatment with MMI in a total of 115 subjects of North China. At the end of the follow-up study, patients were categorized into an effective group (group A) and an ineffective group (group B) according the level of thyroid hormone. Similar to the changes of thyroid hormone, the reductions of sFas and TRAb were significantly different in the two groups (P < 0.05). Meanwhile, we detected that Fas promoter-670 A/G polymorphism existed in the GD patients of North China. We studied the frequencies of genotypes and alleles of the A/G polymorphism in different groups. However, there was no association between different efficacy and Fas promoter polymorphism in patients with GD.

Topics: Adult; Alleles; Antithyroid Agents; China; DNA; fas Receptor; Female; Genotype; Graves Disease; Humans; Male; Methimazole; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Reverse Transcriptase Polymerase Chain Reaction; Thyroid Hormones; Thyrotropin

Antithyroid drugs may be proposed as the firstline therapy for hyperthyroidism due to Graves' disease since some patients undergo prolonged remission after drug withdrawal. On the other hand, some studies, though controversial, indicated that methimazole (MMI) has some immunomodulating activity. We retrospectively analyzed 384 consecutive patients newly diagnosed with Graves' disease in the years 1990-2002 to ascertain whether long-term therapy with low doses of MMI may prevent relapse of thyrotoxicosis. Two hundred and forty-nine patients were included in our study. The date of reduction of MMI dose to 5 mg/day was considered time 0 for survival analysis. In 121 MMI was discontinued in less than 15 months after time 0 (group D), while in the remaining 128 a daily MMI 2.5-5 mg dose was maintained (group M). One hundred and thirty-five patients were excluded for inadequate response to MMI, relapse of thyrotoxicosis that could be related to an improper withdrawal or reduction of MMI, inadequate or too short followup, iodide contamination, steroid or interferon therapy, pregnancy or post-partum. D and M groups did not differ for clinical and hormonal parameters except age, which was lower in D (p=0.019). Age > vs < 35 yr was relevant in survival analysis; therefore patients were divided in 2 groups according to this age cut-off. In younger patients relapse of thyrotoxicosis occurred in 15 patients of group D 2.4-39.6 months (median 19.0) after time 0, and 8 M after 5.9-40.0 (21.3) months, while 14 D and 5 M maintained euthyroidism until the end of the observation after 31.8-95.3 (56.6) months and 30.4-62.1 (46.5) months, respectively. Survival analysis indicated that the risk of relapse was similar in group D and M. In older patients relapse of thyrotoxicosis occurred in 40 patients of group D after 8.2-65.8 (25.4) months and 29 M after 5.8-62.5 (22.4) months, while 52 D and 86 M maintained euthyroidism until the end of the observation, 20.1-168.0 (46.7) months and 24.1-117.4 (53.4) months respectively. Survival analysis indicated that the risk of relapse was increased in group D. Therefore long-term treatment with low doses of MMI seems to prevent relapse in Graves' disease in patients above 35 yr of age. This should be confirmed in a prospective study.

Topics: Adult; Aged; Aged, 80 and over; Antithyroid Agents; Drug Administration Schedule; Female; Graves Disease; Humans; Hyperthyroidism; Immunoglobulins, Thyroid-Stimulating; Kaplan-Meier Estimate; Male; Methimazole; Middle Aged; Recurrence; Retrospective Studies; Substance Withdrawal Syndrome; Thyrotropin; Treatment Outcome

To study the relationship between methimazole (MMI) and antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis.. Thirty-three cases with Graves' disease were tested for serum ANCA before and after taking MMI. At the same time, clinicopathological data of two patients with Graves' disease who had antineutrophil cytoplasmic antibody-positive vasculitis during treatment with MMI were analyzed.. Two patients developed antineutrophil cytoplasmic antibody-positive vasculitis during the medication with MMI for 5-6 years; their major clinical manifestations were hematuria and renal failure. Renal biology showed renal vasculitis and vascular necrosis. The disease was relieved after treatment with immunosuppressor. Serum ANCA in the 33 cases was negative before taking MMI. In 3 cases serum ANCA became positive after taking MMI for 2 months, 3 months and 2 years, respectively. The positive rate is 9% (3/33). The major finding was microscopic hematuria. ANCA positive rate was significantly higher after taking MMI than that before taking MMI (chi2) = 5.3, P < 0.05). Microscopic hematuria disappeared after general treatment.. There may be a relationship between methimazole and development of antineutrophil cytoplasmic antibody-positive vasculitis. Renal impairment can occur. The signs and symptoms of the vasculitis can disappear after proper treatment.

Topics: Adolescent; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Child; Female; Graves Disease; Humans; Kidney; Male; Methimazole; Vasculitis

Topics: alpha-Methyltyrosine; Antihypertensive Agents; Antithyroid Agents; Catecholamines; Enzyme Inhibitors; Female; Fluid Therapy; Graves Disease; Humans; Hypertension; Hypotension; Methimazole; Middle Aged; Pheochromocytoma; Time Factors

Myasthenia gravis (MG) is an acquired autoimmune disorder causing skeletal muscle fatigue and weakness. This is a report of one woman and her daughter presenting with myasthenia and gravis and Grave's disease. It highlights possible hereditary component of this condition which has not been commonly reported in our setting.

Topics: Adult; Antithyroid Agents; Autoimmune Diseases; Cholinesterase Inhibitors; Female; Graves Disease; Humans; Methimazole; Middle Aged; Myasthenia Gravis; Pyridostigmine Bromide; Thyroid Diseases

A unique case of fetal goiter accompanied by bilateral ovarian cysts in a mother treated with methimazole for Graves'disease is reported. The abnormal findings were detected by ultrasound at 31 weeks of gestation. Umbilical fetal blood sampling revealed elevated serum TSH, normal concentrations of free T 4 , normal FSH and LH and high concentrations of E 2 . A series of weekly amniocenteses and intra-amniotic injections of levothyroxine was initiated, along with a reduction of the mother's methimazole dosage. The level of TSH in amniotic fluid was initially high, but was considerably reduced by each injection and followed by a gradual reduction of fetal goiter as well as the left ovarian cyst. The right cyst ruptured spontaneously. At 36 weeks + 4 days, the patient underwent elective caesarean section and gave birth to a female, weighing 2,880 g with 1- and 5-min Apgar scores of 10. The thyroid gland appeared normal in size, and cord blood TSH and free T 4 were both within normal limits. At ultrasound control 6 days later, the right ovarian cyst was not visible, while the left cyst was still present. Thus, our report supports previous findings that fetal goiter can be treated successfully with intra-amniotic injection of levothyroxine.More importantly, it shows that fetal hypothyroidism with elevated levels of TSH can be accompanied by ovarian cysts,suggesting interference between thyreotropic and gonadotropic hormones.

Topics: Amniocentesis; Amniotic Fluid; Antithyroid Agents; Cesarean Section; Female; Fetal Blood; Follicle Stimulating Hormone; Goiter; Graves Disease; Humans; Infant, Newborn; Luteinizing Hormone; Maternal-Fetal Exchange; Methimazole; Ovarian Cysts; Pregnancy; Pregnancy Complications; Thyrotropin; Thyroxine; Ultrasonography

The article describes a case of Graves' disease treated with methimazole and examines the influence of methimazole-induced alterations of thyroid hormone concentrations during warfarin therapy. A 22-year-old woman presented at our endocrinology outpatient clinic with palpitations, sweating, fatigue, tremors, and diarrhea. She had a pain in her right leg and had difficulty walking. Her thyroid profile was consistent with hyperthyroidism. The patient was treated with warfarin 5 mg once a day for deep vein thrombosis for 2 days. Since a therapeutic range of International Normalized Ratio levels could not be achieved, methimazole was stopped due to drug-drug interaction. Lithium was started instead. A euthyroid state was obtained in 2 weeks together with a therapeutic International Normalized Ratio level. Interactions between warfarin and drugs that alter thyroid hormone concentrations have been reported; however, the extent and significance of the interaction between methimazole and warfarin have been inadequately described. Concomitant therapy with warfarin and antithyroid drugs should be managed by frequent monitoring of both thyroid function and the International Normalized Ratio. Lithium is employed only to provide temporary control of thyrotoxicosis in patients who cannot take thionamide and iodide. The administration of lithium alone or in combination with other drugs is shown to be an effective method of controlling hyperthyroidism when conventional antithyroid drugs show adverse effects or become insufficient. When warfarins are used together with antithyroid medications, adequate anticoagulation may not be obtained due to drug-drug interactions. Lithium can be an alternative drug for antithyroid medication in patients on warfarin therapy.

Topics: Adult; Anticoagulants; Antithyroid Agents; Drug Interactions; Female; Graves Disease; Humans; International Normalized Ratio; Lithium Carbonate; Methimazole; Thyroid Hormones; Warfarin

Although transient thyrotoxicosis occurring after antithyroid drug (ATD) withdrawal in patients with Graves' hyperthyroidism has been reported, the prevalence of transient thyrotoxicosis after ATD therapy is as yet unknown. When patients with transient hyperthyroidism are mistakenly regarded as recurrences, they receive unnecessary therapy. The aim of this study was to investigate the prevalence of transient thyrotoxicosis after ATD withdrawal.. We selected 110 consecutive patients with Graves' disease whose ATD therapy was stopped from December 2002 to September 2004 prospectively. Patients were observed for more than 1 year after ATD withdrawal, and 12 patients dropped out. Serum levels of free thyroxine (FT(4)), thyrotropin, and thyrotropin-binding inhibitor immunoglobulin were measured at ATD withdrawal, and 3, 6, and 12 months after withdrawal. When the patients showed mild thyrotoxicosis (serum FT(4) level of less than 3.00 ng/dL), we followed them up for 1 month without medication.. The remission rate of the study group was 61.8% (68/110). Twenty-eight patients became euthyroid after transient thyrotoxicosis, equivalent to 41.2% of the remission patients. Eight of 28 patients showed overt thyrotoxicosis, and the rest subclinical thyrotoxicosis. Transient thyrotoxicosis occurred mostly 3-6 months after ATD withdrawal.. Transient thyrotoxicosis after ATD withdrawal in patients with Graves' disease is not a rare phenomenon. Clinicians should be aware that the recurrence of Graves' disease after the withdrawal of ATD may be transient.

Topics: Adult; Antithyroid Agents; Autoantibodies; Female; Follow-Up Studies; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Prevalence; Prospective Studies; Recurrence; Substance Withdrawal Syndrome; Thyrotoxicosis; Thyrotropin; Thyroxine; Time Factors

A 41-year-old man with progressive limb weakness manifested fluctuating muscle weakness as seen in myasthenia gravis (MG). Laboratory investigations revealed hyperthyroidism without the complication of MG. Electrophysiological studies demonstrated abnormal features of neuromuscular transmissions resembling those of the Lambert-Eaton myasthenic syndrome rather than those of MG. A CT scan showed a mediastinal mass that suggested thymic hyperplasia which often complicates MG or hyperthyroidism. Medical treatment of hyperthyroidism resulted in resolution of MG-like symptoms and regression of thymic hyperplasia on CT concomitant with normalization of thyroid function. This case highlights the fact that careful investigations are needed to differentiate MG-like symptoms from genuine MG in cases of hyperthyroidism with thymic lesions.

Topics: Adult; Antithyroid Agents; Diagnosis, Differential; Graves Disease; Humans; Male; Methimazole; Muscle Weakness; Myasthenia Gravis; Thymus Hyperplasia; Thyrotoxicosis

Topics: Adrenergic beta-Antagonists; Adult; Anesthesia, Intravenous; Antithyroid Agents; Chemical and Drug Induced Liver Injury; Dexamethasone; Drug Therapy, Combination; Female; Graves Disease; Humans; Hypertension; Iopanoic Acid; Kidney Diseases; Methimazole; Preoperative Care; Propranolol; Tachycardia; Thyroidectomy

Topics: Adrenergic beta-Antagonists; Antithyroid Agents; Cholangiopancreatography, Magnetic Resonance; Cholestasis; Graves Disease; Humans; Liver; Liver Function Tests; Male; Methimazole; Middle Aged; Propranolol; Radionuclide Imaging; Thyroid Function Tests; Thyroid Gland; Thyroidectomy; Thyroxine; Ultrasonography

We report the treatment of four thyrotoxic patients. Two were cases of type I amiodarone-induced thyrotoxicosis (AIT) treated with methimazole. The third Graves' disease patient, who became hypothyroid 25 years after subtotal thyroidectomy, developed type II AIT. Furthermore, one case with heart failure and ventricular tachycardia, who developed an adverse reaction to antithyroid agents and was prescribed amiodarone, underwent total thyroidectomy. The clinical course was uneventful, and the patient is doing well. Since amiodarone contains a large amount of iodine, it is frequently difficult to make a differential diagnosis. Surgical treatment of Graves' disease patients is recommended when immediate control of hyperthyroidism and heart failure is required.

Topics: Adult; Amiodarone; Anti-Arrhythmia Agents; Antithyroid Agents; Arrhythmias, Cardiac; Diagnosis, Differential; Graves Disease; Humans; Male; Methimazole; Middle Aged; Thyroidectomy; Thyrotoxicosis

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Hypothyroidism; Methimazole; Nephrosis, Lipoid

Aplastic anemia (AA) is mediated by T-cell autoimmunity in the majority of cases; it is rare and mostly idiopathic in children. We describe a child, who developed AA following Graves' disease which could not be attributed to antithyroid drugs. We hypothesized that both diseases were caused by similar autoimmune process. We monitored the blood counts and did not administer any conventional treatment for AA assuming that the existing anti- hematopoietic stem cell humoral and cellular immunity might subside with induction of remission of Grave's disease. The child went into complete remission with the treatment of the Graves' disease.

Topics: Anemia, Aplastic; Antithyroid Agents; Blood Cell Count; Bone Marrow; Child; Female; Graves Disease; Hormone Replacement Therapy; Humans; Iodine Radioisotopes; Methimazole; Pancytopenia; Recurrence; Remission Induction; Thyrotoxicosis; Thyroxine; Treatment Refusal

The relation between the incidence of methimazole (methylmercaptoimidazole; MMI)-induced agranulocytosis and initial MMI dose was evaluated in a group of 514 patients with Graves' disease who were treated between 1995 and 2005. One hundred and forty-six (28.40%) patients had received an initial dose of 30 mg MMI and 277 (53.89%) patients had been treated with 15 mg MMI. Nine patients (1.75%) developed agranulocytosis due to MMI treatment. Six (4.11%) of 146 patients who received an initial dose of 30 mg MMI, two (4.54%) of 44 patients given an initial dose of 20 mg MMI, and one (0.36%) of 277 patients given an initial dose of 15 mg MMI developed agranulocytosis. There was a statistically significant difference in agranulocytosis incidence between patients receiving an initial dose of 30 mg MMI and those who received an initial dose of 15 mg. Although 8 (4.10%) of 195 patients in the high-dose group (20 mg or higher) developed agranulocytosis, only 1 (0.31%) of 319 patients in the low-dose group (15 mg or lower) did. In conclusion, the incidence of agranulocytosis with low-dose MMI therapy was ten times lower than that of the high-dose regimen.

Topics: Adolescent; Adult; Agranulocytosis; Antithyroid Agents; Dose-Response Relationship, Drug; Female; Graves Disease; Humans; Incidence; Male; Methimazole; Middle Aged; Retrospective Studies

Topics: Adult; Agranulocytosis; Bone Marrow; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Male; Methimazole; Methylprednisolone; Plasma Cells; Thrombocytosis; Treatment Outcome

To determine the present condition of treatment of childhood-onset Graves' disease in Japan, a nationwide questionnaire survey was conducted among councilors of the Japanese Society for Pediatric Endocrinology and the Japan Thyroid Association.. Responses were received from 125 individuals, and the rate of collection of questionnaires was 47%. Methimazole was selected for first-line initial antithyroid drug therapy by 92% of respondents. Antithyroid drugs tended to be given at larger initial doses and over longer periods of time to childhood-onset patients than to adult patients, and these tendencies were more pronounced for pediatric endocrinologists. Combination therapy with an antithyroid drug and thyroxine was used more frequently by pediatric endocrinologists. Thyroidologists had more experience with radioiodine therapy than pediatric endocrinologists. Opinions regarding preparation of guidelines for the initial dose of methimazole in childhood-onset Graves' disease were almost equally divided among the following: the dose of methimazole should be adjusted according to the severity of disease as in adult cases, methimazole should be started at a dose of 1mg/kg per day in all patients, and the dose should be determined based on results of a randomized study.. The present condition of treatment of childhood-onset Graves' disease in Japan was clarified.

Topics: Adolescent; Age of Onset; Antithyroid Agents; Child; Endocrinology; Graves Disease; Health Care Surveys; Humans; Japan; Methimazole; Pediatrics; Practice Patterns, Physicians'; Recurrence; Surveys and Questionnaires

Hyperthyroidism may present with signs and symptoms related to dysfunction of a variety of organs. Cardiovascular pathology in hyperthyroidism is common. A few case reports describe isolated right heart failure, tricuspid regurgitation, and pulmonary hypertension as the prominent cardiovascular manifestations of hyperthyroidism. Although most textbooks do not mention hyperthyroidism as a cause of pulmonary hypertension and isolated right heart failure, the literature suggests that some hyperthyroid patients may develop reversible pulmonary hypertension and isolated right heart failure. We report a case of hyperthyroidism presenting with signs and symptoms of isolated right heart failure, tricuspid regurgitation, and pulmonary hypertension, which resolved with treatment of hyperthyroidism.

Topics: Antithyroid Agents; Female; Graves Disease; Heart Failure; Humans; Hypertension, Pulmonary; Methimazole; Middle Aged; Tricuspid Valve Insufficiency; Ventricular Dysfunction, Right

Th1 and Th2-like cytokines are involved in the pathogenesis of Graves' disease. The shift in balance in IL-12/IL-5 cytokines was applied in judging the immunological events in 74 patients with Graves' disease (50 had ophthalmopathy) during methimazole therapy and in 15 controls. The serum levels of IL-12 and IL-5 were measured with enzyme-linked immunosorbent assay in all Graves' patients. Twelve cases for IL-5 and 20 cases for IL-12 were positive. In Graves' patients only those without ophthalmopathy had higher levels of IL-12 when compared to controls (192.66 +/- 29.19 vs. 85.09 +/- 8.95 pg/ml, P < 0.04). After 2 months of methimazole therapy in Graves' patients without ophthalmopathy an increase in the ratio of IL-12 to IL-5 was also observed as compared to those with eye symptoms (91.78 +/- 34.14 vs. 20.72 +/- 6.36, P < 0.015). Age-related difference in the serum level of IL-5 could be demonstrated between Graves' patients without and those with ophthalmopathy aged < or = 35 years (4.89 +/- 0.57 vs. 50.14 +/- 20.2 pg/ml, P < 0.002). No association was found among the serum levels of IL-5 or IL-12, thyroid hormones and TSH receptor antibodies. The results demonstrated a difference in the balance shift of IL-12/IL-5 between Graves' patients with and without ophthalmopathy. The increased ratio of IL-12 to IL-5 after methimazole therapy could be explained by the elevation of serum IL-12 due to methimazole therapy and the age-related decrease of serum IL-5.

Topics: Adolescent; Adult; Age Factors; Aged; Female; Graves Disease; Graves Ophthalmopathy; Humans; Interleukin-12; Interleukin-5; Male; Methimazole; Middle Aged; Th1 Cells; Th2 Cells; Thyroid Hormones

The peak systolic velocity (PSV) of the inferior thyroid artery (ITA) is increased in untreated hyperthyroid patients with Graves' disease (GD). We investigated the clinical significance of the ITA-PSV and its determinants in hyperthyroid GD patients.. ITA-PSV, together with thyroid volume, was measured by ultrasonography in untreated hyperthyroid GD patients (n=49) and healthy subjects (n=22). Established markers of GD activity such as TSH receptor antibody (TRAb), thyroid stimulating antibody (TSAb), vascular endothelial growth factor (VEGF) and immunoglobulin E (IgE) were simultaneously determined.. ITA-PSV, thyroid volume, VEGF and IgE were significantly higher in hyperthyroid GD patients than in normal subjects. ITA-PSV in hyperthyroid GD patients was correlated positively with serum levels of FT(3), FT(4) and IgE, smoking index and thyroid volume, and negatively with total, HDL- and LDL-cholesterols, but did not correlate significantly with age, triglyceride, TRAb, TSAb or VEGF. In stepwise regression analysis, ITA-PSV showed significant positive and negative associations with IgE and LDL-cholesterol, respectively, in hyperthyroid GD patients. In the pre-treatment hyperthyroid state, FT(4) and ITA-PSV, but not IgE, were found to be significantly and positively associated with the maintenance dose of methimazole (MMI) required to keep serum TSH within normal range for at least 12 months.. These results suggest that ITA-PSV in untreated hyperthyroid GD patients may reflect GD activity and thus MMI sensitivity.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Blood Flow Velocity; Female; Graves Disease; Humans; Immunoglobulin E; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Predictive Value of Tests; Receptors, Thyrotropin; Regional Blood Flow; Thyroid Gland; Thyroxine; Triiodothyronine; Ultrasonography, Doppler; Vascular Endothelial Growth Factor A

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antithyroid Agents; B-Lymphocytes; Graves Disease; Graves Ophthalmopathy; Humans; Immunosuppressive Agents; Lymphocyte Depletion; Methimazole; Rituximab

Hyperthyroidism is one of the most common endocrinology disorders. Treatment can be either pharmacological, surgical or using radioactive iodine. In Europe methimazole is the antithyroid drug of choice because it can be administered in a single daily dose and has a lower risk of adverse reactions. Around 5% of patients taking thionamides can present any of their side effects, which are usually mild. Liver toxicity due to thionamides is very rare, and severe due to propylthiouracil. We present a clinical case of a cholestatic jaundice and acute toxic hepatitis due to methimazole and a cross-reaction with propylthiouracil. Based on this case a review is presented.

Topics: Aged; Antithyroid Agents; Case Management; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Female; Graves Disease; Humans; Methimazole; Thyroidectomy

Topics: Aged; Amlodipine; Atrial Fibrillation; Digoxin; Female; Graves Disease; Humans; Hypertension, Pulmonary; Methimazole; Recurrence; Syncope; Treatment Outcome; Vertigo

Although Graves' disease is considered an autoantibody-mediated, T-helper 2 (Th2)-dominant disease, Th1-dominance may prevail in its initial phase. We longitudinally investigated Th1/Th2 balance in untreated hyperthyroid patients with Graves' disease after treatment of methimazole (MMI), an antithyroid drug.. University clinic outpatients were studied prospectively.. Subjects included 23 untreated hyperthyroid patients with Graves' disease and 17 age-matched control subjects.. Before and after treatment, we measured Th1- and Th2-associated chemokine receptors (CXCR)3 and CCR4, on peripheral blood lymphocytes using flow cytometry, as well as plasma concentrations of their ligands, interferon-inducible protein (IP)-10 and thymus and activation-regulated chemokine (TARC).. The percentage of CXCR3-expressing cells among CD4+T lymphocytes and plasma IP-10 was significantly higher in hyperthyroid Graves' disease patients than in controls. At 12 and 24 weeks after initiation of MMI, percentage of CXCR3-expressing CD4+T lymphocytes had decreased significantly, while the percentage of CCR4-expressing CD4+T lymphocytes had increased significantly at 24 weeks. The CXCR3/CCR4 ratio had decreased significantly at 24 weeks. Plasma concentrations of IP-10 had decreased significantly at 12 and 24 weeks. Plasma concentrations of TARC also had decreased significantly at 24 weeks.. In hyperthyroid patients with Graves' disease in the active phase, Th1 cells rather than Th2 cells predominated among peripheral blood lymphocytes. After initiation of MMI, an ongoing transition from Th1 to Th2 dominance occurred.

Topics: Adult; Antithyroid Agents; Biomarkers; Chemokine CCL17; Chemokine CXCL10; Chemokines, CC; Chemokines, CXC; Female; Flow Cytometry; Graves Disease; Humans; Ligands; Male; Methimazole; Middle Aged; Prospective Studies; Receptors, CCR4; Receptors, Chemokine; Receptors, CXCR3; Th1 Cells; Th2 Cells; Thymus Gland

Graves' disease (GD) is an autoimmune disorder with genetic predisposition. The thyroglobulin (Tg) is a major autoantigen for GD. The human Tg gene polymorphism has specific features that make it important in GD.. This study investigated whether Tg single nucleotide polymorphisms (SNPs) relate to GD development in a Taiwanese population.. This was a case-control association study.. We enrolled 215 Taiwanese patients with GD and 141 controls from the Endocrine Clinic of Kaohsiung Medical University Chung-Ho Memorial Hospital. This study investigated the association between gene polymorphism and relapse of hyperthyroidism after medication was discontinued in three GD patient groups and a control group. We also compared clinical and laboratory data obtained from patients with the three different genotypes with the three different Tg SNPs (E10SNP158, E12SNP, and E33SNP).. We found a significant increase in the T/T genotype of E33SNP compared with the control group (P < 0.001). We also found the E33SNP C/C genotype of the Tg gene was strongly associated with a subgroup of GD patients who were also characterized as having a higher relapse rate, significantly higher levels of persisting TSH-receptor antibody at the end of treatment, a higher frequency in smoking, and a higher incidence of ophthalmopathy (P < 0.05).. This study showed that Taiwanese patients with the C/C genotype of E33SNP, smoking, ophthalmopathy, and positive TSH-receptor antibodies at the end of the treatment were more likely to have a relapse of Graves' hyperthyroidism after antithyroid medication is withdrawn.

Topics: Adult; Antithyroid Agents; Case-Control Studies; Exons; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Propylthiouracil; Receptors, Thyrotropin; Recurrence; Reverse Transcriptase Polymerase Chain Reaction; Taiwan; Thyroglobulin

Topics: Adolescent; Antithyroid Agents; Female; Graves Disease; Humans; Methimazole; Myositis

In addition to the biochemical inhibition of thyroid hormone synthesis, antithyroid drugs including methimazole (MMI) may have immunosuppressive effect through inhibition of major histocompatibility complex (MHC) class I and II expressions on non-professional (thyrocytes) and professional (macrophages and B cells) antigen presenting cells (APCs). Dendritic cells (DCs) are another professional APCs and very likely play the most important role in the primary immune response. Therefore, we focused in this study on evaluating the effect of MMI on DC function in mice. Bone marrow cells cultured with granulocyte macrophage colony stimulating factor and interleukin (IL)-4 expressed high levels of CD11c and moderate levels of MHC class II, both of which are widely used markers for DCs. In vitro incubation of this DC-containing cell population with 10(- 6)-10(- 4) M MMI for 2 days did not change basal- and maturation signal (adenoviral infection and lipopolysaccharide)-induced levels of the cell surface marker expressions such as MHC class I and II, CD86, CD40 and DEC205, and of proinflammatory cytokine IL-6 release. Further we found that treatment of the DC-containing cell population with MMI did not influence the incidence of Graves' hyperthyroidism and anti-thyrotropin receptor (TSHR) antibody titers in a mouse Graves' model we have recently established with DCs infected with adenovirus expressing the TSHR A subunit. Although we cannot completely exclude immunosuppressive effect of MMI on other immune cells, our data indicate that DCs do not appear to be the primary target for the immunosuppressive effect of MMI.

Topics: Animals; Antigen-Presenting Cells; Cells, Cultured; Cytokines; Dendritic Cells; Female; Graves Disease; Histocompatibility Antigens; Immunosuppressive Agents; Methimazole; Mice; Mice, Inbred BALB C; Thyroid Gland; Transfection

Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Child, Preschool; Ectodermal Dysplasia; Female; Graves Disease; Humans; Methimazole; Pregnancy

Topics: Adult; Antithyroid Agents; Graves Disease; Gynecomastia; Humans; Infant, Newborn; Male; Methimazole; Time Factors; Treatment Outcome

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Hypothyroidism; Iodine Radioisotopes; Methimazole; Pregnancy; Puerperal Disorders; Thyroiditis, Autoimmune; Thyroxine

In this study, we investigated whether the CD40 or cytotoxic T lymphocyte-associated molecules-4 (CTLA-4) polymorphisms, which are associated with the susceptibility of Graves' disease (GD), can predict the clinical outcome after antithyroid drug (ATD) withdrawal. All patients with GD were treated with ATD. GD patients were divided into two groups: remission or failure. The remission group was defined as patients who maintained a euthyroid state for 1 year after ATD withdrawal. The failure group was defined as patients who relapsed within 1 year after the discontinuation of ATD or who could not discontinue their ATD treatment within 24 months. The rate of treatment failure after ATD withdrawal was 72.2%. For the susceptible genes, the CC genotype in the CD40, the GG genotype in the CTLA-4 exon 1, and the CC genotype in the CTLA-4 promoter region have shown no significant association with a clinical outcome after ATD withdrawal. However, clinical parameters, such as male gender, severe thyrotoxicosis, high thyroid-stimulating hormone-binding inhibitory immunoglobulin value, and a large goiter, were related to treatment failure. These findings suggest that the genetic markers associated with the development of GD cannot be used to predict the relapse of GD patients in place of clinical parameters.

Topics: Adult; Alleles; Antigens, CD; Antigens, Differentiation; Antithyroid Agents; CD40 Antigens; CTLA-4 Antigen; Female; Genetic Predisposition to Disease; Graves Disease; Humans; Male; Methimazole; Middle Aged; Polymorphism, Genetic; Prognosis; Propylthiouracil; Recurrence; Treatment Outcome

Topics: Adrenergic beta-Antagonists; Antithyroid Agents; Anxiety; Body Temperature Regulation; Diagnosis, Differential; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Muscle Weakness; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Tachycardia; Thyroid Function Tests; Tremor; Weight Loss

A 50-year-old woman was admitted to our hospital because of severe diarrhea, irritableness, and severe pitting edema of the legs. The patient had been well until 5 years before admission, when a tremor and tachycardia developed and a diagnosis of Graves' disease was made. Treatment with methimazole was effective in reducing her tremor and tachycardia; however, she was often nonadherent with her antithyroid medication because of improvement of her symptoms. On admission, a thyroid swelling, exophthalmos, a pleural effusion, and ascites were observed. The results of thyroid function tests (free triiodothyronine: 21.5 pg/mL; free thyroxine: 7.17 ng/dL; thyroid-stimulating hormone (TSH): <0.01 microIU/mL; TSH receptor antibodies: 95.9%) were consistent with Graves' disease. Biochemical analysis of pleural and ascitic fluid was consistent with chylothorax and chylous ascites, respectively. Serum calcium, total protein, and albumin were very low. Her symptoms and signs except severe diarrhea, edema, pleural effusion, and ascites disappeared after receiving intravenous drip infusion of fluid replacement, and methimazole and iodine. Because of malnutrition, she was given a high-calorie intravenous infusion. Three months after admission, her pleural effusion and ascites began to improve, as did her diarrhea and hypoalbuminemia. An appropriate treatment of Graves' disease is crucial to avoid serious sequelae of longstanding, poorly controlled hyperthyroidism.

Topics: Antithyroid Agents; Chylothorax; Chylous Ascites; Diarrhea; Female; Graves Disease; Humans; Methimazole; Middle Aged; Patient Compliance

We describe a case of concomitant Graves' disease and demyelination, with optic neuritis and cerebellar dysfunction, in an adolescent girl. Autoimmune thyroid disease with encephalopathy is the hallmark of Hashimoto's encephalopathy, linking thyroid and central nervous system dysfunction. However, to our knowledge, Graves' disease has not been previously reported in association with clinically isolated demyelinating disease in childhood.

Topics: Antithyroid Agents; Autoantigens; Brain; Child; Cluster Analysis; Demyelinating Diseases; Female; Graves Disease; Humans; Magnetic Resonance Imaging; Methimazole; Thyroid Gland

Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Choanal Atresia; Female; Graves Disease; Humans; Infant, Newborn; Maternal-Fetal Exchange; Methimazole; Pregnancy; Pregnancy Complications

To evaluate the influence of sex as well as pubertal stage at diagnosis on the growth outcome of childhood thyrotoxicosis.. Retrospective, collaborative study.. Longitudinal auxological evaluation in 101 patients (M/F 23/78) for 4.7 +/- 3.1 years subdivided according to pubertal stage at diagnosis into prepubertal (group I) and pubertal (group II).. At diagnosis height and bone age (BA) standard deviation score (SDS) were positive both in girls and boys of groups I and II. In boys of group II, height SDS was significantly higher than in girls of the same group (P = 0.007) and in boys of group I (P = 0.026). During the follow-up, in group I, height SDS remained positive without significant differences between boys and girls, and in group II, height SDS remained significantly lower in girls than in boys. The age at onset of puberty and the age at menarche were within the normal range. Final height (FH) was within target height (TH) range in all groups The FH SDS and the height gain (FH-TH) were similar in girls and in boys in group I and significantly higher in boys than in girls (P < 0.05) in group II. The boys of group II showed a mean height gain significantly greater than that found in all the other groups.. Despite the advancement of BA at presentation, there were no adverse effects on subsequent growth and FH; the growth outcome seems to be better in boys than in girls in group II.

Topics: Adolescent; Antithyroid Agents; Child; Female; Follow-Up Studies; Graves Disease; Growth; Humans; Male; Menarche; Methimazole; Propylthiouracil; Puberty; Regression Analysis; Retrospective Studies; Sex Factors; Statistics, Nonparametric; Thyroidectomy

CXCL10 plays an important role in the initial phases of Graves' disease (GD) and autoimmune thyroiditis (AT); however, until now, CXCL10 serum levels (sCXCL10) in patients with GD have never been evaluated in relation to thyroid function and treatment.. To evaluate sCXCL10 in GD.. Cross-sectional.. One hundred and three GD, 164 AT, 20 nontoxic multinodular goitre (NTMNG), 16 toxic nodular goitre (TNG) patients and 70 healthy controls (age- and sex-matched).. We measured sCXCL10 in patients and controls, to relate this parameter to the clinical phenotype.. Mean sCXCL10 in GD and AT patients were comparable (122+/-81 and 133+/-102 pg/ml) and significantly higher (P<0.01) than in controls or NTMNG patients (73+/- 32 and 76+/- 25 pg/ml, respectively). Hyperthyroid GD had significantly higher sCXCL10 than euthyroid or hypothyroid GD (145+/- 92, 107+/- 56 and 105+/- 46 pg/ml, respectively; P=0.01). GD patients with untreated hyperthyroidism had higher sCXCL10 than hyperthyroid or euthyroid GD patients under methimazole (MMI) treatment (166+/-125, 124+/- 41 and 94+/- 35 pg/ml, respectively; P=0.006). Comparable sCXCL10 levels were observed in newly diagnosed untreated hyperthyroid GD patients with respect to untreated patients with relapse of hyperthyroidism after a previous MMI course (176+/-125, 155+/- 97 pg/ml, respectively). GD had similar sCXCL10 to AT and higher than TNG patients or controls (all age- and sex-matched) (144+/- 81, 149+/- 114, 101+/- 27 and 86+/- 44 pg/ml, respectively; P=0.02).. sCXCL10 is associated with the active phase of GD in both newly diagnosed and relapsing hyperthyroid patients. The reduction in sCXCL10 in treated patients with GD may be related to the immunomodulatory effects of MMI.

Topics: Adult; Antibodies; Antithyroid Agents; Chemokine CXCL10; Chemokines, CXC; Cross-Sectional Studies; Female; Goiter, Nodular; Graves Disease; Humans; Interferon-gamma; Male; Methimazole; Middle Aged; Phenotype; Receptors, Thyrotropin; Thyroid Gland; Thyroiditis, Autoimmune; Thyrotropin; Treatment Outcome; Triiodothyronine

We describe two cases of increases in serum creatine kinase (CK) concentrations in children undergoing treatment of Graves' disease with antithyroid medications. Presenting complaints consisted of myalgias and muscle cramping in both patients, and increases in serum CK levels were noted 1 mo after initiation of antithyroid drugs. Both patients were euthyroid at the time of CK elevation. While the mechanisms for this process are not clear, it is likely that the acute decrease of thyroid hormones in tissues following a state of chronic hyperthyroidism may result in relative hypothyroid states and subsequent alterations in CK concentrations.. Although this side effect has been reported in adults, it is a novel finding in children. Clinicians should be aware of the rare potential for elevations in serum CK when initiating treatment for Graves' disease in children.

Topics: Adolescent; Antithyroid Agents; Child; Creatine Kinase; Female; Fructose-Bisphosphate Aldolase; Graves Disease; Humans; Hypothyroidism; Methimazole

We performed a quantitative retrospective analysis of serum thyrotropin receptor antibody (TRAb) concentrations measured by a second-generation radioreceptor assay in 58 patients with Graves' disease (GD) at the onset of the disease, at the end of 18 month methimazole (MMI) treatment, and after MMI withdrawal in order to evaluate the correlation between the presence of these antibodies and the relapse of hyperthyroidism. Sixty healthy subjects were enrolled as a control group.. Before MMI treatment the best cutoff TRAb value for identifying patients with GD was 1.45 UI/L (specificity, 100%; sensitivity, 98.3%). At the end of MMI treatment, serum TRAb concentrations were significantly lower (p < 0.001) than those measured at baseline, but they were still significantly higher (p < 0.001) than those found in the control subjects. At the end of MMI treatment, 44 patients (75.9%) had positive TRAb values (>1.45 UI/L). After MMI withdrawal (median, 15 months), 34 patients (58.6%) became hyperthyroid, 4 patients (6.9%) became hypothyroid, and 20 patients (34.5%) remained euthyroid. There was a significant correlation between serum TRAb concentrations at the end of MMI treatment and the percentage of patients who became hyperthyroid (r: 0.56; p < 0.001) and the time of appearance of hyperthyroidism (r: -0.38; p = 0.03). All 4 patients with TRAb values below 0.9 UI/L at the end of MMI treatment remained euthyroid throughout the follow-up period. Among the 27 patients who had serum TRAb values higher than 4.4 UI/L, 23 developed hyperthyroidism and 4 hypothyroidism. The TRAb values between 0.9 and 4.4 UI/L did not discriminate between the 27 patients (46.6%) who remained euthyroid from those who had relapse of hyperthyroidism. Thus a different TRAb end of treatment cutoff was calculated to identify patients who became again hyperthyroid. This TRAb cutoff value was 3.85 UI/L (sensitivity, 85.3%; specificity, 96.5%). All but 1 patient who had serum TRAb values above 3.85 UI/L became hyperthyroid after MMI was withdrawn (positive predictive value, 96.7%). In these patients, relapse of hyperthyroidism was independent of the changes in serum TRAb concentrations (r: 0.27; p = 0.15) and occurred after a median period of 8 weeks (range, 4-48). Hyperthyroidism also developed in 5 of 24 patients who had serum TRAb concentrations lower than 3.85 UI/L at the end of MMI treatment. In these 5 patients the relapse of hyperthyroidism occurred after a median period of 56 weeks (range, 24-120) and was always accompanied by an increase in serum TRAb concentrations.. TRAb persist in the blood of most patients with GD after 18 months of MMI treatment. Both the frequency and the time of appearance of hyperthyroidism are closely correlated with serum TRAb concentrations at the end of MMI treatment. Our data would suggest that TRAb maintain stimulating activity after a full course of MMI treatment in the large majority of patients with GD. However, it is likely that the potency of these antibodies and/or the thyroid response to them change during treatment, as suggested by the different values measured in euthyroid control subjects and in euthyroid patients after MMI treatment.

Topics: Adolescent; Adult; Aged; Antibodies; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Predictive Value of Tests; Receptors, Thyrotropin; Recurrence; Retrospective Studies; Sensitivity and Specificity; Substance Withdrawal Syndrome

We report four cases of Graves' disease that developed after painful Hashimoto's thyroiditis. All were middle-aged women, who had high titers of anti-thyroid antibodies and thyrotoxicosis at the onset of painful Hashimoto's thyroiditis. After 2 to 7 years, they developed Graves' disease with positive antibody against the thyrotropin receptor. Their clinical courses of Graves' disease went favorably due to the treatment with antithyroid drug or radioactive iodine therapy. Painful Hashimoto's thyroiditis is an atypical variant of Hashimoto's thyroiditis and is one form of destructive thyroiditis. Thyroid damage due to painful Hashimoto's thyroiditis may be associated with the development of Graves' disease.

Topics: Antithyroid Agents; Blood Sedimentation; C-Reactive Protein; Female; Glucocorticoids; Graves Disease; Hashimoto Disease; Humans; Methimazole; Middle Aged; Prednisolone; Thyroid Function Tests

Topics: Antithyroid Agents; Diabetes Mellitus, Type 1; Drug Hypersensitivity; Graves Disease; Humans; Male; Methimazole; Middle Aged

Severe pancytopenia is a rare but severe complication of thyrotoxicosis. In this report, we describe four patients with Graves' disease who presented with pancytopenia at diagnosis. Methimazole (30-40 mg/d) or propylthiouracil (400 mg/d) restored normal hematopoiesis in three of the patients. The remaining patient evolved to aplastic anemia under therapy with methimazole (60 mg/d), but had an increased peripheral blood count that almost reached normal values after radioiodinetherapy and standard immunosuppressive treatment with antithymocyte globulin (700 mg/d, intravenous infusion for 5 days), oral cyclosporin (400 mg/d), prednisone (30-60 mg/d), and granulocyte colony-stimulating factor (150 microg subcutaneous injection, 3 times per week). We conclude that: (1) a hematologic evaluation of all patients with Graves' disease should be performed before administering antithyroid drugs, (2) antithyroid drugs may be administered to patients with pancytopenia and bone marrow hypercellularity but a reevaluation of the bone marrow must be done if there is no recovery of the peripheral blood cell count when euthyroidism state is achieved, (3) standard immunosuppressive treatment of aplastic anemia caused by antithyroid drugs restores normal hematopoiesis, and (4) a thyroid evaluation of patients with pancytopenia should be done, even though no related symptoms are found.

Topics: Adolescent; Adult; Aged; Female; Graves Disease; Humans; Male; Methimazole; Pancytopenia

Thyrotoxicosis occurs more frequently during the post-partum period than at other times in women of childbearing age. Graves' disease and post-partum thyroiditis are two major causes of thyrotoxicosis in this period. The major task lies in differentiation of these two diseases in the post-partum period; since throtoxicosis caused by post-partum thyroiditis usually does not require treatment. The radioiodine uptake is elevated or normal in Graves' disease and low in post-partum thyroiditis, and TSH-receptor antibodies are positive in Graves' and negative in post-partum thyroiditis. Post-partum thyrotoxicosis due to Graves' disease may be treated with radioiodine but it requires radiation safety measurements for infant and is contraindicated if the mother is breast-feeding. Antithyroid drugs are the mainstay of the treatment of post-partum thyrotoxicosis. Recent investigations conclude that neither propylthiouracil nor methimazole cause any alterations in thyroid function and physical and mental development of infants breast-fed by lactating thyrotoxic mothers, and both can be safely administered in moderately high doses during lactation.

Topics: Antithyroid Agents; Breast Feeding; Female; Graves Disease; Humans; Infant, Newborn; Iodine Radioisotopes; Methimazole; Propylthiouracil; Puerperal Disorders; Radiotherapy; Thyroidectomy; Thyroiditis; Thyrotoxicosis; Thyrotropin; Thyroxine; Triiodothyronine

Topics: Adult; Female; Graves Disease; Hashimoto Disease; Humans; Methimazole; Pregnancy; Pregnancy Complications; Thyroxine

To describe a case of Graves' disease treated with methimazole and examine the influence of thyroid hormone alteration on warfarin anticoagulation.. A 54-year-old man presented to the emergency department with palpitations, fatigue, weight loss, and anxiety attacks. He was taking no medications at that time. An electrocardiogram showed new onset atrial fibrillation. His thyroid profile was consistent with hyperthyroidism. The patient was admitted to the intensive care unit and started on methimazole 30 mg/day, metoprolol, enoxaparin, and warfarin 5 mg/day. Postdischarge doses of warfarin and methimazole were adjusted over the next several months based on thyroid panel results indicative of hypothyroidism. Postdischarge changes in methimazole dose caused alterations in thyroid function and intensity of anticoagulation as measured by international normalized ratio.. Interactions between warfarin and drugs that alter thyroid hormone concentrations have been reported; however, the extent and significance of the interaction between methimazole and warfarin have been inadequately described. Thyroid hormone concentrations influence the metabolic rates of proteins and, thus, can alter the amount of vitamin K-dependent clotting factors, which in turn can alter the extent of inhibition by warfarin. This may lead to changes in the intensity of anticoagulation and thereby increase the risk of thromboembolic or hemorrhagic events.. Changes in thyroid hormone concentrations have the potential to significantly alter the extent of warfarin-induced anticoagulation. Clinicians must be aware of the need for close anticoagulation monitoring and dosage adjustment in patients receiving concomitant warfarin and methimazole. The full extent of this interaction may be delayed following a change in methimazole dose.

Topics: Anticoagulants; Antithyroid Agents; Drug Interactions; Electrocardiography; Graves Disease; Humans; Male; Methimazole; Middle Aged; Thyroid Function Tests; Thyroid Hormones; Warfarin

A 39 year-old man was admitted to our hospital because of severe headache with fever continuing over two weeks. Three days after admission he developed aphasia and right hemiparesis, when his CT revealed subarachnoid hemorrhage at the left sylvian fissure. He was diagnosed as suffering from cerebral venous thrombosis because empty delta sign was positive on the enhanced brain CT. Suprasagittal sinus and bilateral transverse sinuses were not detected on the cerebral angiography. He was also diagnosed as having Graves' disease for the first time on the basis of free T3 13.56 pg/ml, free T4 4.65 ng/dl, TSH < 0.01 IU/ml, anti-TSH receptor antibody 4.3 IU/l, and thyroid stimulating antibody 224%. On the examination, homocystine and activities of antithrombin III, protein C, and protein S were normal. Antinculear, anti-DNA, anti-Sm, anticardiolipin beta2GP-I antibodies, and PR3ANCA were negative. Factor VIII activity, however, markedly increased over 300%, which has been known to increase in the cases of hyperthyroidism. He recovered well after the treatment with thiamazole in addition to warfarin followed by intravenous heparin. There are only six cases of cerebral venous thrombosis due to hyperthyroidism with increased factor VIII level. All of those cases were female, and 5 of them were taking oral contraceptives. This is a first Japanese male case.

Topics: Adult; Anticoagulants; Antithyroid Agents; Factor VIII; Female; Graves Disease; Humans; Intracranial Thrombosis; Male; Methimazole; Thrombophilia; Treatment Outcome; Warfarin

A 79-year-old woman was admitted to our hospital because of forgetfulness for a month followed with rapid development of consciousness disturbance. After admission, the depressed consciousness level fluctuated but continued for more than a month. Thyroid function tests showed increased free T3 and T4 level, lowered level of TSH, and increased anti-TSH receptor antibody titer. A diagnosis of Graves' disease was made but we could find none of thyrotoxic manifestations such as goiter, exophthalmos, tachycardia, high body temperature, or sweating. Administration of thiamazole rapidly improved her consciousness level. It should be kept in mind that hyperthyroidism in elderly could present solely with psychoneurologic symptoms or consiousness disturbance.

Topics: Aged; Antithyroid Agents; Biomarkers; Consciousness Disorders; Female; Graves Disease; Humans; Methimazole; Thyroid Hormones; Treatment Outcome

Prediction of remission is one of the main problems of antithyroid drug (ATD) therapy for Graves' disease especially in patients who are treated with a minimum maintenance dose of ATD. We evaluated the ability of new sensitive TSH receptor antibody (TRAb) assays to predict remission in Graves' patients using two commercially available kits (TRAb-CT from Cosmic Corporation and TRAb-Dyno from Yamasa Corporation), compared to the original PEG assay. When a euthyroid state was achieved for more than 6 months with methimazole 5 mg/day or propylthiouracil 50 mg/day and thereafter for three months with 5 mg every other day or 50 mg every other day, respectively, we discontinued ATD medication. One year of observation after discontinuation of ATD was completed in 71 patients (60 females, median age 43 years, range 18-71), and TRAb values from these patients were analyzed in relation to prognosis. Twenty-six (37%) of the 71 patients had relapse of thyrotoxicosis and 45 remained euthyroid. The median TRAb levels in the relapse group were significantly higher than those in the remission group (P < 0.05). Relapse occurred in 15/51 patients negative by TRAb-CT, in 11/20 patients positive by TRAb-CT (chi2 = 4.1; P < 0.05), in 11/42 patients negative by TRAb-Dyno and in 15/29 patients positive by TRAb-Dyno (chi2 = 4.8; P < 0.05). By contrast, relapse occurred in 23/64 patients with negative TRAb by PEG assay and in 3/7 patients with PEG assay positive values (n.s.). All patients with TRAb-CT values of 30% inhibition or greater, or TRAb-Dyno values of 3.0 U/L or greater relapsed during the observation period. Thus, measurement of TRAb by the new sensitive assays is useful for prediction of remission in our patients.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Autoantibodies; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Predictive Value of Tests; Propylthiouracil; Reagent Kits, Diagnostic; Recurrence; Thyrotropin; Thyroxine

The interferon-gamma-inducible chemokine CXCL10 is highly expressed in infiltrating inflammatory cells, and in thyrocytes in patients with Graves' disease. The aim of this study was to measure serum levels of CXCL10 in relation to thyroid function and treatment.. Serum levels of CXCL10 were measured in 22 patients with Graves' disease when hyperthyroid, when euthyroid under methimazole therapy, and 3 days after near-total thyroidectomy. They were compared with levels in three groups of age- and sex-matched controls: 44 subjects with no thyroid disorder, 44 patients with euthyroid autoimmune thyroiditis and 20 with toxic nodular goitre.. Basal serum levels of CXCL10 in patients with Graves' disease were higher than levels in patients with toxic nodular goitre or no thyroid disorder, and similar to levels in patients with autoimmune thyroiditis (mean(s.d.) 167(121), 100(24), 78(46) and 142(107) pg/ml respectively; P < 0.010). Among patients with Graves' disease, serum levels of CXCL10 were significantly higher in those aged over 50 years (P = 0.010), with a hypoechoic pattern at thyroid ultrasonography (P < 0.001) or with hypervascularity (P = 0.001). CXCL10 levels in patients with Graves' disease decreased significantly when euthyroidism was achieved by methimazole therapy (P < 0.010), and a further decrease was observed after thyroidectomy (P < 0.010).. Serum levels of CXCL10 are higher in newly diagnosed hyperthyroid patients with Graves' disease than in those with toxic nodular goitre, and decrease when euthyroidism is achieved with antithyroid therapy. This high level may be related to the active inflammatory phase of Graves' disease. A further reduction of CXCL10 levels after thyroidectomy indicates that it is produced mainly in the thyroid in patients with autoimmune thyroid disease.

Topics: Antithyroid Agents; Case-Control Studies; Chemokine CXCL10; Chemokines, CXC; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Retrospective Studies; Thyroidectomy; Treatment Outcome

Topics: Adolescent; Antithyroid Agents; Blepharoptosis; Child, Preschool; Diagnosis, Differential; DNA, Mitochondrial; Female; Graves Disease; Humans; Immunoglobulins, Intravenous; Infant; Male; Methimazole; Mutation; Neuroblastoma; Paraneoplastic Syndromes, Nervous System

Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antithyroid Agents; Autoantibodies; B-Lymphocytes; Female; Glucocorticoids; Graves Disease; Graves Ophthalmopathy; Humans; Immunoglobulins, Thyroid-Stimulating; Methimazole; Middle Aged; Recurrence; Remission Induction; Rituximab; Thyroid Diseases

Hyperglycemic hyperosmolar state (HHS) is an acute complication mostly occurring in elderly type 2 diabetes mellitus (DM). Thyrotoxicosis causes dramatic increase of glycogen degradation and/or gluconeogenesis and enhances breakdown of triglycerides. Thus, in general, it augments glucose intolerance in diabetic patients. A 23-yr-old female patient with Graves' disease and type 2 DM, complying with methimazole and insulin injection, had symptoms of nausea, polyuria and generalized weakness. Her serum glucose and osmolarity were 32.7 mM/L, and 321 mosm/kg, respectively. Thyroid function tests revealed that she had more aggravated hyperthyroid status; 0.01 mU/L TSH and 2.78 pM/L free T3 (reference range, 0.17-4.05, 0.31-0.62, respectively) than when she was discharged two weeks before (0.12 mU/L TSH and 1.41 pM/L free T3). Being diagnosed as HHS and refractory Graves' hyperthyroidism, she was treated successfully with intravenous fluids, insulin and high doses of methimazole (90 mg daily). Here, we described the case of a woman with Graves' disease and type 2 DM developing to HHS.

Topics: Adult; Diabetes Mellitus, Type 2; Female; Fluid Therapy; Graves Disease; Humans; Hyperglycemic Hyperosmolar Nonketotic Coma; Hyperthyroidism; Insulin; Methimazole; Thyroid Function Tests

The appropriate period of antithyroid drug (ATD) discontinuation before radioiodine therapy is the most critical problem in Graves' disease patients under going treatment with ATD. To determine the optimal period that does not alter the outcome of radioiodine therapy or exacerbate hyperthyroidism, we compared serum FT4 levels at radioiodine uptake (RAIU) and therapy outcomes between a 2-day withdrawal group and 7-day withdrawal group. We prospectively recruited 43 patients for the 2-day withdrawal protocol and retrospectively reviewed 49 patients treated with radioiodine following the protocol of 7-day withdrawal. There was no significant difference in RAIU between the 2 groups. The mean serum FT4 level measured on the first day of 24-h RAIU of the 7-day group was significantly higher than that in the 2-day group. There were no significant differences in the outcomes at each point (6 months, 1 year, and 2 years after therapy) between the 2 groups. Our results indicated that withdrawal of ATD for 2 days is superior to 7 days in that 2 days discontinuation did not exacerbate hyperthyroidism. In order to prevent serum thyroid hormone increase after ATD withdrawal and radioiodine therapy, a 2-day ATD withdrawal period before radioiodine therapy may be useful for high-risk patients such as the elderly and patients with cardiac complications. We believe that the 2-day ATD withdrawal method may be useful for patients undergoing treatment with ATD who are to undergo radioiodine therapy.

Topics: Adult; Antithyroid Agents; Drug Administration Schedule; Female; Graves Disease; Humans; Hyperthyroidism; Iodine Isotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Retrospective Studies; Thyroxine; Treatment Outcome; Withholding Treatment

In this study, we set out to evaluate the costs and effectiveness of the 2 most used therapies in our region, ATD or RAI. 23 patients, 6 men and 16 women, with a mean age of 35.4 years, treated with ATD, and 35 patients, 5 men and 30 women, mean age of 39.4 years, treated with RAI, were studied. After 2 years receiving ATD, 21 patients achieved euthyroidism and 2 remained hyperthyroid. In the RAI group, 21 patients presented hypothyroidism and 13 became euthyroid. To calculate the costs of each therapy, we analyzed the number of visits during this period, the laboratory data and the drugs needed, such as tiamazol and/or thyroxine. The group treated only with ATD needed a higher number of visits and laboratory measurements, with the mean total cost of R dollars 1,345.81, while the RAI group spent a mean amount of R dollars 622.94. Therefore, the costs of the RAI treatment were 53.5% lower than clinical therapy with ATD. The present study demonstrates that RAI treatment has a lower cost than ATD, being very effective in controlling the hyperthyroidism of Graves disease.

Topics: Adolescent; Adult; Antithyroid Agents; Cost-Benefit Analysis; Female; Follow-Up Studies; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Retrospective Studies; Treatment Outcome

Thyroid hormone lowers the seizure threshold. We present the case of a female patient who developed generalized convulsions emerging with Graves' disease, and clarified the clinico-electroencephalographic characteristics. Before treatment, electroencephalography (EEG) showed 2- to 2.5-Hz diffuse spike and wave (SW) bursts, apparent during and after hyperventilation without any distinct absence seizure. Thiamazole treatment without any anticonvulsant led to a euthyroid state, convulsions resolved and EEG abnormalities normalized promptly. Clinical seizures were generalized tonic-clonic convulsions during sleep, and EEG showed diffuse SW bursts induced by hyperventilation. These characteristics suggested that epilepsy might correspond to idiopathic generalized epilepsy (IGE). IGE might be susceptible to hyperthyroidism. Cases of IGE emerging with hyperthyroidism, even if EEG paroxysms are advanced, may be improved using antithyroid pharmacotherapy alone.

Topics: Adolescent; Antithyroid Agents; Electroencephalography; Female; Follow-Up Studies; Graves Disease; Humans; Methimazole; Seizures

The study was designed to estimate the influence of hyperthyroidism and antithyroid treatment on oxidative stress peripheral parameters in Graves' disease patients with and without infiltrative ophthalmopathy.. Free radical generation and scavenging plasma indices were determined in 47 patients with hyperthyroidism due to Graves' disease (22 with and 25 without infiltrative ophthalmopathy), as well as in 24 healthy volunteers after euthyroidism achievement with methimazole.. In the hyperthyroid patients, hydrogen peroxide, lipid hydroperoxides, thiobarbituric acid-reacting substances, ceruloplasmin, superoxide dismutase, and catalase were increased. Glutathione peroxidase and glutathione reductase, however, were reduced. Methimazole treatment resulted in all markers being normalized in the patients without infiltrative ophthalmopathy, yet oxidative stress was still present in the ophthalmopathy group.. We suggest that apart from the thyroid metabolic status influence, it is orbital inflammation that triggers changes in blood extracellular indices of reactive oxygen species metabolism.

Topics: Antithyroid Agents; Carboxylic Acids; Female; Graves Disease; Humans; Hydrogen Peroxide; Male; Methimazole; Middle Aged; Oxidative Stress; Reactive Oxygen Species; Thiobarbituric Acid Reactive Substances; Thyrotropin; Thyroxine; Triiodothyronine

Here we report a case of idiopathic thrombocytopenic purpura accompanied by Graves' disease. Improvement in thyroid function with methimazole led to the spontaneous recovery of the platelet count from 8 x 10(9)/L to 84 x 10(9)/L. Furthermore, the second fall and recovery of the platelet count well coincided with the recurrence of hyperthyroidism after the discontinuation of methimazole and its normalization by resumption of the drug, respectively. These parallel fluctuations of platelet and thyrotropin because of the cessation and resumption of antithyroid therapy suggests that correction of hyperthyroidism may be beneficial to the control of an imbalance in the immune system which impairs not only thyroid but also the platelet.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Methimazole; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Thyrotropin

In Graves' ophthalmopathy (GO) intercellular adhesion molecule-1 (ICAM-1) is thought to play a key role in lymphocyte infiltration into the orbit, and serum levels of its soluble form are positively correlated to clinical activity score (CAS). Serum antibodies against collagen XIII (CollXIIIAb), a plasma membrane protein expressed at a low level in almost all connective tissue-producing cells, have been detected in GO, but their significance is unclear. The aim of this study was to search for CollXIIIAb in Graves' patients with and without ophthalmopathy and to correlate their levels with CAS and with serum soluble ICAM-1 (sICAM-1) values.. We studied 66 patients with Graves' disease whose sera had been previously tested for sICAM-1 levels, grouped as follows: 28 with moderate and active ophthalmopathy (group 1), 12 of them hyperthyroid (group 1a) and 16 euthyroid (group 1b); 13 with mild and inactive ophthalmopathy and normal thyroid function (group 2); 25 without ophthalmopathy (group 3), 11 of them hyperthyroid (group 3a) and 14 euthyroid (group 3b). Finally, 26 sera of normal controls were studied.. CollXIIIAb were evaluated by an enzyme-linked immunosorbent assay (ELISA) method.. In group 1 patients, CollXIIIAb were detected at high levels in 8/12 (66.6%) in group 1a [optical density (OD) ranging from 0.529 to 0.894] and in 10/16 (62.5%) in group 1b (OD 0.560-0.855). In group 2 patients, CollXIIIAb were detected but at low levels (OD 0.205-0.260) in 4/13 patients (30.7%). In group 3 patients, CollXIIIAb were present at low levels in 6/11 (54.5%) of group 3a and in 5/14 (35.7%) of group 3b (OD 0.215-0.290 and 0.144-0.245, respectively). CollXIIIAb were detected in only 4/26 normal controls (15%) but at low levels (OD 0.150-0.185). CollXIIIAb values in both groups 1a and 1b were significantly higher than those of the remaining groups. A positive correlation between CollXIIIAb levels and CAS but not thyroid hormone levels was found in groups 1a, 1b and 2. Moreover, a positive correlation between CollXIIIAb levels and sICAM-1-values was also evidenced in all three groups.. Our results suggest that CollXIIIAb could be considered as a further good marker of active inflammatory processes involving the adipose connective tissue in GO. In particular, the high levels of CollXIIIAb in sera of Graves' patients with active ophthalmopathy could reflect an increased expression of type XIII collagen on the membrane of activated fibroblasts in these patients. Thus, the evaluation of these antibodies could be added to other known markers as a useful and inexpensive tool in monitoring Graves' patients and in modulating the treatment of GO.

Topics: Acute Disease; Adult; Antithyroid Agents; Autoantibodies; Biomarkers; Case-Control Studies; Chi-Square Distribution; Collagen Type XIII; Female; Graves Disease; Humans; Intercellular Adhesion Molecule-1; Male; Methimazole; Middle Aged

Topics: Antithyroid Agents; Drug Therapy, Combination; Graves Disease; Humans; Hyperthyroidism; Methimazole; Thyroxine

Euthyroid pregnant women with a previous history of Graves' disease treated with radioiodine or surgery may have persistently elevated TSH receptor antibody (TRAb) levels, putting their offspring at risk for fetal hyperthyroidism (FH) and/or neonatal hyperthyroidism (NH).. We performed a literature review using a MEDLINE search to determine if and how anti-thyroid drugs (ATD) were utilized in euthyroid pregnant women with previous Graves' disease to prevent FH/NH.. There are 11 published reports involving 13 pregnancies where ATDs were utilized to prevent FH in euthyroid mothers with a previous history of Graves' disease. Subjects were treated if high titres of TRAb (> 5-fold above normal) were noted on either radioreceptor assay or various bioassays. Such intervention appeared beneficial. Thirteen live births were observed when previously these mothers collectively experienced six miscarriages, stillborn or infant deaths attributed to FH or NH. Developmental consequences such as craniosynostosis or dysmorphic features were not observed in the infants described. Both propylthiouracil and methimazole were used effectively. When utilized, cordocentesis (or periumbilical blood sampling) to determine fetal thyroid status and TRAb levels proved to be of value in establishing the diagnosis and guiding therapy.. Maternal ATD prevent the serious consequences of FH/NH and should be considered for euthyroid Graves' mothers with high TRAb titres.

Topics: Adult; Antithyroid Agents; Biological Assay; Databases, Bibliographic; Embryo, Mammalian; Female; Fetal Monitoring; Graves Disease; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Thyroid Gland

An association between Graves' disease (GD) and chronic hepatitis C (C-HC) has been observed both in the presence and the absence of recombinant interferon-alpha (rIFN-alpha) treatment. rIFN-alpha-induced GD is characterized by suppressed thyroid-stimulating hormone levels; normal or elevated free triiodothyronine (FT3) and free thyroxine (FT4) values; the presence of thyroid peroxidase antibodies, antithyroglobulin antibodies, and thyroid receptor antibodies; and high iodine thyroid uptake. In contrast, GD developed during C-HC without rIFN-alpha is less clearly defined. In this study, we examined two groups of patients: group A, 28 patients with C-HC treated with rIFN-alpha who developed GD after 1 to 9 months, and group B, 10 patients with C-HC who developed GD without a previous rIFN-alpha treatment. At the time of GD, both groups started methimazole therapy; thyroid function was reevaluated after 3, 6, 9, and 12 months. Group A patients continued IFN. After 12 months, all patients of group A were euthyroid, and 21 of them (75%) had already stopped methimazole treatment, whereas all patients of group B were euthyroid and only 2 (20%) had stopped methimazole. In conclusion, the data show a better course of GD, with a more precocious and significantly higher number of recoveries in patients with rIFN-alpha-induced GD than in rIFN-alpha-unrelated disease. Further studies are needed to establish whether the two types of GD differ not only from a clinical point of view but also because of different underlying pathogenetic mechanisms.

Topics: Antiviral Agents; Autoantibodies; Female; Graves Disease; Hepacivirus; Hepatitis C, Chronic; Humans; Interferon Type I; Iodide Peroxidase; Male; Methimazole; Middle Aged; Receptors, Thyroid Hormone; Recombinant Proteins; Thyrotropin; Thyroxine; Treatment Outcome; Triiodothyronine

Appropriate methimazole dosing for initial treatment of childhood Graves' disease is uncertain. A retrospective chart review was performed on 5 to 17 year-old children treated for Graves' disease. Patients were divided into two groups depending on initial methimazole dosing: low-dose and high-dose regimens using <0.5 mg/kg/day and >0.5 mg/kg/day, respectively. The low-dose regimen was effective in 5/12 (42%) of patients and the high-dose regimen was effective in 27/33 (82%) of patients (p = 0.016). There was also a statistically significant dose/time interaction for levels of free thyroxine (T4) (p = 0.025). During treatment, 63.3% of diagnosable samples showed unambiguous hyperthyroidism or triiodothyronine (T3) toxicosis, 16.7% elevated free T3 with normal free T4 and T3 levels, indicating borderline hyperthyroidism, and 20% showed thyroid-stimulating hormone (TSH) suppression with normal or low levels of free T4 and free T3, indicating delayed recovery of pituitary TSH secretion. Free T3 levels combined with concurrent TSH levels permit differentiation of mild hyperthyroidism from delayed pituitary recovery.

Topics: Adolescent; Antithyroid Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Pituitary Diseases; Retrospective Studies; Thyrotoxicosis; Thyrotropin; Thyroxine; Triiodothyronine

Thyrotoxic hypokalemic periodic paralysis (THPP) is a very rare complication of thyrotoxicosis in whites, but is more frequently reported in individuals of Asian descent. Hypokalemia, with associated flaccid paralysis, and signs of hyperthyroidism, are the hallmark. We have reported a case of a 28-yr-old white man with Graves' disease presenting with a 2-wk history of episodic flaccid quadriplegia. Physical examination disclosed a resting tachycardia and symmetrical, proximal weakness involving both arms and legs. Electrocardiogram and electrolyte analysis showed a severe hypokalemia, and thyroid function tests revealed hyperthyroidism. The patient was diagnosed as having Graves' hyperthyroidism and THPP. Paralysis resolved with potassium supplements. He was treated with propranolol and, subsequently, methimazole. He had no further episodes of hypokalemic paralysis. To the best of the author's knowledge, and after a Medline search, THPP has not been described previously in a Turkish man.

Topics: Adult; Antithyroid Agents; Electrocardiography; Graves Disease; Humans; Hypokalemia; Hypokalemic Periodic Paralysis; Male; Methimazole; Potassium Chloride; Thyrotoxicosis; Water-Electrolyte Balance

Topics: Antithyroid Agents; Drug Therapy, Combination; Graves Disease; Humans; Iodine Radioisotopes; Methimazole; Recurrence; Remission Induction; Smoking Cessation; Thyroxine; Time Factors

Clinical and serological profiles of idiopathic and drug-induced autoimmune diseases can be very similar. We compared data from idiopathic and antithyroid drug (ATD)-induced antineutrophil cytoplasmic antibody (ANCA)-positive patients. From 1993 to 2003, 2474 patients were tested for ANCA in the Laboratory for Allergy and Clinical Immunology in Belgrade. Out of 2474 patients, 72 (2.9%) were anti-proteinase 3 (PR3)- or anti-myeloperoxidase (MPO)-positive and their clinical and serological data were analyzed. The first group consisted of ANCA-associated idiopathic systemic vasculitis (ISV) diagnosed in 56/72 patients: 29 Wegener's granulomatosis (WG), 23 microscopic polyangiitis (MPA) and four Churg-Strauss syndrome. The second group consisted of 16/72 patients who became ANCA-positive during ATD therapy (12 receiving propylthiouracil and four receiving methimazole). We determined ANCA and antinuclear (ANA) antibodies by indirect immunofluorescence; PR3-ANCA, MPO-ANCA, anticardiolipin (aCL) and antihistone antibodies (AHA) by ELISA; and cryoglobulins by precipitation. Complement components C3 and C4, alpha-1 antitrypsin (alpha1 AT) and C reactive protein (CR-P) were measured by nephelometry. Renal lesions were present in 3/16 (18.8%) ATD-treated patients and in 42/56 (75%) ISV patients (p <0.001). Skin lesions occurred in 10/16 (62.5%) ATD-treated patients and 14/56 (25%) ISV patients (p <0.01). ATD-treated patients more frequently had MPO-ANCA, ANA, AHA, aCL, cryoglobulins and low C4 (p <0.01). ISV patients more frequently had low alpha1 AT (p = 0.059) and high CR-P (p <0.001). Of 16 ATD-treated patients, four had drug-induced ANCA vasculitis (three MPA and one WG), while 12 had lupus-like disease (LLD). Of 56 ISV patients, 13 died and eight developed terminal renal failure (TRF). There was no lethality in the ATD-treated group, but 1/16 with methimazole-induced MPA developed pulmonary-renal syndrome with progression to TRF. ANCA-positive ISV had a more severe course in comparison with ATD-induced ANCA-positive diseases. Clinically and serologically ANCA-positive ATD-treated patients can be divided into two groups: the first consisting of patients with drug-induced WG or MPA which resemble ISV and the second consisting of patients with LLD. Different serological profiles could help in the differential diagnosis and adequate therapeutic approach to ANCA-positive ATD-treated patients with symptoms of systemic disease.

Topics: Adolescent; Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Antibody Specificity; Antithyroid Agents; Autoantigens; Autoimmune Diseases; Churg-Strauss Syndrome; Cyclophosphamide; Female; Fluorescent Antibody Technique, Indirect; Follow-Up Studies; Granulomatosis with Polyangiitis; Graves Disease; Hashimoto Disease; Humans; Hyperthyroidism; Immunoprecipitation; Kidney; Lung; Male; Methimazole; Middle Aged; Myeloblastin; Nephelometry and Turbidimetry; Peroxidase; Polyarteritis Nodosa; Prednisone; Pregnancy; Pregnancy Complications; Propylthiouracil; Retrospective Studies; Serine Endopeptidases; Skin; Vasculitis; Vasculitis, Leukocytoclastic, Cutaneous

The present study was performed to elucidate the relationship between CTLA-4/CD28 molecules and stimulating (TSAb) and blocking (TBAb) antibodies to the TSH-receptor (TSH-R) in Graves' disease. CD28 and CD152 (CTLA-4) are glycoprotein molecules which provide a potent costimulatory signal for T-cell activation and proliferation via interactions with their ligands, B7.1/B7.2 molecules, which are present on the surface of antigen-presenting cells. The aim of the study was to estimate the expression of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4, CD152), CD28, B7.1 (CD80), and B7.2 (CD86) molecules on peripheral blood cells in patients with Graves' disease (GD) (n = 55, mean age 15.5 +/- 5.1 years) and nontoxic nodular goiter (NTNG) (n = 55, mean age 15.2 +/- 4.5 years), in comparison with sex and age-matched healthy control subjects (n = 55, mean age 15.2 +/- 3.9 years). The expression of the costimulatory molecules on mononuclear cells was analyzed by three-color flow cytometry using a Coulter EPICS XL cytometer. Detection of TSAb and TBAb to the TSH-R using JPO9 CHO cells in unfractionated serum was measured by a highly sensitive commercial radioimmunoassay. When compared with healthy control subjects and euthyroid patients with GD, untreated patients with GD showed a significant increase of CD152+ (p < 0.001, p < 0.001) and CD28+ (p < 0.01, NS) T lymphocytes, respectively. After 6-12 months of methimazole therapy, the percentage of these cells in the peripheral blood of hyperthyroid patients returned to normal values. In addition, patients with GD showed an increase in the percentage of both B7.1 (3.8%) and B7.2 (18.4%) molecules on activated monocytes, compared to patients with NTNG (0.5% p < 0.05, 2.5% p < 0.01, respectively) and healthy control subjects (0.2% p < 0.05, 0.8% p < 0.003, respectively). In patients with untreated GD there was a statistically significant positive correlation between the expression of CTLA-4 on the surface of peripheral blood T cells and the index of TSAb antibodies (R = 0.54, p < 0.001) as well as a negative correlation with TBAb antibody titer (R = -0.58, p < 0.001). However, no such correlations were noted with regard to CD28 and anti-TPO, anti-TG, and TRAb antibodies. We conclude that changes in the expression of costimulatory molecules on the surface of peripheral blood T cells and their significant relationship with the level of antithyroid antibodies indicate an involvement of these molecules in the pathogenes

Topics: Adolescent; Antigens, CD; Antigens, Differentiation; Autoantibodies; CD28 Antigens; Child; CTLA-4 Antigen; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Iodide Peroxidase; Lymphocyte Count; Lymphocyte Subsets; Male; Methimazole; Receptors, Thyrotropin; T-Lymphocytes; Thyrotropin; Thyroxine; Triiodothyronine

The aim of the present study was to evaluate a new proposal for increasing compliance to the clinical management of patients with Graves' disease (GD) in a large and public University Hospital. The patients were carefully selected (no previous GD treatment, goiter volume less than 6 mL must be living in the metro area of São Paulo), received medication at no cost, were contacted frequently by the social worker and alerted for the date of consultation and only referred to a single endocrinologist during all phases of treatment. We recruited 229 patients with GD that were initially treated with methimazole (MMI--60 mg q.d) in a single daily dose followed by a combination of MMI (20 mg) plus L-T4 (100 microg) daily for 24 months. Only 83 patients (36.2%) completed the protocol and were subdivided in: Group 1 (n= 34) that were in remission for 3 years after discontinuation of the MMI and Group 2 (n= 49) that presented recurrence of GD between 2 and 36 months without MMI. Predictive factors associated with remission were: decrease of the glandular volume, serum TG< 40 ng/mL and normal TRAb values. We concluded that in spite of a careful protocol planned to increase compliance, more than 60% of patients with GD did not complete the therapeutic trial and were referred for radioiodine treatment. The solution for this low therapeutic success for GD should be the possible identification of factors that would indicate patients that are not inclined to follow a long period of clinical therapy.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Clinical Protocols; Cost-Benefit Analysis; Female; Follow-Up Studies; Graves Disease; Health Care Costs; Hospitals, Public; Hospitals, University; Humans; Male; Methimazole; Middle Aged; Patient Compliance; Patient Dropouts; Recurrence; Retrospective Studies; Urban Population

Struma ovarii is the most common monodermal ovarian teratoma and consists mainly of thyroid tissue. Only 5% of patients with this tumor have features of hyperthyroidism. The pathophysiology of hyperthyroidism in struma ovarii is not clear.. We describe a case of benign struma ovarii, presenting with the clinical features of an ovarian cancer: large complex pelvic mass, large amount of ascites and markedly elevated CA-125 serum levels. The patient was initially treated for Graves' disease, on the basis of ultrasonographic, laboratoristic and scintigraphic evidence. The resistance to the medical treatment led to thyroidectomy. After surgery the hyperthyroidism persisted and, suddenly, the patient presented ascites. A large pelvic mass was then diagnosed which, at the pathologic examination, was diagnosed as a struma ovarii.. The struma ovarii always has to be considered when a pelvic mass is associated with features of hyperthyroidism.

Topics: Adult; Ascites; CA-125 Antigen; Female; Graves Disease; Humans; Hyperthyroidism; Methimazole; Ovarian Neoplasms; Ovariectomy; Struma Ovarii; Thyroidectomy; Thyroxine

Drug-induced hypersensitivity syndrome is one of the most severe forms of drug eruption and is characterized by high fever and multiorgan involvement. Reactivation of human herpesvirus-6 (HHV-6) or cytomegalovirus (CMV) has been suggested to be involved in this syndrome, although the exact role of these viruses remains elusive. We report the case of a 50-year-old Japanese male with Graves' disease who developed hypersensitivity syndrome caused by the antithyroid drug methimazole (MMI). After treatment with MMI 30 mg three times daily for 1(1/2) months, the patient developed generalized exfoliative erythematous eruption and high fever. Cessation of treatment with the drug improved his condition. Readministration of MMI worsened his clinical features. Treatment with high-dose methylprednisolone for 6 days and subsequent administration of prednisolone 20 mg twice daily improved his clinical manifestations. Elevated titers of anti-HHV-6 immunoglobulin G (IgG) and anti-CMV IgG antibodies were observed, and these gradually decreased during the clinical course, indicating reactivation of HHV-6 and CMV. Drug-induced lymphocyte stimulation test for MMI was negative. This is the first reported case of MMI-induced hypersensitivity syndrome associated with the reactivation of HHV-6 and CMV.

Topics: Antibodies, Viral; Antithyroid Agents; Cytomegalovirus; Drug Hypersensitivity; Graves Disease; Herpesvirus 6, Human; Humans; Immunoglobulin M; Male; Methimazole; Middle Aged; Virus Activation

Topics: Adult; Antiviral Agents; Early Diagnosis; Female; Graves Disease; Hepatitis C, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Methimazole; Polyethylene Glycols; Recombinant Proteins; Treatment Outcome

A 60-year-old woman was admitted to a hospital complaining of dizziness and general fatigue in October, 2004. Because of heart failure and severe anemia, she was referred to our hospital. Based on a positive direct Coombs test and an elevated level of platelet-associated IgG (PAIgG), the patient was diagnosed as having autoimmune hemolytic anemia (AIHA) associated with idiopathic thrombocytopenic purpura (ITP), i.e., Evans syndrome. Basedow disease was also diagnosed due to hyperthyroidism with an elevation of anti-thyroid stimulating hormone (TSH) receptor antibodies. Both the Evans syndrome and Basedow disease were considerably ameliorated with plasma exchange, corticosteroid and thiamazole therapy. Although Basedow disease is known to be associated with hematological disorders such as AIHA or ITP, the combination of Basedow disease and Evans syndrome is rare. We report here a case of Basedow disease associated with Evans syndrome.

Topics: Anemia, Hemolytic, Autoimmune; Drug Therapy, Combination; Female; Graves Disease; Humans; Methimazole; Methylprednisolone; Middle Aged; Plasma Exchange; Pulse Therapy, Drug; Purpura, Thrombocytopenic, Idiopathic; Syndrome; Treatment Outcome

Antibody synthesis follows interactions between the T cell receptor (TCR) on activated T lymphocytes and the main histocompatibility complex (MHC) present on APC cells, resulting in lymphocyte proliferation, as well as cytokine synthesis and release. The involvement of costimulatory markers OX40/4-1BB/4-1BBL leads to the enhancement of signals which are necessary for lymphocyte activation in addition to the antigen-specific signal and may prevent anergy. The aim of this study was to estimate the expression of OX40 and 4-1BB molecules on peripheral blood cells in patients with Graves' disease (GD) (n = 35, mean age 16.5 +/- 6.1 years) and non-toxic nodular goiter (NTNG) (n = 35, mean age 16.2 +/- 4.7 years), in comparison with sex- and age-matched healthy controls (n = 35, mean age 16.2 +/- 2.1 years). Expression of the costimulatory molecules on mononuclear cells was analyzed by three-color flow cytometry using a Coulter EPICS XL cytometer. Stimulating and blocking antibodies to the TSH-receptor using JPO9 CHO cells in unfractionated serum were measured by a highly sensitive commercial radioimmunoassay. The analysis of OX40/4-1BB expression in patients with newly recognized Graves' disease revealed a statistically significant increase in the percentage of CD134+ T cells (7% vs 1.4%, p <0.001) and CD137+ T cells (3.2% vs 0.8%, p <0.04) compared to the control group. After 2-6 months of methimazole therapy, the percentage of these cells in the peripheral blood of hyperthyroid patients returned to normal values. In addition, the expression of 4-1BBL (CD137L) was detected only on the surface of active monocytes in patients with untreated GD (3.8%), while in the group with nodular goiter and controls the values were trace (0.6% and 0.2%, respectively). We conclude that the changes of expression of costimulatory molecules on the surface of peripheral blood T cells and their significant relationship with the level of antithyroid antibodies indicate an involvement of these molecules in the pathogenesis of Graves' disease. A marked increase in the percentage of CD134/ CD137+ T cells at disease onset may indicate the need for more aggressive therapy in Graves' disease and for a greater duration than the standard 3-year period.

Topics: Adolescent; Adult; Animals; Antithyroid Agents; Autoantibodies; Child; CHO Cells; Cricetinae; Female; Flow Cytometry; Graves Disease; Humans; Immunophenotyping; Male; Membrane Glycoproteins; Methimazole; Monocytes; OX40 Ligand; Tumor Necrosis Factors

The treatment of Graves' disease (GD) with antithyroid drugs (ATD) leads to remission of the disease in approximately half of patients treated for at least six months, and the overall relapse rate is high, ranging from 60% to 80%. The presence of prognostic features for achieving a remission after medical treatment is a matter of discussion in the literature. The aim of this study is to evaluate the effect of different ATD regimens available in Brazil (propylthiouracil--PTU and methimazole--MMI) on remission and relapse rates of GD, as well as to determine possible predictors of remission and relapse of the disease and the side effects profile. We reviewed the records from all patients submitted to medical treatment of GD (and with no report of prior treatment of the disease) for at least six months and followed for at least 12 months after the drug withdrawal at Hospital Universitário Clementino Fraga Filho (HUCFF), between October 1978 and August 2003. We identified 127 patients, with the age ranging from 18 to 88 years (mean 39.3 +/- 12.8). Remission was observed in 58 patients (45.7%) and relapse occurred in 31 (53.4%), at a mean period of 14.5 +/- 16.1 months. We verified that the duration of symptoms before the beginning of medical treatment, age and gender did not influence the rate of remission and the relapse risk, whereas the presence of large goiter size (> 40 grams), Graves' ophthalmopathy and use of high daily doses of ATD (> or = 600 mg of propylthiouracil/60 mg of methimazole MMI) were associated with a decreased remission rate. Moreover, patients who presented a TSH measurement < 0.4 microIU/mL between 4 to 5 weeks after the drug withdrawal showed an increased relapse cumulative probability. In conclusion, our results confirms that lasting remission rate of GD treated with ATD is relatively low. We concluded that the combination of goiter size > 40 g, ophthalmopathy, and use of daily doses of PTU > or = 600 mg or MMI > or = 60 mg was vigorously related to lack of remission of GD. Furthermore, TSH measurement between 4 to 5 weeks after the drug withdrawal seems to be a useful tool to determine the remission chance and the relapse risk of the disease.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antithyroid Agents; Cohort Studies; Female; Follow-Up Studies; Graves Disease; Graves Ophthalmopathy; Humans; Male; Methimazole; Middle Aged; Multivariate Analysis; Propylthiouracil; Recurrence; Remission Induction; Thyrotropin; Time Factors; Treatment Outcome

We studied the A/G single nucleotide polymorphism (SNP) at position 49 in exon 1 of the cytotoxic T lymphocyte-associated molecule-4 gene in 148 Chinese Graves' disease (GD) patients and 171 controls. Our primary aim was to test for the association of this SNP with the relapse of the hyperthyroidism after antithyroid withdrawal. Our secondary aim was to investigate the relationship between GD patients and controls according to the SNP genotypes. All GD patients were divided into the following three groups according to the time of relapse after drug discontinuation: group 1, early relapse within 9 months; group 2, relapse between 10 and 36 months; and group 3, relapse 3 or more years after discontinuation of treatment. There was a significant difference of genotype frequencies (P < 0.001) and allele frequencies (P < 0.001) among the three groups of patients. The frequency of the G/G genotype decreased from 79% to 64% and 39% in groups 1, 2, and 3, respectively. Compared with controls, a strong association (P < 0.001) of G allele was found for group 1, and moderate significance (P = 0.04) was found for group 2, but no association (P = 0.33) was found for group 3. At the end of treatment, the percentage of patients with persistent TSH-receptor antibody was statistically different (A/A, 9.0%; A/G, 20.8%; G/G, 45.5%; P = 0.004). Using 3 yr as the cutoff point for multivariate logistic regression analysis, we found that the G/G genotype (adjusted odds ratio, 3.1 compared with A/G plus A/A; 95% confidence interval, 1.3-7.1), larger goiter size at the end of treatment, and positive TSH-receptor antibody at the end of treatment were independent risk factors of recurrence. We conclude that the A/G polymorphism of the cytotoxic T lymphocyte-associated molecule-4 gene affects the progress of GD. The G/G genotype is associated with poor outcome.

Topics: Adult; Alleles; Antigens, CD; Antigens, Differentiation; Antithyroid Agents; CTLA-4 Antigen; Female; Gene Frequency; Genotype; Graves Disease; Humans; Logistic Models; Male; Methimazole; Middle Aged; Odds Ratio; Polymorphism, Single Nucleotide; Propylthiouracil; Recurrence; Taiwan; Treatment Outcome

The aim of this study was to evaluate the ability of the more sensitive second-generation TSH receptor (TRAb) assay to predict recurrent Graves' disease (GD) vs. remission depending on TRAb levels. 93 patients with active GD were included in the study. By using a cut-off limit of 1.0 IU/l, all 93 patients were positive for TRAb (median: 4.6 IU/l) at the time of their first visit (single point measurement in median 5.1 months after initial diagnosis). Subsequently, 33 patients went into remission and were euthyroid during follow-up (median follow-up: 21.7 months), whereas 60 patients did not go into remission or developed relapse over the following 24 months. Median TRAb levels in the group of remission were significantly (p < 0.0001) lower than TRAb values in the relapse group (2.1 compared to 8.6 IU/l). Applying ROC plot analysis to compare different TRAb thresholds, a cut-off of 10 IU/l was established. Here, the specificity for relapse was 97 % as only 1 of 29 patients with TRAb values above 10 IU/l went into remission during follow-up, whereas all other 28 patients developed a relapse (positive predictive value for relapse: 96.4 %). In contrast, TRAb values lower than 10 IU/l had no impact on the prediction of remission. In conclusion, our data clearly indicate that TRAb measurement is useful for identifying patients that will not benefit from long-term antithyroid drug treatment.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Autoantibodies; Carbimazole; Female; Graves Disease; Humans; Immunologic Techniques; Male; Methimazole; Middle Aged; Predictive Value of Tests; Receptors, Thyrotropin; Recurrence; Remission Induction; ROC Curve

Graves' disease (GD) is an autoimmune disorder characterized by hyperthyroidism, which can relapse in many patients after antithyroid drug treatment withdrawal. Several studies have been performed to predict the clinical course of GD in patients treated with antithyroid drugs, without conclusive results. The aim of this study was to define a set of easily achievable variables able to predict, as early as possible, the clinical outcome of GD after antithyroid therapy.. We studied 71 patients with GD treated with methimazole for 18 months: 27 of them achieved stable remission for at least 2 years after methimazole therapy withdrawal, whereas 44 patients relapsed. We used for the first time a perceptron-like artificial neural network (ANN) approach to predict remission or relapse after methimazole withdrawal. Twenty-seven variables obtained at diagnosis or during treatment were considered.. Among different combinations, we identified an optimal set of seven variables available at the time of diagnosis, whose combination was useful to efficiently predict the outcome of the disease following therapy withdrawal in approximately 80% of cases. This set consists of the following variables: heart rate, presence of thyroid bruits, psycological symptoms requiring psychotropic drugs, serum TGAb and fT4 levels at presentation, thyroid-ultrasonography findings and cigarette smoking.. This study reveals that perceptron-like ANN is potentially a useful approach for GD-management in choosing the most appropriate therapy schedule at the time of diagnosis.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Neural Networks, Computer; Prognosis; Recurrence; Remission Induction; Risk Factors; Therapy, Computer-Assisted; Treatment Outcome

Activation of cell-mediated immunity by soluble interleukin-2 receptor alpha (sIL-2Ralpha) release is well documented. The aim of this study was to measure serum concentrations of sIL-2Ralpha in patients with autoimmune and non-autoimmune thyroid disorders in different stages of thyroid function, before and after administration of l-thyroxine (l-T4) and its discontinuation as well as before and during methimazole administration.. The study included 80 females: 16 with Graves' disease, 15 with Hashimoto's thyroiditis and subclinical hypothyroidism, 14 with Hashimoto's thyroiditis with fibrosis and clinical hypothyroidism, 20 after subtotal thyroidectomy following nodular non-toxic goitre and 15 healthy controls. Patients were examined at two different time points. Serum concentrations of sIL-2Ralpha were measured with the use of enzyme immunoassay technique.. Souble IL-2Ralpha serum concentration increased in patients with untreated Graves' disease and decreased after methimazole treatment. In Hashimoto's thyroiditis, the sIL-2Ralpha level was within the normal range, in Hashimoto's thyroiditis with clinical hypothyreosis it was low and after l-T4 administration it increased in both patient groups. After thyroidectomy, patients treated with l-T4, had increased levels of sIL-2Ralpha which decreased after discontinuation of therapy. There were a significant positive correlation between sIL-2Ralpha and free thyroxine in patients with (i). Graves' disease both before and after methimazole administration, (ii). Hashimoto's thyroiditis (with subclinical hypothyroidism) both before and after l-T4 therapy, (iii). Hashimoto's thyroiditis with fibrosis and (iv). overt hypothyroidism before l-T4 administration and in individuals during long-term l-T4 treatment (after subtotal thyroidectomy).. Serum sIL-2Ralpha concentration in autoimmune thyroid diseases depends on thyroid function. In both autoimmune and non-autoimmune thyroid diseases, thyroxine stimulates the release of sIL-2Ralpha.

Topics: Adult; Antithyroid Agents; Case-Control Studies; Female; Graves Disease; Humans; Hypothyroidism; Interleukin-2 Receptor alpha Subunit; Male; Methimazole; Middle Aged; Receptors, Interleukin; Thyroid Diseases; Thyroidectomy; Thyroiditis, Autoimmune; Thyroxine

Aplastic anemia is a rare but severe complication of methimazole (MMI) treatment for Graves' disease. We present a case of a 53-year-old Japanese female who had been treated with 30 mg/d of MMI for 30 days for Graves' disease and was subsequently admitted to the Japan Self Defense Forces (JSDF) Central Hospital with a mild sore throat and high-grade fever that began the previous day. The patient had a reduced white blood cell count (WBC) count of 0.9 x 10(3) per microliter with severe granulocytopenia and increased lymphocytes, a platelet count of 49 x 10(3) per microliter, and hemoglobin of 10.6 g/dL. Bone marrow (BM) aspirates showed hypocellular bone marrow with plasmacytosis. Because of poor recovery of her peripheral blood values after withdrawal of MMI, she was given transfusions of platelets and erythrocytes thereafter. This is the second report of plasmacytosis in bone marrow of MMI-induced aplastic anemia, and suggests that immunogenic mechanisms may cause this rare complication.

Topics: Anemia, Aplastic; Antithyroid Agents; Bone Marrow; Drug Administration Schedule; Erythrocyte Transfusion; Female; Graves Disease; Humans; Methimazole; Middle Aged; Plasma Cells; Platelet Transfusion

Thyroidectomy (TX) is no longer the preferred choice for the therapy of hyperthyroid Graves' disease but is an alternative in patients who are noncompliant with or have reactions to antithyroid drugs, have moderate to severe ophthalmopathy, have large goiters, or who refuse (131)I therapy and/or long-term antithyroid drug therapy. Seventeen clinically and biochemically severely thyrotoxic patients (16 female, mean age of 35 yr), all but one with large goiters, underwent TX after rapid preparation. The potent inhibitors of the deiodination of T(4) to T(3), iopanoic acid (IOP) (500 mg twice a day) and dexamethasone (DEX) (1 mg twice a day), were given with propylthiouracil or methimazole, when possible, and beta-blockers. Thyroid function tests were obtained before treatment and at TX. All patients were thyrotoxic (mean +/- SE: T(4), 21.6 +/- 1.2 micro g/dl; free T(4) index (FTI), 10.3 +/- 0.8; total T(3), 510 +/- 48 ng/dl). IOP and DEX rapidly lowered T(3) values (P < 0.0001; total T(3), 147 +/- 13 ng/dl) with a smaller but significant (P < 0.05) decrease in T(4)/FTI (T(4), 17.9 +/- 1.3 micro g/dl; FTI, 7.9 +/- 0.6). All patients were clinically euthyroid before surgery. None developed hypoparathyroidism, laryngeal nerve damage, or worsening of ophthalmopathy after surgery. The restoration of hyperthyroid Graves' disease to euthyroidism is rapidly accomplished with IOP and DEX, beta-blockers, and, when possible, antithyroid drugs. This is especially relevant in noncompliant patients with large goiters.

Topics: Adrenergic beta-Antagonists; Adult; Antithyroid Agents; Dexamethasone; Female; Glucocorticoids; Graves Disease; Humans; Iopanoic Acid; Male; Methimazole; Preoperative Care; Propylthiouracil; Severity of Illness Index; Thyroidectomy; Time Factors; Treatment Outcome; Triiodothyronine

A 28-year-old woman with thyroid hemiagenesis, who had been diagnosed as having Graves' disease, became pregnant during the course of methimazole treatment. The treatment was terminated in the second trimester. She delivered a normal infant at full term. She became thyrotoxic 3 months after the delivery, hypothyroid 6 months after the delivery, and finally euthyroid 11 months after the delivery without undergoing any treatment. This clinical course indicates that she developed silent thyroiditis after the delivery. A diagnosis of thyroid hemiagenesis was made on the basis of ultrasonography of the thyroid and 99mTc-pertechnetate thyroid scintiscan.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Hypothyroidism; Methimazole; Pregnancy; Pregnancy Complications; Puerperal Disorders; Thyroid Gland; Thyroiditis

Antineutrophil cytoplasmic antibody (ANCA)-mediated vasculitis can be induced by propylthiouracil (PTU) and methimazole (MMI) for the treatment of Graves' disease. This study investigated the prevalence of ANCA positivity and its clinical correlates in Taiwanese patients with Graves' disease treated with PTU or MMI.. Eighty nine patients with Graves' disease who were currently being treated with PTU (n = 47) or MMI (n = 42) were included in the study. Sera were screened for ANCA by indirect immunofluorescence. The antigenic specificity of myeloperoxidase or proteinase-3 was measured by enzyme-linked immunosorbent assay. Thyroid autoantibodies against microsomal antibodies (AMA) and thyroglobulin antibodies were detected by indirect passive hemagglutination assays, and thyroid autoantibodies against thyrotropin receptor were detected by a radioreceptor assay. The correlations among ANCAs, clinical manifestations, gender, duration of treatment, and thyroid autoantibodies were analyzed by logistic regression.. 20.2% of patients with Graves' disease receiving PTU and MMI were seropositive for ANCA; all of them were perinuclear-ANCA (p-ANCA)-positive. The frequency of p-ANCA-positive status in the PTU treatment group was significantly higher than in the MMI treatment group (31.9% vs 7.1%; p = 0.01). The mean duration of PTU treatment was 25 +/- 16 months, and was 30 +/- 21 months for the MMI treatment. In the PTU treatment group, the average duration of treatment in p-ANCA-positive patients was significantly longer than in p-ANCA negative patients (32.9 +/- 16.3 vs 19.6 +/- 12.1 months, p = 0.04). In addition, the prevalence of AMA positivity was significantly lower in p-ANCA-positive patients than in p-ANCA negative patients (53.3% vs 90.6%; p = 0.01).. Only p-ANCA positivity was found in long-term treatment with PTU and MMI in Graves' disease. A higher frequency of p-ANCA positivity was found in the PTU treatment group than in the MMI treatment group. However, the presence of AMA was less frequent in p-ANCA-positive patients compared to p-ANCA-negative patients treated with PTU.

Topics: Adolescent; Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Prevalence; Propylthiouracil; Taiwan

Topics: Adult; Anti-Bacterial Agents; Antithyroid Agents; Bone Marrow; Bone Marrow Diseases; Drug Therapy, Combination; Female; Gingival Hemorrhage; Graves Disease; Humans; Methimazole; Pancytopenia; Pharyngitis; Plasma Cells; Thyroidectomy; Tonsillitis

There is probably a systemic shift of cytokine production in patients with Graves' disease (GD) toward the Th2 cytokine response. Methimazole (MMI) is the first choice for patients with GD and presumably has some direct immunomodulatory action. The aim of this study was to evaluate the balance shift in Th1/Th2 cytokines in patients with GD after 1 yr of MMI treatment, when compared to the same balance in patients with newly diagnosed GD before treatment and in healthy controls. Peripheral blood mononuclear cells (PBMC) were isolated from 17 healthy volunteers, from 18 patients with newly diagnosed GD before treatment and from 15 euthyroid patients with GD after 1 yr of MMI treatment. The PBMC were activated with ionomycin and phorbol 12-myristate 13-acetate (PMA). The concentrations of Th1/Th2 related cytokines [interferon (IFN)-gamma, interleukin (IL)-12 vs IL-4, IL-10] in the culture supernatants were measured by ELISA. PBMC from patients with GD after treatment produced significantly more IFN-gamma and IL-4 than PBMC from patients with GD before treatment, but there were no significant differences in calculated ratios of Th1 against Th2 cytokines between these two groups. When compared to PBMC from healthy controls, PBMC from patients with GD after treatment produced significantly more IL-4 and significantly less IL-12. The calculated IL-12/IL-4 ratio after treatment was significantly lower than the same ratio from healthy controls. In conclusion, our results show no significant change in the ratio between Th1 and Th2 cytokines produced by PBMC from patients with GD after 1 yr of MMI treatment, when compared to the ratio before treatment. The ongoing prevalence of the Th2 immune response after treatment speaks against the immunomodulatory action of the drug on the systemic level.

Topics: Antithyroid Agents; Cells, Cultured; Cytokines; Graves Disease; Humans; Interferon-gamma; Interleukin-10; Interleukin-12; Interleukin-4; Ionomycin; Methimazole; T-Lymphocytes; Tetradecanoylphorbol Acetate; Th1 Cells; Th2 Cells

One hundred and forty patients with Graves' disease [32 new patients, 54 treated with propylthiouracil (PTU) for a mean of 27.2 months and 54 treated with methimazole (MMI) for a mean of 48.6 months] were tested for anti-thyroid microsomal antibody (AMA), anti-thyroglobulin antibody (ATA), thyroid binding inhibitory immunoglobulin (TBII), and the non organ specific autoantibodies [i.e., anti-nuclear antibody (ANA), anti-double stranded DNA antibody (anti-dsDNA Ab), anti-cardiolipin antibody (aCL Ab) and anti-beta2-glycoprotein I antibody (IgG beta2GPI)]. Treatment with MMI or PTU produced a significant difference in IgG aCL Ab production but not in ANA, dsDNA Ab, IgM aCL or IgG beta2GPI. For those treated with MMI but not those treated with PTU, ANA and anti-dsDNA Ab were positively correlated. IgG and IgM aCL Ab were positively correlated overall and for those on MMI but not PTU treatment. No significant difference was found for any of the four non organ specific antibodies in AMA positive or negative patients but there was a significant difference in IgG aCL positivity rates for ATA positive and negative patients. On the other hand, ANA negative patients were significantly more likely to have higher TBII values. These results suggest that the appearance of the non organ specific autoantibodies is probably largely a coincidental effect of polyclonal activation - except, perhaps, for IgG aCL, which may be related to treatment.

Topics: Adolescent; Adult; Aged; Antibodies, Anticardiolipin; Antibodies, Antinuclear; Antithyroid Agents; Autoantibodies; Enzyme-Linked Immunosorbent Assay; Female; Graves Disease; Humans; Logistic Models; Male; Methimazole; Middle Aged; Propylthiouracil

CD28 and CTLA-4 are glycoprotein molecules providing the potent costimulatory signal for T cells activation and proliferation via interactions with their ligands B7/BB1 molecule, present on the surface of Ag-presenting cells (APC). The present study was performed to elucidate the relationship between CTLA-4/CD28 molecules and stimulating (TSAb) or blocking (TBAb) antibodies to the TSH-receptor in Graves' disease. The aim of the study was to estimate the expression of CTLA-4 (cytolitic T lymphocyte associated antigen-4, CD152), CD28, B7.1 (CD80) and CD7.2 (CD86) molecules on peripheral blood cells in patients with Graves' disease (GD) (n=28, mean age 15.4), in patients with nontoxic nodular goiter (NTNG) (n=28, mean age 15.6 years) in comparison with sex- and age-matched healthy control subjects (n=28, mean age 15.9 years). The expression of the costimulatory molecules on mononuclear cells was analyzed by the three-color flow cytometry using a Coulter EPICS XL cytometer. Detection of stimulating and blocking antibodies to the TSH-receptor using JPO9 CHO cells in unfractionated serum was measured by a highly sensitive commercial radioimmunoassay. In untreated Graves' patients we observed a significant increase of CD152+ (p<0.004, p<0.004, p<0.001) and CD28+ (p<0.02, p<0.02, p<0.02) T lymphocytes in comparison to the non-toxic nodular goiter patients, healthy control subjects and euthyroid Graves' patients. After 2-6 months of methimazole therapy, the percentages of these cells in the peripheral blood of hyperthyroid patients returned to normal values. The analysis of CD3+ T lymphocytes co-expressing CD152 and CD28 antigens on peripheral blood revealed increased percentages of CTLA-4/CD28 positive cells in patients with Graves' disease (p<0.004, p<0.04) compared to the controls and euthyroid Graves' patients, while B7.1 (CD80) and B7.2 (CD86) molecules were detected only in some hyperthyroid patients on activated monocytes. In addition, 75% of children with untreated hyperthyroidism had positive TSAbs, whereas TBAbs were measured in 3 out of 7 TSAb negative patients with Graves' disease. In untreated Graves' patients a correlation between percentage of CD152+ T cells and serum level of stimulating and blocking antibodies to the TSH-receptor was found, while no such correlation was detected in relation to CD28+ T cells. We conclude that the changes of the expression of costimulatory molecules on peripheral blood mononuclear cells could be an important marker

Topics: Adolescent; Antigens, CD; Antigens, Differentiation; Antithyroid Agents; B7-1 Antigen; B7-2 Antigen; Case-Control Studies; CD28 Antigens; Child; Chromatography, High Pressure Liquid; CTLA-4 Antigen; Female; Flow Cytometry; Gene Expression; Goiter, Nodular; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Membrane Glycoproteins; Methimazole; Poland; Receptors, Thyrotropin; Regression Analysis; Statistics, Nonparametric; Time Factors

An association between mitral valve prolapse (MVP) and hyperthyroidism has been described in adults. However, the long-term prognosis when associated with significant mitral regurgitation remains unclear. Three consecutive children with Graves' disease were found to have a loud mitral regurgitation murmur (grade III/VI) and echocardiographic evidence of MVP with moderate mitral regurgitation. The cardiac manifestations included palpitations, exertional dyspnea, and exercise intolerance. The electrocardiograms at presentation were sinus tachycardia in all cases. All had hyperthyroidism and positive thyroid antibodies. Exophthalmos occurred in two and appeared later than the cardiac symptoms in one. The cardiac murmur disappeared in all patients when antithyroid agents controlled the hyperthyroidism. Follow-up echocardiography showed normal in one and MVP with mild mitral regurgitation in two. We conclude that MVP and significant mitral regurgitation can occur in children with hyperthyroidism, especially those with Graves' disease. The prognosis is good after adequate medical control of the hyperthyroidism.

Topics: Adolescent; Child; Child, Preschool; Female; Follow-Up Studies; Graves Disease; Humans; Methimazole; Mitral Valve Insufficiency; Mitral Valve Prolapse; Risk Assessment; Severity of Illness Index; Thyroid Function Tests; Treatment Outcome

To evaluate cardiovascular consequences of combined treatment in Graves' disease patients with addition of thyroxine (LT4) to antithyroid drugs in doses sufficient to suppress serum thyrotropin (TSH) levels below normal.. Eleven premenopausal female patients who reached subnormal TSH levels (<0.3 microIU/mL) under the combined therapy were evaluated by equilibrium radionuclide ventriculography at rest, and during the peak stage of fixed moderate exercise workload (75W) initially at diagnosis and after at least 8 months of stable euthyroidism, as judged by peripheral free thyroxine and triiodothyronine. The control group included 12 euthyroid healthy women.. Post-treatment resting systolic and diastolic blood pressure, heart rate, and left ventricular (LV) systolic function were similar to control values. Log-transformed TSH releasing factor-stimulated TSH response correlated with LV resting early diastolic peak filling rate (PFR) (r=0.802, p=0.003) and resting diastolic blood pressure (r=0.795, p=0.003), which, in turn, was a significant predictor of basal renin secretion (r=-0.84, p=0.001). Treated patients had increased peak exercise systolic blood pressure (median 175, interquartile range 25 vs median 156, interquartile range 29 mmHg, p=0.019), delayed recovery of post-exercise heart rate to basal levels, and reduced exercise ejection fraction (median 66, interquartile range 9 vs median 74, interquartile range 13 %, p=0.037) in comparison with controls. Exercise ejection fraction was inversely related to exercise diastolic blood pressure, (r=-0.818, p=0.002); and exercise systolic blood pressure to exercise time to peak filling rate in a heart rate-independent manner, (rpartial=0.89, p<0.001).. Persistent TSH suppression in LT4-treated Graves' disease patients promotes pressure dependent renin secretion, and modulates resting early LV diastolic relaxation. It is also associated with exaggerated exercise systolic blood pressure response and decreased ejection fraction response to exercise.

Topics: Adult; Antithyroid Agents; Cardiovascular System; Case-Control Studies; Drug Therapy, Combination; Exercise; Female; Gated Blood-Pool Imaging; Graves Disease; Humans; Methimazole; Premenopause; Statistics, Nonparametric; Thyrotropin; Thyroxine; Ventricular Function, Left

Granulocyte colony-stimulating factor (G-CSF) levels in serum were determined by a highly-sensitive chemiluminescent enzyme immunoassay (limit of detection, 0.5 pg/ml) in 54 patients with Graves' disease including 6 patients complicated with methimazole-induced agranulocytosis. Serum G-CSF levels in patients with Graves' disease were not different from normal subjects and did not correlate with serum FT4 level or circulating neutrophil counts. Before the onset of agranulocytosis, there was no difference in serum G-CSF level between the patients complicated with agranulocytosis and the uncomplicated patients. When circulating neutrophil counts decreased to less than 0.5 x 10(9)/L, serum G-CSF level elevated with the mean of 106.8 +/- 82.2 (SD) pg/ml, but the level did not correlate with the duration of agranulocytosis. Interestingly, maximum serum G-CSF level during the treatment with recombinant human G-CSF (100 microg/day) was related to bone marrow finding at the onset of agranulocytosis and correlated with the duration of agranulocytosis (r = 0.824, p < 0.05). In conclusion, measuring serum G-CSF levels with a highly-sensitive chemiluminescent enzyme immunoassay revealed that 1) thyrotoxicosis does not affect serum G-CSF level, 2) serum G-CSF level during antithyroid drug treatment does not play an important role in development of agranulocytosis, 3) the maximum serum G-CSF level in the course of agranulocytosis is related to the responsiveness of bone marrow to G-CSF and the recovery time from agranulocytosis.

Topics: Adult; Agranulocytosis; Antithyroid Agents; Bone Marrow; Female; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Luminescent Measurements; Male; Methimazole; Middle Aged; Neutrophils; Recombinant Proteins

Local inflammation is characterized by oxidative stress present in situ, and may also influence reactive oxygen species peripheral metabolism. Infiltrative ophthalmopathy is considered as an inflammatory disorder of autoimmune background. This study estimated influence of hyperthyroidism and antithyroid treatment on peripheral parameters of oxidative stress in 65 Graves' patients (40 with and 24 without infiltrative ophthalmopathy). Age- and sex-matched 25 healthy volunteers served as controls. In all hyperthyroid patients hydrogen peroxide (H2O2), lipid hydroperoxides (ROOH), malondialdehyde, ceruloplasmin (CP), superoxide dismutase (SOD) and catalase (CAT) were increased, whereas glutathione peroxidase (GPx) and glutathione reductase (GR) were reduced. One-month methimazole treatment produced further elevation in H2O2 in all patients and CAT in the ophthalmopathy group, as well as partial reversal of SOD and CP in all patients, ROOH, GPx and GR in the non-ophthalmopathy group and CAT in patients without ophthalmopathy. In summary, our results confirm that changes of blood extracellular indices of reactive oxygen species metabolism in Graves' disease are influenced by the thyroid metabolic status. However, the differences of the parameters analysed after achievement of euthyroidism in the patients with and without infiltrative ophthalmopathy suggest an involvement of factors, presumably connected with orbital inflammation, which modify oxidative stress intensity.

Topics: Adult; Antithyroid Agents; Case-Control Studies; Catalase; Ceruloplasmin; Female; Graves Disease; Humans; Hydrogen Peroxide; Lipid Peroxides; Male; Malondialdehyde; Methimazole; Middle Aged; Oxidative Stress; Reactive Oxygen Species; Superoxide Dismutase; Treatment Outcome

Antithyroid drugs are effective in some patients with Graves' disease but not in others. The factors responsible for this difference are still unknown. We examined the relationship between the nature of anti-TSH receptor (TSH-R) antibodies and responsiveness to drugs in Graves' disease.. Twenty-eight untreated patients with Graves' disease were treated with thiamazole and followed for up to 13 years.. Antithyroid microsomal antibodies (MCHAs) and antithyroglobulin antibodies (TGHAs) were measured by the passive haemagglutination method. Anti-TSH-R antibodies were measured by a radioreceptor assay (TBII), and thyroid-stimulating antibodies (TSAbs) and TSH-stimulation blocking antibodies (TSBAbs) were measured by bioassays using FRTL-5 cells. Blocking antibodies were also measured by the conversion assay. In order to confirm the usefulness of the conversion assay, in vitro experiments using mixtures of TSAb serum and TSBAb serum were performed.. In in vitro conversion experiments, the conversion assay sensitively detected coexisting blocking antibodies. TSBAb was found in seven patients and a positive conversion ratio was found in four patients, and, of these, three patients had both antibodies. Finally, eight patients (28.6%) had blocking antibodies and 25 of 28 patients (89.3%) had stimulating antibodies. These patients with blocking antibodies (Group A) responded well initially to antithyroid drugs and showed earlier normalization of the serum T4 level (3.0 +/- 1.2 weeks) than patients without blocking antibodies (Group B, 10.7 +/- 8.5, P < 0.001). Unexpectedly, remission of Graves' thyrotoxicosis was earlier in Group B (5.1 +/- 4.4 years) than in Group A (8.0 +/- 4.3 years, P < 0.05). Other parameters, including serum T4, goitre size, ophthalmopathy, TBII, TSAb, TGHA and MCHA, were not different between the two groups.. Graves' patients with coexisting blocking antibodies initially respond well to thiamazole but are relatively slow to achieve remission. Measurement of blocking antibodies may be useful for selection of treatment options in Graves' disease.

Topics: Adult; Aged; Antithyroid Agents; Female; Follow-Up Studies; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Microsomes; Middle Aged; Patient Selection; Remission Induction; Statistics, Nonparametric; Thyroglobulin; Thyroxine

Retrospective studies have shown antineutrophil cytoplasmic antibody (ANCA) positivity in patients treated for Graves' hyperthyroidism; ANCA has been attributed to either antithyroid drugs or to the disease itself. The aim of this study was to determine ANCA in Graves' disease patients at diagnosis and after treatment with methimazole and to evaluate the relationship between ANCA and hyperthyroidism evolution. Thirty patients recently diagnosed with Graves' hyperthyroidism were prospectively studied. ANCA were determined by indirect immunofluorescence. ANCA autoantibodies against specific antigens (proteinase 3, myeloperoxidase, bactericidal/permeability-increasing protein (BPI), cathepsin, lysozyme, elastase, and lactoferrin) were detected by ELISA. The median observation period was 22 months. Kaplan-Meier analysis was performed to identify ANCA as an outcome variable. Twenty patients (67%) were ANCA positive before the onset of treatment, and four (19%) remained positive after 1 yr of antithyroid drug treatment. No differences were observed in any clinical or analytical features between patients with or without positive ANCA. Before treatment, BPI-positive patients required radioiodine treatment or presented relapse more rapidly than BPI-negative patients (log-rank test P < 0.0002). Patients with Graves' hyperthyroidism show positive ANCA before medical treatment, which points to a relationship with the autoimmune disease itself. Our results suggest that BPI-positive patients tend to relapse with antithyroid medication.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antibody Specificity; Antimicrobial Cationic Peptides; Antithyroid Agents; Blood Proteins; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique, Indirect; Graves Disease; Humans; Iodine Radioisotopes; Male; Membrane Proteins; Methimazole; Middle Aged; Myeloblastin; Peroxidase; Prognosis; Prospective Studies; Recurrence; Serine Endopeptidases

The aim of the present study was to determine the proportion of gamma/delta T-lymphocytes and CD16/CD56 (CD3- and CD3+) cells in the peripheral blood of children and adolescents with Graves' disease (GD; n = 27; mean age, 15.5 +/- 5.1 y) and nontoxic nodular goiter (NTNG; n = 25; mean age, 15.2 +/- 5.7 y), in comparison with sex- and age-matched healthy control subjects (n = 25; mean age, 15.9 +/- 2.4 y). In addition, in patients with GD, we investigated the effect of methimazole therapy on the proportion of these cells. We also looked for associations among the parameters investigated. The percentages of gamma/delta TCR+CD3+ lymphocytes and CD3+, CD16/56+CD3+, and natural killer (NK) cells were analyzed by the three-color flow cytometry using a Coulter EPICS XL cytometer. In patients with untreated GD, we observed a significant decrease in gamma/delta T (CD3+) (p < 0.002), CD16/56(CD3+) (p < 0.001), and NK (p < 0.001) cells in comparison with the healthy control subjects. After 2-6 mo of methimazole therapy, the percentages of gamma/delta TCR+CD3+ and CD16/56(CD3+) cells in peripheral blood of hyperthyroid patients returned to the normal values, whereas the percentages of NK cells normalized after 18-24 mo of therapy. These abnormalities were absent in children and adolescents with NTNG. Furthermore, there was no difference in the percentage of CD3+ lymphocytes in all of the groups. In the patients with untreated GD, we found a negative correlation between free thyroxine concentration in blood serum and the percentages of CD16/56 (CD3-) and gamma delta T cells (r = -0.5, p < 0.035; r = -0.4, p < 0.02). No such correlation was detected in patients with NTNG. We conclude that the abnormal distribution of CD16/CD56 (CD3- and CD3+) cells and gamma/delta T lymphocytes in the peripheral blood in children and adolescents with untreated GD suggests their role in the development of autoimmunity.

Topics: Adolescent; Antithyroid Agents; CD56 Antigen; Child; Female; Graves Disease; Humans; Male; Methimazole; Receptors, Antigen, T-Cell, gamma-delta; Receptors, IgG; T-Lymphocyte Subsets; T-Lymphocytes

Topics: Antithyroid Agents; Female; Graves Disease; Humans; Hypothyroidism; Methimazole; Middle Aged; Psychotic Disorders; Recurrence; Thyroid Diseases; Thyroxine; Treatment Outcome

Topics: Adult; Antithyroid Agents; Clinical Trials as Topic; Evidence-Based Medicine; Expert Testimony; Female; Graves Disease; Humans; Iodine Radioisotopes; MEDLINE; Methimazole; Middle Aged; Patient Compliance; Propylthiouracil; Randomized Controlled Trials as Topic; Thyroid Function Tests

Increased oxidative stress, with elevated levels of free radicals, together with diminished antioxidation have been described previously in models of hyperthyroidism and in patients with Graves' disease. However, controversial results have been found about the antioxidant status and its response to treatment.. To evaluate the antioxidant/oxidant balance in active Graves' disease and the effects of treatment with methimazole (MMI) and 131 iodine (131I).. We studied 69 hyperthyroid (H) patients, 58 female and 11 male, 16-50 years old; total T3: 8 +/- 2 nmol/l, total T4: 264 +/- 65 nmol/l (all mean +/- SD), TSH: 0.1 +/- 0.1 mIU/l, TSH receptor antibody 41 +/- 21%, highest 131Iodine uptake: 67 +/- 16%. As a control group (C), 19 normal adults were studied.. Parameters evaluated were: tert-butyl hydroperoxide initiated chemiluminiscence (CL), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx) and total reactive antioxidant potential (TRAP).. In patients vs. controls there was an increase in CL levels (6207 +/- 1434 vs. 3000 +/- 851 cpm/mg of haemoglobin, P < 0.001), decrease in SOD (0.4 +/- 0.1 vs. 0.7 +/- 0.2 U/mg prot, P < 0.05; corresponding to 0.15 micro g/ml), CAT (2.8 +/- 0.6 vs. 3.8 +/- 0.7 pmol/mg prot, P < 0.001) and GSH (1.2 +/- 0.4 vs. 2 +/- 0.7 mmol/l erythrocytes, P < 0.05). The decrease in GPx and TRAP did not show significant differences. The parameters were also recorded in 30 patients who became euthyroid after treatment: 20 of them under MMI therapy (2-12 months) and the rest 3-6 months after 131Iodine administration. All the parameters evaluated were normalized after MMI; however, CL levels stayed high after 131I and only CAT and GSH levels returned to normal values.. Our results confirm the imbalance of the antioxidant/oxidant status in hyperthyroid patients. MMI treatment was more effective than 131I therapy to improve that balance. We speculate on the benefits of antioxidant therapy administrated together with the habitual treatment of hyperthyroidism, especially in patients after 131I therapy.

Topics: Adolescent; Adult; Antithyroid Agents; Biomarkers; Catalase; Erythrocytes; Female; Glutathione; Glutathione Peroxidase; Graves Disease; Humans; Iodine Radioisotopes; Luminescent Measurements; Male; Methimazole; Middle Aged; Oxidative Stress; Superoxide Dismutase

To investigate whether variations over time of TSH-receptor antibodies (TRAb) and antibodies against G2s (G2sAb) and extraocular muscles (EMAb) can predict worsening of ophthalmopathy in Graves' patients treated with intravenous glucocorticoid (IVGC) therapy.. Of 65 consecutive patients with treated Graves' disease and severe and active ophthalmopathy (GO) chosen to undergo IVGC treatment, only 57 patients, persistently euthyroid under methimazole therapy, were studied longitudinally for ocular parameters, TRAb, G2sAb and EMAb before therapy, at the end of therapy and, subsequently, every month for 21 months.. TRAb was detected by radioimmunoassay (RIA), G2sAb by enzyme-linked immunosorbent assay (ELISA) and EMAb by indirect immunofluorescence.. Forty-three out of 57 patients (75.4%, group 1) responded positively to therapy [improvement in diplopia and decrease in proptosis and clinical activity score (CAS)] but 14 (24.6%) did not (group 2). During follow-up after IVGC therapy, 12 out of 43 patients in group 1 (28%) showed a worsening in GO (group 1a), while 31 (72%) had stable ocular conditions or further improvement (group 1b). At the start of the study, TRAb, G2sAb and EMAb were not significantly different among the three groups. At the end of IVGC therapy TRAb levels decreased significantly with respect to starting values in all three groups of patients, whereas G2sAb and EMAb decreased significantly in groups 1a and 1b but not in group 2. During the subsequent follow-up, 10 patients in group 1a one/two months before and all 12 patients at the time of GO worsening showed an increase in G2sAb and EMAb but not in TRAb, which were consistently absent or present at low titre in all patients in this group. In group 1b TRAb, G2sAb and EMAb further decreased or became negative during the follow-up period. In all patients, TRAb were positively correlated with both CAS and proptosis only at the start of the study; by contrast, a significant correlation between both G2sAb and EMAb and diplopia was observed in groups 1a and 1b at all the times during the study, except one/two months before the worsening of GO in group 1a.. Our results indicate that TRAb, G2sAb and EMAb can be considered sensitive markers of Graves' ophthalmopathy during the initial stages of ophthalmopathy, but that only G2sAb and EMAb seem to be good predictive markers of the outcome in patients after corticosteroid therapy. Thus, taking into account the cost/benefit ratio, a longitudinal evaluation of either EMAb or G2sAb could be useful in monitoring the intravenous glucocorticoid therapy in patients with severe and active ophthalmopathy to predict a possible worsening of Graves' ophthalmopathy.

Topics: Adult; Antithyroid Agents; Autoantibodies; Biomarkers; Diplopia; Exophthalmos; Eye; Eye Proteins; Female; Follow-Up Studies; Glucocorticoids; Graves Disease; Humans; Infusions, Intravenous; Male; Membrane Proteins; Methimazole; Methylprednisolone; Middle Aged; Receptors, Thyrotropin; Statistics, Nonparametric

Topics: Antithyroid Agents; Atenolol; Biological Transport; Female; Graves Disease; Humans; Iodine Radioisotopes; Methimazole; Middle Aged; Radiography; Radionuclide Imaging; Syndrome

Hormone secretion by thyrocytes occurs by fluid phase uptake and lysosomal degradation of the prohormone thyroglobulin (Tg). However, some Tg internalized by megalin bypasses lysosomes and is transcytosed across cells and released into the bloodstream. Because the hormone content of Tg is variable, we investigated whether this affects transcytosis. We found that rat Tg with a low hormone content [low-hormonogenic rat Tg (low-horm-rTg)] is transcytosed by megalin across thyroid FRTL-5 cells to a greater extent than rat Tg with a high hormone content [hormonogenic rat Tg (horm-rTg)]. In immunoprecipitation experiments, the Tg sequence Arg-2489-Lys-2503 (required for binding to megalin and heparan sulfate proteoglycans) was found to be more exposed in low-horm-rTg, which accounted for its preferential transcytosis. Thus, removal of surface heparan sulfate proteoglycans from FRTL-5 cells or blocking of 2489-2503 reduced transcytosis of low-horm-rTg to a greater extent than that of horm-rTg. Preferential transcytosis of low-horm-rTg affected hormone release. Thus, the increase in hormone release from horm-rTg in FRTL-5 cells determined by megalin blocking (due to reduced transcytosis and enhanced Tg degradation) was rescued by low-horm-rTg, suggesting that megalin is required for effective hormone release. This finding was confirmed in a small number of megalin-deficient mice, which had serological features resembling mild hypothyroidism. Reduced hormone formation within Tg in vivo, due to treatment of rats with aminotriazole or of patients with Graves' disease with methimazole, resulted in increased Tg transcytosis via megalin, in confirmation of results with FRTL-5 cells. Our study points to a major role of megalin in thyroid homeostasis with possible implications in thyroid diseases.

Topics: Adult; Amitrole; Animals; Dose-Response Relationship, Drug; Endocytosis; Enzyme-Linked Immunosorbent Assay; Female; Graves Disease; Heparitin Sulfate; Homozygote; Hormones; Humans; Hypothyroidism; Low Density Lipoprotein Receptor-Related Protein-2; Male; Methimazole; Mice; Mice, Transgenic; Middle Aged; Models, Biological; Precipitin Tests; Rats; Rats, Inbred Lew; Thyroglobulin; Thyroid Gland; Thyroid Hormones

We describe a patient with right adrenal tumor detected incidentally. The tumor was diagnosed as pheochromocytoma by endocrinological and radiological studies, and was removed surgically. Graves' disease, which had been in remission for more than two decades after discontinuation of antithyroid drug treatment, relapsed during preoperative evaluation of pheochromocytoma when the patient was treated with alpha- and beta1-adrenergic antagonists. Administration of methimazole resulted in a rapid improvement of thyroid function and the patient remained euthyroid on small doses of methimazole. This case may suggest possible involvement of excessive catecholamine secretion and beta2-adrenergic receptor activation by pheochromocytoma in the relapse of Graves' disease.

Topics: Adrenal Gland Neoplasms; Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Antithyroid Agents; Dose-Response Relationship, Drug; Doxazosin; Female; Graves Disease; Humans; Hypertension; Incidental Findings; Methimazole; Middle Aged; Pheochromocytoma; Propanolamines; Recurrence

The aim of the study was to evaluate the usefulness of TRAb determinations in prognosing and monitoring the efficacy of conservative treatment in Graves' disease. The examinations were performed in 54 patients. During the 18-month observation all the patients were treated with Tiamazol. The control group consisted of 20 healthy volunteers. The TRAb levels were determined before as well as 12 and 18 months after thyrostatic treatment. Simultaneously, the levels of TSH and FT4 were analysed. Moreover, all the patients underwent ultrasound examinations to assess the size of the thyroid gland. The findings of the 18-month follow up showed that in 31 patients (57%) the thyroid function became normal (group I--euthyreosis), in 23 patients (43%) hyperactivity persisted (group II--hyperthyreosis). The TRAb levels were analysed in both groups of patients. An increased initial level of TRAb was found in the hyperactivity group mean -54.39 + 31.21 U/l which was statistically significantly different from the TRAb levels in the euthyreosis group mean -29.13 +/- 19.14 U/l and in controls mean -2.75 +/- 2.06 U/l (p < 0.001 for both parameters). After 12-month treatment increased values of antibodies were still observed in this group of patients (mean -39.96 +/- 33.40 U/l) in comparison with the euthyreosis group (mean -9.87 +/- 8.33 U/l) and controls (mean -2.75 +/- 2.06 U/l) (p < 0.001 for both parameters). After 18-month treatment the TRAb levels in group II remained increased (mean -40.17 +/- 33.06) while in group I normal levels were achieved. The sizes of the thyroid gland were compared between the individual groups. In the hyperactivity group after 18-month treatment, the thyroid size was the biggest (mean -41.09 +/- 13.94 ml) and was statistically significantly different when compared to the average size in the euthyreosis group mean -31.65 +/- 11.74 ml (p < 0.01) and in controls mean -14.45 +/- 2.37 ml (p < 0.001). The levels of antibodies against TSH receptors are useful parameters in prognosis and monitoring the treatment effectiveness in Graves' disease. High initial levels of antibodies are the poor prognostic factors. The TRAb determinations are of some prognostic value not only before but also 12 months since the onset of therapy. The lack of antibody level normalization during treatment is connected with persisting hyperactivity. The TRAb concentration correlates with the thyroid size.

Topics: Adult; Antithyroid Agents; Biomarkers; Case-Control Studies; Evaluation Studies as Topic; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Predictive Value of Tests; Prognosis; Receptors, Thyrotropin; Time Factors; Treatment Outcome

We report a 26-year-old woman presented at the day of admission in the I.C.U. with increased perspiration, plethora and distinct tetany of both legs. Particularly unusual was an exophthalmus on both sides, a rectal temperature of 38.3 degrees Celsius and a blood pressure of high level (180/110 mmHg). Laboratory findings were a low serum calcium concentration of 2.86 mval/l, a hyperphosphataemia (5.0 mg/dl), free thyroxine of 31.7 pmol/l, TSH basal of < 0.01 U/ml and positive MAK and TRAK. Serum parathormone concentration was excessively high: 766 ng/l (12-72). Ultrasound of the thyroid gland revealed a normal size with a volume of 10.4 ml; the echosonic state was not typical for Graves' disease. The initial treatment consisted of high dose thiamazole and hydrocortisone intravenous, calciumcarbonate and propranolol per os. After acute situation the treatment continued with thyreostatics, calcitriol and calciumcarbonate. The symptoms at the day of admission (tetany) disappeared within 2 days; only local paraesthesia of fingers persisted longer. Normalization of thyroid parameters was reached after 11 days; the serum calcium concentration persisted on an increasing but still lower level than standard (3.8 mval/l). During substitution parathormone decreased to 443 ng/l. What is unusual about this case is the combined appearance of autoimmunethyreoiditis (Graves' disease) and pseudohypoparathyroidism.

Topics: Adult; Calcitriol; Calcium; Calcium Carbonate; Female; Graves Disease; Humans; Methimazole; Parathyroid Hormone; Phosphates; Propranolol; Pseudohypoparathyroidism; Thyrotropin; Thyroxine

Patients with Graves' disease (n = 61) treated with propylthiouracil (PTU) or thiamazole (MMI) were studied retrospectively to investigate differences in the prevalence of anti-myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO-ANCA) in relation to treatment with anti-thyroid drugs. The patients were divided into two groups: PTU-treated group (n = 32) and MMI-treated group (n = 29). There were no significant differences between the two groups in terms of age, gender distribution, or duration of treatment. In the PTU group, 8/32 (25%) patients were positive for MPO-ANCA, whereas in the MMI group, 1/29 (3.4%) patients were positive. There were no significant differences in age, duration, or dosage between the MPO-ANCA positive and negative patients. Most of the MPO-ANCA positive patients were asymptomatic, except for two patients in whom rheumatic arthritis or membranous glomerulonephritis developed. None of the MPO-ANCA positive patients were diagnosed as having classical ANCA-associated vasculitis. Thus, there is a high frequency of MPO-ANCA in patients with Graves' disease treated with PTU, compared with patients treated with MMI, although classical ANCA-associated vasculitis develops in only a few MPO-ANCA positive patients.

Topics: Adult; Antibodies; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Peroxidase; Propylthiouracil

Pretibial myxedema (PM) is a localized thickening of the pretibial skin due to accumulation of acid mucopolysacharides (glycosaminoglycans). Its pathogenesis is still under investigation. Pretibial myxedema, exophthalmus and thyroid acropachy are the dassic extrathyroidal manifestations of Graves' disease. Almost invariably, PM follows the onset of ophthalmopathy, developing after the diagnosis and treatment of hyperthyroidism. Pretibial myxedema preceding Graves' ophthalmopathy is rare. We report the case of a 28-year-old Greek woman, who presented with multiple, asymptomatic nodules and plaques of the lower legs in the absence of other physical findings. Histopathologic examination revealed deposition of mucopolysacharides in the lower dermis. Laboratory investigation showed elevated serum T3 and T4 and depressed TSH levels. In our patient, pretibial myxedema was the earliest manifestation, leading to the diagnosis of Graves' disease.

Topics: Administration, Oral; Administration, Topical; Adrenal Cortex Hormones; Adult; Biopsy, Needle; Diagnosis, Differential; Female; Follow-Up Studies; Graves Disease; Humans; Immunohistochemistry; Lower Extremity; Methimazole; Myxedema; Severity of Illness Index; Thyroid Function Tests; Treatment Outcome

To evaluate the bone mineral density at lumbar spine and at femoral neck in a group of young adults in whom Graves' disease developed during childhood and adolescence.. We examined 28 patients (5 male, 23 female, age 20.9 +/- 3.3 years) who were 11.8 +/- 2.9 years old at the onset of Graves' disease. They were treated either with methimazole (14 patients) or with methimazole plus l-thyroxine (14 patients). At the time of the investigation, 13 patients were considered cured following antithyroid treatment, 2 were still on antithyroid drugs, 3 were on replacement therapy with l-thyroxine because of hypothyroidism, and 10, treated either surgically or with (131)I, were on replacement therapy. The bone mineral density was measured at the lumbar spine (L2-L4) and at the femoral neck, using dual-energy X-ray absorptiometry.. The spinal bone mineral density SD score was -0.28 +/- 1.02, the femoral neck bone mineral density SD score was 0.36 +/- 1.02, and both were not different from zero (NS). We did not find any correlation between the bone mineral density of the femoral neck and that of the lumbar spine and the clinical parameters.. Graves' disease, beginning in childhood and adolescence, when appropriately treated, does not affect attainment of peak bone mass.

Topics: Absorptiometry, Photon; Adolescent; Adult; Bone Density; Female; Femur Neck; Graves Disease; Humans; Lumbar Vertebrae; Male; Methimazole; Puberty; Thyroxine

Topics: Adolescent; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Fluorescent Antibody Technique, Indirect; Graves Disease; Humans; Lupus Erythematosus, Cutaneous; Methimazole; Skin Diseases, Vesiculobullous; Treatment Outcome; Vasculitis

The aim of the study was to estimate the expression of beta1 integrin CD49d (very late antigen-4), beta2 integrin CD11a (lymphocyte function-associated antigen 1 alpha), L-selectin (CD62L), and intercellular adhesion molecule-1 [ICAM-1 (CD54)] on peripheral blood mononuclear cells in patients with Graves disease (GD) (n = 45, mean age 15.9 +/- 5.9 y), in patients with nontoxic nodular goiter (NTNG) (n = 25, mean age 15.2 +/- 5.7 y), and in sex- and age-matched healthy control subjects (n = 25, mean age 15.9 +/- 2.4 y). The expression of the lymphocyte adhesion molecules was analyzed by the three-color flow cytometry. Decreased percentages of CD49d+ and CD11a+ lymphocytes were observed in untreated Graves' patients in comparison to healthy controls (p < 0.007, p < 0.036) and non-toxic nodular goiter patients (p < 0.006, p < 0.019). The analysis of CD62L+ and CD54+ antigen expression on peripheral blood lymphocytes revealed increased percentages of L-selectin- and ICAM-1-positive cells in patients with GD (p < 0.005 for CD62L, p < 0.008 for ICAM-1) before methimazole therapy, compared with healthy controls. These abnormalities were absent in children with NTNG. In patients with untreated GD, a positive correlation was found between serum levels of free thyroxine and the percentage of CD54+ lymphocytes (r = 0.47, p < 0.036). Statistically significant negative correlations existed between free thyroxine concentration in blood serum and the percentage of CD11a+ lymphocytes (r = -0.39, p < 0.033). No such correlation was detected between the percentage of lymphocyte markers and serum levels of antithyroid antibodies. We conclude that the alterations in the expression of adhesion molecules on peripheral blood mononuclear cells might suggest their role in the development of GD.

Topics: Adolescent; Adult; Antithyroid Agents; Autoantibodies; Child; Female; Flow Cytometry; Graves Disease; Humans; Immunophenotyping; Integrin alpha4beta1; Lymphocyte Function-Associated Antigen-1; Lymphocytes; Male; Methimazole; Thyroid Hormones

Topics: Antithyroid Agents; Follow-Up Studies; Graves Disease; Humans; Iodine Radioisotopes; Methimazole; Prednisolone; Randomized Controlled Trials as Topic; Reference Values

A 30-year-old female patient, diagnosed as having Graves' disease in 1996, was treated with propylthiouracil (PTU) for 4 years. She developed a low-grade fever from December 1999. As myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) vasculitis is one of the adverse effects of PTU, we examined serum MPO-ANCA level and found it was positive, but cytoplasmic-ANCA (c-ANCA) was negative. There were no symptoms that indicated other diseases associated with MPO-ANCA. She was confirmed to be at 6 weeks gestation, and thyroid hormone levels were elevated at that time. We discontinued PTU and gave methyl-mercaptoimidazole (MMI), and the titer of MPO-ANCA fell along with fever. Therefore we estimated the case as probable MPO-ANCA positive vasculitis induced by PTU. MMI was also suspended because of the development of hepatic dysfunction. After thyroid function was normalized by administration of potassium iodide, she underwent subtotal thyroidectomy, and delivered a 2350 g infant at 38 weeks' gestation, which was less than the normal birth weight of 2400 g. MPO-ANCA is considered to be one reason of low birth weight infant including hyperthyroidism. It is necessary to consider the appearance of the possibility of MPO-ANCA positive vasculitis in patients who are treated with PTU.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Female; Graves Disease; Humans; Infant, Low Birth Weight; Infant, Newborn; Methimazole; Peroxidase; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Propylthiouracil; Thyroidectomy; Vasculitis

Graves' disease (GD) has been reported to be frequently complicated with other autoimmune diseases. However, it is rarely complicated with scleroderma-polymyositis overlap syndrome. Recently, we encountered a 35-year-old woman who developed GD and immune thrombocytopenic purpura during follow-up observation of scleroderma-dermatomyositis overlap syndrome. Platelet counts recovered after high-dose gamma-globulin therapy and bolus methylprednisolone therapy. The present case is the first report of a combination of scleroderma, dermatomyositis, GD, and immune thrombocytopenic purpura. The patient was anti-Ku antibody-positive and had relatively low natural killer T cell counts, both of which might contribute to the complication of multiple autoimmune diseases.

Topics: Adult; Anti-Inflammatory Agents; Antigens, Nuclear; Antithyroid Agents; Autoantibodies; Dermatomyositis; DNA Helicases; DNA-Binding Proteins; Female; Graves Disease; Humans; Ku Autoantigen; Methimazole; Platelet Transfusion; Propylthiouracil; Purpura, Thrombocytopenic, Idiopathic; Scleroderma, Systemic; Steroids

The aim of this study was to analyze the serum levels of activin A in hyperthyroid patients with Graves' disease. Serum activin A and FSH levels were measured in a total of 93 females (64 regularly cycling and 29 post-menopausal). Of these, 20 were hyperthyroid patients with Graves disease, 33 were euthyroid goitrous patients (20 had autoimmune thyroiditis AT and 13 only had goiter) representing the internal control group and 40 were healthy subjects representing the external control group. Serum levels of activin A were higher in goitrous patients with AT than in control subjects (p=0.0388). Activin A levels were almost doubled in the cycling and in post-menopausal hyperthyroid women (0.91+/-0.21 vs 0.43+/-0.07 microg/l; p<0.0001 and 0.92+/-0.22 vs 0.48+/-0.24 microg/l; p=0.0001, respectively). In 10 cycling hyperthyroid patients, studied even after methimazole treatment, that increase was substantially reversed, once euthyroidism was attained (p=0.002). These findings indicate that thyroid function and autoimmune processes significantly affect serum levels of activin A in patients with Graves' disease.

Topics: Activins; Adult; Aged; Autoantibodies; Female; Follicle Stimulating Hormone; Graves Disease; Humans; Inhibin-beta Subunits; Methimazole; Middle Aged; Postmenopause; Thyrotropin; Thyroxine

In a 76-year-old woman with hyperthyroidism, hyperprolactinemia and thickening of the pituitary stalk on magnetic resonance imaging (MRI) was presented. Thyroid stimulating antibody (TSAb) was positive and anti-pituitary antibodies against 49 and 68 kD human anterior pituitary membrane antigens were detected immunologically. Secretion of pituitary hormones was almost normal except for suppressed TSH and hyperprolactinemia. As autoimmune etiologies were likely involved in the disorders, autoimmune hypophysitis associated with Graves' disease was arrived at as the plausible diagnosis.

Topics: Aged; Antithyroid Agents; Female; Graves Disease; Humans; Hyperprolactinemia; Magnetic Resonance Imaging; Methimazole; Pituitary Diseases; Treatment Outcome

Radioactive iodine ((131)I) has become the most widely used therapy for patients with hyperthyroidism caused by Graves' disease in the United States. There remains, however, significant variability among (131)I dosing regimens, and it is clear that most patients ultimately develop hypothyroidism after therapy. To avoid persistent hyperthyroidism, we adopted a high dose (131)I therapy protocol based on measurement of 24-h thyroid (123)I uptake designed to deliver 8 mCi (296 MBq) to the thyroid gland 24 h after (131)I administration. To evaluate the efficacy of this protocol, we reviewed our clinical experience over a 7-yr period. We treated 261 patients (219 women and 42 men) with hyperthyroidism caused by Graves' disease with (131)I [mean dose, 14.6 mCi (540 MBq)] between 1993 and 1999. Before treatment, 207 (79%) had received an antithyroid drug (109 propylthiouracil and 98 methimazole). We determined their thyroid status 1 yr after treatment in relation to age, pretreatment with an antithyroid drug, pretreatment thyroid size, and dose of (131)I retained in the thyroid 24 h after treatment. Among the 261 patients, 225 (86%) were euthyroid or hypothyroid 1 yr after treatment, and 36 patients (14%) had persistent hyperthyroidism and required a second treatment. The patients who had persistent hyperthyroidism were younger (P < 0.01), had larger thyroid glands (P < 0.01), higher pretreatment thyroid (123)I uptake values (P < 0.01), and higher serum T(4) concentrations (P < 0.01) and were more likely to have taken antithyroid medication before administration of (131)I (P = 0.01). Five of these patients developed transient hypothyroidism, followed by thyrotoxicosis. There was an asymptotic, inverse relationship between the retained dose of (131)I at 24 h and persistent hyperthyroidism, revealing a 5-10% failure rate despite delivery of up to 400 microCi (14.8 MBq)/g. A dose of (131)I that results in accumulation of 8 mCi (296 MBq) in the thyroid gland 24 h after administration is an effective treatment for the majority of patients with Graves' hyperthyroidism. Young patients with larger thyroid glands, higher serum T(4) concentrations, and higher 24-h thyroid (123)I uptake values, and those pretreated with antithyroid medication for greater than 4 months are at higher risk for treatment failure. A higher dose of (131)I may be advisable in such patients.

Topics: Adult; Antithyroid Agents; Dose-Response Relationship, Radiation; Female; Graves Disease; Humans; Hypothyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Retreatment; Retrospective Studies; Thyrotoxicosis; Treatment Outcome

Acquired hemophilia due to autoantibody to Factor VIII coagulant (Factor VIIIc) is a rare event which may be observed in patients with different autoimmune diseases. To our knowledge, this association has been reported only once in patients with autoimmune thyroid disease. Here we describe a patient presenting with a severe hemorrhagic disorder due to Factor VIIIc antibody in whom biochemical screening for thyroid diseases led to a diagnosis of hyperthyroid Graves' disease not associated to overt clinical features. This case underlines the importance of carrying out a complete screening for autoimmunity, including thyroid autoimmune disease, in all patients with apparently isolated serum Factor VIIIc inhibitors.

Topics: Antithyroid Agents; Autoantibodies; Autoimmune Diseases; Factor VIII; Female; Graves Disease; Hematuria; Hemoperitoneum; Hemophilia A; Humans; Hysterectomy; Leiomyoma; Methimazole; Middle Aged; Ovariectomy; Postoperative Hemorrhage; Thyroid Hormones; Thyrotropin; Uterine Neoplasms

In this study, we retrospectively analyzed 18 patients in whom antithyroid drug (ATD)-induced agranulocytosis developed during treatment of Graves' disease. All patients were more than 20 years of age, and we saw no correlation between age and the development of agranulocytosis. In 17 of 18 patients, ATD-induced agranulocytosis developed within 2 to 12 weeks of starting ATD treatment. Development of agranulocytosis was related to the dose of ATD. In some patients, agranulocytosis developed abruptly, and even weekly routine WBC and granulocyte counts failed to predict all case occurrences. Fever and sore throat were the earliest symptoms of agranulocytosis; patients who developed either of these symptoms were closely monitored immediately with WBC and granulocyte count examinations. In this series of patients, treatment with granulocyte-macrophage colony stimulating factor (GM-CSF) increased the granulocyte counts, whereas the effectiveness of glucocorticoid treatment was not confirmed.

Topics: Adult; Agranulocytosis; Antithyroid Agents; Female; Glucocorticoids; Granulocyte-Macrophage Colony-Stimulating Factor; Graves Disease; Humans; Leukocyte Count; Male; Methimazole; Middle Aged; Propylthiouracil; Retrospective Studies

Prospective studies of Graves-Basedow disease in Spain are scarce. Our objective was to evaluate the clinical and biochemical evolution of a cohort of patients with Graves-Basedow disease.. 202 patients with Graves-Basedow disease diagnosed between January 1997 and June 1999.. 5.9% of patients received 131I and 2.5% underwent surgery after treatment with methimazole. A relapse was observed in 23.3% patients. In the survival analysis, significant differences with regard to the rate of relapse were observed according to the goitre degree.. In our study, all patients reached remission with methimazole. There was a high rate of relapse following discontinuation of therapy within the first months. Goitre size at the time of diagnosis was a significant determining factor of relapse.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Antithyroid Agents; Child; Cohort Studies; Data Interpretation, Statistical; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Recurrence; Sex Factors; Survival Analysis; Time Factors

We present a case of a 40-years-old woman with an acute posterior multifocal placoid pigment epitheliopathy (APMPPE) associated with recent instauration hyperthyroidism symptoms. A Graves' disease was diagnosed and the patient was initially controlled with antithyroid drugs. The epitheliopathy evolution was relatively favourable without relapse. Two years later a thyroidectomy was performed.. We have not found in the literature any APMPPE case associated with Graves' disease. We only found an APMPPE case associated with a subacute thyroiditis. Little is known about the APMPPE causes, it could be that placoid epitheliopathy and Graves' disease had a common autoimmune origin. We can not forget that our finding could be only a matter of chance.

Topics: Acute Disease; Adult; Antithyroid Agents; Choroid; Combined Modality Therapy; Female; Fluorescein Angiography; Graves Disease; Hormone Replacement Therapy; Humans; Ischemia; Methimazole; Pigment Epithelium of Eye; Radiography; Retinal Diseases; Thyroidectomy; Thyroiditis, Subacute; Thyroxine

Pancytopenia is a rare complication of the thionamide therapy reported secondary to aplastic anemia, the bone marrow being invariably hypocellular. We present a case of a 16-year-old female with Graves' disease who presented with massive bone marrow plasmocytosis mimicking multiple myeloma. The patient had already been on methimazole for a month when she was admitted to the Pediatric Unit with the diagnosis of sepsis. CBC revealed pancytopenia. Bone marrow aspirations showed hypocellular-normocellular bone marrow, 98% of plasma cells. At that time, MMI was discontinued and the patient was started on broad-spectrum antibiotics, dexamethasone, and G-CSF. Bone marrow aspiration day +4 still showed hypo-normocellular marrow, with remaining 6% plasma cells. Myeloma screen was negative; ANC >1,000 at day +7, platelets >50,000 at day +24. Twenty-four months after patient's discharge, her clinical condition, CBC, and bone marrow remained normal. To our knowledge this is the first report of pancytopenia due to MMI, where the usual hypoplasia found is replaced by massive plasmocytosis.

Topics: Adolescent; Antithyroid Agents; Bone Marrow; Bone Marrow Diseases; Diagnosis, Differential; Female; Graves Disease; Humans; Leukocytosis; Methimazole; Multiple Myeloma; Pancytopenia; Plasma Cells

It has been shown that human thyrocytes can synthesize cytokines which activate T and B lymphocytes. These immune cells play important roles in the initiation and continuation of thyroid autoimmunity. The aim of this study was to estimate serum concentrations of soluble interleukin-6 receptor (sIL-6R), interleukin-6 (IL-6) and interleukin-8 (IL-8) in patients with Graves' disease (GD) (n=44, mean age 14.8 years), in patients with nontoxic nodular goiter (NTNG) (n=36, mean age 15.6 years) and in a group of healthy controls (n=20, mean age 14.5 years). ELISA was used to determine the concentration of cytokines, antithyroglobulin and antithyroid peroxidase antibodies in patients with thyroid disease. Radio receptor assay (RRA) was performed to detect anti-TSH receptor autoantibodies (TRAb). Serum levels of IL-6, sIL-6R and IL-8 were markedly elevated in patients with GD before treatment with methimazole (p<0.0001 for IL-6, p<0.006 for sIL-6R, p<0.004 for IL-8) and after 8 weeks of therapy (p<0.011 for IL-6, p<0.04 for IL-8). However, following 24 months of treatment, normal serum concentrations of these cytokines were restored. Furthermore, patients with NTNG showed a slightly elevated concentration of cytokines (IL-6, IL-8). Serum levels of tri-iodothyronine in patients with GD positively correlated with serum concentrations of IL-6 (r = 0.35, p<0.025) and sIL-6R (r = 0.31, p<0.047), while no correlation was found between thyroxine and cytokines. Moreover, we observed a positive correlation between serum levels of TPO-Abs, TRAb and IL-6 (r = 0.43, p<0.008; r = 0.5, p<0.003) and between TPO-Abs and IL-8 (r = 0.67, p<0.0001). However, in patients with NTNG no correlation was observed between serum levels of antithyroid antibodies or thyroid hormones and serum levels of cytokines. We conclude that the cytokines (IL-6, sIL-6R, IL-8) could play an important role in the development of Graves' disease and that their levels are modulated by thyreostatic treatment.

Topics: Adolescent; Antithyroid Agents; Autoantibodies; Child; Female; Goiter, Nodular; Graves Disease; Humans; Interleukin-6; Interleukin-8; Male; Methimazole; Receptors, Interleukin-6; Thyroid Gland; Thyroid Hormones; Thyroxine

A 65-year-old woman with Graves' disease presented marked diurnal changes in white blood cell (WBC) and granulocyte counts. Granulocyte count was low and sometimes decreased to 0.2-0.3 x 10(9)/l in the early morning and increased in the afternoon irrespective of her thyroid status. She did not develop sore throat or fever during the investigation period. The present study indicates that these unusual diurnal changes in WBC and granulocyte counts should be considered in the differential diagnosis of agranulocytosis in Graves' disease patients treated with an antithyroid drug.

Topics: Aged; Agranulocytosis; Antithyroid Agents; Circadian Rhythm; Female; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Leukocyte Count; Methimazole

We report a case of pulmonary metastatic thyroid carcinoma complicated with Graves' disease. A 56-year-old Japanese woman was referred to the Niigata Cancer Center Hospital for isotope therapy for pulmonary metastatic thyroid carcinoma. In 1993, she received a left-hemithyroidectomy. In 1999, the remnant thyroid was resected for isotope therapy of metastatic lesions in the lungs. Although she had been receiving suppressive therapy with levothyroxine, her general condition was good, and TRAb was positive before the operation. After a total thyroidectomy, the patient became thyrotoxic. For functioning metastatic lesions, the patient was treated with 5550 MBq of 131I and methimazole. Thyroid function was normalized after the therapy but TRAb and TSAb levels remained high.

Topics: Antithyroid Agents; Autoantibodies; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Iodine Radioisotopes; Lung Neoplasms; Methimazole; Middle Aged; Receptors, Thyrotropin; Thyroid Neoplasms; Thyroidectomy; Thyrotropin; Thyroxine; Tomography, X-Ray Computed; Triiodothyronine

We report the case of a 31-year-old man with Graves' disease who manifested malignant hyperthermia during subtotal thyroidectomy. His past medical history and family history were unremarkable. Before surgery, his condition was well controlled with propylthiouracil, beta-adrenergic blocker and iodine. During the operation, anesthesia was induced by intravenous injection of vecuronium and thiopental, followed by suxamethonium for endotracheal intubation. Anesthesia was maintained with nitrous oxide and sevoflurane. One hour after induction of anesthesia, his end tidal carbon dioxide concentration (ET(CO2)) increased from 40 to 50 mmHg, heart rate increased from 90 to 100 beats per min and body temperature began to rise at a rate of 0.3 degrees C per 15 min. Suspecting thyroid storm, propranolol 0.4 mg and methylprednisolone 1,500 mg were administered, which, however, had little effect. Despite the lack of muscular rigidity, the diagnosis of malignant hyperthermia was made based on respiratory acidosis. Sevoflurane was discontinued and dantrolene was given by intravenous bolus. Soon after the treatment, ET(CO2), heart rate and body temperature started to fall to normal levels. His laboratory findings showed abnormally elevated serum creatine phosphokinase and myoglobin but normal thyroid hormone levels. Since dantrolene is efficacious in thyrotoxic crisis and malignant hyperthermia, an immediate intravenous administration of dantrolene should be considered when a hypermetabolic state occurs during anesthesia in surgical treatment for a patient with Graves' disease.

Topics: Acidosis, Respiratory; Adult; Anesthetics; Antithyroid Agents; Carbon Dioxide; Creatine Kinase; Dantrolene; Diagnosis, Differential; Goiter; Graves Disease; Heart Rate; Humans; Male; Malignant Hyperthermia; Methimazole; Methyl Ethers; Muscle Relaxants, Central; Myoglobin; Nitrous Oxide; Propylthiouracil; Sevoflurane; Succinylcholine; Thiopental; Thyroidectomy; Thyroxine; Triiodothyronine; Vecuronium Bromide

We analyzed the relationship between serum IgE concentrations and the remission or recurrence of Graves' disease. One hundred seven patients with Graves' disease were treated with methimazole (MMI). Serum IgE concentration greater than 170 IU/ml was found in 41 of 107 untreated patients (38.3%). However, the presence of TSH-binding inhibiting immunoglobulin or thyroid-stimulating antibody did not correlate with the IgE concentrations. Remission was found in 20 of 41 patients with elevated IgE concentrations (48.8%) after 18 months of MMI treatment, as opposed to 53 of 66 patients with normal concentrations (80.3%) (P = 0.0014). MMI treatment was discontinued in 73 patients who were followed for 26-48 months. The recurrence of Graves' disease was found in 13 patients, whereas the remaining 60 were still in remission. The rate of long-standing remission was lower in patients with elevated than normal IgE concentration (34.1% vs. 69.7%, P = 0.0007). We also analyzed serum levels of interleukin (IL)-13. Although IL-13 was not detected in all patients, the detection rate was higher in patients without remission and in those with recurrence than in those with long-standing remission (47.1%, 38.5%, and 13.3%, respectively; P = 0.0012). More patients with elevated IgE were positive for allergic diseases and for family history of allergic diseases in their first-degree relatives. We conclude that the elevation of IgE and the higher detection rate of IL-13 are associated with both remission and recurrence of Graves' disease.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Autoantibodies; Disease-Free Survival; Family; Female; Follow-Up Studies; Graves Disease; Humans; Hypersensitivity; Immunoglobulin E; Interleukin-13; Male; Methimazole; Middle Aged; Recurrence; Thyroglobulin; Thyrotropin; Thyroxine; Time Factors

The purpose of this study was to evaluate if there is an association between the antithyroid drug dose that is needed to establish euthyroidism and thyroid blood flow measurements. A total of 23 Graves' disease patients with euthyroidism taking antithyroid drug therapy were enlisted to undergo spectral duplex sonography of the thyroid arteries and color-flow mapping of the thyroid gland. Color pixel density (CPD) was calculated with computer assistance from the color-flow maps. There was a strong correlation between the CPD and methimazole dose (rp = 0.79). Methimazole maintenance dosage could be predicted from CPD values with a coefficient of determination of 0.62. In conclusion, CPD measurements could be a useful tool for the clinical endocrinologist to estimate the antithyroid drug dose that is needed to maintain euthyroidism.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Male; Methimazole; Regional Blood Flow; Thyroid Gland; Ultrasonography, Doppler, Color

There is controversy over the factors that may influence the outcome of radioiodine therapy for benign thyroid diseases. Antithyroid medication has been claimed to negatively influence the effectiveness of radioiodine therapy in Graves' disease. In a longitudinal study, we assessed the influence of sex, age, antithyroid drugs, target radiation dose, target mass, applied activity, delivered dose, interval between last meal and application, and TSH, FT3 and FT4 levels on the outcome of radioiodine therapy. One hundred and forty-four patients (111 female, 33 male) suffering from Graves' disease (GD) and 563 patients (434 female, 129 male) with toxic nodular goitre (TNG) were entered in the study and followed up until 8 months after therapy. Treatment was defined as successful when the TSH level was found to be normal or elevated. Ninety-eight GD patients and 418 TNG patients were successfully treated. Forward stepwise multiple regression analysis models retained only the target mass in GD and the applied activity in TNG as significantly associated with the outcome of therapy. The predictive value of all variables involved was extremely low in both disease groups. Whereas concomitant antithyroid medication had no influence in GD, it adversely influenced radioiodine therapy of TNG. This effect may be attributed to a radioiodine "steal phenomenon" induced by TSH-stimulated normal thyroid tissue, which causes overestimation of the uptake in toxic nodules.

Topics: Aged; Antithyroid Agents; Carbimazole; Female; Goiter, Nodular; Graves Disease; Humans; Iodine Radioisotopes; Longitudinal Studies; Male; Methimazole; Middle Aged; Prospective Studies; Radiotherapy Dosage; Thyrotropin; Thyroxine; Treatment Outcome; Triiodothyronine

Topics: Antithyroid Agents; Follow-Up Studies; Graves Disease; Humans; Iodine Radioisotopes; Methimazole; Prednisolone; Randomized Controlled Trials as Topic; Reference Values

There is an increasing evidence that CD3+ cells, bearing gammadelta T cell receptors representing a minor subpopulation of T cells in the peripheral blood of humans are involved in the development of autoimmunity. The aim of the present study was determination of the gammadelta T cell subpopulation levels in the peripheral blood of subjects with Graves' disease and newly diagnosed type 1 diabetes in comparison to age-matched healthy controls. The percentages of CD3+, CD8+, gammadelta TCR+CD8+, gammadelta TCR+CD8- lymphocyte subsets were measured by flow cytometry. In the peripheral blood of newly diagnosed Graves' disease patients we showed a significant decrease of gammadelta TCR+ cells and gammadelta TCR+CD8- subset content in comparison to the percentages observed in subjects after methimazole treatment and in healthy controls. We also found a significant increase of gammadelta TCR+CD8+ cells in the peripheral blood of subjects with insulin-dependent diabetes, treated with insulin for 3-6 months. The present findings confirm our previous hypothesis that gammadelta TCR+CD8+ lymphocyte subset could play a role in the pathogenesis of diabetes type 1, probably as regulatory T cells and could be induced by delivery of exogenous insulin. Our results suggest that gammadelta T cells (gammadelta TCR+CD8- subset) could also play an important role in the development of Graves' disease and that their levels are modulated by thyreostatic treatment.

Topics: Adolescent; Adult; Antithyroid Agents; Case-Control Studies; CD3 Complex; CD8-Positive T-Lymphocytes; Diabetes Mellitus, Type 1; Female; Graves Disease; Humans; Male; Methimazole; Receptors, Antigen, T-Cell, gamma-delta; T-Lymphocyte Subsets

We reported the case of a 19-year-old female complicated with Basedow disease. She was admitted, complaining of headache and endocrine function tests showed hyperthyroidism. CT scan revealed left intraventricle hemorrhage and angiography revealed the stenoses at the terminal portion of the bilateral internal carotid arteries (ICA) without basal moyamoya vessels. During the angiography, a thyroid crisis occurred and we initiated the antithyroid therapy. Bilateral CAG a month after the onset revealed that the stenoses had improved partially and the stenosis was thought to be vasospasm caused by the intraventricle hemorrhage. But as the collateral circulation had already been established soon after the hemorrhage, we suspected that the stenoses at the terminal portion of the ICA had existed before the intraventricle hemorrhage. Angiography was performed one year after the onset and bilateral CAG revealed that the stenoses at the terminal portion of the ICA had also improved. As some investigators have mentioned that Basedow disease might be associated with the causal genesis of Moyamoya disease, we suspected that Basedow disease might have played an important role in vasospasm after hemorrhage and that the stenoses at the terminal portion of the ICA might have existed before the hemorrhage took place.

Topics: Adult; Antithyroid Agents; Carotid Artery, Internal; Carotid Stenosis; Cerebral Angiography; Female; Graves Disease; Humans; Methimazole

Therapy with anti-thyroid drugs is the initial option mostly used in our country for the treatment of hyperthyroidism due to Graves-Basedow disease. To evaluate the long term results of this kind of therapy, a total of 773 patients were studied who were diagnosed from 1975 to 1994 in three hospitals in Northern Spain (Hospital Central de Asturias, Hospital de Cruces and Hospital de Navarra) after a mean follow-up time after anti-thyroid drug withdrawal of 46 +/- 33.1 months. The results showed a likelihood of hyperthyroidism relapse of 42.9%, 59.8%, 67.9% and 78.9% at one, three, five and ten years, respectively. Goitre size was correlated very significantly with the likelihood of relapse (p < 0.0001). In contrast, only TBII positivity at the end of therapy among the remaining parameters (age, sex, goitre size, length of therapy, positivity of anti-thyroid antibodies and TBII) influenced significantly on the relapse likelihood (p < 0.05). In conclusion, after a long term follow-up after anti-thyroid therapy, a high relapse rate of hyperthyroidism in Graves-Basedow disease, which amounts up to 79% at ten years, was observed. Goitre size was the main predictive factor for this relapse.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antithyroid Agents; Carbimazole; Child; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Prognosis; Propylthiouracil; Recurrence; Spain

Sarcoidosis is a systemic chronic granulomatous disease of unknown etiology most commonly affecting young females. The disease was first described in the thyroid gland in 1938. Our patient, a 27-year-old male with known sarcoidosis, was referred to the National University Hospital for acute symptoms of thyrotoxicosis (weight loss of 6 kg, tremor, thyroid enlargement, and tachycardia). Laboratory findings showed suppressed serum thyrotropin (TSH, <0.03 mU/L [0.5-4.20]), increased total thyroxine (T4) (223 nmol/L, [60-140]), and triiodothyronine (T3) (8.5 nmol/L, [1.5-2.7]). Furthermore, Tc-99m pertechnetate scintigraphy disclosed diffuse accumulation of the isotope confirming the diagnosis of Graves' disease. During the next 18 months of antithyroid treatment (thiamazole, Thycapzol) hyperthyroidism was difficult to control, the thyroid gland gradually enlarged, and surgery was recommended. Initially, the patient declined surgery but after an additional 18 months, he accepted surgery. During the 36-month period of antithyroid drug treatment TSH was suppressed (<0.01 mU/L) and T3 often elevated despite high doses of thiamazole. Total thyroidectomy was performed, and histologic examination of the removed thyroid tissue confirmed the diagnosis of Graves' disease and also the presence of sarcoid granuloma and metastatic papillary adenocarcinoma with spread to neck lymph nodes. Four months later, a modified radical neck dissection was performed with removal of neck lymph nodes followed by external radiation therapy (2 Gy x 32 fractions to the neck). The concomitant presence of sarcoidosis, papillary carcinoma, and Graves' disease in a thyroid gland, to our knowledge, has not previously been described in the literature.

Topics: Adult; Antithyroid Agents; Carcinoma, Papillary; Granuloma; Graves Disease; Humans; Lymphatic Metastasis; Male; Methimazole; Sarcoidosis; Thyroid Diseases; Thyroid Neoplasms; Thyrotropin; Thyroxine; Triiodothyronine

The aim of the present study was to evaluate serum soluble interleukin-1 receptor antagonist (sIL-1RA) concentration and its relationship with the degree of cigarette smoking in patients with Graves' ophthalmopathy (GO).. Twenty-two consecutive GO patients (20 women, two men; age range 25-68 years, mean 48 years; 12 smokers, 10 non-smokers) submitted to IV glucocorticoid pulses over a 3-month period.. sIL-1RA levels were measured by an immunoenzymatic assay (sensitivity, 4 ng/l; normal range, 50-290 ng/l) before glucocorticoid treatment, after two months of therapy, and 3 months after drug withdrawal.. Thirteen patients responded to treatment (59%; five smokers and eight non-smokers), nine were non-responders (41%; seven smokers and two non-smokers). Baseline median sIL-1RA concentration did not differ in smokers and non-smokers (222 and 173 ng/l, respectively; P = 0.69). Likewise, no significant differences were found between the two groups during treatment (537 and 389 ng/l, respectively; P = 0.28); sIL-1RA concentration after treatment was higher in smokers (258 vs. 94 ng/l; P = 0.02). There was no correlation between basal sIL-1RA levels and the degree of cigarette smoking. Likewise, there was no difference in sIL-1RA levels in responders and non-responders, either at baseline (186 vs. 216 ng/l; P = 0.83), during or after treatment.. Our study suggests that circulating soluble interleukin-1 receptor antagonist levels, both at baseline and during glucocorticoid treatment, are neither influenced by cigarette smoking nor predictive of subsequent response to glucocorticoid treatment.

Topics: Adult; Aged; Antithyroid Agents; Biomarkers; Case-Control Studies; Female; Glucocorticoids; Graves Disease; Humans; Interleukin 1 Receptor Antagonist Protein; Linear Models; Male; Methimazole; Methylprednisolone; Middle Aged; Sialoglycoproteins; Smoking; Statistics, Nonparametric; Thyroxine; Treatment Outcome

To examine the dynamics of oxidative stress in patients with hyperthyroidism before and during the treatment with methimazole using the measurement of conjugated dienes, malondialdehyde, and Schiff bases in blood serum.. In eight female patients with diagnosed Graves disease and 8 healthy control subjects (7 females and one male) several parameters of oxidative stress (the level of conjugated dienes [CD], malondialdehyde [MDA] and Schiff bases [SB]) were estimated before and during the treatment with methimazole (Metizol -POLFA) as well as by hormonal and immunological tests. In addition, serum levels of TSH, free thyroxine (FT4), free triiodothyronine (FT3), antibodies against thyroperoxidase (anti-TPO) and thyroglobulin (anti-Tg) and low density lipoprotein-cholesterol fraction (LDL-Ch) were estimated.. We observed increased concentrations of free thyroxine (FT4) and free triiodothyronine (FT3), as well as of antithyroperoxidase (anti-TPO) and antithyroglobulin (anti-Tg) antibodies. At the same time, TSH level was significantly suppressed. The concentrations of thyroid hormones and of TSH normalised after the methimazole treatment. The examined parameters, i.e., CD, MDA, and SB, were evaluated as proportions of each of them to the level of low density lipoproteins-cholesterol fraction (LDL-Ch). This fraction of cholesterol contains many polyunsaturated fatty acids, being a substrate for the peroxidation of lipids. Additionally, the CD/MDA ratio was calculated.. The increase of the CD/LDL ratio in Graves hyperthyroidism and its normalisation in the course of the treatment with methimazole suggests that the drug can be protective against the oxidative stress induced by overproduction of thyroid hormones. The ratio of CD/MDA decreased in all the patients, as compared to the control group, showing a high speed of lipid peroxidation.

Topics: Antithyroid Agents; Autoantibodies; Cholesterol, HDL; Cholesterol, LDL; Female; Graves Disease; Humans; Iodide Peroxidase; Lipid Peroxidation; Male; Malondialdehyde; Methimazole; Oxidative Stress; Thyroglobulin; Thyrotropin; Thyroxine; Triglycerides; Triiodothyronine

In the present study we have measured the concentrations of interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and IL-1 receptor antagonist (IL-1Ra) in the serum of patients with Graves' disease (GD). By multivariate analysis, we have evaluated the effect of antithyroid treatment, thyroid function, the presence or absence of active thyroid-associated ophthalmopathy (TAO), the patient's smoking habits and the relation to circulating anti-thyrotropin (TSH) receptor (TRAb) and anti-thyroperoxidase antibodies (TPOAb).. We studied 84 GD patients, 51 untreated and 33 receiving methimazole (MMI) therapy. Twenty-three (45%) untreated patients and 18 (54%) patients on MMI had active TAO. We also studied 67 normal subjects as controls. Thirty-one GD patients (43%) and 16 controls (36%) were smokers.. Serum IL-6 concentrations were significantly higher in both untreated patients (P<0.001) and treated patients (P<0.006), when compared with controls. Serum sIL-6R concentrations were significantly affected by treatment (P=0.001). Serum IL-1Ra concentrations were not different in GD patients, whether treated or untreated, compared with controls. Serum IL-6 concentrations were not influenced by thyroid function and there was a significant interaction between treatment and the presence of active TAO (P=0.003). In hyperthyroid patients with active TAO serum, sIL-6R concentrations were significantly higher than in those with inactive TAO (P=0.003). In untreated GD patients there was no significant effect of thyroid function and TAO activity on the serum concentrations of TNF-alpha and IL-1 beta. Serum IL-1Ra concentrations were not affected by the presence of TAO. Smoking had no effect on serum IL-6, sIL-6R, TNF-alpha, IL-1 beta and IL-1Ra concentrations, even in the presence of an active TAO. Serum concentrations of IL-6, sIL-6R, TNF-alpha and IL-1 beta and IL-1Ra were not different in patients with and without TRAb or TPOAb, in relation to either thyroid function, TAO activity or smoking.. Our work shows that: (i) the proinflammatory cytokine pattern in GD is greatly influenced by antithyroid drug treatment; (ii) the increased circulating IL-6/sIL-6R concentrations observed in patients with active TAO may derive from the activation of humoral reactions in sites other than the thyroid; and, (iii) cigarette smoking has no effect on serum IL-1/IL-1Ra concentrations in TAO.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Autoantibodies; Cytokines; Eye Diseases; Female; Graves Disease; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Interleukin-6; Iodide Peroxidase; Male; Methimazole; Middle Aged; Receptors, Interleukin-1; Receptors, Interleukin-6; Receptors, Thyrotropin; Sialoglycoproteins; Smoking; Solubility; Thyroid Gland; Tumor Necrosis Factor-alpha

Here we report three cases of hyperthyroid Graves' disease that occurred after partial thyroidectomy for papillary carcinoma. In Case 1, the patient first developed hyperthyroidism 2 years after resection of left thyroid lobe, was treated for 2 years with antithyroid drug which was then discontinued, and relapsed with periodic paralysis after 8 years of remission. In Case 2, a hyperfunctioning remnant thyroid was noted 22 years after right hemithyroidectomy. In Case 3, where thyrotoxic symptoms became evident 7 weeks after right hemithyroidectomy, autoantibodies to thyroglobulin and thyroid microsome were positive in preoperative serum, in line with a report by others detecting these antibodies in 2 out of 3 such cases examined. Later bioassay revealed activity of thyroid stimulating antibodies in that serum, with further increase in titer in the sample taken at the clinical manifestation. Hence in Case 3, surgical stress may have altered immunological homeostasis, promoting a preclinical Graves' disease to full-blown hyperthyroidism.

Topics: Adult; Antithyroid Agents; Autoantibodies; Carcinoma, Papillary; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Receptors, Thyrotropin; Recurrence; Sodium Pertechnetate Tc 99m; Thyroid Neoplasms; Thyroidectomy; Thyrotropin

In hyperthyroid Graves' disease, short-term methimazole is sufficient to induce lasting remission in some patients, but even long-term treatment fails to do so in others. We have evaluated the role of autoimmune abnormalities in the helper T cell type 2 (TH2)-interleukin-13 (IL-13)-TSH receptor system in maintaining hyperthyroidism by comparing IgE levels in patients with various thyroid diseases. One hundred and ninety-three patients with hyperthyroid Graves' disease were treated with methimazole, and blood samples were obtained to measure serum levels of T4, T3, TSH, thyroglobulin, antimicrosomal antibody, TSH binding inhibitory Ig (TBII), thyroid-stimulating antibody, thyroid stimulation-blocking antibody, IgE, interferon-gamma, IL-4, and IL-13. Elevation of serum IgE (> or = 170 U/mL) was found in 35.5% of patients with hyperthyroid Graves' disease, and serum levels of T4, T:1, antimicrosomal antibody, and TBII were significantly greater in patients with IgE elevation than in those with normal serum IgE. During methimazole treatment, there was a parallel decrease in the serum T4 concentration in the presence or absence of an IgE elevation. However, there was a significantly smaller decrease in TBII in patients with elevated IgE than in those with normal IgE. As a result, the remission rate was significantly greater in patients with normal IgE than in those with IgE elevation. Serum levels of IL-13 were elevated in 64.7% of patients with IgE elevation in the absence of detectable TH1 marker, interferon-gamma. These findings suggest that in one third of patients with hyperthyroid Graves' disease, TH2 cells are stimulated and secrete excess amounts of IL-13, which subsequently stimulates B cells to synthesize more TSH receptor antibody and IgE, so that during methimazole treatment TBII decreases less in patients with IgE elevation, producing a lower remission rate.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antithyroid Agents; Biomarkers; Female; Goiter; Goiter, Nodular; Graves Disease; Humans; Immunoglobulin E; Male; Methimazole; Middle Aged; Reference Values; Th2 Cells; Thyroiditis, Autoimmune; Thyroxine; Time Factors; Triiodothyronine

Topics: Adult; Antithyroid Agents; Graves Disease; Humans; Knee; Male; Methimazole; Muscle Weakness; Paraplegia; Thyroid Function Tests

Thionamides are used in the treatment of Graves' disease (GD) and act mainly by inhibiting the organification of iodide, but also lower the levels of thyroid autoantibodies, sometimes leading to long-term remission. Fas ligand (FasL) induces apoptosis of susceptible cells by cross-linking its own receptor, Fas. While Fas is present in a wide variety of normal tissues, FasL expression is limited mainly to cells of the immune system, where it acts as an effector molecule of cell-mediated cytotoxicity, and to the placenta, brain, eye, and testis where it presumably contributes to their immune-privileged status by eliminating infiltrating lymphocytes. We examined immunohistochemically the presence of FasL in thyroid tissue from 15 glands of thionamide-treated GD patients and in 8 normal thyroid control specimens. We also investigated the presence of FasL in thionamide-treated thyrocytes in vitro and their ability to induce Fas-mediated apoptosis in lymphocytes. We found that FasL expression was very weak to undetectable in normal thyroid tissue and cultured thyrocytes, whereas it was strong in thionamide-treated GD glands and cultured thyrocytes. Methimazole-treated thyrocytes induced FasL-dependent apoptosis in cocultured lymphocytes, whereas methimazole treatment of lymphocytes grown in the absence of thyrocytes had no such effect. We conclude that FasL is highly expressed in follicular cells of thyroid glands obtained from thionamide-treated Graves' patients and may contribute to the immunomodulatory effect of thionamides in this disease.

Topics: Adult; Antithyroid Agents; Apoptosis; Carbimazole; Cells, Cultured; Coculture Techniques; Fas Ligand Protein; Female; Graves Disease; Humans; Immunoblotting; Immunohistochemistry; Jurkat Cells; Male; Membrane Glycoproteins; Methimazole; Middle Aged; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Thyroid Gland

Topics: Abnormalities, Drug-Induced; Adult; Child, Preschool; Ectodermal Dysplasia; Epilepsy; Face; Female; Fingers; Graves Disease; Humans; Maternal-Fetal Exchange; Methimazole; Nails, Malformed; Pregnancy; Skin Abnormalities

We previously showed that myasthenia gravis (MG) has a mild clinical expression when associated with autoimmune thyroid diseases (AITD). In the present study we have investigated the frequency of thyroid-associated ophthalmopathy (TAO) in patients with Graves' disease (GD) associated with MG as compared with GD patients without MG. A total of 418 patients with GD were studied, 31 with MG and 387 without MG. TAO was evaluated by physical examination, exophthalmometry, computerized tomography, and computerized visual fields assessment. The overall prevalence of TAO was similar in GD patients with MG (61.2%) and in those without MG (56.4%). When the analysis was restricted to GD patients with ocular MG, a greater frequency of TAO was found (84.6%), compared with GD patients without MG or with GD patients with generalized MG, although the differences did not reach the statistical significance. GD patients with MG had a significantly greater prevalence (12.9%) of euthyroid ophthalmopathy (clinically overt ophthalmopathy without previous and/or current hyperthyroidism) than those without MG (3.1%; p = 0.003). The results suggest a preferential association between the ocular manifestations of GD and MG, which may be due to immunological cross-reactivity against common autoimmune targets in the eye muscle as well as to a common genetic background.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Myasthenia Gravis; Thyroidectomy; Thyroxine; Tomography, X-Ray Computed; Visual Fields

We have previously reported that serum soluble interleukin-2 receptor (sIL-2R) and IL-12 levels were significantly increased in hyperthyroid Graves' disease. In this study, we investigated serum IL-18 levels in patients with either Graves' disease or Hashimoto's thyroiditis. The serum IL-18 levels in Graves' disease were significantly increased in the hyperthyroid state and were decreased during treatment with methimazole or propylthiouracil. On the other hand, the levels in Hashimoto's thyroiditis in the hypothyroid state showed no significant differences from those in healthy subjects. When liothyronine sodium was administered orally to healthy subjects, serum IL-18 levels were not changed. Positive correlations between serum IL-18 and IL-12, IL-12 and sIL-2R, and sIL-2R and IL-18 levels were noted in Graves' disease. These results suggest that Th1 cytokines might play an important regulatory role in Graves' disease.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Female; Graves Disease; Humans; Interleukin-18; Male; Methimazole; Middle Aged; Propylthiouracil; Thyroiditis, Autoimmune; Triiodothyronine

Propylthiouracil (PTU)-induced antineutrophil cytoplasmic antibody (ANCA)-related vasculitis and nephritis were recently reported in about 30 patients with hyperthyroidism. The objective of this study was to clarify the prevalence of ANCA and the relationship between ANCA and thyroid antibodies in children with Graves' disease. Titers of myeloperoxidase (MPO)-ANCA in sera of 51 patients with childhood onset Graves' disease (16 before treatment, 25 and 10 treated with PTU and methimazole, respectively) were measured by enzyme-linked immunosolvent assay. Antithyroglobulin antibodies (TGAbs) and antithyroperoxidase antibodies (TPOAbs) were also measured by RIA in 25 PTU-treated patients. No patients had clinical manifestations of vasculitis and nephritis. MPO-ANCA was positive in 6.7% of patients before treatment and in 64.0% of those treated with PTU and in none of those treated with methimazole. MPO-ANCA had a significantly positive correlation with TGAbs (P < 0.05) and no significant correlation with TPOAbs. These findings show the high prevalence of the MPO-ANCA positivity in PTU-treated childhood onset Graves' disease, suggesting that PTU may not be preferred as the first line for the treatment of children with Graves' disease. The significant correlation between MPO-ANCA and TGAbs indicates that the severity of Graves' disease may be a factor responsible for the MPO-ANCA positivity. The cross-reactivity between MPO-ANCA and TPOAbs may not play a role in the high prevalence of MPO-ANCA in the patients exposed to PTU.

Topics: Adolescent; Age of Onset; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Iodide Peroxidase; Japan; Male; Methimazole; Peroxidase; Propylthiouracil; Thyroglobulin

The aim of this study was to ascertain the utility of echo-Doppler in the analysis of the low resistance thyroid vascularization in diffuse toxic goiter (DTG), and the effectiveness of Lugol's solution (iodine-iodide solution) in patients undergoing thyroidectomy.. Twenty-five patients with diffuse toxic goiter were evaluated and compared with 19 normal subjects. Patients were treated with increasing doses of Lugol's solution 2% for 7 days until a total dose of 75 mg of iodine was given. Echo-Doppler was performed on the last day of treatment, 12 hours before operation.. Mean basal Doppler Resistance Index (RI) of intrathyroid arterial flow was significantly lower in patients with DTG compared with normal controls (0.4718 +/- 0.0625 versus 0.55 +/- 0.05, range: 0.472 to 0.643; p = 0.008). Moreover, the RI was significantly increased in patients with DTG after Lugol's solution (+16.46 +/- 10.22%, range: -2.59 to +39.97; p< 0.0005).. Echo-Doppler RI allowed documenting lower arterial resistances within the thyroid gland in patients with DTG. The use of preoperative Lugol's solution therapy induces normalization of those changes for safer thyroidectomy.

Topics: Adult; Antithyroid Agents; Arteries; Blood Loss, Surgical; Case-Control Studies; Combined Modality Therapy; Drug Monitoring; Female; Graves Disease; Hemostatics; Humans; Iodides; Male; Methimazole; Middle Aged; Preoperative Care; Thyroid Function Tests; Thyroid Gland; Thyroidectomy; Ultrasonography, Doppler; Vascular Resistance

To compare the potential benefits of 36-month treatment with 6- and 18-month treatment of antithyroid drug in patients with hyperthyroidism due to Graves' disease (GD).. 183 GD patients were studied prospectively. All patients received methimazole (MMI) at decreasing doses for 6, 18 or 36 months. The relapse rates 18 months after MMI withdrawal were compared between the three therapy groups.. The relapse rate 18 months after the discontinuation of treatment was higher in patients treated for 6 months than in those treated for 18 or 36 months. There was no significant difference between 18-month and 36-month treatment groups. At the end of therapy, serum thyroid stimulating antibody (TSAB) and TSH receptor antibody (TRAB) titers were greater in patents treated for 6 months (320 +/- 191 for TSAB and 8.72 +/- 5.23 for TRAB) and 18 months (165 +/- 87 and 4.55 +/- 4.17) than in those treated for 36 months (126 +/- 77 and 2.19 +/- 2.64), but no statistical difference was found between the three groups before MMI treatment. TSAB and TRAB titers were higher in patients who relapsed after discontinuation of MMI (287 +/- 94 and 6.14 +/- 2.37, respectively) compared with those who remained euthyroid through the 18-month follow-up period (144 +/- 61 and 1.97 +/- 1.06).. Negative TSAB or TRAB at the end of antithyroid therapy is a good indicator for a long-term remission after treatment withdrawal. However, treatment duration greater than 18 months does not improve remission rate of GD.

Topics: Adolescent; Adult; Antithyroid Agents; Child; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Prospective Studies; Recurrence; Remission Induction

Three patients, females aged 62, 67 and 32 years, were presented with fever and sore throat and had severe agranulocytosis (granulocyte count < 100/microliter). All had Graves' disease and were being treated with thiamazole 30 mg once a day. Thiamazole was discontinued and treatment with antibiotics initiated. None of the patients received granulocyte-colony stimulating factor (G-CSF). The mean recovery time of granulocytes was 9 days and there were no fatalities. Patients who receive antithyroid agents should be warned against the serious and potentially lethal side effect of agranulocytosis.

Topics: Adult; Aged; Agranulocytosis; Antithyroid Agents; Bone Marrow Examination; Female; Fever; Graves Disease; Humans; Methimazole; Middle Aged; Pharyngitis; Remission Induction; Sepsis

Spontaneous remission of Graves' disease with a decrease of thyroid stimulating antibody (TSAb) activity is commonly observed in pregnancy. In this article, however, a Graves' patient who developed primary hypothyroidism with an appearance of thyroid stimulation-blocking antibody (TSBAb) activity in late pregnancy is reported. A 25-year-old woman presented with clinical and biochemical hyperthyroidism with an elevation of 99mTcO4- thyroid uptake (4.7%; normal range, 0.7%-3.0%) and mildly elevated activity of thyrotropin-binding inhibitory immunoglobulin (TBII; 30.4%). She was euthyroid with normal TBII (8.0%) and TSAb (126%) before pregnancy, when the patient was taking a 5-mg daily dose of methimazole (MMI). MMI was stopped by the patient when she became pregnant. Subsequently, the patient progressed into primary hypothyroidism with a marked elevation of TBII activity (78.4%) in the third trimester of the pregnancy (at that time, TSAb activity was not detected). TSBAb measured 2 weeks later was detected at the activity of 85.0%. Replacement therapy was initiated with levothyroxine (LT4) (0.05-0.1 mg/day), which was discontinued on the 55th day postpartum because of the onset of mild thyrotoxicosis followed by short-term euthyroid state despite high TSBAb activity. Subsequently, because the patient developed primary hypothyroidism 5 months after delivery, replacement therapy with LT4 (0.1-0.125 mg/day) was readministered. Thus, it is suggested that the development of hypothyroidism with the appearance of TSBAb in Graves' patients can occur even in late pregnancy.

Topics: Adult; Antithyroid Agents; Autoantibodies; Female; Graves Disease; Humans; Hypothyroidism; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third; Receptors, Thyrotropin; Thyroxine

Radioiodine treatment use is frequent in patients with benign hyperfunctioning thyroid diseases and the side-effects are rare. In this paper we described the appearance of TSH-receptor antibodies and the concomitant development of persistent hyperthyroidism in a patient with hyperfunctioning thyroid adenoma after 131I treatment. A 70-year-old man presented a hyperfunctioning thyroid adenoma with suppressed uptake in the adjacent normal gland. Antibodies against the thyroglobulin (TgAb), thyroid peroxidase (TPOAb) and TSH-receptor (TRAb) were absent. One year after remission by radioiodine therapy the patient developed severe and persistent hyperthyroidism associated with diffuse 131I uptake in the gland. TgAb and TPOAb remained absent, but TRAb were present. Although spontaneous development of Graves' disease cannot be excluded, the time sequence and the negative familial and personal history for autoimmune diseases suggest a possible connection between the two phenomena. The release of TSH-receptor antigen from follicular cells damaged by 131I may have triggered the autoimmune response turning a toxic nodular goiter patient into a Graves' disease patient.

Topics: Adenoma; Aged; Antithyroid Agents; Autoantibodies; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Iodine Radioisotopes; Male; Methimazole; Receptors, Thyrotropin; Thyroid Neoplasms; Thyrotropin; Thyroxine; Triiodothyronine

Hyperthyroidism of Graves' disease (Morbus Basedow) is known to involve the thyroid gland in toto, unlike Graves' ophthalmopathy which clinically may either be unilateral or bilateral. We report a 31-year-old Caucasian female patient who presented with unilateral goiter and clinical and laboratory evidence for hyperthyroidism. High-resolution ultrasonography of the thyroid gland revealed a morphology indicative of an autoimmune thyroid disease strictly limited only to the right lobe. 123I-scintiscanning showed a homogenous but several fold increased uptake of the radionuclide in the right lobe of the thyroid gland, whereas the uptake in the left lobe did not differ from the uptake in normal controls. Cytology of the fine needle aspirate of the right lobe revealed a remarkable inflammatory background mainly by presence of lymphocytes, a finding which was not seen in the cytology of the left lobe. Furthermore, both serum antibodies to TSH-receptors and thyroid peroxidase were significantly increased. Consequently, hyperthyroidism of Graves' disease with the involvement of only one lobe of the thyroid gland was diagnosed.

Topics: Adult; Antithyroid Agents; Autoantibodies; Biopsy, Needle; Female; Goiter; Graves Disease; Humans; Iodide Peroxidase; Methimazole; Radionuclide Imaging; Receptors, Thyrotropin; Thyroglobulin; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine; Ultrasonography

Iodine-induced thyrotoxicosis or "jodbasedow phenomenon" has been reported throughout the world since iodine has been administered to treat endemic goitre. Nowadays, iodinated radiocontrast agents and the antiarrhythmic drug amiodarone are the most common sources of excess iodine load subsequently leading to iodine-induced thyrotoxicosis, especially in elderly patients with underlying goitre. The aim of the study was to identify the number of cases of iodine-induced thyrotoxicosis among patients with thyrotoxicosis in a large urban hospital. Over an 18-month period thyrotoxicosis has been diagnosed in a total of 39 patients. Eight patients with iodine-induced thyrotoxicosis (5 female, 3 male; mean age 60.6 years) have been identified (20%). In all patients with iodine-induced thyrotoxicosis, iodine exposure with a mean iodine dose of 21.5 g was documented 2 to 16 weeks before diagnosis (iodinated radiocontrast agents in 5 patients, amiodarone in 2 patients, kelp tablets in 1 patient). Clinical features were predominantly tachyarrhythmias and heart failure, while 6 of 8 patients had goitre (thyroid volume 31 to 193 ml). Thyroid antibodies were not detected. Diagnosis was confirmed in 5 of 8 patients with increased urinary iodine concentrations (3436 to > 6000 nmol/24 h), and in 3 of 8 patients with a low tracer uptake in thyroid scintigraphy (1 to 4%). Treatment consisted of methimazole in all patients, additional tional beta-blockers and lithium in 4 patients, and prednisone in 5 patients. The mean treatment ment duration was 9.2 months, and patients became euthyroid after a mean treatment duration of 6.4 weeks. One patient (with still elevated free thyroxine levels) died of myocardial infarction 4 weeks after antithyroid drug therapy had been installed. The incidence, mechanisms and features of iodine-induced thyrotoxicosis are discussed. Iodine-induced thyrotoxicosis is a common disease, and the recognition and treatment of iodine-induced thyrotoxicosis, particularly in elderly patients and patients with goitre, are of clinical importance.

Topics: Adult; Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Antithyroid Agents; Contrast Media; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Graves Disease; Humans; Iodine; Male; Methimazole; Middle Aged; Thyroid Function Tests; Thyrotoxicosis

The patient, a 24-year-old man, had suffered from hunger, sweating, tachycardia and palpitation for three years. He was diagnosed as having Graves' disease (GD) and treated with methimazole (MMI) for 3 months. He noted that palpitation and perspiration seemed to particularly occur when he was hungry, and thus he was examined to determine whether these symptoms were caused by hypoglycemia. As a markedly elevated immunoreactive insulin level and the presence of insulin antibody in serum were found, he was diagnosed as having insulin autoimmune syndrome (IAS). HLA typing revealed the patient to be positive for group Bw62/Cw4/DR4, which is reportedly a specific HLA type in MMI-treated euthyoroid GD patients with IAS. In spite of the continuation of MMI treatment, the % binding of IRI decreased and the hypoglycemic episode disappeared. In contrast to the previously reported MMI induced IAS in GD cases, MMI is unlikely to have exacerbated IAS in the present case, although his HLA combination is identical to that of the previous cases.

Topics: Adult; Antithyroid Agents; Autoantibodies; Autoimmune Diseases; Follow-Up Studies; Graves Disease; Histocompatibility Testing; Humans; Hyperthyroidism; Hypoglycemia; Insulin; Male; Methimazole; Syndrome; Thyroid Hormones

We present here a case of prominent hypercalcemia accompanied by hypothalamic tumor and Graves' disease. A 24-year-old man with hypothalamic tumor showed hypopituitarism, central diabetes inspidus (DI) and hyperthyroidism. Nausea, loss of thirst and appetite, and general fatigue were found with the unveiling of hypercalcemia and hypernatremia. Parathyroid hormone (PTH) and 1alpha-dihydroxyvitamin D levels were suppressed with a normal range of PTH-related protein values. One-desamino-(8-D-arginine)-vasopressin (DDAVP) and half-saline administration normalized hypernatremia, while hypercalcemia was still sustained. Administration of cortisone acetate and thiamazole reduced the elevated serum Ca level. In the present case, concurrent hyperthyroidism was assumed to accelerate skeletal mobilization of calcium into the circulation. Hypocortisolism and central DI was also considered to contribute, to some extent, to the hypercalcemia through renal handling of Ca.

Topics: Adult; Antithyroid Agents; Calcitriol; Calcium; Cortisone; Craniotomy; Deamino Arginine Vasopressin; Diabetes Insipidus; Drug Therapy, Combination; Germinoma; Graves Disease; Humans; Hypercalcemia; Hypernatremia; Hyperthyroidism; Hypopituitarism; Hypothalamic Neoplasms; Magnetic Resonance Imaging; Male; Methimazole; Parathyroid Hormone; Parathyroid Hormone-Related Protein; Peptide Fragments; Proteins; Renal Agents; Sodium; Teratoma

Diagnostic confusion between thyroid disease and myasthenia gravis (MG) can arise because the two may have similar clinical features, and also because of the more frequent coexistence of these autoimmune disorders in the same individual. In MG, autoantibodies directed against the acetylcholine receptor result in muscle weakness. Thymic pathology is well recognized in MG, with thymic hyperplasia frequent in early onset MG and thymoma more common in later onset MG. In Graves' disease, autoantibodies against thyroid antigens result in hyperthyroidism. A seldom-recognized feature of Grave's disease is the occurrence of an enlarged thymus (thymic hyperplasia) on chest CT, or of thymic lymphoid hyperplasia pathologically.. This report describes a case in which the discovery of a mediastinal mass during imaging of the thyroid, and the presence of myasthenic-like symptoms, in a patient with Graves' disease prompted investigations into whether the patient also had MG.. Despite symptoms which strongly suggested MG, subsequent investigations did not confirm the diagnosis, and treatment of Grave's lead to a resolution of the symptoms and regression of the thymic enlargement seen on CT.. The case study highlighted clinical similarities between Grave's disease and myasthenia gravis which might cause diagnostic confusion, and also the investigations which are useful in order to differentiate the two diseases. In addition to common clinical features, the autoimmune diseases Grave's disease and myasthenia gravis may both produce radiological thymic enlargement.

Topics: Adult; Anti-Anxiety Agents; Anti-Inflammatory Agents; Antithyroid Agents; Diagnosis, Differential; Female; Graves Disease; Humans; Methimazole; Myasthenia Gravis; Prednisone; Propranolol; Radiography; Thymus Hyperplasia; Thyrotropin; Thyroxine

A 69-year-old man had hypothyroid dementia as a result of I-131 therapy and an overdose of methimazole. Tc-99m HMPAO SPECT revealed diffuse cerebral hypoperfusion. The findings of brain SPECT normalized with the disappearance of symptoms and a return to the euthyroid state. There was a 25% or 26% reduction of the mean cerebral blood flow during dementia. This may be the first report in which SPECT brain imaging revealed reversible hypoperfusion associated with reversible hypothyroid dementia.

Topics: Aged; Antithyroid Agents; Brain; Cerebrovascular Circulation; Dementia; Graves Disease; Humans; Hypothyroidism; Iodine Radioisotopes; Male; Methimazole; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

To evaluate the efficacy of antithyroid medication in the initial treatment of pediatric Graves' disease and the frequency of use and outcome of radioiodine as second-line therapy.. Retrospective review.. Tertiary care children's hospital.. Thirty-three patients (29 female, 4 male; mean age 12.7 years) who started treatment for hyperthyroidism between Jan. 1, 1990, and Dec. 31, 1994.. Initial treatment with propylthiouracil or methimazole (with addition of levothyroxine if needed to maintain euthyroidism); subsequent treatment with radioiodine.. 1) Clinical and laboratory features at the time of diagnosis; 2) doses and duration of antithyroid drug treatment and response to treatment; 3) need for treatment with levothyroxine to maintain euthyroidism during the trial of antithyroid medication; 4) indications for radioiodine therapy, and the dose and number of treatments with 131iodine (131I); 5) thyroid status at last follow-up visit (at least 2 years after diagnosis).. All patients were initially treated with antithyroid drugs, and levothyroxine was added in 16 subjects to maintain euthyroidism. The median duration of drug treatment was 21 months. Ultimately, 24/33 patients (73%) received radioiodine following a trial of antithyroid drugs because of a) side effects of antithyroid medication (in 3 patients); b) inadequate response to medication (in 8 patients); and c) relapse (in 13 patients), which occurred at a median of 6 (range 1 to 16) months following cessation of drug therapy. Five patients required a second dose of radioiodine and 2 patients required 3 doses. Of the 24 patients treated with radioiodine, at last follow-up after the most recent treatment (median 18.5, range 3 to 55 months), 6 patients were euthyroid, 16 required thyroxine replacement, and 2 were-still, or again, hyperthyroid.. In our population of children and adolescents, treatment of hyperthyroidism with antithyroid drugs frequently resulted in either side effects, inadequate response to medication or subsequent relapse, all of which led to radioiodine therapy. We conclude, therefore, that radioiodine could be considered as one of the first-line options in older children and adolescents with hyperthyroidism.

Topics: Adolescent; Adult; Antithyroid Agents; Child; Combined Modality Therapy; Drug Evaluation; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Propranolol; Propylthiouracil; Retrospective Studies; Thyroxine; Treatment Outcome

To investigate the possible participation of immunoglobulin E (IgE) in the autoimmune process of Graves' disease, incidence of elevation of serum IgE level, TSH receptor antibody (TRAb), and thyroid status were studied in 66 patients with hyperthyroid Graves' disease, 54 patients with Hashimoto's thyroiditis, 19 patients with bronchial asthma, and 15 patients with pollen allergy. In hyperthyroid Graves' patients, elevation of serum IgE levels (> or = 170 U/mL) was found in 19 of 66 patients (29%), 11 of whom had hereditary and/or allergic conditions. Elevations of serum IgE levels were found in 63% of patients with bronchial asthma and in 40% of patients with pollen allergy. Mean values of serum IgE were the same in patients with hyperthyroid Graves' disease and with bronchial asthma. During methimazole treatment TRAb decreased without fluctuation of IgE levels in both groups. The decrease in TRAb was significantly greater in patients with normal IgE than in patients with IgE elevation. After prednisone administration, reduction in TRAb was greater in patients with normal IgE than that in patients with IgE elevation. High incidence of IgE elevation in hyperthyroid Graves' disease and slower reduction in TRAb in association with IgE elevation suggest a difference in the autoimmune processes in Graves' disease with and without elevation of IgE.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Asthma; Female; Glucocorticoids; Graves Disease; Humans; Hypersensitivity; Immunoglobulin E; Male; Methimazole; Middle Aged; Pollen; Prednisone; Thyroid Diseases; Thyroid Gland

Topics: Antithyroid Agents; Female; Graves Disease; Humans; Hyperthyroidism; Infant, Newborn; Male; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Skin Abnormalities

The relationship between the method of treatment of hyperthyroidism due to Graves' disease and the course of Graves' ophthalmopathy is debated. Antithyroid drug therapy is associated with no change, or even amelioration, of ophthalmopathy. Although controversial, radioiodine may be followed by progression of eye disease, preventable by glucocorticoid administration. Whether thyroidectomy affects the course of ophthalmopathy is uncertain.. In a case control study, the course of non-severe Graves' ophthalmopathy after thyroidectomy was investigated and the results compared with those observed in patients treated with methimazole.. Thirty patients with Graves' hyperthyroidism and non-severe/absent ophthalmopathy were treated with near-total thyroidectomy (Group 1, Tx), after achievement of euthyroidism with methimazole. After surgery, all patients started levothyroxine replacement therapy. Sixty patients treated with methimazole, matched for age, sex, duration of hyperthyroidism, degree of ocular involvement and smoking habits, were used as controls (Group 2, MMI).. Patients were seen every 1-2 months for 12 months for thyroid tests and ocular evaluation.. In Group 1, ocular parameters did not change in 17 of 18 patients with pre-existing ophthalmopathy, and in 12 patients without ophthalmopathy. Eye manifestations worsened only in one (3.3%) patient with pre-existing ophthalmopathy. In Group 2, ocular parameters did not change in 58 patients (33 with, and 25 without ophthalmopathy), while new ophthalmopathy occurred in two without pre-existing eye disease. One of the 30 patients treated by surgery (3.3%) had permanent hypoparathyroidism.. Treatment of Graves' hyperthyroidism with near-total thyroidectomy in patients with non-severe or absent pre-existing ophthalmopathy is not associated in the short term with significant effects on the course of ophthalmopathy.

Topics: Adult; Antithyroid Agents; Case-Control Studies; Chi-Square Distribution; Exophthalmos; Female; Graves Disease; Humans; Male; Methimazole; Statistics, Nonparametric; Thyroidectomy; Treatment Failure; Visual Acuity

The thyroid stimulating immunoglobulins are generally believed to be the cause of hyperthyroidism in Graves' disease. Placental transfer of these antibodies from a mother with autoimmune thyroid disease can result in fetal thyroid disorders. We report the case of a 31-year-old woman who had a history of Graves' disease. She received thyroxine therapy for post thyroidectomy hypothyroidism. Two years after the thyroidectomy, she became pregnant. Unfortunately, intrauterine fetal death occurred in midgestation. One year later, she became pregnant again. In the 26th week of gestation, fetal thyrotoxicosis was diagnosed using clinical pictures, including fetal tachycardia and cardiomegaly, and a hormonal evaluation of a periumbilical blood sampling (T4: 18 micrograms/dl, T3: 65.3 ng/dl, TSH: < 0.03 microU/ml) was performed. Antimicrosomal antibodies were not detectable in either the maternal or fetal blood. In this case, high levels of TBII were detected during pregnancy and crossed the placenta to result in a thyrotoxic fetus in the second pregnancy. We recommend that both the regular monitoring of the thyrotropin receptor antibodies of pregnant women with a history of autoimmune thyroid disease, and routine measurements of the fetal heart rate and intrauterine growth during gestation be mandatory for the early detection of fetal thyroid disorders. Cordocentesis for measuring fetal thyroid function is helpful in reaching a definite diagnosis and for guiding therapy.

Topics: Adult; Autoantibodies; Female; Fetal Diseases; Fetal Growth Retardation; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Infant, Newborn; Male; Methimazole; Pregnancy; Pregnancy Complications; Receptors, Thyrotropin; Recurrence; Thyrotoxicosis

A wide variety of adverse effects of methimazole (MMI) have been reported. Here we report a new MMI-induced disorder, acute pancreatitis and parotitis. Three weeks after a woman started MMI treatment for Graves' disease, she developed a high fever, painful parotid swelling and dull pain in the upper abdomen with elevation of the serum levels of salivary and pancreatic enzymes. These abnormalities disappeared soon after the withdrawal of MMI. However, the same abnormalities were rapidly provoked when MMI was reintroduced. Marked increases in the leucocyte count and CRP were also observed during these episodes. The possible mechanisms of MMI-induced pancreatitis/parotitis are discussed.

Topics: Acute Disease; Aged; Antithyroid Agents; Female; Graves Disease; Humans; Methimazole; Pancreatitis; Parotitis

A case of a very rare association of toxic adenoma and papillary carcinoma with Graves' disease is presented. A 34-year-old woman developed Graves' disease with mild ophthalmopathy. An ultrasound revealed diffuse thyroid enlargement with a hypoechoic pattern and a hypoechoic nodule with regular edges of 1.6 cm in diameter at the lower pole of the left lobe. A thyroid 131I scintiscan showed a diffuse and homogeneous 131I distribution. The 131I uptake (RAIU) was elevated. One year later, while still on a low dose of methimazole, the patient had a recurrence of hyperthyroidism following an iodine load from a contrast agent. A further thyroid ultrasound confirmed the previously described pattern but showed a new hypoechoic nodule of 1.1 cm with irregular edges in the left lobe. A thyroid 131I scintiscan this time demonstrated a hyperactive area localised in the larger nodule and a lower diffuse uptake of the remaining tissue. Because of the worsening of the symptoms of hyperthyroidism, the patient had a left lobectomy. On histological examination, the larger nodule was well encapsulated and showed the characteristics of a hyperfunctioning follicular adenoma. The smaller nodule was a typically unencapsulated papillary carcinoma. Several other microfoci of papillary carcinoma were also found in the adjacent tissue. Completion of thyroidectomy was therefore performed, followed by 131I ablative therapy and thyroxine suppressive treatment. This observation suggests that the chronic abnormal stimulation of the thyroid gland by the thyroid-stimulating antibody (TSAb) may facilitate the neoplastic transformation of the thyrocytes in individuals with a critical genetic background.

Topics: Adenoma; Adult; Antithyroid Agents; Carcinoma, Papillary; Female; Graves Disease; Humans; Iodine Radioisotopes; Methimazole; Thyroid Neoplasms; Thyroidectomy; Thyroxine; Ultrasonography

The expression and synthesis of insulin-like growth factor-1 (IGF-I) and IGF-binding protein-3 (IGFBP-3) are regulated by various hormones and nutritional conditions. We evaluated the effects of thyroid hormones on serum levels of IGF-I and IGFBP-3 levels in patients with autoimmune thyroid diseases including 54 patients with Graves' disease and 17 patients with Hashimoto's thyroiditis, and in 32 healthy age-matched control subjects. Patients were subdivided into hyperthyroid, euthyroid and hypothyroid groups that were untreated, or were treated with methylmercaptoimidazole (MMI) or L-thyroxine (L-T4). Serum levels of growth hormone (GH), IGF-I and IGFBP-3 were determined by radioimmunoassay. Serum GH levels did not differ significantly between the hyperthyroid and the age-matched euthyroid patients with Graves' disease. The serum levels of IGF-I and IGFBP-3 showed a significant positive correlation in the patients (R=0.616, P<0.001). The levels of both IGF-I and IFGBP-3 were significantly higher in the hyperthyroid patients with Graves' disease or in those with Hashimoto's thyroiditis induced by excess L-T4 administration than in control subjects. Patients with hypothyroid Graves' disease induced by the excess administration of MMI showed significantly lower IGFBP-3 levels as compared to those in healthy controls (P<0.05). Levels of IGFBP-3, but not IGF-I levels, showed a significant positive correlation with the levels of free T4 and free T3. In Graves' disease, levels of TPOAb, but not of TRAb, showed a significant positive correlation with IGFBP-3. We conclude that in patients with autoimmune thyroid diseases, thyroid hormone modulates the synthesis and/or the secretion of IGF-I and IGFBP-3, and this function is not mediated by GH.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Human Growth Hormone; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Japan; Male; Methimazole; Middle Aged; Reference Values; Regression Analysis; Thyroiditis, Autoimmune; Thyroxine

Topics: Antithyroid Agents; Combined Modality Therapy; Exophthalmos; Graves Disease; Humans; Iodine Radioisotopes; Methimazole; Prednisone

We investigated the interrelationship and the influence of thyroid-stimulating antibodies (TSAb), TSH-blocking antibodies (TSHBAb), and of radioiodine (131I)-induced thyroid damage in the early (within 1 yr) outcome of thyroid function in hyperthyroid patients with Graves' disease (GD) treated with 131I. TSAb, TSHBAb, and ultrasound thyroid volume (as an index of thyroid damage) were simultaneously measured before and at 1, 3, 6, and 12 months after 131I in 31 GD patients. One year after radioiodine, 9.7% of patients were hyperthyroid (Hyper-group), requiring methimazole; 12.9% were euthyroid (Eu-group); and 77.4% were hypothyroid (Hypo-group). Pretreatment thyroid volume in the Eu-group and Hyper-group was significantly greater (P = 0.009) than in the Hypo-group. Pre-131I TSAb levels were higher in the Hyper-group vs. the Hypo-group (P = 0.01) or the Eu-group (P = 0.03). A significant post-131I increase in TSAb levels occurred in 66% of patients developing hypothyroidism but not in those remaining hyperthyroid. After 131I, TSHBAb appeared in 7 patients, in all but one associated with high levels of TSAb. One year after radioiodine: 1) the mean percent reduction in thyroid volume was greater in the Hypo-group (80.7%) or the Eu-group (83.5%) than in the Hyper-group (35.7%) (P = 0.007 and 0.0033 respectively); 2) hypothyroid patients had smaller (P = 0.0058) post-131I thyroids than hyperthyroid patients; and 3) TSAb were still elevated in 75% hypothyroid patients, but all of them had a thyroid volume < or = 8 mL, indicating major postradioiodine gland damage.. 1) the early outcome of thyroid function after 131I for GD is mainly related to pretreatment thyroid volume and to the degree of its reduction after therapy; 2) high TSAb levels before 131I are associated with a relative resistance to therapy; 3) a postradioiodine increase in TSAb levels is related to the development of hypothyroidism; and 4) the concomitant appearance of TSHBAb and disappearance of TSAb are not frequent after 131I and play a role in the development of early postradioiodine hypothyroidism only in a minority of patients.

Topics: Adult; Aged; Antithyroid Agents; Autoantibodies; Female; Follow-Up Studies; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Immunoglobulins, Thyroid-Stimulating; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Thyroid Gland; Thyrotropin; Time Factors; Ultrasonography

We report on a 3-year-old boy with bilateral choanal atresia, hypoplastic nipples, and developmental delay who had been exposed to carbimazole in utero because of maternal Graves disease. His combination of abnormalities and facial appearance strongly resembles that of a previously reported child exposed to methimazole (which is the active metabolite of carbimazole) in utero. We suggest that this represents a rare but distinct syndrome of methimazole teratogenicity, probably related to first-trimester exposure. Recognition of such teratogenic effects is clearly important for genetic counselling and for management of subsequent pregnancies.

Topics: Abnormalities, Multiple; Antithyroid Agents; Child, Preschool; Choanal Atresia; Chromosomes, Human, Pair 22; Face; Female; Graves Disease; Hearing Loss; Humans; In Situ Hybridization, Fluorescence; Male; Methimazole; Muscle Hypotonia; Nipples; Pregnancy; Pregnancy Complications; Teratogens

The case presented is a 12 year-old girl with hyperthyroidism due to juvenile Grave's disease, who during the course of treatment developed hypothyroidism due to TSH-receptor blocking antibodies, measured by bioassay. The bioassay used was performed on CHO-R cells measuring c-AMP. The role of radioreceptor assays and bioassays in measuring TSH receptor antibodies in hyper- and hypothyroid Graves' disease in discussed.

Topics: Age Factors; Antibodies, Blocking; Antithyroid Agents; Child; Female; Graves Disease; Humans; Hypothyroidism; Methimazole; Receptors, Thyrotropin; Thyroxine

We describe a 75-year-old man who had had a lump in his neck for about 15 years. At his first visit to our hospital, poorly differentiated papillary carcinoma of the thyroid was diagnosed by means of aspiration cytology; x-rays revealed the presence of lung metastases. He was thyrotoxic with positive thyroid stimulating antibody (TSAb). He was reluctant to undergo surgery. In an early stage of the treatment for Graves' disease, he became hypothyroid with decreased TSAb activity and strongly positive thyroid stimulation blocking antibody (TSBAb), and rapid growth of the thyroid carcinoma with anaplastic transformation was observed. The increase in the size of the transformed thyroid carcinoma was shown to be exponential by ultrasonography. This is a rare case in which anaplastic transformation of the thyroid papillary carcinoma became apparent during treatment of Graves' disease with varied activity of thyrotropin receptor antibodies.

Topics: Aged; Antibodies; Antithyroid Agents; Carcinoma; Carcinoma, Papillary; Graves Disease; Humans; Hypothyroidism; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Receptors, Thyrotropin; Thyroid Neoplasms; Ultrasonography

Topics: Adult; Antithyroid Agents; Arthritis; Female; Graves Disease; Humans; Methimazole

Thyroidal and orbital lymphocytic infiltration in Graves' disease, as well as identification of somatostatin receptors on lymphocytes, has provided a rationale for receptor imaging with the radiolabeled somatostatin analog pentetreotide. Recently, we demonstrated that in contrast to controls, Graves' patients showed markedly increased orbital accumulation of pentetreotide. Longitudinal and follow-up data are presented here.. In 20 (16 hyperthyroid) Graves' patients with active eye disease, planar (thyroid) and SPECT (orbit) images were performed 4 and 24 hr after injection of 111In-pentetreotide (222 MBq) before and 3 mo after starting antithyroid and combined steroid and orbital radiotherapy.. Thyroidal uptake decreased during methimazole treatment (4 hr postinjection, median: hyperthyroid 989 counts/pixel/MBq injected activity, euthyroid 253 counts, p = 0.001; 24 hr, 437 versus 95 counts/pixel/MBq, p = 0.005). Fourteen patients (70%) responded to steroid and radiotherapy. The pentetreotide orbit-to-brain ratio decreased markedly after completion of therapy (4 hr: 25 before versus 6.2 after therapy, p = 0.0003; 24 hr: 9.6 versus 2.7, p = 0.003). A high pretreatment ratio correlated with a response to therapy (p = 0.001: in 14 of 16 patients with a ratio > 10, 4 hr postinjection, ophthalmopathy improved; positive predictive value: 90%; median activity score before 6 versus 2 after therapy, p = 0.0001) in contrast to none of the four cases with a ratio less than 10 (score 5 versus 4, p = 0.08).. Pentetreotide scans may be regarded as a semiobjective tool in the evaluation of Graves' disease, both at initial stages as well as during treatment.

Topics: Anti-Inflammatory Agents; Antithyroid Agents; Cobalt Radioisotopes; Female; Follow-Up Studies; Graves Disease; Humans; Indium Radioisotopes; Longitudinal Studies; Male; Methimazole; Middle Aged; Predictive Value of Tests; Prednisolone; Prospective Studies; Radioisotope Teletherapy; Radiopharmaceuticals; Receptors, Somatostatin; Sensitivity and Specificity; Somatostatin; Tomography, Emission-Computed, Single-Photon

Clinical evaluation was conducted to ascertain whether thyrotropin receptor antibody (TRAb) in the normal range may still be involved in the regulation of thyroid function after prolonged treatment for Graves' disease. All patients (n = 33) were treated with antithyroid drugs for an average of 10.6 years and were under euthyroid conditions in which normal blood levels of tri-iodothyronine (T3) were significantly correlated with blood thyrotropin (TSH) levels, but not with titers of TRAb. A significant correlation was observed between TRAb titer and thyroid-stimulating antibody (TSAb) activity. In contrast, this correlation was not found in normal subjects. After administration of T3 (75 microg daily for 8 days), the patients showed increased levels of T3 with concomitant suppression of TSH levels. Under these conditions, linear regression analysis showed significant correlations of TRAb titer and TSAb activity with 24-h thyroid radioiodine uptake (r = 0.641 and 0.621 respectively, P < 0.01), in contrast to declining blood thyroxine levels. Moreover, the immunoglobulin G (IgG) of the patients precipitated to a greater extent than IgG from normal subjects a peptide consisting of the amino acid sequence near the terminus of the human TSH receptor. These findings indicated that TRAb at normal levels possessed significant unremitting activities on thyroid function despite long-term treatment in euthyroid patients with Graves' disease.

Topics: Adult; Aged; Antithyroid Agents; Female; Graves Disease; Humans; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Precipitin Tests; Propylthiouracil; Receptors, Thyrotropin; Thyroid Function Tests; Thyrotropin; Thyroxine; Triiodothyronine

Agranulocytosis is a serious side effect of anti-thyroid drugs (ATD). Granulocyte colony-stimulating factor (G-CSF) is one of the cytokines that increase granulocyte number. The aim of this study was to examine the sequential variation of serum G-CSF levels in patients with Graves' disease before and after ATD therapy.. Sixty-three patients with Graves' disease were studied before, during and after treatment with methimazole (MMI). Serum samples from 71 healthy subjects were used as controls.. Serum levels of G-CSF were measured by a novel chemiluminescent enzyme immunoassay, which was sensitive enough to determine G-CSF levels in healthy subjects. Blood granulocyte counts, serum, thyroid hormone and TSH levels, and titres of thyroid autoantibodies were also measured.. Serum G-CSF levels in Graves' patients before and 2 weeks after MMI were significantly higher than in healthy subjects. There was a significant correlation between serum G-CSF levels and granulocyte counts in untreated patients with Graves' disease. Untreated patients with granulocyte counts less than 2 x 10(9)/I had significantly lower serum G-CSF levels as compared with other untreated patients. Serum G-CSF levels gradually decreased thereafter. No correlation was observed between serum G-CSF levels and serum thyroid hormone levels or titres of thyroid autoantibodies. After ATD treatment, no correlation was found between serum G-CSF levels and granulocytes counts. There was no significant correlation between the change of serum G-CSF levels and that of granulocyte counts before and after MMI treatment. Graves' patients with mild agranulocytosis had normal or elevated serum G-CSF levels.. Significantly elevated serum G-CSF levels were observed in patients with Graves' hyperthyroidism. During ATD therapy, deficiency of G-CSF was not identified as a cause of agranulocytosis in this study.

Topics: Adult; Antithyroid Agents; Autoantibodies; Female; Granulocyte Colony-Stimulating Factor; Granulocytes; Graves Disease; Humans; Immunoenzyme Techniques; Leukocyte Count; Luminescent Measurements; Male; Methimazole; Middle Aged; Thyroid Hormones

This study investigated T-cell activation markers HLA-DR and CD69 in both naive (CD45RA+) and memory (CD45RA-) CD4+ as well as CD8+ T cells in peripheral blood of patients with autoimmune thyroiditis (AT, N = 28) or hyperthyroid untreated Graves' disease (GDH, N = 34) using three-color flow cytometry. It was demonstrated that patients with AT, but not those with GDH, expressed increased amounts of HLA-DR antigen compared to healthy subjects (HS, N = 26) on total CD4+ (AT: 14.1%; GDH: 11.3%; HS: 10.9%) and CD8+ cells (AT: 31.9%; GDH: 23.5%; HS: 19.4%) as well as on CD45RA- CD4+ cells (AT: 11.2%; GDH: 7.7%; HS: 7.9%). In GDH (+71%) and AT (+91%) only the proportion of HLA-DR+ CD45RA+ CD8+ cells was increased vs HS. Furthermore, euthyroid GD patients on methimazole (GDE, N = 22) displayed greater HLA-DR+ expression on total and CD45RA- cells within both CD4+ (+37 and 40%, respectively) and CD8+ cells (+47 and 93%, respectively) than GDH. In addition, total and CD45RA+ CD4+ and CD8+ cells were increased vs HS. In contrast, proportions of CD69 positive T cells were increased in AT and GDH on total CD4+ (+97 and 74%, respectively) and CD8+ (+95 and 68%, respectively) cells and all subsets thereof (except for CD45RA- cells in GDH), but normalized upon thyrostatic treatment. We conclude that patients with autoimmune thyroid disease harbor an almost twofold greater proportion vs HS of (a) HLA-DR+ CD45RA+ CD8+ T cells, and of (b) CD69 on total CD4+ and CD8+ cells, and an even more marked elevation on their CD45RA+ subset in AT and untreated GD. In addition, (c) thyrostatic treatment by methimazole in GD is accompanied by a further increase in circulating HLA-DR+ CD4+ and CD8+ cells and their CD45RA- subsets, but decreased CD69 expression. These data suggest association of HLA-DR expression with ongoing autoimmunity, while increased CD69 expression relates in part also to elevated thyroid hormone concentration in GDH.

Topics: Adult; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; Antithyroid Agents; Autoimmune Diseases; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Female; Graves Disease; HLA-DR Antigens; Humans; Lectins, C-Type; Leukocyte Common Antigens; Lymphocyte Activation; Male; Methimazole; Middle Aged; Thyroid Diseases

We evaluated the concentration of epidermal growth factor (EGF) in platelets, serum and plasma obtained from 47 patients with Graves' disease, 7 with hypothyroidism and 20 healthy subjects. The platelets of the subjects were collected from platelet rich plasma and lysed by freezing and thawing. Subsequently the platelet debris was treated with Triton X-100. The EGF concentration was determined by homologous radioimmunoassay. The concentration of EGF in the platelets in 14 patients with untreated Graves' disease was significantly higher than that in the healthy controls. After treating these 14 patients with antithyroid agents, the EGF concentration in the platelets decreased to the level of the healthy controls. The EGF concentration in the platelets in the 7 untreated hypothyroid patients decreased after replacement therapy with thyroxine. The mean volume of the platelets in the 14 patients with untreated Graves' disease was significantly larger than in the control and decreased after treatment with antithyroid agents. The serum and plasma levels of EGF in the 7 untreated hypothyroid increased after replacement therapy. In conclusion, thyroid function affected the concentration of EGF in the platelets of patients with thyroid disorders.

Topics: Adult; Blood Platelets; Epidermal Growth Factor; Female; Graves Disease; Humans; Hypothyroidism; Male; Methimazole; Middle Aged; Platelet Count; Propylthiouracil; Thyroid Diseases; Thyroxine

Graves' disease is an autoimmune disorder characterized by the presence of antibodies against thyrotropin receptor (TRAb). Stem cell factor (SCF), derived from bone marrow, is known to promote lymphohematopoiesis. To investigate the relation between the alteration in plasma levels of SCF, thyroid hormone status, and TRAb measured by thyrotropin binding inhibition (TBI), 13 untreated, 21 treated, and 4 relapsed hyperthyroid Graves' disease patients, 21 patients with Hashimoto's thyroiditis, 6 patients with subacute thyroiditis, and 11 control subjects were examined. In untreated hyperthyroid Graves' disease patients, serum levels of thyroxine (T4) and triiodothyronine decreased rapidly by methimazole treatment, and TBI decreased progressively, but variably. Simultaneously, the elevated plasma levels of SCF decreased gradually and progressively. The plasma levels of SCF correlated curvilinearly with the serum levels of T4. In 4 patients with relapsed hyperthyroid Graves' disease, TBI was marginally positive in 3 patients and negative in 1, but plasma levels of SCF were elevated significantly in all 4 patients. In patients with subacute thyroiditis and Hashimoto's thyroiditis with or without T4 replacement, plasma levels of SCF did not differ from that of controls. These findings indicate that the elevation of plasma levels of SCF relates to the longstanding thyrotoxic state and that short-term thyrotoxicosis does not significantly affect plasma levels of SCF. It remains to be determined whether the elevation in plasma levels of SCF is induced by excess thyroid hormone, reflecting the hypermetabolic state, or whether the elevation of plasma levels of SCF contributes to stimulation of lymphocytes producing TRAb.

Topics: Acute Disease; Adolescent; Adult; Aged; Antithyroid Agents; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Recurrence; Stem Cell Factor; Thyroid Gland; Thyroiditis; Thyroiditis, Autoimmune

Topics: Antithyroid Agents; Exophthalmos; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Prednisone

Topics: Adrenergic beta-Antagonists; Antithyroid Agents; Atenolol; Chronic Disease; Diagnosis, Differential; Drug Therapy, Combination; Female; Graves Disease; Humans; Methimazole; Middle Aged; Thyrotoxicosis

Power spectral analysis (PSA) of the variation in heart rate is useful in determining the relative activity of the sympathetic and parasympathetic nerves. In this study, PSA was used to investigate the relationship between abnormalities in autonomic nerve function and the presence of thyroid disorders in patients with autoimmune thyroid diseases. The low frequency (LF) or high frequency (HF) components of R-R variations were determined by PSA. The coefficient of variation of the R-R time intervals (CV(R-R)) was positively correlated with HF in healthy subjects. In untreated hyperthyroid patients with Graves' disease, the CV(R-R) and HF values were significantly lower than in healthy controls. Moreover, the LF/HF ratio in patients with untreated Graves' disease was significantly higher, and the LF/HF ratio in hypothyroid patients with Hashimoto's thyroiditis was significantly lower than in healthy controls. A negative correlation was observed between serum levels of free thyroid hormones (FT4 and FT3) and HF in Graves' disease patients. In some hyperthyroid patients, antithyroid drug therapy or beta-blocker administration gradually restored reduced HF values. Present results suggest that relative vagal nerve activity is reduced in hyperthyroid patients and that this reduction is reversible according to the decrease in serum levels of thyroid hormones.

Topics: Adrenergic beta-Antagonists; Adult; Antithyroid Agents; Autonomic Nervous System; Female; Graves Disease; Heart Rate; Humans; Male; Methimazole; Middle Aged; Propranolol; Sympathetic Nervous System; Thyroiditis, Autoimmune; Thyrotropin; Triiodothyronine

The major adverse reactions of antithyroid drugs are hematologic; aplastic anemia (AA) is one of the rarest and most severe complications. Use of recombinant human hemopoietic colony-stimulating factor was reported to be of benefit in patients who developed agranulocytosis, although there is still some doubt regarding the efficacy in AA. We present a case of a 58-year-old female patient with Graves' disease who developed AA in the third exposure to methimazole (MMI). The withdrawal of MMI and early treatment with 5 microg/kg per day recombinant human granulocyte colony-stimulating factor (G-CSF) for 9 days, allowed a favorable recovery of peripheral blood cell count. We conclude that the use of hemopoietic colony stimulating factors might be a suitable means to achieve the correction of severe thionamide-induced hematologic adverse reactions.

Topics: Anemia, Aplastic; Blood Cells; Bone Marrow; Female; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Methimazole; Middle Aged; Recombinant Proteins

Two cases are reported in which a rare hyperthyroidism appeared: in a female after radioiodine therapy for toxic multinodular goiter and in a male after spontaneous regression of a toxic adenoma. Both subjects showed a relapse of hyperthyroidism after a period of well-being lasting almost eight months in the first and three years in the second. Thyroid scans were consistent with an immunogenic hyper-thyroidism because there was a diffuse trapping of 131I in the thyroids while the previous autonomously functioning nodules became "cold". Serum TSH was undetectable, free thyroid hormones were increased, TgAb and TRAb were always normal in both patients, TPO became moderately positive only in the female. TRAb were evaluated only by radioimmunoassay. In these patients a diagnosis of Graves'-like disease was made because of the clinical and scintigraphic pattern. Moreover US did not reveal nodular areas different from those highlighted by scans. None of the subjects developed ophthalmopathy and/or dermopathy. Our remarks show that in particular subjects, genetically susceptible to autoimmunity, the release of antigenic materials secondary to destruction of thyroid nodules can trigger an autoimmune thyroid response resembling Graves' disease. Therefore all patients carrying autonomous nodules should be carefully evaluated for a possible autoimmune disposition before treatment and after admission. Radionuclide imaging is a simple, reliable, non invasive technique which can be applied in the evaluation of the etiology of the relapses.

Topics: Adenoma; Aged; Antithyroid Agents; Autoimmune Diseases; Female; Goiter, Nodular; Graves Disease; Humans; Male; Methimazole; Middle Aged; Radionuclide Imaging; Thyroid Neoplasms

Previous studies of leptin in thyrotoxic human subjects have been short-term and cross-sectional. We have measured serum leptin concentrations in thyrotoxic patients in order to study the influence of endogenous thyroid hormones on the relationship between serum leptin and fat mass. DESIGN PATIENTS, MEASUREMENTS: In 10 fasting thyrotoxic patients (8 females, 2 males, mean age: 51 years) we measured serum leptin (microgram/l), total thyroxine (TT4), total triiodothyronine (TT3), thyrotropin (TSH) and by Dual Energy X-ray Absorptiometry (DEXA) total fat mass (TFM, kg) at time of diagnosis (0 months, baseline) and during 12 months treatment with thiamazole. For comparison 16 fasting thiamazole-treated euthyroid patients (14 females, 2 males, mean age: 38 years) were studied after one year follow-up (26 months (15-48)) and 18 normal controls (12 females, 6 males, mean age: 39 years).. The serum leptin concentration was 9.1 (1.3 micrograms/l (mean (SEM) in the thyrotoxic patients and increased significantly to 16.0 (1.3 micrograms/l (P < 0.0005) after 12 months treatment compared to both normal subjects and their own baseline. There was a significant correlation between serum leptin concentration and TFM in the normal control group (r = 0.79, P < 0.00009), in the thiamazole-treated euthyroid group (r = 0.85, P < 0.00003) and in the baseline thyrotoxic group (r = 0.84, P < 0.002) but the serum leptin/TFM ratio increased significantly during 12 months of antithyroid drug treatment from 0.34 (1.2 micrograms/l/kg to 0.53 (1.2 micrograms/l/kg (P < 0.03).. The thiamazole-treated thyrotoxic patients increased their serum leptin concentrations during 12 months antithyroid drug treatment without a significant corresponding degree of changes in TFM as expected from normal controls. It is suggested that the metabolic state in thyrotoxic patients can influence the regulation of serum leptin concentrations without any associated changes in TFM.

Topics: Adult; Aged; Antithyroid Agents; Body Composition; Female; Follow-Up Studies; Graves Disease; Humans; Leptin; Male; Methimazole; Middle Aged; Proteins; Statistics, Nonparametric; Thyroid Hormones

To investigate the effect of hyperthyroidism on respiratory muscle function and its possible mechanism, the thyroid function, serum enzymology, serum potassium, pulmonary function and respiratory muscle function were examined in 60 patients with Grave's disease before treatment and 26 patients among them after treatment, and 20 normal subjects as control. T3, T4, and FT4 increased while FVC and PImax, which reflect the respiratory muscle strength, and Pi/PImax, which reflects the reserve capacity of inspiratory muscle, decreased significantly in the 60 patients with Grave's disease, compared with the ones of normal subjects. The comparison of above measurements in the 26 patients between before- and after-treatment showed that respiratory muscle strength increased obviously along with the improvement of throid function. The serum enzymology, potassium and TSH, however, were not abnormal and not changed after treatment. The thyroid functions in 10 patients with hyperthyroid heart disease were not different, compared with the ones of other 50 patients without hyperthyroid heart disease, but their respiratory muscle strength was significantly lower than the ones of latter. The above results suggested that hyperthyroidism could lead to significant decrease of respiratory muscle strength and its reserve capacity, whereas treatment for hyperthyroidism would improve respiratory muscle function, so the measurement of respiratory muscle function in hyperthyroidism cases might be useful in prediction of hyperthyroid heart disease.

Topics: Adult; Aged; Antithyroid Agents; Creatine Kinase; Female; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Respiratory Function Tests; Respiratory Muscles; Thyroid Gland

To analyse the routine WBC count's effect on predicting antithyroid drugs-induced agranulocytosis developing and risk factors of antithyroid drugs-induced agranulocytosis.. Retrospective analysis of 18 Graves' cases with agranulocytosis induced by antithyroid drugs during 1984-1995.. Most of antithyroid drugs-induced agranulocytosis happens 2-12 weeks after the administration of antithyroid drug, and are related with the drug's doses. Some agranulocytosis happens abruptly, routine WBC and granulocyte count can not predict some agranulocytosis developing. Fever and throat sore are the intitial symptoms of agranulocytosis, if it happens, the WBC and granulocyte count must be checked immediately. The treatment of granulocyte-macrophage colony stimulating factor is effective, the corticosteroid therapy seems not to be useful for the recovery of granulocyte count.

Topics: Adult; Agranulocytosis; Antithyroid Agents; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Propylthiouracil; Retrospective Studies

Topics: Adult; Antithyroid Agents; Graves Disease; Humans; Kidney Failure, Chronic; Male; Methimazole; Pancytopenia; Propylthiouracil

A report is presented of a girl with Graves' disease, which was diagnosed at the age of 1.7 years. The mother had no thyroid disease. The patient developed signs of hyperthyroidism shortly before her first birthday, and the most prominent manifestations were accelerated skeletal maturation and linear growth, and dilatation of the brain ventricles. The latter manifestation, which has not been reported previously, was reversible upon normalisation of thyroid function with antithyroid treatment for three years.

Topics: Adrenergic beta-Agonists; Antithyroid Agents; Brain Diseases; Cerebral Ventricles; Child, Preschool; Dilatation, Pathologic; Drug Therapy, Combination; Female; Graves Disease; Growth Disorders; Humans; Infant; Methimazole; Propranolol; Treatment Outcome

We describe 4 patients with Graves disease who had abnormal increases of serum creatine kinase (CK) concentrations during treatment with antithyroid medications. Three of the patients experienced myalgia and muscle cramps. All of the patients manifested an increase in serum CK levels 1 to 3 months after the administration of antithyroid drugs. Thyrotropin concentrations and cardiac systolic time indexes during the elevation of serum CK concentrations were not consistent with hypothyroidism. The mechanisms are not obvious, but it is likely that the rapid decrease of thyroid hormones in tissues may temporarily cause hypothyroid states, resulting in alterations in CK concentrations. It is suggested that hasty correction of thyrotoxicosis should be avoided in susceptible patients, unless the thyrotoxic conditions are critical.

Topics: Adult; Antithyroid Agents; Creatine Kinase; Female; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Thyroid Hormones

A 38-year-old caucasian woman developed typical Graves' hyperthyroidism and ophthalmopathy while being chronically treated for pemphigus vulgaris with low doses of glucocorticoids capable of effectively controlling skin disease. HLA typing showed positivity for DR3 and DR4, suggesting a genetic susceptibility for both Graves' disease and pemphigus vulgaris. The apparent contradiction whereby thyroid autoimmune disease flared up during therapy with glucocorticoids, known for their immunosuppressive effects, may be related to the dose of steroids. It is possible that high doses of glucocorticoids, commonly employed in the treatment of severe Graves' ophthalmopathy, might indeed suppress the disease, whereas the low doses used in this patient might precipitate or aggravate it.

Topics: Adult; Drug Administration Schedule; Female; Graves Disease; Humans; Iodine Radioisotopes; Methimazole; Pemphigus; Prednisone; Thyroid Function Tests

Cryofibrinogenemia is a cryopathy in which hypersensitivity to cold is a prominent feature. Cryofibrinogenemia developed in an 18-year-old Japanese female patient during methimazole therapy for Graves' disease. She developed cryopathy (livedo reticularis, Raynaud's phenomenon and acral ulcer) and polyarthralgia during methimazole therapy, and we detected cryofibrinogen in her plasma. Her symptoms resolved after administration of prostaglandins and anticoagulants. Several reports indicate that methimazole therapy induces autoantibody-related disease. In the present case, we cannot exclude the possibility that methimazole therapy contributed to the cryofibrinogenemia.

Topics: Adolescent; Anticoagulants; Antithyroid Agents; Arthralgia; Cryoglobulins; Female; Fibrinogens, Abnormal; Foot Ulcer; Graves Disease; Humans; Methimazole; Prostaglandins, Synthetic; Raynaud Disease; Skin Diseases, Vascular

Topics: Aged; Agranulocytosis; Antithyroid Agents; Female; Fever; Graves Disease; Humans; Methimazole; Pharyngitis

Retroocular fibroblast proliferation is believed to be a key component in the pathogenesis of Graves' ophthalmopathy. In the present study, we assessed the ability of superoxide radicals, generated using the xanthine oxidase/hypoxanthine system to induce cellular proliferation in cultured human retroocular fibroblasts obtained from two patients with severe Graves' ophthalmopathy and two control patients undergoing corrective eye surgery. In tissue obtained from patients with Graves' ophthalmopathy, fibroblast proliferation, as assessed by [3H]-thymidine incorporation, was induced by superoxide radicals in a dose-dependent manner. Xanthine oxidase or hypoxanthine alone had no proliferative effect, and control retroocular fibroblasts showed no proliferation in response to superoxide generation. Preincubation with the antithyroid drug methimazole, at concentrations ranging from 0-25 microM, prevented superoxide-induced fibroblast proliferation in a dose-response pattern. Preincubation with the xanthine oxidase inhibitor, allopurinol (1.0 mM) or the antioxidant nicotinamide (10 microM) also inhibited superoxide-induced fibroblast proliferation, whereas propylthiouracil (10 microM) had little effect. These studies suggest a pathway through which oxygen free radicals may contribute to the retroocular fibroblast proliferation observed in patients with Graves' ophthalmopathy.

Topics: Allopurinol; Analysis of Variance; Antioxidants; Antithyroid Agents; Cell Division; Connective Tissue; Dose-Response Relationship, Drug; Enzyme Inhibitors; Fibroblasts; Graves Disease; Humans; Methimazole; Niacinamide; Reactive Oxygen Species; Smoking; Superoxides; Xanthine Oxidase

Amiodarone-induced thyrotoxicosis (AIT) occurs both in abnormal thyroid glands (nodular goiter, latent Graves' disease) (type I AIT) or in apparently normal thyroid glands (type II AIT). Differentiation of the two forms is crucial, because type I AIT responds well to methimazole and potassium perchlorate combined treatment, whereas type II AIT is effectively managed by glucocorticoids. Differential diagnosis is often difficult, although thyroid radioactive iodine uptake is usually low-to-normal in type I and low-suppressed in type II, and serum interleukin-6 levels are normal/slightly elevated in type I, markedly elevated in type II. Color flow Doppler sonography (CFDS) is a technique that shows intrathyroidal blood flow and provides real-time information on thyroid morphology and hyperfunction. To investigate the usefulness of CFDS in differentiating the two types of AIT, 27 consecutive AIT patients, 11 type I and 16 type II, were evaluated by CFDS before starting antithyroid treatment. Gender, age, severity of thyrotoxicosis, and cumulative amiodarone dose were similar in the two groups. All type II AIT patients had a CFDS pattern 0 (ie, absent vascularity), in agreement with the pathogenesis of the disease, due to thyroid damage. Likewise, nine patients with subacute thyroiditis, another destructive process of the thyroid gland, also had a CFDS pattern 0. Eleven patients with type I AIT had a CFDS pattern ranging from pattern I (presence of parenchymal blood flow with patchy uneven distribution) (7 patients, 64%) to pattern II (ie, mild increase of color flow Doppler signal with patchy distribution) (1 patient, 9%) and pattern III (markedly increased color flow Doppler signal with diffuse homogeneous distribution)(3 patients, 27%), similar to that found in patients with untreated Graves' disease patients, thus indicating a hyper-functioning gland. Control subjects and euthyroid patients under long-term amiodarone treatment had absent thyroid hypervascularity and a CFDS pattern 0. These findings demonstrate that CFDS distinguishes type I and II AIT. Because of its rapidity and noninvasive features, CFDS represents a valuable tool for a quick differentiation between the two types of AIT. This can avoid any delay in initiating the appropriate treatment for a rapid control of thyrotoxicosis in patients whose tachyarrhythmias or other cardiac disorders make thyroid hormone excess extremely deleterious.

Topics: Adult; Aged; Amiodarone; Antithyroid Agents; Diagnosis, Differential; Female; Glucocorticoids; Goiter, Nodular; Graves Disease; Humans; Male; Methimazole; Middle Aged; Perchlorates; Potassium Compounds; Thyrotoxicosis; Ultrasonography, Doppler, Color

This prospective study was designed to investigate the usefulness of granulocyte count measurements 4 hours after injection of granulocyte colony-stimulating factor (G-CSF) for detecting recovery from antithyroid drug (ATD)-induced granulocytopenia or agranulocytosis. Granulocyte and white blood cell counts were measured 4 hours and 24 hours after patients with ATD-induced granulocytopenia had been given an injection of 75 micrograms of G-CSF (1.1 to 1.9 micrograms/kg; 1.5 +/- 0.2 micrograms/kg [mean +/- standard deviation]). Thirty-seven patients were studied and divided into three groups based on their initial granulocytopenic granulocyte count: 28 with mild (granulocyte count 0.501 to 1.0 x 10(9)/L), 6 with moderate (granulocyte count 0.101 to 0.5 x 10(9)/L), and 3 with severe (granulocyte count less than 0.1 x 10(9)/L) ATD-induced granulocytopenia. Twenty-five of the 28 patients with mild granulocytopenia and 4 of the 6 patients with moderate granulocytopenia were found to have recovered from the granulocytopenia both 4 hours and 24 hours after injection, and their granulocyte counts remained normal thereafter. However, the other 3 patients with mild granulocytopenia, 2 patients with moderate granulocytopenia, and all 3 patients with severe granulocytopenia had not recovered by either 4 or 24 hours after the G-CSF injection. Despite daily G-CSF injections, the granulocyte continued to decrease in most cases. It took 2 to 11 days for these counts to recover from granulocytopenia. These results indicate that granulocyte count measurement 4 hours after injection of G-CSF is useful for detecting recovery from ATD-induced granulocytopenia or agranulocytosis and for predicting disease severity. Accordingly, its measurement enables physicians to make an appropriate decision about whether a patient with ATD-induced granulocytopenia should be treated in the hospital or in the outpatient clinic.

Topics: Adolescent; Adult; Agranulocytosis; Antithyroid Agents; Female; Granulocyte Colony-Stimulating Factor; Granulocytes; Graves Disease; Humans; Kinetics; Leukocyte Count; Male; Methimazole; Middle Aged; Propylthiouracil; Prospective Studies

We report here a patient with recurrent Graves' disease on hemodialysis. She also suffered from angina pectoris, which was probably a manifestation of Graves' disease due to the increased oxygen demands in the presence of fixed coronary lesions. Although antithyroid drugs induced mild granulocytopenia, propylthiouracil (PTU) or methimazole (MMI) was not discontinued during the administration of granulocyte colony-stimulating factor (G-CSF). The patient received sodium iodine-131 therapy, and became euthyroid with no chest pain. To our knowledge, this is the first case that illustrated the usefulness of G-CSF for antithyroid drug-induced granulocytopenia prior to thyroid ablation for Graves' disease complicated with chronic renal failure and angina pectoris.

Topics: Agranulocytosis; Angina Pectoris; Antithyroid Agents; Female; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Iodine Radioisotopes; Kidney Failure, Chronic; Methimazole; Middle Aged; Propylthiouracil; Renal Dialysis

Abnormal bone metabolism in patients with Graves' thyrotoxicosis is well documented, but the precise time-course of its recovery remains poorly understood. The present study was undertaken to clarify longitudinal improvement in bony manifestations, especially in cortical bone, and bone metabolic markers in thyrotoxicosis.. Two year prospective follow-up study in patients with Graves' disease.. Ten consecutive patients with Graves' disease (seven males and three females, of mean (+/-SEM) age 39.3 +/- 3.9 years) were enrolled in the study and treated with antithyroid drugs. Thirteen sex- and age-matched patients with the disease in remission served as controls.. Bony manifestations were evaluated both by fine cortical bone striations in the metacarpals on magnified roentgenograms and lumbar bone mineral density (BMD) measurement. Urinary deoxypyridinoline (dPYR) and serum pyridinoline cross-linked telopeptide domain of type I collagen (ICTP) were monitored as markers of bone resorption, as well as serum osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (PICP) and alkaline-phosphatase (ALP) as markers of bone formation.. Initial elevated free thyroid hormone levels were normalized within a month of starting therapy. Striation indices of the metacarpals were 1.89 +/- 0.16 before therapy, higher than those of 0.49 +/- 0.12 in the controls (P < 0.0001); the indices gradually decreased to 1.00 +/- 0.20 (12 months) and 0.48 +/- 0.12 (24 months). Lumbar BMD Z-scores increased from -0.22 +/- 0.46 to 0.21 +/- 0.47 (12 months) and 0.68 +/- 0.48 (24 months) (P = 0.0029). Before therapy, urinary dPYR and serum ICTP concentrations were much higher than the control values (dPYR, +553%; ICTP, -396%, P < 0.0001), which declined promptly in the 2nd month. Serum OC, PICP and ALP were also significantly higher than in controls at first (OC, +287%; PICP, +225%; ALP, +196%), and remained elevated until 4 or 8 months.. Bone resorption and cortical bone striations occur in untreated patients with Graves' thyrotoxicosis. The bone resorption rapidly ameliorates after normalization of thyroid hormone levels. In contrast, the accelerated bone formation persists for at least 4-8 months, suggesting positive uncoupling of bone remodelling. This dominant bone formation could result in the improvement in cortical bone striations and the increase in bone mineral density of trabecular bone.

Topics: Adolescent; Adult; Alkaline Phosphatase; Amino Acids; Antithyroid Agents; Biomarkers; Bone and Bones; Collagen; Collagen Type I; Female; Follow-Up Studies; Graves Disease; Humans; Male; Methimazole; Middle Aged; Osteocalcin; Peptide Fragments; Peptides; Procollagen; Prospective Studies

Thionamide therapy is a mainstay of the treatment of hyperthyroidism complicated by pregnancy, but it can expose the fetus to hypothyroidism. In terms of fetal thyroid status, propylthiouracil (PTU) has been preferred over methimazole (MMI) based on experimental data on limited transplacental passage, and lower doses have been recommended. However, neither of these practices is supported by convincing clinical evidence. We compared the effect of maternal ingestion of PTU with that of MMI on fetal thyroid status using cord sera at delivery in 77 mothers with Graves' hyperthyroidism who were receiving thionamides and whose free T4 (FT4) levels were within the normal range. We also examined the dose effects on fetal thyroid status in these women. Thirty-four women were taking PTU (group P), and 43 were taking MMI (group M). Neither the mean fetal FT4 nor the mean fetal TSH level was significantly different between the two groups. No significant difference in the occurrence of low FT4 levels or high fetal TSH levels was found between group P and group M (low FT4, 6% vs. 7%; high TSH, 21% vs. 14%). Little relationship was observed between maternal doses and fetal thyroid status; in fact, when low doses of both PTU (100 mg daily or less) and MMI (10 mg daily or less) were administered, high TSH levels in the fetus were observed in 7 of the 34 fetuses (21%) and in 6 of the 43 fetuses (14%), respectively. Higher doses were associated with normal or low fetal TSH levels. These findings demonstrate that in terms of fetal hypothyroidism-inducing potential, there is little reason to choose PTU over MMI. Individualized, not uniformly low, doses of these drugs may prevent fetal hypothyroidism.

Topics: Female; Fetal Blood; Fetal Diseases; Graves Disease; Humans; Hypothyroidism; Maternal-Fetal Exchange; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyrotropin; Thyroxine

Collagen type I is the main collagen type found in bones. Carboxyterminal propeptide, deriving and cleaved from procollagen type I (PICP) during collagen synthesis, is delivered into the blood, where it might represent an useful marker of bone formation similarly to osteocalcin. PICP, osteocalcin, alkaline phosphatase, serum and urinary calcium excretion were measured in 58 premenopausal females affected by Graves' disease and also 28 of them after attainment of euthyroidism by methimazole treatment to study these biochemical indices of bone remodelling before and after treatment. Before therapy PICP (mean +/- S.D.: 244.2 +/- 112.3 vs. 136.8 +/- 32.4 micrograms/l), osteocalcin (mean +/- S.D.: 17.8 +/- 6.7 vs. 7.5 +/- 2.7 micrograms/l) and other markers were significantly (p < 0.05) higher than sex and age matched controls (n = 24). Treatment induced a significant decrease of PICP, alkaline phosphatase, calcaemia and calciuria compared to pretreatment values, while osteocalcin did not significantly differ (mean +/- S. D.: 17.8 +/- 6.7 vs. 14.7 +/- 8.7 micrograms/l). These data suggest that hyperthyroidism due to Graves' disease causes an increase of serum levels of these markers, but further studies are necessary to asses the differences between PICP and osteocalcin as markers of osteoblast activity in hyperthyroidism.

Topics: Adult; Alkaline Phosphatase; Bone and Bones; Calcium; Female; Graves Disease; Humans; Male; Methimazole; Osteoblasts; Osteocalcin; Peptide Fragments; Procollagen

We recently observed 2 lactase-deficient women with Graves' disease who consistently developed severe diarrhea after ingestion of thionamide (methimazole and propylthiouracil) tablets containing lactose as carrier. The strict temporal relationship between ingestion of lactose-containing tablets and appearance of intestinal symptoms, as well as the absence of side effects following ingestion of methimazole tablets without lactose as carrier, provided the clue for the diagnosis. To our knowledge, severe diarrhea resulting from carrier lactose has not been previously reported for antithyroid drugs, and should be considered in occasional cases of patients with gastrointestinal symptoms on thionamide therapy.

Topics: Adult; Antithyroid Agents; beta-Galactosidase; Diarrhea; Drug Carriers; Female; Graves Disease; Humans; Lactase; Lactose; Lactose Intolerance; Methimazole; Propylthiouracil

At present, the in vivo response of T, B and natural killer (NK) cells to antithyroid drug therapy remains largely unknown. In the present study, we have prospectively analyzed the in vivo effects of methimazole treatment on a large number of circulating T and NK cell subsets, some of them expressing cell surface activation antigens involved in the very early phase of the immune response, in a group of 17 hyperthyroid, untreated patients with Graves' disease (GD). As one of the first events during T cell activation is the expression of interleukin (IL) receptors, we also studied the binding of IL-2 and IL-6 to T cells. Patients with Graves' disease were sequentially studied at diagnosis/before treatment (day 0) and 7, 14, 30, 90 and 180 days after methimazole therapy. The results were compared with both a group of 19 age- and sex-matched control volunteers and a group of 20 untreated/euthyroid patients with Graves' disease in long-term remission. The combination of flow cytometry and three-color immunofluorescence revealed a clear (P < 0.01) decrease in the percentage of NK cells before and during the whole course of therapy with respect to both controls and patients with Graves' disease who were in long-term remission. Before therapy, a marked increase (P < 0.001) in the ratio of B to NK cells was also observed; thereafter, a slight decrease in this ratio was observed, although normal values were detected only in patients in long-term remission. Expression of the CD69 early activation antigen in the hyperthyroid untreated patients with Graves' disease was clearly increased (P < 0.01) with respect to both controls and patients with Graves' disease who were in long-term remission. This abnormal CD69 expression was found to be significantly reduced (P < 0.001) by methimazole therapy, and this represents a new effect of the drug. Expression of the low-affinity receptor for IL-2 (CD25)--another early T cell activation marker--was not altered in Graves' disease, but the binding of IL-2 and IL-6 to T cells exhibited a progressive and parallel increase during the first 30 days of therapy, decreasing thereafter. Our results show that methimazole therapy downregulates the abnormally high expression of the CD69 early activation antigen on T cells, being less effective on inducing changes in other T cell activation markers and in NK cells.

Topics: Adult; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; Antithyroid Agents; Flow Cytometry; Fluorescent Antibody Technique; Graves Disease; Humans; Interleukin-2; Interleukin-6; Killer Cells, Natural; Lectins, C-Type; Lymphocyte Count; Methimazole; Middle Aged; Protein Binding; T-Lymphocytes

Topics: Antithyroid Agents; Child; Child, Preschool; Diagnosis, Differential; Graves Disease; Humans; Methimazole

Topics: Antithyroid Agents; Carbimazole; Drug Therapy, Combination; Graves Disease; Humans; Immunosuppression Therapy; Methimazole; Recurrence; Thyroxine

Hyperthyroidism (H) has been implicated as a primary cause of decreased exercise tolerance. To our knowledge, analysis of respiratory gas exchange, an efficient noninvasive method in evaluating cardiopulmonary capacity, has not been performed in patients with H.. Using cardiopulmonary exercise testing, 12 consecutive women with Graves' H were examined and controlled in euthyroidism (E). Eighteen women with E, in whom cardiac catheterization had ruled out heart disease, served as control subjects (C).. The ventilatory anaerobic threshold was determined by means of the V-slope method. Ergometry was performed with patients in a semisupine position using a continuous ramp protocol of 20 W/min. Echocardiography at rest was performed in all patients.. In patients with H, heart rate at rest was higher than in patients with E (p < 0.05) and showed a markedly lower increase between rest and anaerobic threshold compared with E patients (p = 0.007) and C (p = 0.009). Work rate was reduced (H, 50% vs E, 70%; p = 0.038). In H patients, the anaerobic threshold occurred at 59.6% of maximal oxygen uptake and 72% in E patients, respectively (p = 0.024). In H patients, the linear regression of the heart rate to oxygen uptake ratio showed a reduced slope in comparison with E patients (p = 0.001) and C (p = 0.004). In patients with H, a reduced tidal volume (p = 0.021) and an increased respiratory rate (p = 0.003) in comparison to patients with E were demonstrated. Echocardiographically, H patients had an increased ejection fraction (p = 0.008) and a higher cardiac index (p = 0.008) in comparison with E patients.. Analysis of respiratory gas exchange showed marked alterations of cardiopulmonary exercise capacity in H patients, which are reversible in E patients. The impaired chronotropic response during exercise might be the primary limiting factor of reduced work capacity in patients with H.

Topics: Adult; Aged; Anaerobic Threshold; Antithyroid Agents; Cardiac Output; Echocardiography; Exercise Test; Exercise Tolerance; Female; Graves Disease; Heart; Heart Rate; Humans; Linear Models; Lung; Methimazole; Middle Aged; Oxygen Consumption; Prospective Studies; Pulmonary Gas Exchange; Rest; Stroke Volume; Supine Position; Tidal Volume

To determine the association between HLA class II genes and methimazole-induced agranulocytosis in patients with Graves disease.. Case-control study.. Kuma Hospital, which specializes in thyroid diseases, in Kobe, Japan.. 24 patients with Graves disease who had methimazole-induced agranulocytosis diagnosed by peripheral granulocyte counts of less than 0.5 x 10(9)/L, and 68 patients with Graves disease treated with methimazole, who were free from agranulocytosis. Controls were 525 healthy, unrelated Japanese student volunteers at Kyushu University in Japan.. All HLA class II genes were analyzed for polymorphisms at the DNA level by using the polymerase chain reaction sequence-specific oligonucleotide probes method. The allele frequencies in the agranulocytotic Graves disease group were compared with those in the nonagranulocytotic Graves disease and control groups.. A strong positive association was seen in DRB1*08032 between the agranulocytotic group and both the control and nonagranulocytotic Graves disease groups.. The HLA DRB1*08032 allele was strongly associated with susceptibility to methimazole-induced agranulocytosis, suggesting that cellular autoimmunity may be involved in its development.

Topics: Agranulocytosis; Antithyroid Agents; Autoimmunity; Graves Disease; HLA-DR Antigens; Humans; Methimazole; Polymorphism, Genetic; T-Lymphocytes

Topics: Antithyroid Agents; Drug Therapy, Combination; Graves Disease; Humans; Methimazole; Thyroxine; Treatment Failure

Several studies have shown that thyroid hormones are able to influence selected immune responses such as cell mediated immunity, differentiation of B lymphocytes and the activity of NK cells. These hormones can also regulate the metabolism of glucose and glutamine in rat macrophages and their effects seem to occur mainly through the Krebs cycle. Alterations in the hexokinase, citrate synthase, glucose-6-phosphate dehydrogenase and glutaminase activities in lymphocytes from patients with Graves' disease, either untreated or on methimazole (MMI) therapy were investigated. Experiments were also done in vitro to determine the activities of these enzymes in normal lymphocytes cultured for 24 h in the presence of MMI T3 and T4 using concentrations close to the physiological. Changes in the conversion of [U-14C]-glucose and [U-14C]-glutamine to 14CO2 as caused by the addition of MMI, T3 or T4 to the culture medium were also evaluated. The results indicate that high levels of thyroid hormones might stimulate the metabolism of glucose and glutamine for a short period of time but, if the stimulus is maintained, the utilization of glutamine by lymphocytes is then suppressed. Moreover, MMI does affect lymphocyte metabolism but the significance of this finding for its immunosuppressive effect remains to be examined.

Topics: Adult; Autoantibodies; Carbon Dioxide; Carbon Radioisotopes; Cells, Cultured; Citrate (si)-Synthase; Culture Media; Female; Glucose; Glucosephosphate Dehydrogenase; Glutaminase; Glutamine; Graves Disease; Hexokinase; Humans; Lymphocytes; Male; Methimazole; Middle Aged; Thyroid Function Tests; Thyroid Gland; Thyroxine; Triiodothyronine

Changes in patients' body composition following therapy for Graves' disease were assessed by dual energy X-ray absorptiometry (DXA). The subjects were 21 patients (6 males, 15 females) who were treated with 131I. Their ages ranged from 24 to 75 years (median 51.2 years). Changes in body composition were analyzed by evaluating the fat mass (FM) and lean mass (LM). Both FM and LM were significantly increased after therapy. The increase in LM was greater in the males, whereas in females, no significant difference was noted between the changes in FM and LM. The distributions of FM and LM were examined in the arms, legs and trunk after therapy, and FM was significantly increased in the trunk, while LM was increased in the legs. DXA is useful for the assessment of body composition as well as bone mineral content in follow-up study of Graves' disease.

Topics: Absorptiometry, Photon; Adult; Aged; Antithyroid Agents; Body Composition; Bone Density; Female; Follow-Up Studies; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged

Some patients with Graves' disease respond well to anti-thyroid drug treatment but others do not. Factors determining the patient's responsiveness to the medical treatment are unclear, but the intrathyroidal iodine pool is believed one of the important factors. In this study, we found that delta radioactive iodine uptake (RAIU) (RAIU at 24 h-RAIU at 3 h) is useful in predicting early response to treatment with methimazole (MMI). Among 32 patients with Graves' disease, who were given 30 mg MMI as an initial dose, 11 patients responded quickly to MMI-treatment. Within one month, serum free T4 levels decreased to below the normal range in 6 patients (< 10.3 pmol/L) or decreased from beyond the highest level of the assay (> 125 pmol/L) to the normal range in 5 patients. When these rapid responders (group A) were compared with the remaining 21 patients who showed a more gradual response to MMI-treatment (group B), a different pattern of 123I-thyroid uptake was noted. RAIU at 3 h was significantly higher in group A than in group B, while RAIU at 24 h was similar in the two groups. As a result, rapid responders had a significantly lower delta RAIU value than gradual responders (-0.7 +/- 8.4% in group A, 14.2 +/- 8.2 in group B, P < 0.01). No significant difference was found between the two groups in various pre-treatment parameters such as severity and duration of thyrotoxicosis, the titer of TSH receptor antibodies (TRAb), frequency of positive antithyroglobulin antibodies (TGHA), urinary excretion of iodine and thyroid volume. The incidence of positive antithyroid microsomal antibodies (MCHA) was higher in group A than in group B, and thyroid ultrasonography showed a tendency to low echogenicity in group A. delta RAIU was negatively correlated with the reduction in the serum free T4 level during the first two weeks after MMI-treatment was initiated (r = -0.60, P < 0.01). Moreover, delta RAIU correlated positively with the biological half-life of the intrathyroidal iodine, calculated in a different series of 24 patients with Graves' disease who received radioisotope treatment (r = 0.54, P < 0.01). The low delta RAIU value is considered to reflect the rapid turnover of the intrathyroidal iodine, and may be related to the small intrathyroidal iodine pool. delta RAIU is useful in predicting early responsiveness of patients with Graves' disease to MMI-treatment.

Topics: Adult; Female; Graves Disease; Half-Life; Humans; Iodine; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Thyroid Gland; Thyroxine; Ultrasonography

A 56-year-old female with Graves' disease who presented with decreased secretion of gonadotropins is described. She was admitted to hospital because of her being in a state of confusion. One month before admission she had been diagnosed as having Graves' disease and was treated with methimazole since then. Plasma LH and FSH levels were undetectable, and their responses to LH-RH were extremely decreased in spite of undetectable levels of plasma estradiol and estriol. One year after treatment, both basal and stimulated values of LH and FSH reverted to normal as did those of TSH. Reversible suppression of gonadotropins as described herein has never been reported in cases of Graves' disease.

Topics: Antithyroid Agents; Body Weight; Female; Follicle Stimulating Hormone; Follow-Up Studies; Gonadotropin-Releasing Hormone; Graves Disease; Humans; Luteinizing Hormone; Methimazole; Middle Aged; Thyrotropin; Thyroxine; Time Factors; Triiodothyronine

Increased serum interleukin-6 (IL-6) concentrations have been reported in patients with thyroid destructive processes. In the present study we measured IL-6 and soluble IL-6 receptor (sIL-6R) concentrations in the serum of normal subjects and patients with Graves' disease using a high sensitivity sandwich enzyme-linked immunoassay. We found increased serum IL-6 and sIL-6R concentrations (69.3 fmol/L, and 964 pmol/L, respectively) in 49 hyperthyroid patients with Graves' disease (GD) compared to those in controls [55.8 fmol/L (P = 0.019) and 772 pmol/L (P = 0.007), respectively]. In 31 newly diagnosed GD patients, serum concentrations of IL-6 and sIL-6R during the hyperthyroid phase were elevated, and after therapy with methimazole only, serum sIL-6R concentrations returned to normal (940 vs. 726 pmol/L; P < 0.001) but serum IL-6 did not. Serum sIL-6R concentrations (mean +/- 2 SD) were higher in GD patients with active inflammatory thyroid-associated ophthalmopathy than those in patients with inactive or absent thyroid-associated ophthalmopathy (P < 0.05). In conclusion, we have demonstrated activation of the IL-6 system in GD and, for the first time, have measured and found increased serum sIL-6R concentrations in hyperthyroid GD patients.

Topics: Adolescent; Adult; Aged; Antigens, CD; Antithyroid Agents; Enzyme-Linked Immunosorbent Assay; Female; Graves Disease; Humans; Interleukin-6; Male; Methimazole; Middle Aged; Osmolar Concentration; Receptors, Interleukin; Receptors, Interleukin-6; Reference Values; Remission Induction; Solubility; Thyroid Gland

Topics: Antithyroid Agents; Carbimazole; Drug Therapy, Combination; Graves Disease; Humans; Immune Tolerance; Methimazole; Remission Induction; Thyroid Hormones; Thyroxine; Triiodothyronine

Topics: Graves Disease; Humans; Iodine; Methimazole; Thyroid Hormones

Increases in thyroid cell major histocompatibility complex (MHC) class I and class II expression have been suggested to be an important factor in the development or perpetuation of Graves' disease. It is hypothesized that elevations result in abnormal presentation of thyroid antigens to immune cells, and that iodide and/or methimazole (MMI) are effective therapeutic agents because, at least in part, of their suppression of MHC expression. In this report, we show that Graves' patients pretreated with iodide only 4 days before surgery have lower levels of MHC class I and class II RNA levels in their thyroid tissue than do patients with no iodide pretreatment (P < 0.001 and 0.03, respectively). Because patients in both groups are treated with MMI and because the change is independent of the amounts of MMI used to treat patients, the class I and class II changes cannot be ascribed to MMI. The iodide action to decrease MHC class I and class II RNA levels was duplicated using cultured human thyroid cells in vitro; the iodide effect was dependent on the iodide concentration, was not duplicated by chloride, was not associated with an alteration in cAMP levels or with a change in thyrotropin receptor RNA levels, and was evident in gamma-interferon-treated cells. The data suggest, therefore, that the therapeutic action of iodide in Graves' patients is associated with decreased MHC gene expression, that this action is a direct effect of high concentrations of iodide on the thyroid cells, and that altered MHC gene expression in the target tissue may well be associated with the development or perpetuation of Graves' disease.

Topics: Adolescent; Adult; Blotting, Northern; Blotting, Western; Cells, Cultured; Female; Gene Expression Regulation; Genes, MHC Class I; Genes, MHC Class II; Graves Disease; Humans; Iodides; Male; Methimazole; Middle Aged; RNA, Messenger; Thyroid Gland

A characteristic thyroid ultrasonographic picture with diffuse or scattered low echogenicity has been described in Graves' disease (GD). Thyroid hypoechogenicity in GD at onset has been considered a prognostic index of relapse after medical treatment; moreover, thyroid hypoechogenicity is regularly observed in GD at the onset, but not in patients with 'burned-out' disease. The aim of this study was to evaluate the usefulness of thyroid hypoechogenicity changes in predicting GD relapse.. Longitudinal prospective study of previously untreated patients with GD.. Thirty-nine consecutive patients aged 10-72 years were treated with methimazole (MMI) for 12-24 months on a titration regimen. Evaluation of patients in remission or with relapse was done 12 and 24 months after MMI withdrawal.. Thyroid ultrasonography and TSH receptor antibodies (TRAb) were evaluated in basal conditions and then one month after MMI withdrawal. Thyroid hypoechogenicity score (assessed by the same observer with the same equipment) was graded as: 0 absent; 1 mild; 2 moderate; 3 marked. At the withdrawal evaluation a score < 2 and a TRAb value < 10 U/l were considered as normal.. Twelve and 24 months after withdrawal, there were 10 (25.6%) and 17 (44.7%) relapses, respectively. Neither thyroid hypoechogenicity score nor TRAb values evaluated in basal conditions, showed significant differences between patients remaining euthyroid and those who became again hyperthyroid. In the whole group, the thyroid hypoechogenicity score was significantly lower at the withdrawal than in basal conditions (1.1 +/- 1.1 vs 2 +/- 0.8; P < 0.0001); it was significantly lower in patients in remission (P < 0.001), but not in those who relapsed. The thyroid hypoechogenicity score at withdrawal was normal in 23/29 (79.3%) of patients still euthyroid and in 4/10 (40%) of those who relapsed up to the 12th month (P < 0.05); it was normal in 19/21 (90.4%) of patients still euthyroid and in 7/17 (41.2%) of those who relapsed up to the 24th month (P < 0.05). A normal thyroid hypoechogenicity score at withdrawal of MMI had a higher specificity (0.95) and sensitivity (0.59) with respect to TRAb values (0.86 and 0.53, respectively) for the prediction of the relapse of hyperthyroidism at the 24th month.. Basal thyroid hypoechogenicity cannot be used as an index of relapse of GD. MMI treatment induces evident changes in thyroid hypoechogenicity, mainly in patients who subsequently go into remission. The absence or a low grade of thyroid hypoechogenicity after MMI treatment seems to be a favourable prognostic index of remission of hyperthyroidism in GD.

Topics: Adolescent; Adult; Aged; Autoantibodies; Child; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Prognosis; Prospective Studies; Receptors, Thyrotropin; Recurrence; Thyroid Gland; Ultrasonography

The immunosuppressive effects of antithyroid drug therapy are well recognized; however, the cellular mechanisms underlying their action remain largely unknown. In the present paper we have prospectively analyzed the in vivo effects of methimazole treatment on a large number of circulating B cell subsets, involved in the effector phase of the immune response, in a group of 18 hyperthyroid patients with Graves' disease (GD). The patients were sequentially studied before (day 0) and 7, 14, 30, 90 and 180 days after methimazole therapy. The results were compared with both a group of 19 age- and sex-matched healthy controls and a group of 20 untreated/euthyroid GD patients in long-term remission. The combination of flow cytometry and three colour immunofluorescence revealed a clear increase (P < 0.001) in the numbers of circulating total B cells (CD19+) due to a significant increase (P < 0.001) in the CD5+, FMC7+, CD5+/ FMC7+ and CD23+ B cell subsets in hyperthyroid GD patients with respect to both healthy individuals and to GD patients in long-term remission. The absolute numbers of all these B cell subsets analyzed before treatment, although abnormal, were not statistically different from those observed during the whole period of therapy. When comparing the percentages of these B cell subsets during treatment, significant changes (P < 0.001) were only observed in the proportion of CD5+, CD5+/FMC7+ and CD5- B cells at the end of the follow-up period with respect to those found both before and during the first month of therapy. Whereas CD5+ and CD5+/FMC7+ B cells decreased (P < 0.001) after 3 months of therapy, CD5- B cells showed a significant increase (P < 0.001) at the end of therapy. It is remarkable that the percentage of CD5+, CD5+/FMC7+, CD5- and CD23+ B cell subsets were abnormal during the whole period of treatment and that they never reached normal values. These results show that, in vivo, GD patients treated with methimazole exhibited an abnormal but rather stable pattern of B cell distribution, similar to that present in hyperthyroid untreated GD patients, except for the CD5+ and CD5- B cell populations. Our findings suggest that in vivo methimazole therapy would not directly have an important influence on circulating B cell subsets.

Topics: Adult; Antibodies; Antibodies, Monoclonal; Antithyroid Agents; B-Lymphocyte Subsets; CD5 Antigens; Female; Flow Cytometry; Fluorescent Antibody Technique, Direct; Graves Disease; Humans; Iodide Peroxidase; Lymphocyte Count; Male; Methimazole; Middle Aged; Prospective Studies; Receptors, IgE; Thyroglobulin; Thyroid Hormones

Adhesion molecules relate to cell invasion of autoimmune thyroid disease. We studied plasma soluble P-Selectin (platelet activation-dependent granule-external membrane protein), E-Selectin (endothelial leukocyte adhesion molecule) and L-Selectin (leukocyte endothelial cell adhesion molecule-1) levels in patients with Graves' disease before and during methimazole treatment. Plasma P-, E- and L-Selectin levels in patients with untreated Graves' disease were significantly higher than those in normal subjects. Plasma P-Selectin levels decreased when their thyroid functions were normal for more than 6 months after the start of methimazole treatment. No significant change in plasma E- and L-Selectin levels in patients with Graves' disease was found between hyperthyroid state and euthyroid state after the start of methimazole treatment, but plasma L-Selectin levels in patients with untreated Graves' disease were significantly lower than those in the patients in the first euthyroid state. There was no significant correlation between plasma P-Selectin levels and serum FT4 levels, nor between plasma P-Selectin levels and serum FT3 levels. These results suggested that thyroid hormones might reflect expression of P-, L- and E-Selectin from endothelial cells, or lymphocytes, or platelets in patients with Graves' disease.

Topics: Adult; Antithyroid Agents; Autoantibodies; E-Selectin; Female; Graves Disease; Humans; L-Selectin; Male; Methimazole; Middle Aged; P-Selectin; Receptors, Thyrotropin; Thyroiditis, Subacute; Thyrotropin; Thyroxine; Triiodothyronine

Aplastic anemia is the rare hematologic complication of the antithyroid medication. We present here the case of 39-years old female who was treated with Thiamazole due to Graves disease. This and the others cases cited in the literature indicate that antithyroid drugs-induced aplastic anemia is characterised by severe clinical status and profound marrow hypoplasia or aplasia but good prognosis with short term recovering.

Topics: Adult; Anemia, Aplastic; Antithyroid Agents; Female; Graves Disease; Humans; Methimazole

Topics: Agranulocytosis; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Injections, Subcutaneous; Male; Methimazole; Middle Aged; Recombinant Proteins; Time Factors

Regulation of anti-TSH receptor antibody (anti-TSH-R antibody) in Graves' patients (n = 11) by anti-idiotypic antibody was studied using patients sera before and after one year of Methimazole treatment. Patients sera with high level of anti-TSH-R antibody (110 + 41.9 U/I) were incubated with pooled control and autologous (with low level or anti-TSH-R antibody negative) sera containing equimolar IgG G. The mixture was centrifuged and the supernatants were tested for anti-TSH-R antibodies (TRAK, Henning). It was found that the autologous sera from patients with remission were able to suppress significantly the titre of anti-TSH-R antibodies (p < 0.001), whereas the controls were capable of a less remarkable inhibition. F(ab')2 fragments of autologous IgG from remission could also suppress the levels of TSH-R antibodies. It was concluded that anti-anti-TSH-R antibodies in sera of Graves' patients might be, at least in part, responsible for inducing and maintaining remission and suppression of autoantibodies to TSH-R. It is hypothesized that the idiotype system is part of the network of natural autoantibodies and that its perturbation may give rise to pathogenetic antibodies. On the basis of this observation the autologous sera could have therapeutical implication in an accelerated remission of hyperthyroidism in Graves' disease.

Topics: Adult; Antibodies, Anti-Idiotypic; Antithyroid Agents; Autoantibodies; Dose-Response Relationship, Immunologic; Female; Graves Disease; Humans; Immunoglobulin Fab Fragments; Immunoglobulin G; Immunologic Factors; In Vitro Techniques; Iodide Peroxidase; Male; Methimazole; Middle Aged; Receptors, Thyrotropin; Thyroglobulin; Thyrotropin

To find a simple and reliable method for predicting the long-term remission of Graves' disease, we studied the outcome of 182 methimazole-treated patients with Graves' disease, whose thyroidal RAIU became < 12% after T3 administration. The patients were treated with methimazole over 2 years. T3 suppression test was done 6 months after the disappearance of TSH-receptor antibody (TRAb); the patients took T3 for 14 days, and on the 14th day, blood was obtained for serum T3, T4, and TSH determination, and RAIU was measured. These 182 patients were followed for 5 years after methimazole withdrawal. We divided the 182 methimazole-treated patients, whose thyroidal RAIU became < 12% after T3 administration, into two groups based on the outcome after the discontinuation of methimazole; 40 patients (22%) had an overt recurrence (group A) and the other 142 (78%) did not (group B). The degree of serum T4 suppressibility by T3 was less in group A than in group B. In group A, the number of the patients with a serum T4 < 60% of the pre-T3 levels is less than that with a serum T4 > or = 60%, but, in group B the former is more than the latter. The serum T4 < 60% of the pre-T3 level was significantly associated with the remission.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Case-Control Studies; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Prognosis; Recurrence; Thyroid Function Tests; Thyroxine; Triiodothyronine

In order to investigate the extrapituitary action of TRH on the thyroid, serum T3, T4, and TSH levels after im administration of TRH were analyzed in 63 patients with untreated hyperthyroid Graves' disease, in 60 euthyroid patients with treated Graves' disease, in 8 patients with subacute thyroiditis, and in 140 healthy subjects. TRH administration in the healthy subjects resulted in a significant increase in serum T3 and T4 levels after 2 h. However, in the patients with untreated hyperthyroid Graves' disease, a significant decrease in serum T3 and T4 levels with undetectable TSH was found 2 h after TRH administration. In the patients with subacute thyroiditis, serum T3 levels also significantly decreased after TRH administration. When a decrease in serum T3 and T4 levels after TRH administration in the patients with hyperthyroid Graves' disease was analyzed in terms of thyroid microsomal antibody and thyroglobulin antibody, a decrease in serum T3 and T4 levels was largest in patients with thyroid microsomal antibody and thyroglobulin antibody. In contrast, an increase in serum T3 and T4 levels in response to TRH in the euthyroid patients with Graves' disease was largest in patients without thyroid autoantibodies. It is concluded that TRH acts directly on the thyroid to suppress the thyroid hormone secreting activity in the absence of circulating TSH and that thyroid autoantibodies affect thyroidal response after TRH administration.

Topics: Adolescent; Adult; Aged; Autoantibodies; Child; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Reference Values; Thyroid Gland; Thyroiditis, Subacute; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

Declining thyroid autoantibodies during treatment and decreased lymphocytic infiltration after treatment of patients with Graves' disease suggest immunosuppressive actions of antithyroid drugs. However, the recent report of similar relapse rates after low and high dose carbimazole treatment of Graves' disease seems to contradict the immunosuppression thesis. We therefore determined the intrathyroidal methimazole concentrations with a high performance liquid chromatography method in 17 patients undergoing subtotal thyroid resection for relapsing Graves' disease. The intensity of the intrathyroidal infiltration by immunoglobulin G-producing plasma cells, activated T cells, and antigen presenting cells, and the total number of lymphocytes were identified immunohistologically with monoclonal antibodies for kappa- and lambda-immunoglobulin light chains, UCHL1, and the S100 antibody, respectively, followed by morphometry. The intrathyroidal methimazole concentration and the cumulative preoperative methimazole doses did not correlate with the intensity of the intrathyroidal infiltration by any of these immunocompetent cells. Comparison of groups with significantly different intrathyroidal methimazole concentrations (134 ng/g, n = 8 vs. 993 ng/g, n = 7) showed no significant differences for any of the intrathyroidal immunocompetent cells. These findings suggest that there is no dose-related effect of methimazole on the intensity of the intrathyroidal autoimmune process of patients with relapsing Graves' disease. They provide an explanation for why it does not seem justifiable to recommend higher methimazole doses than those required for the control of hyperthyroidism with the goal of immunosuppression.

Topics: Adult; Antibodies, Monoclonal; Antigen-Presenting Cells; Carbimazole; Dose-Response Relationship, Drug; Graves Disease; Humans; Immunoglobulin G; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Immunohistochemistry; Lymphocytes; Methimazole; Prospective Studies; Recurrence; T-Lymphocytes; Thyroid Gland; Thyroidectomy; Tissue Distribution

Thionamides are often used acutely to control the symptoms of thyrotoxicosis associated with Graves' disease before definitive treatment with radioiodine. Several reports have suggested that pretreatment with thionamides reduces the efficacy of radioiodine therapy in patients with Graves' disease, but other data refute this. This study retrospectively reviewed the records of 95 patients with Graves' disease treated with radioiodine. Pretreatment with thionamides resulted in significantly greater (2 1/2-fold) treatment failure rate than in patients not pretreated with thionamides but given a comparable dose of radioiodine. Higher serum thyroxine concentration at the time of diagnosis was also an independent factor associated with radioiodine treatment failure.

Topics: Adult; Chi-Square Distribution; Contraindications; Discriminant Analysis; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Retrospective Studies; Thyrotoxicosis; Thyroxine; Treatment Failure

In 1986, a 26-year-old female had been diagnosed as having Graves' disease and had been treated with methimazole for four months. After the treatment with propylthiouracil for another four months, she had been treated with methimazole once again. She was in complete remission for two years. She again experienced symptoms of hyperthyroidism, and treatment with methimazole was started again. On the thirteenth day after treatment, she experienced hypoglycemic attacks with skin eruption. The plasma glucose was 57 mg/dl, 125I-Insulin binding 69%, free IRI 196 microU/ml. The patient had the HLA-DRB1*0406.

Topics: Adult; Autoantibodies; Autoimmune Diseases; Female; Graves Disease; Humans; Hyperinsulinism; Hypoglycemia; Insulin Antibodies; Methimazole

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Drug Combinations; Female; Graves Disease; Humans; Ketorolac Tromethamine; Medication Errors; Methimazole; Tolmetin; Tromethamine

Topics: Graves Disease; Humans; Methimazole; Recurrence; Thyroxine

Human T-lymphotropic virus type I (HTLV-I) is responsible for a certain form of uveitis [HTLV-I-associated uveitis (HAU)]. A previous history of Graves' disease has been reported in 9-17% of the patients with HAU. In this study, the prevalence of patients with either HTLV-I antibody or uveitis was evaluated in 819 consecutive patients with thyroid disorders between 1991 and 1992. Serum HTLV-I antibody was found in 25 of 392 patients with Graves' disease, 19 of 257 with chronic thyroiditis, and 3 of 170 with nodular goiter. Five of 25 HTLV-I-positive patients with Graves' disease developed HAU. All of these 5 patients had been treated with methylmercaptoimidazole (MMI). Within a few months before the onset of uveitis, 3 patients were hyperthyroid, and 2 were hypothyroid. In 2 of 5 patients, an exacerbation of uveitis occurred soon after the readministration of MMI for the relapse of hyperthyroidism. None of the 367 HTLV-I negative patients with Graves' disease nor 22 HTLV-I-positive patients with chronic thyroiditis or nodular goiter developed uveitis. It was therefore suggested that Graves' disease, thyroid dysfunction and/or MMI administration might be related to the development of HAU.

Topics: Adult; Aged; DNA, Viral; Female; Graves Disease; HTLV-I Antibodies; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Methimazole; Middle Aged; Polymerase Chain Reaction; Uveitis

The aim of this study was to evaluate through the auditory brainstem responses (ABRs) the electrical events generated along the auditory pathway in 56 adult patients affected with hyper- and hypothyroidism. Twenty-four normal-hearing hyperthyroid patients affected with Graves' disease and 32 normal-hearing hypothyroid patients (9 with subclinical and 23 with overt hypothyroidism) were subjected to standard (clicks at 21 pps) and sensitized ABR with masking wide-band (masking noise). In addition, thyroid scintiscan and ultrasonography, free T3 and T4, total T3 and T4, TSH, antimicrosomal and antithyroglobulin antibodies, audiogram and impedance tests were performed in all the patients. This study was repeated after 6-12 months of treatment in conditions of euthyroidism. The results showed changes of ABRs both in the standard procedure as well as in the sensitized test in 6 hyperthyroid (25%) and 8 hypothyroid patients (25%). All the patients with abnormal ABRs had overt hypothyroidism (8/23; 34.7%). The ABRs became normal in 5 out of 6 Graves' patients after 6-12 months of methimazole treatment. ABRs remained abnormal in all the hypothyroid patients despite their having been on L-thyroxine treatment for 6-12 months and were euthyroid for at least 5 months before the study was repeated. These findings suggest that ABR abnormalities are indicative only of a nonspecific injury in the bulbo-ponto-mesencephalic centers. Alterations of ABRs in thyroid diseases are not specific in relation to hyper- or hypothyroidism. Lastly, there is a relationship between ABR abnormalities and the degree of hypothyroidism, even if ABR alterations are not always reversible after long-term therapy.

Topics: Adult; Evoked Potentials, Auditory, Brain Stem; Female; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Middle Aged; Thyroid Diseases; Thyroxine

Topics: Graves Disease; Humans; Iodine Radioisotopes; Methimazole; Practice Patterns, Physicians'; Thyroxine

The effects of hyperthyroidism on uric acid metabolism were investigated. First, the serum uric acid level was measured in 92 patients with hyperthyroidism due to Graves' disease, eight patients with subacute thyroiditis, six patients with hypothyroidism, and 70 sex- and age-matched controls. Second, the correlation between serum thyroxine (T4) and serum uric acid was obtained in hyperthyroid Graves' disease patients before and during antithyroid drug therapy. Finally, uric acid clearance (CUA) was determined in untreated patients with hyperthyroidism due to Graves' disease. Serum uric acid was significantly elevated in patients with hyperthyroidism, and the elevation correlated well with serum T4 before treatment as a group and during treatment in each patient. A significant elevation of serum uric acid was not present in patients with a transient mild thyrotoxicosis due to subacute thyroiditis. Serum uric acid was significantly decreased in patients with hypothyroidism. Renal excretion of uric acid clearly increased in hyperthyroid patients, and CUA also increased. The increase in CUA corresponded to the increase in renal plasma flow (RPF), which was measured by p-aminohippuric acid clearance. The fractional excretion of uric acid as determined by CUA/glomerular filtration rate (GFR) was similar and within the normal range in hyperthyroid patients and normal controls. A significant inverse correlation between CUA and serum uric acid concentration was present in hyperthyroid patients as in normal controls, indicating that the renal handling of uric acid in the tubule affected uric acid excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Child; Female; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Kidney; Male; Methimazole; Middle Aged; Regional Blood Flow; Thyroxine; Uric Acid

Thyrostatic treatment of pregnant women with Graves' disease is a special problem. Observation of 46 pregnancies of 35 women suffering from Graves' disease has been summarized. The outcome was successful in 45 cases. Methimazole and propylthiouracil was administered to the patients without thyroxine. Therapy was needed for the two thirds of the mothers. At the end of the second trimester the thyrostatic agent could have been withdrawn in the 77% of the cases. Antithyroid treatment administered in low dose at the time of conception did not affect the outcome. Premature delivery rate and the number of neonates with low weight did not increased. Transient hyperthyrotropinaemia was observed in one case. Likewise, one infant suffered from neonatal thyrotoxicosis. 37% of the mothers had postpartal recurrence of hyperthyroidism.. the free thyroxin level monitoring is essential during thyrostatic treatment. Thyrotropin receptor antibody investigation, having predictive value for neonatal thyrotoxicosis, should be done, too. Postpartal thyroid control is necessary for elucidate a hyperthyroid relapse, the rate of which was almost 40%.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Hyperthyroidism; Infant, Newborn; Maternal-Fetal Exchange; Methimazole; Predictive Value of Tests; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prognosis; Recurrence; Thiouracil; Thyrotoxicosis; Thyroxine; Treatment Outcome

A 24-year-old woman with Graves' disease treated with methimazole for 4 years, developed recalcitrant ulcers on the lower legs. Histological studies demonstrated vasculitis in deep dermal vessels accompanied by C3 deposition. Laboratory investigation revealed lupus-like abnormalities (leucocytopenia, positive antinuclear and antidouble strand (ds) DNA antibodies, and positive ANCA). The leg ulcers dramatically improved after methimazole was withdrawn. In addition, leucocytopenia and the immunological abnormalities soon faded. Although lupus-like syndrome is well known to be induced by antithyroid drugs, vasculitis is a rare complication. To the best of our knowledge, this is the first report describing ANCA-associated vasculitis caused by methimazole.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Autoantibodies; Biomarkers; Female; Graves Disease; Humans; Lupus Vulgaris; Methimazole; Skin Ulcer; Vasculitis

We treated a patient who was hyperthyroid due to Graves' disease and strongly resistant to methimazole (MMI): in spite of good compliance, she needed 150 mg of MMI daily to control her hyperthyroidism. To elucidate the reasons of resistance to MMI, her serum and intrathyroidal MMI concentrations were determined by high pressure liquid chromatography (HPLC). After taking a 30 mg dose of MMI, she had a similar serum MMI concentration-time curve to that of a normal subject: drug malabsorption and rapid drug metabolism were not evident when studied after surgical treatment. After her serum containing MMI was incubated with Protein G, the MMI concentration of the fraction not bound to Protein G did not change significantly from that of untreated serum: the possibility of anti-MMI IgG antibody production was considered unlikely. Furthermore, the intrathyroidal concentration of MMI in a surgically obtained tissue specimen was 3 micrograms/g wet tissue and appeared to be comparable with those of other Graves' tissues reported. Considering that the patient had been taking 150 mg per day of MMI by the time of thyroidectomy, her intrathyroidal MMI concentration was relatively low, suggesting possible impairment of intrathyroidal MMI accumulation. The possibilities of impaired intrathyroidal actions and the severity of hyperthyroidism, especially high T3 levels, also remained as possible causes. In conclusion, here was a severely hyperthyroid patient who was poorly responsive to conventional doses of MMI, and impairment of thyroid uptake of MMI or of pathways after uptake were considered as possible mechanisms.

Topics: Adult; Antithyroid Agents; Chromatography, High Pressure Liquid; Drug Resistance; Female; Graves Disease; Humans; Methimazole; Thyroid Hormones; Tissue Distribution

A 26-year-old woman was admitted to hospital with high fever, severe tonsillitis, and gastroenteritis. Because of Graves' disease she had been treated with methimazole for 18 months. Leukopenia and agranulocytosis in combination with a typical bone marrow, exhibiting a complete arrest of myelopoiesis at the stage of promyelocytes led to the diagnosis of an antithyroid therapy induced agranulocytosis. After 1 week of antibiotic treatment without changes in neutrophil counts, granulocyte colony stimulating factor treatment at a dose of 300 micrograms/day subcutaneously was started. Twenty-four hours after the first administration the neutrophil counts began to rise, to 4389/microliters, with a maximum after the third administration and stabilizing at normal levels within 10 days. Since agranulocytosis is considered to be a severe and fatal complication of methimazole therapy, treatment with granulocyte colony stimulating factor seems to be useful for this life-threatening condition.

Topics: Adult; Agranulocytosis; Bone Marrow; Female; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Immunologic Factors; Infections; Leukocyte Count; Methimazole

The targeting and recruitment of inflammatory cells to vascular endothelium in Graves' disease (GD) is mediated by intercellular adhesion molecule-1 (ICAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1), and vascular cell adhesion molecule-1 (VCAM-1). We have studied serum levels of soluble ICAM-1 (sICAM-1), soluble ELAM-1 (sELAM-1), and soluble VCAM-1 (sVCAM-1) in patients with GD (n = 21) and in patients with iodine-deficient goitre (IDG) (n = 23). The serum levels of sICAM-1 were markedly elevated in patients with GD before treatment with thiamazole (median 560 ng/ml versus 185 ng/ml in patients with IDG). In addition, elevated serum concentrations of sELAM-1 (median 85 ng/ml versus 33 ng/ml, respectively) and sVCAM-1 (median 42 ng/ml versus 15 ng/ml, respectively) were observed in patients with GD (P < 0.01 for all). The serum levels of sELAM-1 and sVCAM-1 dropped significantly after initiation of therapy and were within the normal range after 4, and 8 weeks of therapy, respectively. Serum levels of sICAM-1 were elevated even after 8 weeks of therapy. Serum levels of sVACM-1 and sICAM-1 correlated with the serum concentrations of anti-thyroid-stimulating hormone (TSH)-receptor antibodies (TSHR-R) (n = 21; r = 0.929 and r = 0.810, respectively) and anti-thyroid peroxidase antibodies (TPO-Ab) (n = 21; r = 0.673 and r = 0.750, respectively). However, no correlation between sELAM-1 and TPO-Ab, TSHR-R, and anti-thyroglobulin antibodies (Tg-Ab), respectively, could be found. In addition to thyroid hormones and autoantibodies, serum concentrations of sELAM-1 and sVCAM-1, but not sICAM-1, could be useful as clinical markers for disease activity.

Topics: Autoantibodies; Cell Adhesion Molecules; E-Selectin; Endothelium, Vascular; Female; Goiter; Graves Disease; Humans; Immunoenzyme Techniques; Intercellular Adhesion Molecule-1; Iodine; Male; Methimazole; Thyroid Hormones; Thyroxine; Vascular Cell Adhesion Molecule-1

A 35-year-old female hematology technician with Graves' disease developed agranulocytosis a few days after starting therapy with Tapazole (methimazole). Because of a recent report of use of recombinant human granulocyte colony-stimulating factor (G-CSF) in patients with propylthiouracil-induced agranulocytosis, 5 micrograms/kg/day G-CSF was administered and her granulocyte count returned to normal after three doses, on the sixth day after the last dose of methimazole. We conclude that in patients with drug-induced agranulocytosis, the use of G-CSF, in addition to discontinuation of the offending drug, hastens recovery and reduces morbidity.

Topics: Adult; Agranulocytosis; Blood Cell Count; Female; Granulocyte Colony-Stimulating Factor; Granulocytes; Graves Disease; Humans; Methimazole; Recombinant Proteins

Radioiodine therapy has become a cornerstone of treatment of hyperthyroidism. However, the timing of its administration varies between 1) the time of initial diagnosis with concurrent therapy with beta adrenergic blocking drugs or 2) following induction of euthyroidism with thioamide, Propylthiouracil or Methimazole. This study assessed 24-HR 131I uptake values and the thyroid scan in 24 subjects with hyperthyroidism at the time of diagnosis and again after attaining the euthyroid state with Propylthiouracil or Methimazole. Propylthiouracil of Methimazole was withdrawn seven days prior to the second 24-HR 131I uptake and scan. In all subjects, as a group, 24-HR 131I uptake increased following antithyroid therapy as compared to the time of initial of diagnosis [76 + 5% Vs. 54 + 4%; p < 0.01]. The thyroid gland size decreased in nine of twenty-four subjects, but remained unchanged in the remaining subjects. Since 24-HR 131I uptake and the gland size are the major factors influencing the therapeutic radioiodine dosage, it is possible that initial therapy with thioamide drugs may reduce the therapeutic dose of 131I in subjects with hyperthyroidism belonging to both groups, i.e., Graves' disease and Multinodular toxic goiter by inducing a rise in 24-HR 131I uptake. Furthermore, the shrinkage of thyroid glands may further decrease the radioiodine dosage in patients with Graves' disease.

Topics: Adult; Aged; Combined Modality Therapy; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Thyroid Gland

Topics: Adult; Carbimazole; Female; Fetus; Graves Disease; Humans; Maternal-Fetal Exchange; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Function Tests; Thyroid Gland; Thyrotoxicosis

Topics: Adenoma; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Neoplasms

Insulin autoimmune syndrome (IAS) includes fasting or reactive hypoglycemia, hyperinsulinemia and the presence of insulin-binding antibodies in patients who have never been exposed to exogenous insulin. The report concerns a 34-year-old male patient with Graves' disease who had history of having taken methimazole for two months, without any consequence, 4 years previously. However, when methimazole was again administered for three weeks followed by a week of carbimazole, the patient suffered hypoglycemia 4 times during the next 4 weeks. He denied history of diabetes mellitus (DM), of taking any oral hypoglycemic agent or of having received insulin injection. Laboratory data showed total serum insulin level > 320 microU/mL, free insulin 55 microU/mL and insulin antibody 88.3%. Oral glucose tolerance test (OGTT) revealed DM pattern. Since the patient had history of allergy to anti-thyroid drugs before this event, so he was treated with radioiodine (131I). There was no episode of hypoglycemic attack during 15 months of follow-up.

Topics: Adult; Autoimmune Diseases; Carbimazole; Graves Disease; Humans; Insulin; Male; Methimazole

To investigate the possible major source of thyroid autoantibodies production, blood samples were obtained from thyroid vein, jugular vein and peripheral vein during subtotal thyroidectomy in 12 patients with Graves' disease (11F, 1M; age 16-39 yr). Among them, 7 were treated preoperatively by methimazole, 4 by iopanoic acid and 1 by propranolol. All blood samples were assayed for thyroglobulin (Tg), thyrotropin binding inhibition immunoglobulin (TBII), antithyroglobulin antibody (TgAb) and antimicrosomal antibody (McAb). Tg, a native product of thyroid gland, was markedly elevated in the thyroid veins, over 4 to 6 folds that of jugular veins or peripheral veins. However, the level of thyroid autoantibodies including TBII, TgAb and McAb in the thyroid veins were not significantly different from that in the jugular or peripheral veins. Our preliminary data suggest that it is thyroglobulin, and not thyroid antibodies that is present at higher level in the thyroid vein than the periphery.

Topics: Adolescent; Adult; Antibodies; Autoantibodies; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Iopanoic Acid; Male; Methimazole; Microsomes; Propranolol; Radioimmunoassay; Thyroglobulin; Thyroid Gland; Thyroxine; Triiodothyronine

Type 1 collagen is the major organic constituent of the bone: its synthesis is reflected by the serum levels of type 1 procollagen C-terminal propeptide (PICP), which is therefore considered an index of osteoblastic activity. Serum PICP along with other serum and urinary markers of bone metabolism were measured in 16 untreated premenopausal females affected by Graves' disease and also in 7 of them after attainment of euthyroidism by methimazole treatment. Before treatment PICP was higher than sex and age-matched controls (324.19 +/- 101.74 vs. 131.44 +/- 26.25 micrograms/l, p < 0.001). Osteocalcin, alkaline phosphatase, serum calcium and urinary excretions of calcium and hydroxyproline were significantly increased with respect to controls, whereas parathormone was lower. Treatment induced a significant decrease of PICP, as well as calcemia, calciuria and hydroxyprolinuria compared to pretreatment values, while osteocalcin and alkaline phosphatase did not significantly differ. Non parametric correlation analysis showed positive correlation of free T3 and PICP (rs = 0.73, p < 0.005), osteocalcin and alkaline phosphatase; PICP was also significantly correlated with osteocalcin and alkaline phosphatase. Our data suggest that hyperthyroidism due to Graves' disease causes an increase of serum concentrations of PICP, which decrease after attainment of euthyroidism. The differences between PICP and BGP as markers of bone synthesis need to be further clarified.

Topics: Alkaline Phosphatase; Calcium; Female; Graves Disease; Humans; Hydroxyproline; Methimazole; Osteocalcin; Parathyroid Hormone; Peptide Fragments; Premenopause; Procollagen

We examined the effects of anti-thyroid drug treatment on serum autoantibodies against thyroid hormones (thyroid hormone autoantibodies, THAA), thyroglobulin (Tg) and thyroid peroxidase (TPO) in patients with Graves' disease by measuring each autoantibody level before and after treatment. Six patients among 40 untreated patients with Graves' disease had anti-thyroxine (T4) antibodies. One patient had both anti-T4 and anti-triiodothyronine (T3) antibodies. Thus the prevalence of THAA in untreated Graves' disease was 7 out of 40 (17.5%). Changes in T4-Ab levels after treatment varied. In five cases (cases 3-7) levels decreased 4-7 months after treatment. However, in the other two cases levels fluctuated 1, 3, 6 and 12 months after treatment. None of the previously THAA-negative patients became positive after treatment. Anti-Tg antibody (Tg-Ab) was positive in 34 out of 40 (85%) untreated cases and its level decreased in both THAA positive and negative patients after treatment. Anti-thyroid peroxidase antibody (TPO-Ab) was positive in 32 of the 40 (80%) untreated Graves' patients and its level significantly decreased after treatment. Our findings suggest that treatment with anti-thyroid drugs does not produce THAA in Graves' disease.

Topics: Adult; Autoantibodies; Female; Graves Disease; Humans; Iodide Peroxidase; Male; Methimazole; Propylthiouracil; Reference Values; Thyroglobulin; Thyroid Hormones; Thyroxine; Triiodothyronine

Visualization of malignant lymphomas and granulomatous disease is possible by [111In-DTPA-D-Phe1]octreotide scintigraphy through binding of the radioligand to somatostatin receptors on activated leukocytes. Because thyroidal and orbital tissues are infiltrated by activated leukocytes in Graves' disease, a cross-sectional study to visualize disease activity with [111In-DTPA-D-Phe1]octreotide scintigraphy was performed. A correlation between thyroidal [111In-DTPA-D-Phe1]octreotide accumulation and free T4 (disease expression) and thyroid binding-inhibiting immunoglobulins (disease activity) is present in untreated hyperthyroid Graves' disease. There is also a correlation between orbital [111In-DTPA-D-Phe1]octreotide uptake and the clinical activity score (disease activity) and total eye score (disease expression), respectively, in Graves' orbitopathy. Visualization of thyroidal and orbital Graves' disease is feasible, but further investigation is necessary to establish the role of [111In-DTPA-D-Phe1]octreotide scintigraphy in representing disease activity and expression and in predicting therapeutical outcome.

Topics: Eye; Eye Diseases; Graves Disease; Humans; Indium Radioisotopes; Methimazole; Octreotide; Pentetic Acid; Radionuclide Imaging; Thyroid Gland; Thyroxine

Cell-mediated immunity is important in the pathogenesis of Graves' disease. Activation of T cells is apparently associated with the release of soluble CD8 (sCD8) and CD4 (sCD4) molecules from the corresponding T cell subset. To test the possibility that the concentrations of these molecules may be related to Graves' disease activity, we measured serum sCD8 and sCD4 concentration in 58 Graves' patients using ELISA technique before and after treatment with methimazole as well as in 10 patients with toxic nodular goiter. sCD8 was significantly elevated in thyrotoxic patients [609.9 +/- 118 (SD) U/ml] compared to controls (264.1 +/- 98.8, p < 0.001) and normalized when patients became euthyroid as a result of methimazole treatment (278.7 +/- 89.1). The mean sCD8 concentration in the patients with toxic nodular goiter was 302 +/- 28 U/ml, no different from control. The sCD4 level in the Graves' disease group was not different from control values and did not change significantly with treatment. Correlations were found between the levels of serum thyroid hormone(s) and sCD8 concentration but not with anti-TSH receptor antibodies in the 50 patients with Graves' disease. In addition, serum sCD8 studied prospectively in eight patients after discontinuation of methimazole, increased before the rise in serum T4, and well before the clinical relapse of thyrotoxicosis. It is concluded that sCD8 is a useful marker for the activation of CD8+ cells in Graves' disease.

Topics: Adult; Biomarkers; CD4 Antigens; CD8 Antigens; Female; Graves Disease; Humans; Immunity, Cellular; Lymphocyte Activation; Male; Methimazole; Middle Aged; Recurrence; Solubility; T-Lymphocyte Subsets; Thyroxine; Time Factors; Triiodothyronine

Graves' hyperthyroidism is due primarily to overproduction of antibodies to thyrotropin receptors (TR-ab), which stimulate the thyroid gland and cause hyperthyroidism. Antibody production during antithyroid drug therapy is an important determinant of the course of the disease. We therefore observed the changes of serum TR-ab, thyroglobulin (Tg) and thyroid hormone levels in response to administration of L-thyroxine (T4) in Graves' hyperthyroid patients during antithyroid drug therapy. Serum levels of TR-ab, Tg and other thyroid hormones were measured by radioimmunoassay (RIA) during either methimazole treatment alone or in combination with thyroxine in 60 Graves' hyperthyroid patients. The patients initially were treated with 30 mg of methimozole daily for 3 months, which was then reduced to 15 mg daily for the following 3 months. All patients were euthyroid 6 months after the start of antithyroid therapy and the TR-ab level decreased from 61 +/- 11% (+/- SD) to 28 +/- 7% (p < 0.01). Patients then were divided into three groups: group A (N = 25), whose TR-ab level was 10% or more (the cut-off value for positivity), received 0.1 mg of T4 and 10 mg of methimazole daily for 6 months; group B (N = 15), whose TR-ab level also was 10% or more and was age- and thyroid function-matched with group A, received only 10 mg of methimazole daily for 6 months; group C (N = 20), with a TR-ab level of less than 10%, received 10 mg of methimazole alone daily for 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Antibodies; Drug Therapy, Combination; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Receptors, Thyrotropin; Thyroglobulin; Thyroid Gland; Thyroid Hormones; Thyroxine

A 17-year-old Japanese woman developed a lupus erythematosus-like syndrome during treatment for Graves' disease with thiamazole and propylthiouracil. Erythema, arthralgia, and low grade fever developed during therapy with thiamazole; purplish-red erythema developed during therapy with propylthiouracil. Antinuclear antibodies, anti-single-stranded DNA antibodies, and anti-double-stranded DNA antibodies were positive throughout the administration of these two drugs. Eruptions and other symptoms improved after their discontinuation. The titers of autoantibodies also decreased two months after withdrawal. The patient had HLA DR4.

Topics: Adolescent; Antibodies, Antinuclear; DNA; DNA, Single-Stranded; Female; Graves Disease; Humans; Immunoglobulin M; Lupus Erythematosus, Systemic; Methimazole; Propylthiouracil; Skin Tests

We have recently reported that many euthyroid patients with a history of Graves' disease treated years earlier with methimazole (MMI) have a positive iodide (500 micrograms)-perchlorate discharge test (I-ClO4 test), suggesting a permanent thyroid iodide organification defect. We now report the results of the I-ClO4 test in patients with hyperthyroid Graves' disease before beginning a 1-yr course of MMI therapy and 40 days after MMI was discontinued. Twenty-nine patients (25 women and 4 men; mean age, 38 +/- 1.7 yr) with their first episode of hyperthyroid Graves' disease were studied. Before MMI therapy, I-ClO4 tests were carried out, and serum T4, T3, and TSH were measured to confirm the diagnosis of hyperthyroidism. A positive I-ClO4 test is defined as more than 15% 131I discharged from the thyroid 1 h after the administration of 1 g KClO4. Patients were then treated with 20 mg MMI for the first 2 months and variable doses thereafter for the next 10 months to maintain euthyroidism. Serum T4, T3, and TSH were measured monthly. Forty days after MMI was discontinued, I-ClO4 tests were repeated, and serum T4, T3, and TSH were measured every 2 months thereafter. Before MMI treatment, the I-ClO4 test was positive in 20 of 29 patients (69%) and negative in 9. The favorable responses (normal serum T4 and T3 values) to MMI therapy were similar in both groups. We have thus far studied 16 patients after MMI was discontinued and 9 of 12 patients (75%) with a negative I-ClO4 test after MMI therapy, and 1 of 4 patients (25%) with a positive test remained in remission for a mean of 7 months. We conclude that the I-ClO4 test is frequently positive in patients with untreated hyperthyroid Graves' disease, suggesting either an inability to organify the increased iodide concentrated by the hyperfunctioning gland or the concomitant presence of Hashimoto's thyroiditis, which almost always is associated with a positive I-ClO4 test. The former hypothesis is more likely, because many patients with a positive I-ClO4 test before MMI therapy had a negative test after MMI was discontinued.

Topics: Adult; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Perchlorates; Thyroid Gland; Thyroid Hormones; Thyroxine; Triiodothyronine

Spiroergometry might be applicable to detect alterations of cardiopulmonary functions related to hyperthyroidism. Thus, cardiac and respiratory changes as well as work capacity in hyperthroid female patients were to be assessed with the help of the Cardiopulmonal Exercise Test System. Twelve female hyperthyroid patients with Graves' disease of whom all were controlled in euthyroidism, were examined. Eighteen euthyroid female patients in whom intracardiac catheter examination ruled out cardiopulmonary disease served as controls. The anaerobic threshold was determined by means of the V-slope method. An echocardiography was performed in all patients. Ergometry was performed in a semisupine position using a continuous ramp protocol of 20 watt/min. A markedly reduced work capacity, and a high heart rate in rest and exercise were found. In the ratio heart rate/oxygen uptake a lower rise (p = 0.001) due to a decreased growth in the heart rate was noticed. Regarding the pulmonary system a decreased tidal volume in hyperthyroidism (p = 0.021), and a higher breathing frequency (p = 0.003) were recognized, as well as an impaired oxygen consumption, in comparison with the euthyroid state. Also, echocardiographically an increased cardiac index (p = 0.008) and a markedly reduced stroke volume (p = 0.005) in comparison to the control group were observed. Heart rate, work capacity, oxygen uptake, and the ratio heart rate to oxygen uptake were normalized in euthyroidism. With the help of the CPX-System noninvasive measure of marked cardiopulmonary changes in hyperthyroidism are possible, especially the lower growth of the heart rate in exercise, which might be the limiting factor of work capacity.

Topics: Adult; Aged; Echocardiography; Exercise Test; Female; Graves Disease; Hemodynamics; Humans; Hyperthyroidism; Lung Volume Measurements; Methimazole; Middle Aged; Oxygen; Thyroid Hormones

We present two cases of systemic lupus erythematosus (SLE) associated with both Basedow's disease and fatty liver. The first case is a 46-year-old Japanese female who was admitted because of high fever and general fatigue. She had been diagnosed as having Basedow's disease and treated with thiamazole for over 4 years. Since thiamazole-induced lupus was unlikely because of high titer anti-nuclear antibody and anti-DNA antibody and low levels of complements, a diagnosis of SLE was made. The upper abdominal ultrasound study and the specimen obtained by liver biopsy performed before initiating steroid therapy demonstrated marked fatty liver. SLE itself is considered as an etiology of fatty liver in this case. The second case was a 25-year-old Japanese female with SLE. She had been treated with prednisolone for 13 years and was complicated with Basedow's disease 10 years later. Fatty liver was also demonstrated in this patient on ultrasonography, and was thought to be resulted from long-term steroid hormone administration.

Topics: Adult; Fatty Liver; Female; Graves Disease; Humans; Lupus Erythematosus, Systemic; Methimazole; Middle Aged; Prednisolone

To determine whether there is an age-related difference in the therapeutic response to antithyroid drugs in hyperthyroid Graves' disease.. Retrospective analysis of treatment duration and recurrence rate.. Two hundred and twenty-two patients who have triiodothyronine-suppressible thyroids within 4 years of methimazole treatment.. Serum thyroid hormone levels, serum thyrotropin receptor antibody titer, and thyroidal radioiodine uptake.. A longer period of methimazole treatment was needed to normalize serum thyroid hormone levels and to restore normal thyroidal triiodothyronine suppressibility in young than in aged patients. There was an average 10-month lag between normalization of thyrotropin receptor antibody titer and restoration of thyroidal triiodothyronine suppressibility in both young and aged patients. Recurrence after discontinuation of methimazole was more frequent in young than in aged patients.. Aged patients with hyperthyroid Graves' disease show a more favorable response to antithyroid drugs than young counterparts.

Topics: Adolescent; Adult; Aged; Aging; Child; Female; Graves Disease; Humans; Lymphocyte Subsets; Male; Methimazole; Middle Aged; Recurrence; Retrospective Studies; Sex Factors; Thyrotropin-Releasing Hormone; Triiodothyronine

IL-2 production by mitogen-induced peripheral blood mononuclear cells was reported to be reduced in several autoimmune diseases, including Graves' disease (GD). This production defect in hyperthyroid GD was restored to normal by antithyroid drug therapy or during remission. However, its underlying mechanism and role in the autoimmune process are still uncertain. The present study was undertaken in order to screen the in vitro IL-2 generating system for putative factors responsible for its failure, and to see to what extent this was reversible. Thyroid hormone or antithyroid drugs had no effect on IL-2 production in vitro. Cultures were found to be free of soluble inhibitors of IL-2 production or action. IL-1 deficiency as a cause of the IL-2 defect was ruled out; rather, Graves' adherent cells were found to be activated in being capable of secreting large amounts of IL-1 and prostaglandin E2 (PGE2). The latter was not found to be responsible for the decreased IL-2 production. IL-2 production by Graves' mononuclears was completely restored to normal by: (i) adherent cell depletion, irradiation or substitution with normal adherent cells; (ii) preincubation of mononuclears for 24-72 h before mitogen stimulation; (iii) the synergistic action of a phorbol ester and a calcium ionophore. These data indicate that inhibition by activated adherent cells accounts for the in vitro IL-2 production defect in GD. This inhibition is not mediated by soluble factors, but probably through direct interaction with the producing cells, and is reversible in rested cultures or through a bypassed signal transduction.

Topics: Cell Adhesion; Cells, Cultured; Dose-Response Relationship, Drug; Graves Disease; Humans; Interleukin-1; Interleukin-2; Leukocytes, Mononuclear; Methimazole; Orbit; Propylthiouracil; Tetradecanoylphorbol Acetate; Triiodothyronine

Topics: Agranulocytosis; Female; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Methimazole; Middle Aged; Remission, Spontaneous

The primary objective of this study was to ascertain the effectiveness of granulocyte colony-stimulating factor in the treatment of antithyroid drug-induced granulocytopenia of varying degree. Sixteen patients with Graves' disease with antithyroid drug-induced granulocytopenia (granulocyte counts < 1.0 x 10(9)/L) each received a daily dose of 75 micrograms of granulocyte colony-stimulating factor administered subcutaneously. Within 24 hours of the first injection, the granulocyte count increased (0.6 to 12.3 x 10(9)/L) in all 10 patients with mild granulocytopenia (granulocyte counts between 0.5 and 1.0 x 10(9)/L) and all three with moderate granulocytopenia (granulocyte counts < 0.5 x 10(9)/L). The three remaining patients with severe granulocytopenia (agranulocytic), whose granulocyte counts were zero, did not recover from granulocytopenia until the 6th, 7th, and 14th days of treatment with granulocyte colony-stimulating factor. Examination of bone marrow taken at the onset of the disease in all three agranulocytic patients showed a prominent decrease in granulocytic series, while identical examination in six of eight patients with mild to moderate granulocytopenia showed close to normal granulocytic series. There was no elevation of serum granulocyte colony-stimulating factor concentration in four patients with mild granulocytopenia and one with moderate granulocytopenia at the onset of their disease, whereas those of the remaining three patients with severe granulocytopenia (agranulocytic) increased at onset of agranulocytosis. This information led us to conclude that: (1) granulocyte colony-stimulating factor is effective in the treatment of antithyroid drug-induced mild to moderate granulocytopenia and (2) in severe agranulocytic cases, granulocyte colony-stimulating factor is not effective. Accordingly, we were again reminded of the importance of early diagnosis and treatment of antithyroid drug-induced agranulocytosis.

Topics: Adult; Aged; Agranulocytosis; Female; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Male; Methimazole; Middle Aged; Propylthiouracil; Recombinant Proteins

In view of the adverse effects of the administration of pharmacological quantities of iodine to euthyroid patients with a history of a wide variety of thyroid disorders, it has been suggested that iodine-containing medications and radioopaque dyes containing iodine should be avoided, if possible, in patients with underlying thyroid disease. We have now prospectively studied the effects of pharmacological doses of a saturated solution of potassium iodide (SSKI) on thyroid function in euthyroid patients with a previous history of hyperthyroid Graves' disease successfully treated with antithyroid drugs. Ten euthyroid women (mean age, 56 yr) who had hyperthyroid Graves' disease successfully treated with methimazole 36.4 +/- 4.7 months earlier were evaluated before, during, and after the administration of 10 drops SSKI daily for 90 days. The following thyroid function tests were obtained: serum T4, T3, TSH, TSH receptor antibody (TSH-RAb), and antithyroid peroxidase antibody (AbTPO) concentrations; TRH tests; and iodine perchlorate discharge tests. Serum T4, T3, basal and TRH-stimulated TSH, and TSH-RAb values were normal before SSKI administration, but serum AbTPO levels were markedly positive in 7 and iodine perchlorate discharge tests were positive in 4 of these 10 women. During SSKI administration, basal and TRH-stimulated serum TSH values increased above normal in 2 women with normal serum T4 and T3 concentrations; thyroid hormone values and TRH tests were normal in the other 8 patients and similar to values observed in 4 euthyroid women without a history of thyroid disease given SSKI. Serum AbTPO increased slightly, but significantly, during SSKI administration in the 7 women with positive values at baseline (P < 0.05). TSH-RAb remained undetectable. After SSKI withdrawal, the 10 women were reevaluated 60 and 120 days later. Two women developed a blunted TSH response to TRH, but normal serum T4 and T3 concentrations, and 2 women developed overt hyperthyroidism, with undetectable basal and TRH-stimulated serum TSH and elevated serum T4 and T3 concentrations, requiring methimazole therapy. All values in the remaining 6 women were similar to those present before SSKI administration. These results suggest that some euthyroid patients with a history of antithyroid drug therapy for Graves' disease may develop thyroid dysfunction during and after excess iodine administration. The development of subclinical hypothyroidism during SSKI administration was not clini

Topics: Antithyroid Agents; Female; Graves Disease; Humans; Methimazole; Middle Aged; Potassium Iodide; Reference Values; Solutions; Thyroid Function Tests; Thyroid Gland; Time Factors

A clone of Chinese hamster ovary (CHO) cells transfected with the cloned human TSH receptor (CHO-R) was used to optimize an assay for thyroid-stimulating antibody (TSAb), measuring adenylate cyclase stimulation by purified immunoglobulin G from patients with Graves' disease. Optimal sensitivity to bovine TSH (1 mU/L) and TSAb was obtained using hypotonic buffer and measuring extracellular cAMP. In time-response experiments, TSAb stimulation was maximal after 2 h of incubation in hypotonic buffer. Under these conditions, a significant stimulation by Graves' immunoglobulin G was obtained with 33 of 35 (94%) samples from patients with untreated Graves' disease and with 21 of 23 (91%) from patients who relapsed after a course of antithyroid drugs. On the other hand, TSAb was detected in only 12 of 20 (60%) patients who were euthyroid during methimazole treatment and in 4 of 11 (36%) who were euthyroid after a course of antithyroid drugs. All samples from Graves' patients were also tested for TSAb activity on FRTL-5 cells. The results of cAMP stimulation in FRTL-5 and CHO-R showed a fairly good correlation (r = 0.60; P < 0.0001). In particular, of the 58 patients with active Graves' disease (35 with untreated hyperthyroidism and 23 relapsed after methimazole), 43 (74%) were positive in both assays, 3 (5%) were negative in both, 11 (19%) were negative in FRTL-5 and positive in CHO-R, and 1 (1.7%) was negative in CHO-R and positive in FRTL-5. In conclusion, CHO cells transfected with the cloned human TSH receptor are suitable for the clinical assay of TSAb. The sensitivity of this assay is higher than that obtained using FRTL-5 cells, having the additional advantages of expressing the human TSH receptor and requiring less cumbersome procedures for cell culture.

Topics: Adenylyl Cyclases; Animals; Autoantibodies; Cell Line; CHO Cells; Cloning, Molecular; Cricetinae; Cyclic AMP; Graves Disease; Humans; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Kinetics; Methimazole; Receptors, Thyrotropin; Thyroid Gland; Thyrotropin; Transfection

We present two cases of Graves' disease whose initial thyroidal scintiscan with 99mTcO4- (Case 1) and 123I (Case 2) showed unilateral diffuse uptake of radioisotopes. Initial diagnosis was possibility of malignancy in Case 1 and Graves' disease or Plummer's disease in Case 2. Both cases underwent right hemithyroidectomy. Histopathology of the resected thyroid gland in both showed hyperplastic columnar epithelium and infiltrative lymphocytes which was compatible with Graves' disease. Twenty seven (Case 1) and eight months (Case 2) after operation, both presented with thyrotoxic symptoms associated with enlarged left lobe, increased serum free thyroid hormone concentrations, suppressed TSH concentration, increased thyroidal 123I uptake in the remaining left lobe, and positive thyrotropin receptor antibodies. Both cases were successfully treated with methimazole. It was concluded that initial radioisotope uptake as well as scintigram in rare subgroup of patients with Graves' disease could be similar with that of non-autoimmune autonomous goiter (Plummer's disease).

Topics: Animals; Female; Graves Disease; Humans; Iodine Radioisotopes; Methimazole; Mice; Middle Aged; Radioimmunoassay; Radionuclide Imaging; Technetium; Thyroid Function Tests; Thyroid Gland; Thyroidectomy; Thyroxine; Triiodothyronine

A 36-year-old patient, euthyroid under methimazole treatment, was admitted because of an active Graves' ophthalmopathy and found to have a transient granulocytopenia. Forty-five days after this episode she developed classical agranulocytosis because of which the methimazole was stopped. The agranulocytosis occurred more than 20 months after the initiation of antithyroid drug therapy. Other causes for the initial phase of granulocytopenia were not found.

Topics: Adult; Agranulocytosis; Drug Monitoring; Female; Granulocytes; Graves Disease; Humans; Leukocyte Count; Methimazole; Time Factors

To reduce the number of tablets to be administered daily during antithyroid drug (ATD) treatment of Graves' disease (GD) and to evaluate the effectiveness of adding thyroxine after the patients had become euthyroid during methimazole therapy.. All patients were given gelatin capsules with 30 mg of methimazole 2 times per day for 4-6 weeks, followed by two capsules with 20 mg of methimazole and 75 micrograms of thyroxine to be taken once a day for 18-24 months. Thirty patients with Graves' disease without previous treatment for hyperthyroidism were included. Two were lost to follow-up and 28 (24 women and 4 men; age range 14-53 years; mean 34.2 years) were followed for 18 to 24 months with methimazole and thyroxine medication plus an additional 2 years after the treatment was suspended. After completion of the study the patients were, retrospectively, divided in two groups: group 1 (G1, n = 20) patients considered to be in remission, and group 2 (G2, n = 8) with persistent active Graves' disease.. All patients in group 1 had a significant reduction in the glandular mass, as estimated by ultrasonographic studies (mean +/- SD 67 +/- 13 g to 18 +/- 3 g, p < 0.01) whereas subjects in group 2 had no significant reduction in glandular mass (67 +/- 14 g to 53 +/- 16 g). Thyroglobulin levels (mean +/- SD) in G1 were 54 +/- 55 micrograms/L at baseline and decreased to 15 +/- 9 micrograms/L (p < 0.001), and in G2 thyroglobulin concentrations did not decrease significantly after therapy (58 +/- 20 micrograms/L vs 44 +/- 22 micrograms/L). Also, levels of thyroid-stimulating hormone receptor inhibiting antibody (TRAb) only decreased in G1 (49-21% to 8 +/- 5%; p < 0.001). Nineteen patients (all from G1), were euthyroid 2 years after treatment withdrawal, indicating a remission rate of 67.8%.. The administration of L-thyroxine during anti-thyroid drug treatment, with subsequent inhibition of thyroid-stimulating hormone secretion, may be an important factor in glandular mass reduction, decreasing both the production of antibodies to thyroid-stimulating hormone receptors and the frequency of recurrence of hyperthyroidism.

Topics: Adolescent; Adult; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Graves Disease; Humans; Male; Methimazole; Middle Aged; Patient Compliance; Thyroglobulin; Thyroid Gland; Thyroid Hormones; Thyrotropin; Thyroxine

Topics: Adolescent; Arousal; Female; Graves Disease; Humans; Hyperthyroidism; Methimazole; Motivation; Neurocognitive Disorders

The insulin autoimmune syndrome (IAS) is characterized by the following diagnostic criteria: severe spontaneous hypoglycemia without evidence of exogenous insulin administration, high levels of total serum immunoreactive insulin, and the presence of a high titer of antiinsulin antibody. Just before the onset of IAS, 13 of the 35 (37%) patients with IAS examined in this study had taken methimazole for the treatment of Graves' disease. To investigate the difference between the Graves' disease patients treated with methimazole who developed IAS and other IAS patients, HLA class II genes in both groups were analyzed by serological and DNA typing methods. All 13 patients with Graves' disease who developed IAS possessed a specific allelic combination, Bw62/Cw4/DR4 carrying DRB1*0406, whereas only 1 of 50 Graves' disease patients without IAS had Bw62/Cw4/DR4 (odds ratio, 891; P < 1 x 10(-10)) and carried not DRB1*0406 (odds ratio, 2727; P < 1 x 10(-10)), but DRB1*0405. Of the 22 IAS patients without Graves' disease, 13 had the combination Bw62/Cw4/DR4 carrying DRB1*0406 (odds ratio, 19.0; P < 0.07). Thus, it is highly likely that patients with Graves' disease develop IAS via treatment with methimazole when their Bw62/Cw4/DR4 carry DRB1*0406.

Topics: Adolescent; Adult; Aged; Autoimmune Diseases; Base Sequence; DNA; Female; Graves Disease; Histocompatibility Antigens Class II; HLA-B Antigens; HLA-B15 Antigen; HLA-C Antigens; HLA-DR4 Antigen; Humans; Insulin; Insulin Antibodies; Male; Methimazole; Middle Aged; Molecular Sequence Data; Polymerase Chain Reaction

We studied serum superoxide dismutase (SOD) in patients with Graves' disease. Measurements of immunoreactive Cu, Zn-SOD and SOD-like activities were made by enzyme-linked immunosorbent assay (Ube Industries Ltd) and Nitroblue Tetrazolium method (Wako Ltd), respectively. Serum from patients with untreated Graves' disease had a significantly higher concentration of Cu, Zn-SOD and higher SOD-like activity than those from normal subjects, patients with Graves' disease under treatment over one year, patients with Graves' disease in remission, and patients with untreated Hashimoto's disease. Methimazole treatment produced no significant change in SOD-like activity and Cu, Zn-SOD concentration when patients with Graves' disease had normal thyroid function. These results indicated that oxidative tissue injury existed in patients with Graves' disease with normal thyroid function under treatment; however, we could not clearly establish that thyroid function had a direct connection with oxidative tissue injury.

Topics: Adult; Enzyme-Linked Immunosorbent Assay; Female; Graves Disease; Humans; Male; Methimazole; Superoxide Dismutase; Superoxides; Thyroid Hormones

A prospective study was conducted to evaluate the effect of prolonged treatment of hyperthryoid Graves' disease with methimazole (MMI) for 12 months or Na ipodate for only 6.6 +/- 1.1 months, since the drug had to be discontinued because of persistent or recurrent hyperthyroidism during treatment. The eight patients who were treated with MMI alone for 12 months became euthyroid, and seven remained in remission for at least 6 months after MMI was discontinued. In contrast, only two of 10 patients treated with Na ipodate alone became euthyroid and remained so during therapy. No ipodate was discontinued in the eight patients who did not respond, and they were then treated with MMI. One patient had recurrent hyperthyrodism after NA ipodate was discontinued, and she was then treated with MMI. MMI was efficacious in treating these nine patients, and all patients were euthyroid by the third month of MMI administration. Five of these nine patients remained euthyroid for at least 6 months after MMI was discontinued, a remission rate that was not significantly different from that observed in the eight patients treated only and initially with MMI (Fisher's Exact Test). There was no significant change in serum thyroid peroxidase antibodies during treatment with MMI alone, Na ipodate alone, or Na ipodate followed by MMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Autoantibodies; Body Weight; Female; Graves Disease; Heart Rate; Humans; Ipodate; Male; Methimazole; Prospective Studies; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

We evaluated the determination of serum G-CSF in the diagnosis of granulocytopenia due to methimazole (MMI) in 54 patients with Graves' disease, while they were being treated with MMI, by way of measuring WBC counts and serum levels of G-CSF, thyroid hormones, IgE, and interleukin-2. Serum TSH was measured by immunoradiometric assay, serum G-CSF was done by enzyme immunoassay, thyroid hormones and IgE were done by radioimmunoassay, and serum Interleukin-2 was done by enzyme-linked immunosorbent assay. The population whose G-CSF levels were higher than the minimum detectable level (30pg/ml) was 6 (30%) in normal subjects, 4 (22%) in patients with untreated Graves' disease, 2 (12%) in patients with treated euthyroid Graves' disease, 3 (23%) in patients with Graves' disease who had gone through agranulocytosis, and 2 (33%) in patients with Graves' disease complicated with granulocytopenia. There was no significant change in WBC counts for 4 weeks, but there was a significant difference between WBC counts before treatment and those at 8 weeks after treatment. We observed no significant change of serum G-CSF levels in patients with Graves' disease under treatment. However, there were significantly high levels of serum G-CSF and significantly low counts of WBC in patients with Graves' disease complicated with granulocytopenia induced by MMI, compared with those in normal subjects, patients with untreated Graves' disease, patients with treated euthyroid Graves' disease, and patients with euthyroid Graves' disease who had gone through agranulocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Agranulocytosis; Bone Marrow Cells; Feedback; Female; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Leukocyte Count; Male; Methimazole; Middle Aged

The chance of permanent remission after prolonged drug therapy was investigated in 41 patients with toxic multinodular goiter. For purposes of comparison a group of 41 patients with Graves' disease was also studied. After euthyroidism was achieved all patients received a combination of thionamide and thyroxine for at least 12 months. The minimum follow-up period was 2 yr. Relapse of thyrotoxicosis occurred in 95.1% of patients with toxic multinodular goiter and 34.1% of patients with Graves' disease (p < 0.001). It is concluded that for patients with toxic multinodular goiter early radioiodine therapy or surgery is preferred since prolonged drug therapy seldom produces permanent remission.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antithyroid Agents; Carbimazole; Drug Therapy, Combination; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Radionuclide Imaging; Recurrence; Thyroid Gland; Thyroxine

Thyroxine-binding globulin (TBG) is the major thyroid hormone transport protein. Several inherited TBG variants resulting in partial or complete TBG deficiencies have been shown to be caused by either one or two nucleotide substitutions, or one nucleotide deletion in the coding regions of the TBG gene. In this report, a Japanese female patient (proband) with hyperthyroid state, whose lower TBG levels did not return to normal under the euthyroid state after treatment was examined. Genomic DNA samples from the proband with thyroxine-binding globulin deficiency (termed TBG-Kumamoto) and her family were subjected to the polymerase chain reaction, and the generated DNA fragments were sequenced. A single nucleotide substitution in the codon for the amino acid 363 of native TBG molecule (CCT to CTT) was found, resulting in the replacement of proline by leucine. It was revealed that the proband was a heterozygote and her father was a hemizygote. The mutation was confirmed by the allele-specific amplification of genomic DNAs from the proband and her father using oligonucleotide primers of normal or mutant residues at the 3' position in the polymerase chain reaction. These results indicate that the abnormality of TBG-Kumamoto is the consequence of this mutation. Genetically, this point mutation observed in TBG-Kumamoto might be classified as a new type of TBG deficiency.

Topics: Adult; Base Sequence; Codon; Electrophoresis, Agar Gel; Exons; Female; Genotype; Graves Disease; Humans; Male; Methimazole; Molecular Sequence Data; Oligonucleotide Probes; Pedigree; Point Mutation; Polymerase Chain Reaction; Thyrotropin; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine

A high prevalence of antibodies to double-stranded DNA (AbDNAds) has been recently reported in serum of patients with autoimmune thyroid disorders, but the specificity of this finding has been questioned. For this reason, the prevalence of several antibodies to DNA-related nuclear antigens (AbDRENA) has been evaluated in sera of patients with autoimmune and non-autoimmune thyroid disease. The study group included: 46 Graves' disease patients, 28 Hashimoto's thyroiditis patients, 25 patients with toxic nodular goitre and 11 with non-toxic nodular goitre. Twenty-eight Graves' patients were retested during methimazole (MMI) therapy, and 5 after radioiodine administration. Twenty-two patients with systemic lupus erythematosus and 28 normal subjects served as positive and negative controls, respectively. AbDRENA included: AbDNAds by RIA or immunofluorescence (IF); antibodies to single-stranded DNA (AbDNAss) and antibodies to histone (AbHist) by ELISA methods; antibodies to nuclear antigens (ANA) by immunofluorescence. RIA values were considered to be abnormal when 2 SD above the mean of normal controls. In our study 13% of Graves' patients were positive for AbDNAds by RIA: all of them had negative tests by IF; 11% were positive for AbDNAss, 2% for AbHist and 7% for ANA. A comparable prevalence of positive results for AbDNAds by RIA, with negative IF tests, was found in Hashimoto's thyroiditis patients. No significant changes of antibody levels were observed in Graves' patients during MMI treatment or after radioiodine administration. A positivity for AbDNAds or AbDNAss was found in 8% of patients with toxic nodular goitre, but in none of those with non-toxic goitre.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Antibodies, Antinuclear; Child; Female; Goiter, Nodular; Graves Disease; Humans; Immunoassay; Iodine Radioisotopes; Lupus Erythematosus, Systemic; Male; Methimazole; Middle Aged; Thyroiditis, Autoimmune

The well documented ability of immunoglobulins G (IgGs) from Graves' patients to stimulate cAMP production is believed to be involved in the pathophysiology of this disease. It is still under discussion whether other intracellular messengers known to regulate thyroid function might play a similar role. This study shows that phospholipase-A2, a signal pathway unrelated to cAMP, is activated by Graves' IgGs. The IgGs from 67 patients with active Graves' disease, 8 patients with Graves' disease in remission, 5 patients with idiopathic myxedema, 2 patients with Hashimoto's thyroiditis, 57 patients with nonautoimmune thyroid disease, and 65 normal subjects were tested for their ability to stimulate phospholipase-A2 activity, as measured by arachidonic acid release from FRTL5 thyroid cells. The IgGs from patients with active Graves' disease caused a significant increase in arachidonic acid release compared to those from normal subjects, patients with nonautoimmune thyroid diseases, and patients with Graves' disease in remission (P less than 0.0001). The IgGs from active Graves' patients were also able to increase cAMP accumulation in FRTL5 cells. This effect did not correlate with the ability of the same IgGs to induce arachidonic acid release, suggesting that Graves' IgGs stimulate these two pathways by separate mechanisms. Moreover, a subgroup of IgGs that stimulated phospholipase-A2 did not increase the cAMP levels in FRTL5 cells. Our data suggest a novel mechanism of action of Graves' IgGs, the activation of phospholipase-A2, well distinguishable from the known effect on cAMP accumulation. The assay we describe could be helpful in improving the diagnosis and therapy of Graves' disease and in distinguishing it from nonautoimmune thyroid diseases. It also supplies the basis for a prospective subclassification of the Graves' patients, which might become useful to clarify the pathophysiology of this disease.

Topics: Adolescent; Adult; Aged; Animals; Arachidonic Acids; Cell Line; Cyclic AMP; Female; Graves Disease; Humans; Immunoglobulin G; Male; Methimazole; Middle Aged; Phospholipases A; Phospholipases A2; Propylthiouracil; Rats; Reference Values; Thyroid Diseases; Thyroid Gland; Thyroid Hormones; Thyrotropin

Should one correct for extrathyroidal neck radioactivity ('neck background') when interpreting perchlorate discharge test results? A new background correction method was developed using a linear probe. 123I produces photon peaks at two energy levels: 159 keV (gamma-rays) and 28 keV (X-rays), with an attenuation of 15 and 35% per cm water, respectively. If one fixes the position of the subject's neck, radiation from thyroid 123I produces an X/gamma detection ratio (alpha) which is constant and, due to the anterior localization of the thyroid, higher than the ratio (beta) produced by extrathyroidal 123I. These two ratios can be determined in vivo and used to calculate background-corrected and depth-corrected thyroid uptake. In simulation experiments our method was effective so long as the 'gland' was situated close enough to the 'neck' surface for the difference (alpha-beta) to be less than 0.19. Perchlorate discharge tests were performed in five euthyroid subjects who were pretreated with methimazole. The difference (alpha-beta) ranged from 0.27 to 0.36. Uncorrected, the mean discharge was 57% (range 47-66); corrected, it was 92% (range 88-94). In 15 hyperthyroid Graves' patients, with goitres varying from 13 to 63 ml, alpha-beta ranged from 0.22 to 0.40 and was unrelated to goitre size. The contribution of neck background is quantitatively important, especially when thyroid uptake is low; our new method corrects for it, even with large goitres.

Topics: Graves Disease; Humans; Iodine Radioisotopes; Methimazole; Neck; Perchlorates; Radionuclide Imaging; Thyroid Gland; Time Factors

This paper reports the determined results of OKT3, OKT4, OKT8, ERFC, smIg and CIC, TMCA, TGA in 31 cases of Graves disease and in 20 normal controls. The results showed that the OKT3, OKT4, OKT8, ERFC were significantly lower than those in the normal controls, whereas the smIg was higher than that in normal controls. The difference between the two groups was very significant. Even though the ratio of OKT4/OKT8 showed no significance of both. Typology of Graves disease according to the theory of TCM, all 31 cases were divided into two types: (1) 14 cases of depression of Liver-energy and asthenia of Spleen; (2) 17 cases of deficiency of yin leads to hyperactivity of Fire. The OKT8 and the ratio of OKT4/OKT8 in the latter respectively were lower and higher than those of the former. The difference between the two types was significant (P less than 0.01, P less than 0.05) whereas the positive rates of the CIC, TMCA, TGA also were higher in the deficiency of Yin leads to hyperactivity of Fire than those in the depression of Liver-energy and asthenia of Spleen. After treatment with combined TCM-WM on 31 cases of Graves disease, it was found that the OKT4, OKT8, ERFC were significantly elevated, the smIg was markedly decreased than those without treatment. It was also found that smIg markedly decreased in two types, OKT8, ratio of OKT4/OKT8 in the latter and ERFC in both types all returned to normal. Remainder indexes had no obvious change before and after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; CD4-CD8 Ratio; Drugs, Chinese Herbal; Female; Graves Disease; Humans; Male; Medicine, Chinese Traditional; Methimazole; Middle Aged; T-Lymphocyte Subsets; Yin Deficiency

One hundred and- eighteen newly diagnosed patients with Graves' disease were treated by tapazole for 6 months (short-term course) and followed up for another 12 months. Forty three percent remission rate was found in this group. A regular course of antithyroid drug therapy for 1.5-2 years with 50% remission rate was taken as control. Cost-effectiveness analysis was made to compare the cost in the two different kinds of therapy. The results showed that the total costs of the treatment per 100 cases were 17,746 yuan for the short-term therapy and 30,708 yuan for the regular therapy, with an average of 412.7 yuan and 614.2 yuan per case respectively. In comparison with the short-term therapy, the regular course could remit 7 more cases at a cost of 12,962.40 yuan, with an average of 1851.80 yuan per case. Therefore, the cost was high by prolonged course of therapy to increase slightly remission rate, although it could remit a few more cases. This study suggests that six-month treatment is preferable for those who live in the rural or remote area where the economy was less developed. A longer course of therapy may be unnecessary for those who have been treated by antithyroid drugs for 6 months or longer and are predicted to obtain a possible prolonged remission.

Topics: Cost-Benefit Analysis; Costs and Cost Analysis; Female; Graves Disease; Humans; Male; Methimazole; Remission Induction; Time Factors

Antithyroid drugs, considered the treatment of choice for hyperthyroidism during pregnancy, may have an adverse effect on intellectual development of the offspring. We examined the intellectual capacity of 31 subjects aged 4-23 years, born to women with Graves disease who received antithyroid drugs throughout pregnancy. Methimazole 40-140 mg/week (n = 15) or propylthiouracil 250-1400 mg/week (n = 16) was given. I.Q. was assessed using the Wechsler test appropriate for age. Twenty-five unexposed siblings served as controls. The exposed and unexposed groups did not differ with respect to the total I.Q. Both groups scored equally in verbal and performance skills and in each of six main subcategories of the tests. There was no difference between exposure to methimazole and propylthiouracil or between the higher (greater than 40 mg/week and greater than 600 mg/week, respectively) and lower dosages. All children were euthyroid at birth and none had goitre. We conclude that exposure to methimazole or propylthiouracil during pregnancy in doses sufficient to control maternal hyperthyroidism does not pose any threat to intellectual capacity of the offspring.

Topics: Adolescent; Adult; Child; Child, Preschool; Female; Graves Disease; Humans; Intelligence; Methimazole; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Propylthiouracil

Reactive oxygen species are generated in tissues by activated mononuclear cells and macrophages. These cells infiltrate the thyroid gland in Graves' disease (GD), as well as the retroocular and pretibial space in Graves' ophthalmopathy and pretibial myxedema (PTM). Because a 72 kilodalton heat shock protein (HSP 72) is associated with autoimmune thyroid disease and is selectively expressed in fibroblasts derived from involved sites of patients with Graves' ophthalmopathy and pretibial myxedema, we studied the influence of oxygen free radicals (OFR), oxygen radical scavangers (ORS), and antithyroid drugs on HSP 72 expression in Graves' retroocular fibroblasts. Fibroblast monolayers were exposed to hydrogen peroxide (H2O2) or heat stress with simultaneous treatment, or pretreatment, with the ORS diaminobenzidine, nicotinamide, glutathione, propylthiouracil (PTU), or methimazole (MT). HSP 72 expression was determined by sodium dodecylsulfate polyacrylamide-gel electrophoresis, followed by immunoblotting with an anti-HSP 72 monoclonal antibody and densitometric quantitation of HSP 72 immunoreactivity. Baseline HSP 72 expression in Graves' retroocular fibroblasts was strongly enhanced by H2O2 and heat stress. Both pretreatment and simultaneous treatment with the ORS and any of the antithyroid agents significantly reduced the abundance of H2O2-induced (P less than 0.01), and to a lesser degree heat-induced (P less than 0.05), HSP 72 expression. These results demonstrate that, in Graves' retroocular fibroblasts, H2O2-induced HSP 72 expression is diminished both by classical ORS and by the antithyroid agents PTU and MT. In addition, heat-induced HSP 72 expression appears to be mediated in part by OFR. Stimulation of immunogenic 70 kilodalton HSPs by OFR, derived from immunocompetent cells infiltrating the affected tissues in GD, may play a role in the autoimmune process. The beneficial effect of MT and PTU on the clinical course and immune status of patients with GD may be related to their OFR-scavanging properties.

Topics: 3,3'-Diaminobenzidine; Cells, Cultured; Connective Tissue; Electrophoresis, Polyacrylamide Gel; Eye; Fibroblasts; Fluorescent Antibody Technique; Free Radicals; Gene Expression; Glutamine; Graves Disease; Heat-Shock Proteins; Humans; Hydrogen Peroxide; Immunoblotting; Methimazole; Niacinamide; Oxygen; Propylthiouracil

An abnormal thyroid echographic pattern characterized by a diffuse low echogenicity has been described in Hashimoto's thyroiditis and Graves' disease. The aim of the present work was to study the relationship between thyroid hypoechogenicity and the outcome of treatment for hyperthyroidism with antithyroid drugs in patients with Graves' disease. The study group included 105 patients who underwent a course of methimazole treatment. Thyroid ultrasonography was carried out at diagnosis, and autoantibodies to thyrotropin receptor (TR-ab) were measured at the end of treatment. During the follow-up after methimazole treatment, 87/105 (83%) patients had relapse of hyperthyroidism and 18/105 (17%) were in remission. Recurrence of hyperthyroidism occurred in 71/76 (93%) patients with thyroid hypoechogenicity and in 16/29 (55%) of those with normal thyroid echogenicity (chi 2 = 19.0; p less than 0.0001). Positive TR-ab values at the end of methimazole treatment were found in 59/76 (78%) patients with thyroid hypoechogenicity and in 12/29 (41%) patients with normal thyroid echogenicity (chi 2 = 10.9; p less than 0.0001). Sixty-five/87 (74%) patients with relapse of hyperthyroidism and 6/18 (33%) of those who remained euthyroid were TR-ab-positive at the end of methimazole treatment (chi 2 = 9.8; p less than 0.002). The finding of thyroid hypoechogenicity at diagnosis had higher specificity (0.81) and sensitivity (0.72) with respect to TR-ab positivity at the end of methimazole treatment (0.74 and 0.66 respectively) for the prediction of relapse of hyperthyroidism. Therefore, the evaluation of thyroid echographic pattern can be considered a useful prognostic tool in patients with Graves' disease.

Topics: Adult; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Recurrence; Thyroid Gland; Ultrasonography

In 77 untreated patients (16 males and 61 females, aged 12 to 65 years) with hyperthyroid Graves' disease, and in 107 control subjects (36 males and 71 females, aged 13 to 78 years), blood urea nitrogen (BUN), serum creatinine (Scr) levels, and BUN to Scr ratios (BUN/Scr) were determined. In 53 patients, the determinations were performed before treatment and after restoration of euthyroidism by treatment with an antithyroid drug. In addition, in seven untreated patients and seven normal subjects, renal clearances of creatinine (Ccr), urea nitrogen (Cun), inulin (Cin), and p-aminohippurate (CPAH) were also determined. The distal tubule delivery of chloride (DTD) and the distal fractional chloride reabsorption (DFCR) were also measured in these subjects: DTD = (CH2O + Ccl)/Cin x 100, and DFCR = CH20/(H20 + Ccl) x 100, where CH20 and Ccl stand for clearances of H2O and chloride, respectively. BUN was significantly elevated, while Scr was significantly depressed, in untreated patients with hyperthyroid Graves' disease. Accordingly, the BUN/Scr was markedly elevated. Restoration of euthyroidism accompanied the normalization of all these abnormalities. Ccr and Cun were significantly elevated, but Cin (glomerular filtration rate [GFR]) was slightly, but insignificantly, elevated in the patients. As a result, the ratios Ccr/Cin and Cun/Cin were significantly greater in the patients than in controls (Ccr/Cin, 1.42 v 1.00; Cun/Cin, 0.92 v 0.68). The amounts of urinary creatinine and urea nitrogen (UN) excretion were decreased and increased, respectively, and DTD was significantly depressed, but DFCR was unchanged in the patients. We conclude that BUN is elevated, Scr is depressed, and the BUN/Scr is increased in hyperthyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Urea Nitrogen; Chlorides; Creatinine; Female; Graves Disease; Humans; Kidney; Kidney Function Tests; Kidney Tubules; Male; Methimazole; Reference Values; Renin; Thyroxine; Triiodothyronine

A reversibly decreased iodine absorption was observed in a patient with Graves' disease. This was associated with a reversible interference of iodination and was probably caused by thyrostatic medication.

Topics: Adult; Female; Graves Disease; Humans; Iodine; Methimazole; Thyroxine

Graves' disease in a girl with Turner's syndrome (karyotype 46,Xdel(Xp)) is described. Hyperthyroidism led to a pronounced acceleration of height velocity. During treatment with methimazole and L-thyroxine, height velocity normalized. The patient also developed spontaneous puberty with a clear-cut pubertal growth spurt. Final height, however, did not appear to be influenced either by Graves' disease or by spontaneous puberty.

Topics: Child; Female; Graves Disease; Growth Disorders; Humans; Methimazole; Propranolol; Puberty; Thyroid Function Tests; Thyroxine; Turner Syndrome

A 26-year-old woman who received methimazole treatment for Graves' disease is discussed. Two months following treatment, her serum GOT level rose to 45 K.U, her GPT to 60 K.U, and her lactate dehydrogenase (LDH) to 645 W.U; a hepatic disorder was then suspected. Later, the serum GOT and GPT concentrations decreased to a normal range, but her serum LDH continued to maintain a high level. An LDH isoenzyme analysis showed an abnormally broad LDH. The IgG that was linked to the LDH is suspected to have been the result of her underlying autoimmunity, the methimazole treatment, and the development of her hepatic disorder. Thus, this IgG was thought to be the autoantibody to LDH.

Topics: Adult; Autoantibodies; Female; Graves Disease; Humans; Immunoglobulin G; Immunoglobulin kappa-Chains; Isoenzymes; L-Lactate Dehydrogenase; Liver Diseases; Methimazole

We analyzed the evolution of the ophthalmopathy associated with Graves' hyperthyroidism in 45 patients treated with two different antithyroid drug regimens. Group A patients (n = 31) received either methimazole (40-100 mg daily) or propylthiouracil (400-900 mg daily) combined with T3 daily throughout treatment. Group B patients (n = 14) were treated with conventional regimen with lower doses of either methimazole (5-25 mg daily) or propylthiouracil (50-300 mg daily) and no T3 addition. Eye signs and proptosis measurement were evaluated just before the beginning of the treatment and compared with the results after antithyroid drug withdrawal. Improvement of the eye signs considered on grounds of the NOSPECS classification was greater in group A than group B (p less than 0.01). Also, the decrease in proptosis measurement was greater (p less than 0.01) in patients treated with combined regimen (21.5 +/- 2.4 mm to 20.4 +/- 2.3 mm) than in patients receiving conventional therapy (20.4 +/- 1.6 mm to 20.0 +/- 1.7 mm). Serum thyroglobulin concentrations did not correlate with either the severity or the evolution of the ophthalmopathy. Negative serum antithyroglobulin antibody (TgAb) was associated with the improvement of the ophthalmopathy that was noted in 24 out of 27 patients (Chi-Square = 5.84; p less than 0.001). Thus, serum TgAb levels might have some connection with progression of eye signs but serum Tg concentration does not. Our study suggests that in most patients the transition from hyperthyroidism to euthyroidism induced by antithyroid drug therapy is associated with the improvement of the Graves' ophthalmopathy. However, no marked difference can be drawn between the two treatment regimens.

Topics: Adolescent; Adult; Autoantibodies; Drug Therapy, Combination; Eye Diseases; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Propylthiouracil; Thyroglobulin; Triiodothyronine

Twenty-nine patients (22 female) aged 2 to 17 years were followed with serial measurements of serum triiodothyronine, thyroxine, and thyrotropin during medical therapy for Graves disease. Fourteen patients had 17 instances of hypothalamic-pituitary-thyroid suppression with inappropriately low thyrotropin levels. Five patients had six episodes of low thyroxine and triiodothyronine levels with normal levels of thyrotropin, and 10 patients had 11 episodes of normal thyroxine and triiodothyronine levels with subnormal levels of thyrotropin. We conclude that thyrotropin values may not be reliable for diagnosing either mild hypothyroidism or persistent hyperthyroidism during the medical treatment of Graves disease.

Topics: Adolescent; Child; Child, Preschool; Female; Graves Disease; Humans; Hyperthyroidism; Hypothalamo-Hypophyseal System; Hypothyroidism; Male; Methimazole; Propylthiouracil; Retrospective Studies; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

Intrathyroidal concentrations of methimazole (MMI) were measured by means of high-performance liquid chromatography in 46 patients with Graves' disease who had undergone thyroidectomy. In this experiment, the dose of the drug varied from 5 mg/day to 40 mg/day, and the interval between the last dose and surgery ranged from 2 to 26 hours, and the mode of drug administration varied from a single dose to four divided doses. With dose of MMI from 5 to 15 mg/day, intrathyroid levels of MMI increased with increasing dose, but without significant increase when the dose was above 15 mg/day. There was no difference between patients taking the drug in divided doses and those taking it in one single dose of the same amount, or between patients taking the final dose 2 hours before thyroid excision aud those taking it 26 hours before excision. Our results indicate a saturable uptake mechanism for MMI by the thyroid, and MMI 15 mg/day is the most satisfactory dose for treating hyperthyroidism. The intrathyroidal concentrations are maintained for 26 hours at least, and the single daily dose of MMI is effective and reasonable for treatment of Graves' disease.

Topics: Adolescent; Adult; Aged; Chromatography, High Pressure Liquid; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Thyroid Gland; Thyroidectomy

Topics: Autoantibodies; Congenital Abnormalities; Female; Fetus; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Function Tests; Thyroid Gland

We measured soluble interleukin 2 receptor, a part of the Tac protein (p55), in peripheral blood to study the immunological condition of the T cell in autoimmune thyroid disease. In 26 patients with untreated Graves' disease and 7 hyperthyroid patients with Hashimoto's thyroiditis, the mean levels of soluble IL-2 receptor were both significantly higher than in normal controls (1497 +/- 649 (mean +/- SD), 641 +/- 137 vs 221 +/- 63 10(3) U/l, p less than 0.001). There was good correlation between soluble IL-2 receptor levels and blood thyroxine levels (r = 0.684, p less than 0.001) in patients with untreated Graves' disease, but no correlation of soluble IL-2 receptor with TSH-inhibitory immunoglobulins, TS-ab, thyroidal autoantibodies to thyroglobulin and thyroidal microsomal antigen was found. We thought that the level of soluble IL-2 receptor is not dependent only on immunological conditions, but also on thyroid hormone status. When T3 was administered to subjects in remission from Graves' disease and in normal controls, the soluble IL-2 receptor levels significantly increased. Moreover, the mean level of soluble IL-2 receptor in patients with toxic multinodular goitre was also significantly higher than in normal controls (411 +/- 148 vs 221 +/- 63 10(3)U/l, p less than 0.05). We conclude that the soluble IL-2 receptor levels are higher in sera of subjects with elevated levels of thyroid hormone.

Topics: Adult; Aged; Autoantibodies; Enzyme-Linked Immunosorbent Assay; Female; Goiter, Nodular; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Microsomes; Middle Aged; Propylthiouracil; Receptors, Interleukin-2; Thyroglobulin; Thyroiditis, Autoimmune; Thyrotropin; Thyroxine; Triiodothyronine

This retrospective study serves as an inquiry into the common practice of long-term administration of small maintenance doses of either methyl-mercaptoimidazole (MMI) or propylthiouracil (PTU) to Graves' hyperthyroid patients who became euthyroid with primary large doses of the same drugs. One hundred and two patients with Graves' hyperthyroidism treated with antithyroid drug (ATD) were studied. Sixty-one were treated with conventional long term therapy and 41 were treated with short-term therapy. Small maintenance doses of ATDs were not administered to the short-term therapy patients. The duration of long-term therapy was 28.6 +/- 20.2 months (from 12 to 48 months) and that of short-term therapy was 8.4 +/- 1.8 months (from 5 to 11). Post therapy and follow-up observation continued for 19.0 +/- 2.7 months (16-25 months) in both long-term and short-term patients. Of the 61 long-term therapy patients, 20 were relapsed and 41 (67.2%) continue to remain in remission. So too, of the 41 short-term therapy patients, 14 relapsed and 27 (65.9%) still remain in remission. There was no statistical difference between the long-term and short-term therapy group in age, sex, duration of symptoms before diagnosis, antithyroid antibodies, radioactive iodine uptake, free thyroid hormone levels or goiter size before treatment or in TBII levels at cessation of ATD. It is concluded that 'short-term ATD therapy' without a maintenance dose is sufficient and saves several months of the patient's and clinician's time.

Topics: Adult; Autoantibodies; Drug Administration Schedule; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Propylthiouracil; Remission Induction; Retrospective Studies; Thyroid Gland; Thyrotropin; Triiodothyronine

To investigate the relationships between lymphocyte subsets and thyroid function, peripheral blood lymphocytes were analysed with cell surface antigens of activated (HLA-DR+) T, helper T (CD4+ 2H4-, CD4+ 4B4+) and suppressor-inducer T (CD4+ 2H4+, CD4+ 4B4-) cells subsets in 56 patients with Graves' disease, 16 patients with Hashimoto's thyroiditis, 7 patients with typical subacute thyroiditis and 2 patients with the thyrotoxic phase of autoimmune thyroiditis. Both patients with Graves' disease and Hashimoto's thyroiditis had increased percentages of HLA-DR+ T (Ia+ CD3+) cells as well as HLA-DR+ helper-inducer T (Ia+ CD4+) cells, which seemed to be independent of treatments. The percentage of HLA-DR+ suppressor-cytotoxic T (Ia+ CD8+) cells was increased in euthyroid or hypothyroid patients with Graves' disease following treatment, but was normal in hyperthyroid patients. The percentages of Ia+ CD4+ cells and Ia+ CD8+ were also increased in patients with thyroiditis, whereas these abnormal values normalized in the remission phase. These findings suggest that an increase in Ia+ CD4+ cells characteristically occurs during immune system activation in patients with hyperthyroid Graves' disease, Hashimoto's thyroiditis and the thyrotoxic phase of subacute thyroiditis, whereas the activated CD8+ cells in Graves' disease are induced by antithyroidal therapy.

Topics: Adolescent; Adult; Autoantibodies; CD4 Antigens; CD8 Antigens; Female; Flow Cytometry; Graves Disease; HLA-DR Antigens; Humans; Immunoglobulins, Thyroid-Stimulating; Iodine; Male; Methimazole; Middle Aged; Propylthiouracil; T-Lymphocyte Subsets; Thyroiditis, Autoimmune; Thyroiditis, Subacute

A 56-year-old man presented with clinical and biochemical hyperthyroidism with high thyroid 99mTc uptake, positive result for antimicrosomal antibody (MCHA; 1:8,100) and markedly high activities of thyrotropin-binding inhibitory immunoglobulin (TBII; 90.0%) and thyroid-stimulating antibody (TSAb; 2,400%). Fifty days after the initiation of antithyroid drug therapy, he developed a painful tender enlarged thyroid and an accelerated erythrocyte sedimentation rate (ESR), which were followed immediately by hypothyroidism with a transient increase in MCHA titer (peak; 1:218,700) despite of maintenance of high TBII and TSAb activities. Two and a half months after the recovery from hypothyroidism, recurrent hyperfunction was observed with further elevation of TSAb activity (4,643%). After about 2 weeks, recurrences of a painful tender enlarged thyroid and an accelerated ESR, which were followed by abrupt progression to hypothyroidism, were found. Specimens obtained when he had still slightly tender goiter after the first and second episodes of neck pain showed microscopically extremely extended interstitial fibrosis with collapsed follicles and moderate lymphocytic infiltration. Thyroid-stimulation-blocking antibody was not detected at either onset of hypothyroidism. Thus, it is possible that Graves' disease, subacute aggravation of chronic thyroiditis and hypothyroidism coexist in the same individual. In such patients, thyroid status may be determined by the degree of each of the stimulating factors (TSH, TSAb and/or unknown factors) and suppressive or destructive factors (humoral and/or cellular) and may be changed in a very short interval.

Topics: Autoantibodies; Biopsy, Needle; Blood Sedimentation; C-Reactive Protein; Female; Graves Disease; Humans; Hypothyroidism; Immunoglobulins, Thyroid-Stimulating; Methimazole; Middle Aged; Propylthiouracil; Thyroid Gland; Thyroiditis, Autoimmune; Thyroxine; Triiodothyronine

In three separate studies, members of the American Thyroid Association (ATA), the European Thyroid Association (ETA), and the Japan Thyroid Association (JTA) were surveyed by questionnaire on their management of Graves' disease. The aim was to determine how expert clinical thyroidologists employ diagnostic procedures and the three different therapies that are available for this disorder. In this report, we identify, summarize, compare, and contrast similarities and differences in the results of these surveys in these three different regions of the world. In general, ATA members used fewer diagnostic tests than did their European or Japanese colleagues. For the index patient, radioiodine was the therapy of choice for 69% of ATA respondents but only 22% and 11% of ETA and JTA respondents, respectively. In contrast, only 30.5% of ATA respondents chose antithyroid drugs as first-line therapy compared to 77% of ETA and 88% of JTA respondents. There was consensus on the relative lack of a role for thyroidectomy except for narrow indications. The implications of these differing approaches for the diagnosis and treatment of hyperthyroidism due to Graves' disease are discussed.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Aged; Cholesterol; Europe; Female; Graves Disease; Humans; Iodine; Japan; Male; Methimazole; Propylthiouracil; Severity of Illness Index; Surveys and Questionnaires; Thyroglobulin; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine; United States

The value of the criteria used to anticipate the outcome of treatment of Graves' hyperthyroid patients with methimazole (MMI) remains controversial. We have reported that high MMI doses combined with T3 administration was correlated with higher remission rates. In this study, we used the lowest MMI dose able to control the hyperthyroidism, keeping the free T4 index (FT4I) values below the normal range throughout treatment, and compared the results with patients treated with a high MMI regimen. Both groups received T3. We also evaluated the usefulness of goiter size, serum thyroid-stimulating antibody (TSAb: adenylate cyclase stimulation in human thyroid membrane), thyroglobulin (Tg) levels, and the T3 suppressibility of 24 h RAIU as prognostic markers for the outcome of Graves' disease therapy. Twenty-four Graves' hyperthyroid patients were treated with high MMI dose (mean +/- SD 60 +/- 19, range 40-120 mg daily), and 25 patients received low MMI dose (17 +/- 4.3, 5-20 mg daily). T3, 75 micrograms daily, was given to both groups of patients for 15 +/- 4 (13-22) months of treatment. After cessation of drug therapy, 31 patients (63%) remained euthyroid for 18 +/- 3 (13-49) months of follow-up, 15 (62.5%) and 16 (64%) patients in the high and low dose groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Autoantibodies; Drug Therapy, Combination; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Sensitivity and Specificity; Thyroglobulin; Thyroid Gland; Triiodothyronine

Retrospective analysis of 11 Chinese patients with Graves' thyrotoxicosis developing agranulocytosis during anti-thyroid treatment was done. Seven of them received methimazole and 4 received carbimazole. None of the 11 patients had taken propylthiouracil. The major chief complaints were high fever (100%), chillness (91%), and sore throat (73%). The duration of drug treatment prior to the detection of agranulocytosis ranged from 13 to 63 days (mean +/- 1SE: 33.1 +/- 16.1). At the time of agranulocytosis detected, the peripheral leukocyte counts were 0.5 to 2.1 X 1000/mm3 (mean +/- 1SE: 1.05 +/- 0.47 X 1000/mm3), absolute neutrophil counts 0 to 450/mm3 (mean +/- 1SE: 54.27 +/- 132.12/mm3), and hemoglobin 8.2 to 15.9 g/dl (mean +/- 1SE: 11.85 +/- 2.24 gm/dl). Three of the 11 patients had positive bacterial blood cultures. The recovery time of absolute neutrophil counts above 500/mm3 ranged from 3 to 25 days (mean +/- 1SE: 10.5 +/- 6.6) after discontinuation of antithyroid drugs. Mortality was found in 2 of them (18%).

Topics: Adolescent; Adult; Agranulocytosis; Antithyroid Agents; Carbimazole; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Thyrotoxicosis

This study scrutinizes the correlation between serum free triiodothyronine (FT3) to free thyroxine (FT4) ratios and the eventual outcome of antithyroid drug (ATD) therapy in patients with Graves' disease. Forty-four patients with Graves' thyrotoxicosis were treated with methylmercaptoimidazole (methimazole). During the follow-up, 16 patients relapsed in the short period of one to five months after cessation of the drug (relapse group), and 28 patients remained in remission when checked at 12 to 20 months after treatment (remission group). Serum FT3 to FT4 ratios [(pg/ml/ng/dl) x 10] were less than 55 throughout ATD therapy in 27 of the 28 remission patients whereas the ratios of the relapse group exceeded 55 from the early phase of methimazole treatment in 10 of 16 patients. In eight of these 10 patients the increased ratios were detected within three months of therapy (1 month, 3 patients; 2 months, 4 patients; 3 months, 1 patient). The ratios for the remaining two patients rose above 55 at the fifth and sixth months. There was no statistical difference between the remission and relapse groups in the FT3 to FT4 ratios either before nor at the completion of the treatment. However, a clear difference could be measured at a point during the therapy. Those in whom this difference was pronounced later underwent relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Antithyroid Agents; Female; Follow-Up Studies; Graves Disease; Humans; Male; Methimazole; Middle Aged; Predictive Value of Tests; Radioimmunoassay; Thyroxine; Triiodothyronine

One hundred and twelve new cases of Graves' disease were treated by tapazole for 6 months and followed up for another 12 months. The initial dose was 30 mg/d. Clinical and biochemical euthyroidism was achieved within 1 to 3 months, then a maintenance was given until cessation of drugs at 6 months. One hundred and eleven cases completed the study. Remission and relapse were defined at the end of follow-up for 1 year according to the presence or absence of clinical manifestation of hyperthyroidism and the levels of T3 and T4. The results of the 12-month follow-up showed that 46 of 111 cases were in remission, and the remaining 65 cases suffered relapse. A logistic regression model with 4 variables was established, which included thyroid suppression rate and goitre size by palpation at the end of drug treatment, the level of T3 before therapy, and the patients' age. The model had 81.5% sensitivity, 84.8% specificity and 82.9% (92/111) accuracy in predicting the outcome of Graves' disease after withdrawal of drug for 1 year. The results were much better than any other univariate analysis in this study.

Topics: Adolescent; Adult; Child; Female; Follow-Up Studies; Graves Disease; Humans; Logistic Models; Male; Methimazole; Middle Aged; Prognosis; Recurrence; Triiodothyronine

Soluble interleukin-2 receptor was studied in 20 patients with Graves' disease before and after methimazole treatment. Soluble interleukin-2 receptor level was significantly increased in newly diagnosed Graves' disease compared to controls (667 +/- 270 vs 205 +/- 45 U/ml) (P less than 0.001). In untreated patients' sera the soluble interleukin-2 receptor levels were higher in patients with active ophthalmopathy than in those without eye symptoms. Soluble interleukin-2 receptor levels were normalized in remission induced by methimazole treatment in the majority of patients except those with infiltrative ophthalmopathy. Furthermore, a correlation was found at the hyperthyroid stage of the disease between soluble interleukin-2 receptor level and titre of anti-TSH-receptor antibodies. However, the association with other parameters including anti-eye muscle, anti-thyroid peroxidase, anti-thyroglobulin antibodies was not significant.

Topics: Adult; Antibodies; Eye Diseases; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Receptors, Interleukin-2; Receptors, Thyrotropin; Remission Induction

High serum concentration of soluble interleukin-2 receptor (sIL-2R) is considered a reliable marker of T lymphocyte activation. It has been recently reported that sIL-2R levels are increased in untreated Graves' disease. This finding has been interpreted as the consequence of an active autoimmune state, but the relevance of the thyroid function per se was not investigated. In the present study we assayed sIL-2R by ELISA in 20 normal subjects and in a series of patients with immunogenic (Graves' disease, GD) or nonimmunogenic (toxic adenoma, TA) hyperthyroidism. Significant increased concentrations of sIL-2R were found in 46 patients with untreated hyperthyroid GD (mean +/- SD: 1,683 +/- 1016 U/ml, vs 461 +/- 186 U/ml in normal controls, p less than 0.0001) and in 21 with untreated TA (1,111 +/- 617 U/ml, p less than 0.0001 vs normals). Restoration of the euthyroid state by antithyroid drugs or 131I administration was associated with a normalization of sIL-2R (516 +/- 174 U/ml in 38 patients with GD and 365 +/- 90 U/ml in 12 with TA; p = NS vs normals and p less than 0.001 vs the untreated state for both groups). A highly significant positive correlation between serum sIL-2R and free triiodothyronine (FT3) (r = 0.724, p less than 0.0001) or free thyroxine (FT4) (r = 0.698, p less than 0.0001) concentrations was found in combined sera obtained from all untreated and treated patients, irrespectively of the autoimmune or nonautoimmune nature of the underlying hyperthyroid disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenoma; Adolescent; Adult; Aged; Enzyme-Linked Immunosorbent Assay; Female; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Receptors, Interleukin-2; Thyroid Neoplasms; Triiodothyronine

Activation of T lymphocytes has been found to be associated with an increase in soluble interleukin-2 receptor (sIL-2R) levels. The aim of this study was to investigate serum levels of sIL-2R in 20 untreated patients with Graves' disease and to relate these levels to disease activity and to TSH-receptor, anti-thyroglobulin, anti-microsomal and anti-eye muscle antibodies. sIL-2R levels were significantly increased in newly diagnosed Graves' patients compared with controls (667 +/- 270 vs 205 +/- 45 U/ml) (P less than 0.001). The sIL-2R levels were higher in patients with active infiltrative ophthalmology than in those without eye symptoms (810 +/- 313 vs 525 +/- 180 U/ml). All patients were treated with methimazole for at least 12 months. sIL-2R levels were normalized by methimazole treatment in the majority of patients without ophthalmopathy but not in those with ophthalmopathy. In five patients sIL-2R serum levels were studied after interruption of thyrostatic therapy. An increase was observed in three patients and hyperthyroidism subsequently relapsed in two of these. Furthermore, a correlation was found between soluble interleukin-2 receptor levels and TSH-receptor antibodies but not with other immune parameters examined. Serum sIL-2R represents a useful marker of immunological activity in Graves' disease.

Topics: Autoantibodies; Eye Diseases; Female; Graves Disease; Humans; Male; Methimazole; Prednisolone; Receptors, Interleukin-2; Receptors, Thyrotropin; Thyrotoxicosis

We studied blood coagulation and fibrinolysis activities in hyperthyroidism before and after methimazole or 131I. Fibrinopeptide A and B beta 15-42, in vivo indicators of thrombin and plasmin activity, were measured by RIA, while fibrinogen by the Clauss method. We studied 50 patients, affected by toxic diffuse goiter. We evaluated 21 of them before and after treatment. Fibrinogen, fibrinopeptide A, and B beta 15-42 were higher in patients than in controls (p less than 0.0001). There was no difference in fibrinopeptide A nor in B beta 15-42 before or after treatment. In euthyroidism fibrinogen returned to normal values. Inflammation of the thyroid gland secondary to autoimmunity may activate blood coagulation by release of tissue factor. High fibrinogen before treatment may be explained as an aspecific response. Since it persists in euthyroidism, autoimmunity could account for high fibrinopeptide A and B beta 15-42 aftertreatment.

Topics: Adolescent; Adult; Aged; Blood Coagulation; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Fibrinopeptide A; Fibrinopeptide B; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Peptide Fragments

A new commercially available human thyrotropin immunochemiluminometric assay (ICMA) kit was evaluated. The BeriLux assay (Hoechst Co., Germany) was compared with two other non-radioisotopic methods (AIA-1200 and IMx) and two other immunoradiometric assays (RIA-gnost TSH IRMA and EIKEN IRMA kits) in 32 normal subjects and 104 patients with Graves' disease, divided into seven groups: 1) untreated hyperthyroidism; 2) hyperthyroidism during treatment; 3) euthyroid with negative thyroliberin test (subclinical hyperthyroidism); 4) euthyroid with low thyroliberin test; 5) euthyroid with normal thyroliberin test; 6) euthyroid with high thyrotropin level (subclinical hypothyroidism); and 7) primary hypothyroidism. Patients in groups 2-6 were undergoing treatment with mercazole and propylthiouracil. The new immunoluminometric assay (ILMA) BeriLux kit was shown to have a remarkably improved analytical and clinical sensitivity. The minimal detectable level of thyrotropin in the assay was 0.006 mU/l. The precision was 2.8% and 6.1% at 0.093 +/- 0.003 mU/l and 0.028 +/- 0.002 mU/l, respectively, whereas the precision of the other methods was above 17.2% and 59.4% respectively. Seven patients from the untreated hyperthyroid group were given 500 micrograms thyroliberin i.v. (the thyroliberin test). The thyrotropin pattern before and after thyroliberin administration was always less than 0.006 mU/l with the BeriLux kit, whereas the other methods showed random fluctuations indicating their low accuracy at this concentration. Using the BeriLux kit, 7 of the 16 overt hyperthyroid patients undergoing treatment showed a measurable thyrotropin level below 0.01 mU/l but a negative thyroliberin test.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Evaluation Studies as Topic; Female; Graves Disease; Humans; Immunoassay; Immunoenzyme Techniques; Immunoradiometric Assay; Luminescent Measurements; Male; Methimazole; Middle Aged; Propylthiouracil; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

Eighty-five patients with Graves' disease in clinical remission after treatment for over 1 year by methimazole therapy (36 patients, group A) or subtotal thyroidectomy (49 patients, group B) who became undetectable for serum thyrotropin levels (TSH less than 0.05 mU/l), were further followed for 1 year or more. Eight patients in group A (22%) and 7 patients in group B (14%) relapsed. Eleven patients in group A (30%) and 5 patients in group B (10%) had fluctuating patterns of free T4 in the upper normal to slightly supranormal range indicative of subclinical hyperthyroidism. The remaining patients continued to have undetectable TSH levels or restored normal TSH levels and normal thyroid hormone concentrations in sera. The results of the present study indicate that the occurrence of undetectable serum TSH concentrations in Graves' disease patients previously treated with methimazole or surgery are not necessarily predictive of clinical relapse because the eventual outcome is variable.

Topics: Adult; Follow-Up Studies; Graves Disease; Humans; Methimazole; Middle Aged; Recurrence; Remission Induction; Thyroid Gland; Thyroidectomy; Thyrotropin; Thyroxine; Triiodothyronine

A 29-year-old female patient with Graves' disease who developed thyroid hormone autoantibodies (THAA) under treatment with methimazole is presented. THAA were identified as IgG-kappa. During a first pregnancy that ended by miscarriage in the 3rd month, the titer of anti-thyroxine autoantibodies decreased by about 30%. Relapse of Graves' disease occurred 2 months later and an increase in serum THAA concentration to the initial titer was observed. THAA titer remained unchanged during treatment with methimazole and afterwards during thyroxine supplementation for radioiodine-induced hypothyroidism. During a second pregnancy, a decrease in anti-thyroxine autoantibody titer reached 45% at the time of delivery and an increase by 20% was noted 5 months later. A similar decline in THAA concentration was shown during a third pregnancy. The changes in THAA concentrations observed during pregnancy suggest an immunological influence of pregnancy on the THAA production, as previously demonstrated in other autoimmune diseases, like Hashimoto's thyroiditis.

Topics: Adult; Autoantibodies; Female; Fetal Blood; Graves Disease; Humans; Immunoglobulin G; Immunoglobulin kappa-Chains; Methimazole; Pregnancy; Pregnancy Complications; Thyroid Hormones; Thyroxine; Triiodothyronine

Recently, in vitro production of interleukin-2 receptor induced by mitogens have been shown to be impaired in autoimmune disorders including organo-specific autoimmune diseases. The aim of this study was to investigate serum levels of soluble interleukin-2 receptor in 20 untreated patients with Graves' disease and to follow up their changes in relation to clinical picture and TSH-receptor-, anti-thyroglobulin-, anti-microsomal as well as anti-eye muscle antibodies. Soluble interleukin-2 receptor level was significantly increased in newly-diagnosed Graves' patients compared to controls (667 +/- 270 vs. 205 +/- 45 U/ml) (P less than 0.001). Among the patients sera those with active infiltrative ophthalmopathy had higher soluble interleukin-2 receptor levels than those without eye symptoms (810 +/- 313 vs. 525 +/- 180 U/ml). Soluble interleukin-2 receptor level was normalized in Methimazole-treatment-induced remission in the majority of patients except those with ophthalopathy. In five patients the soluble interleukin-2 receptor levels were studied after interruption of thyrostatic therapy; an increase was observed in three patients; thereafter hyperthyrosis relapsed in two cases. Furthermore, a correlation was found between soluble interleukin-2 receptor levels and TSH-receptor antibodies, however, the association with other immune parameters examined was not significant. In conclusion, an enhanced level of soluble interleukin-2 receptor was detected in patients with untreated Graves' disease. This finding might play a significant role in regulation of impaired cell-mediated immune mechanism and has a prognostic value for relapse of autoreactive processes.

Topics: Adult; Autoantibodies; Biomarkers; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Graves Disease; Humans; Male; Methimazole; Oculomotor Muscles; Receptors, Interleukin-2; Reference Values; Thyroglobulin; Thyrotropin; Triiodothyronine

Radiofluorescent analysis (RFA) with the help of various devices and a new method of investigation was employed for a combined in vivo study of 1) the concentration (in micrograms/l g); and 2) the total amount (in mg) of stable iodine in the thyroid; 3) a scan of the distribution of halogen in the organ; 4) organ mass (in g) in the control groups, in 15 patients with toxic goiter before and after mercasolil therapy, and in 6 patients with endemic goiter after iodine prophylaxis. The importance of some of the indices in the diagnosis and therapy of patients with toxic goiter was shown.

Topics: Adult; Female; Goiter, Endemic; Graves Disease; Humans; Iodine Isotopes; Methimazole; Middle Aged; Spectrometry, X-Ray Emission; Thyroid Diseases; Thyroid Gland

Topics: Adult; Graves Disease; Humans; Methimazole; Propylthiouracil; Thrombocytopenia

The purpose of the study was to determine whether such factors as: initial exacerbation of thyrotoxicosis, blood group (ABO) and the presence of HLA A1, B8 antigens have an influence on the effectiveness of the conservative treatment of thyrotoxicosis in Graves-Basedow disease (G-B disease). Studies were carried out in two groups of 32 women each with G-B disease. The patients in group I were 28-61 years of age, in whom euthyroid state lasting at least 5 years was attained after treatment with methimazole on average over a 15.4 month cycle. The age of the patients in group II was 27-61 years, in whom at least one relapse occurred in 5-year follow-up. The groups of patients did not differ significantly in the clinical exacerbation of thyrotoxicosis measured in the scale of Zgliczyński. The frequencies of occurrence of the particular clinical symptoms of thyrotoxicosis did not differ in both groups, except diarrhoea with occurred significantly more frequently in women of group II (47%) in comparison with group I (15.6%). No characteristic differences were found between both groups in the occurrence of blood group O, A, B, AB and antigen HLA A1. Statistically significant difference was found in the occurrence of antigen HLA B8 and phenotype HLA A1 B8, both between the patient groups and control. Their influence expressed by odds ratio OR = 3 indicated that the chances of effective conservative treatment for the patients in group II were three times smaller than for those in group I.

Topics: ABO Blood-Group System; Adult; Female; Graves Disease; HLA Antigens; Humans; Methimazole; Middle Aged; Thyrotoxicosis

Topics: Autoimmunity; Graves Disease; Humans; Immunity, Cellular; Methimazole; T-Lymphocytes

Topics: Autoantibodies; Graves Disease; Humans; Methimazole; Receptors, Thyrotropin; Recurrence; Time Factors

Topics: Adult; Agranulocytosis; Graves Disease; Humans; Liver; Methimazole; Propylthiouracil

TSH receptor antibodies (TRAb) measured by the TBI residual assay (TBIr) were studied in 3 groups of Graves disease patients, as follows: 54 non treated cases (Group 1), 20 cases under methimazol treatment (Group 2) and 23 patients who were euthyroid after one year of methimazol treatment (Group 3), in order to evaluate the usefulness of TBIr as a recurrence index in Graves disease following antithyroid drug treatment. In group 1, TBIr was positive in 77.7% (45/54) of the cases. In group 2: 45% (9/20) had positive values for TBIr, all of which had a recurrence of disease during the year following the suppression of the treatment. In group 3, 69.5% patients (16/23) were TBIr positive. In 75% (12/16) of them the abnormally high values of TBIr predicted the recurrence, while 71.43% (5/7) of the patients, TBIr negatives, continued the remission 12 months later. By comparing the TBIr values before and after treatment in the group 3 patients, different possibilities were observed: a) TBIr persistently elevated: 52.17% (12/23). The 83.3% (10/12) had a recurrence before 6 months following treatment termination. b) TBIr, initially elevated, but later showing 50% decrease or negative values: 26.09% (6/23). Every patient was euthyroid one year after the treatment ended. c) TBIr persistently negative: 13.04% (3/23). Two of them had recurrence of their disease. d) TBIr negative which changed later to positive: 8.70% (2/23). Both presented a recurrence. In accordance with these results, we believe that abnormally high TBIr values before or after treatment is a useful recurrence index.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antibodies; Graves Disease; Humans; Methimazole; Prognosis; Receptors, Thyrotropin; Recurrence; Thyroid Hormones

We have recently reported that, in patients with hyperthyroidism, the red blood cell (RBC) carbonic anhydrase I (CAI) and zinc (Zn) concentrations both reflect the patient's integrated thyroid hormone level over the preceding few months. In this study, we evaluated the clinical usefulness of determining the RBC CAI and Zn concentrations in patients with various types of thyroid disease. Six patients with painless thyroiditis (PT) had normal RBC CAI concentrations and the two patients tested had normal RBC Zn levels. In four patients with syndromes of inappropriate thyrotropin (TSH) secretion (SITSH) two euthyroid patients had normal RBC CAI and two hyperthyroid patients had subnormal RBC CAI and Zn. In a patient with Graves' disease whose plasma thyroxine (T4) and triiodothyronine (T3) concentrations changed remarkably because of poor compliance with the regimen, the change in plasma thyroid hormone levels preceded the change in the RBC CAI and Zn concentrations by 2 to 3 months. These observations suggest that the measurement of RBC CAI and Zn concentrations may be useful clinically as follows: (1) in differentiating hyperthyroid Graves' disease from transient hyperthyroidism due to destructive thyroiditis; and (2) in obtaining an accurate estimate of the extent of elevated thyroid hormone levels in hyperthyroid patients over time.

Topics: Adult; Carbonic Anhydrases; Erythrocytes; Graves Disease; Humans; Methimazole; Middle Aged; Osmolar Concentration; Thyroid Diseases; Thyroid Function Tests; Thyroid Hormones; Thyroiditis; Zinc

Topics: Autoantibodies; Graves Disease; Humans; Hyperthyroidism; Methimazole; Receptors, Thyrotropin; Thyroxine

The serum BGP level was assayed in patients with hyperthyroidism (untreated and remittent cases). The mean serum BGP concentration was 8.7 +/- 2.5 ng/ml in 54 patients with untreated hyperthyroidism, which was significantly higher than normal range (4.8 +/- 1.3 ng/ml P less than 0.01). Serum BGP had a significant positive correlation with the concentration of T3 and T4, while serum AKP had no correlation with circulating thyroid hormone levels. In the patients with hyperthyroidism, serum T3 and T4 decreased significantly after the first month of methimazole treatment, and fluctuated within the normal range since then. Serum BGP did not show significant change during the first six months of treatment, although they were eventually reduced significantly at the end of six months. These results suggest that serum BGP measurement is a valuable marker of bone metabolism alteration during hyperthyroidism.

Topics: Adult; Alkaline Phosphatase; Female; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Osteocalcin; Radioimmunoassay

Two patients with Graves' disease treated with methimazole (MMI) showed a discrepancy between serum free T4 (FT4) values and other hormone values (especially total T4) which was due to the presence of potent binding activity to labelled T4 analogue (125I-aT4) in their serum. This activity was demonstrated to be in immunoglobulin G (IgG) with kappa light chain isotype in both patients. The binding of 125I-aT4 to their serum was inhibited by unlabelled T4 in a dose-dependent manner. Autoantibodies had almost identical binding affinity to T4 and aT4, although they precipitated more radioactivity when 125I-aT4 was used. The binding of IgG purified from patients' sera to labelled T4 or aT4 was not greater than the corresponding sera, suggesting that the thyroxine binding proteins did not interfere with the assay. Since the specific radioactivity of 125I-aT4 is almost 10 times higher than that of 125I-T4, autoantibodies can precipitate almost 10 times more radioactivity in the FT4 assay than the total T4 assay, thus leading to the spuriously high FT4 values and large discrepancy between FT4 and TT4 values.

Topics: Adult; Autoantibodies; Female; Graves Disease; Humans; Immunoglobulin G; Methimazole; Thyroxine

Three patients with Graves' disease who spontaneously developed hypothyroidism after treatment with antithyroid drugs are described herein. Patient 1 developed a painful tender thyroid enlargement with a fever and accelerated erythrocyte sedimentation rate when she was receiving maintenance therapy with methimazole, and she progressed to persistent hypothyroidism with increased titers of antithyroglobulin and antimicrosomal antibodies and marked reduction of goiter size within the subsequent 2 months. Thyroid-stimulating hormone-binding inhibitory immunoglobulins (TBIIs) and thyroid stimulation-blocking antibody (TSBAb) were absent when she was hypothyroid. Hypothyroidism probably resulted from autoimmune thyroid destruction due to subacute aggravation of Hashimoto's thyroiditis. During the clinical course of patient 2, accelerated erythrocyte sedimentation rate and later transient increases of antimicrosomal and antithyroglobulin antibody titers were observed repeatedly (four times), and she finally fell into overt hypothyroidism. She also had negative results of tests for TBII and TSBAb. Her hypothyroidism appeared to result from repeated thyroid destruction due to aggravation of Hashimoto's thyroiditis. Patient 3 fell into hypothyroidism when receiving a small dosage of methimazole. The TBII and TSBAb were strongly active when she developed hypothyroidism, which thus seemed to be due to blocking antibody. Patients with Graves' hyperthyroidism may eventually progress to hypothyroidism later by several different mechanisms. Severe and sudden or slowly repeated thyroid destruction due to aggravation of Hashimoto's thyroiditis is one mechanism. Another may be the appearance of a blocking antibody to the TSH receptor.

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Hypothyroidism; Methimazole; Middle Aged; Propylthiouracil; Thyroid Function Tests; Thyroiditis, Autoimmune

Topics: Agranulocytosis; Antithyroid Agents; Depression, Chemical; Female; Graves Disease; Humans; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Tablets; Thyroid Hormones

In 80 patients with Basedow's disease (20 nontreated and 60 under treatment with methimazole) were examined. The antibodies inhibiting the binding of TSH (TBII) by the radioreceptor method (Thyrotropin-Receptor-Anti-Körper Assay = TRAK), TRH-test, T3, T4, FT4, FT. TRAK-positive) values above 15 u/l) were 80% of the nontreated and 20% of the treated patients. In the course of 3 up to 6 months from the start of the treatment 60% of the examined patients were negative and at the end of the 18th month--92% were negative. A significant difference in the frequency of the recurrences was found between the TRAK-positive and the TRAK-negative patients. Between the TRAK, FT3, FT4, the size of the struma, the presence of ophthalmopathy [correction of ophthalmycthere] are positive relations. The following conclusions are made: 1. The determination of TBII and TRAK is not only of diagnostic but also of prognostic importance. 2. Methimazole exerts a specific immunosuppressive action and can lead to an immunologic remission in a comparatively short time.

Topics: Adult; Antibodies; Antithyroid Agents; Autoantibodies; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Radioligand Assay; Receptors, Thyrotropin; Time Factors

Changes in thyroid volume during antithyroid drug therapy for Graves' disease compared with circulating thyroid parameters were evaluated. One hundred and forty-four patients with Graves' disease were treated with methimazole. Thyroid volume was measured by ultrasonography (thyroid volume = pi abc/6, where a is length, b width, and c depth). Serum TSH, TSH-binding inhibitory immunoglobulins, thyroid-stimulating antibodies, thyroglobulin, antimicrosomal antibodies, and antithyroglobulin antibodies were also measured. In the whole group of patients, thyroid volume correlated significantly with thyroglobulin (p less than 0.01) and TSH-binding inhibitory immunoglobulins (p less than 0.01), but not with TSH, antimicrosomal antibodies, and antithyroglobulin antibodies. Furthermore, a positive correlation was found between thyroglobulin and TSH-binding inhibitory immunoglobulins (p less than 0.01). In 11 patients the mean thyroid volume decreased significantly after one year of therapy (p less than 0.01), associated with decreasing levels of serum TSH-binding inhibitory immunoglobulins. Ten patients experienced transient hypothyroidism with an overdose of methimazole, and the mean thyroid volume increased significantly (p less than 0.01) with increasing serum TSH levels. In conclusion, it is suggested that TSH receptor antibodies may have a thyroid growth-stimulating effect. In addition, circulating thyroglobulin levels reflect thyroid volume in Graves' disease.

Topics: Adolescent; Adult; Aged; Autoantibodies; Child; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Thyroglobulin; Thyroid Gland; Thyrotropin

One hundred and fifteen new patients with Graves' hyperthyroidism were received thyroid suppression test after cessation of 6 month course of drug therapy. The results of follow up for another 12 months were that one of them had lost, 48 cases were in remission, and 66 cases had relapsed. The present study shows that thyroid suppression test, including the 4th, 6th and 24th hour suppression rates, is useful in predicting the outcome of drug therapy. The effect of 6th hour suppression rate is better than that of 24th and 4th hours, with 75.8% sensitivity, 75.0% specificity and 75.4% accuracy when 30% of thyroid suppression rate is as out-off point which is decided by ROC curve. It is suggested that 6 hour 30% suppression rate is better than the traditional 24 hour 50% suppression rate in the prediction of outcome of drug therapy.

Topics: Adult; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Prognosis; Thyroid Function Tests

The performed studies covered 48 subjects, inhabiting the Western Pomerania, therein 40 patients with hyperthyroidism in the course of Graves-Basedow's disease (32 females and 8 males, aged 21-64 years) as well as 8 healthy individuals (5 females and 3 males, aged 23-36 years, with negative anamnesis towards thyroid diseases), who made up the control group at determining the pharmacokinetic parameters after a single oral dose containing 60 mg of thiamazole. On the basis of estimating the time of treatment with "full dose" of thiamazole, indispensable for attaining clinical euthyreosis, according to criteria provided by Crooks et al., the patients with hyperthyroidism during Graves-Basedow's disease were divided into 2 subgroups: 1). Subgroup IA included 22 patients, in whom the clinical state of euthryreosis was obtained in 28 days of therapy with "full dose" of thiamazole. 2). Subgroup IB encompassed 18 patients, in whom euthyreosis appeared after at least 35-day-long treatment with a "full dose" of thiamazole. The differing behavior of thyroid hormones and thiamazole pharmacokinetics+ in both subgroups of patients has furnished the basis for the following conclusions to be drawn: The patients with hyperthyroidism in the course of Graves-Basedow's disease, attaining rapidly the clinical euthyreosis during the treatment with "full dose" of thiamazole, are found to normalize the concentrations of thyroxine and triiodothyronine in serum after shorter time than it is done by patients requiring a longer drug application in a "full dose". In patients achieving euthyreosis both after short and long time of treatment with "full dose" of thiamazole, the normalization in concentrations of thyroid hormones in serum markedly exceeds, by about 2-4 weeks, the establishing of clinical euthyreosis. In patients, who readily attain the clinical euthyreosis, the concentrations of thiamazole in serum, after a single "full dose" as well as during two-month-long treatment, are significantly higher than in patients reaching euthyreosis slowly, in spite of the fact that there were no outstanding differences in absorbing the drug from the alimentary duct in both subgroups being compared. The cause that the clinical effect varies in the compared subgroups of patients with hyperthyroidism during the Graves-Basedow's disease is the difference in thiamazole metabolism in the organism, most likely in the liver.

Topics: Adult; Dose-Response Relationship, Drug; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Thyroxine; Time Factors; Triiodothyronine

The purpose of this study was to elucidate the mechanism of regulation of serum thyroglobulin concentration in patients with Graves' disease and to establish the clinical usefulness of this measurement.. Serum thyroglobulin concentration was analyzed in relation to serum thyrotropin receptor antibody (TRab) titer and thyrotropin concentration in 166 patients with Graves' disease without thyroglobulin antibody.. A total of 113 patients were treated and had been kept euthyroid for at least 10 months with methimazole and underwent a triiodothyronine (T3) suppression test. At the time of the T3 suppression test, the serum thyroglobulin concentration (ng/mL) was 33 +/- 31 in 80 of them with T3-suppressible (radioiodine uptake less than 12%) thyroids, negative TRab titers (less than 15% displacement), and normal serum thyrotropin concentrations (0.1 to 3.0 mU/L). Patients with T3-non-suppressible thyroids were divided into three subgroups according to serum TRab titers and thyrotropin concentrations: those with a negative TRab titer and a normal serum thyrotropin concentration (n = 9), those with a positive TRab titer and a normal thyrotropin concentration (n = 18), and those with a positive TRab titer and undetectable thyrotropin (n = 6). Serum thyroglobulin concentrations (ng/mL) were 116 +/- 40 in the first group, 249 +/- 194 in the second group, and 399 +/- 205 in the third group. In the other 39 methimazole-treated patients, 72 determinations of serum thyroglobulin concentration were performed either before or during treatment without the T3 suppression test, and it correlated well with the TRab titer but not with the serum thyrotropin concentration. In 14 patients who became hypothyroid due to excess methimazole, the serum thyroglobulin concentration increased concurrently with elevation of the serum thyrotropin concentration and normalized during thyroxine supplementation. In treated patients with T3-suppressible thyroids, the serum thyroglobulin concentration was similar among those with positive (n = 54) and negative (n = 26) microsomal antibody, indicating that the presence of Hashimoto's thyroiditis does not profoundly affect the serum thyroglobulin level. Among 80 patients with T3-suppressible thyroids who were followed without methimazole for a mean period of 31.1 months, eight (10%) experienced a clinically overt recurrence of hyperthyroidism. Serum thyroglobulin concentration and TRab titer (%) in these eight patients were 188.1 +/- 101.7 and 27.8 +/- 12.6, respectively. Thyroglobulin and TRab did not increase in the patients who remained euthyroid (n = 71) or who experienced subclinical recurrence (n = 1).. Abnormal thyroid stimulator(s) and thyrotropin synergistically (if both are present in the serum) or independently (if either one is present) stimulate thyroglobulin secretion in patients with Graves' disease. Therefore, serum thyroglobulin concentration can be a useful means of assessing the degree of thyroidal stimulation and, if serum thyrotropin is normal or suppressed, correlates well with thyroidal stimulation even in patients with a negative TRab titer.

Topics: Adult; Autoantibodies; Biomarkers; Follow-Up Studies; Graves Disease; Humans; Methimazole; Microsomes; Middle Aged; Receptors, Neurotransmitter; Receptors, Thyrotropin-Releasing Hormone; Thyroglobulin; Thyrotropin; Thyrotropin-Releasing Hormone

Thyroid microsomal antigen is considered to be identical with thyroid peroxidase (TPO). Although there have been many reports concerning changes in microsomal autoantibody during the course of antithyroid drug therapy for Graves' disease, little is known about this matter in relation to TPO autoantibody (TPOab). Therefore, in this paper, we studied serial changes in the latter autoantibody. Initial levels of serum TPOab (% immunoprecipitation) in 13 patients with hyperthyroid Graves' disease ranged from -11.3% to +84.5% (mean +/- SD, 38.9 +/- 31.8%). Of three patients with persistently increased serum TPOab throughout drug therapy, all had recurrence of hyperthyroidism after the drug was discontinued. Of seven patients whose TPOab levels were initially high but subsequently decreased, four had remission of the disease after drug therapy. Inhibition by TPOab of the TPO activity was also demonstrated by both guaiacol and iodide assays, and changes in this inhibitory activity during therapy varied among individuals. This inhibition was not correlated with disease remission. The decrease in serum TPOab observed in some antithyroid drug-treated patients may reflect a decline in disease activity or may be a direct effect of the drug.

Topics: Adolescent; Adult; Autoantibodies; Female; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Peroxidase; Precipitin Tests; Thyroid Gland

With regard to their thyroid function, somatic and intellectual development, we compared 17 children of 13 hyperthyroid mothers (group I) receiving antithyroid drug treatment during their pregnancies with 25 children of 15 mothers who were euthyroid without any antithyroid treatment during their pregnancy (group II). Mean duration of maternal treatment was 3.5 months in group I, using carbimazole or thiamazole (N = 12) and propylthiouracil (N = 1). Age at examination in group I was 7.2 +/- 6.2 years, in group II 8.7 +/- 7.1 years (mean +/- SD). Both groups showed no significant differences in the results of the clinical examination and in the degree of their mental and psychomotoric development at the time of study. We found the mean birth weight of the infants in group I significantly lower than in group II (3165 +/- 339 vs 3666 +/- 670 g, p less than 0.03). The individual birth weights, however, were normal for gestational age. The body weight difference between groups disappeared during the further somatic development of the children. The serum concentration of free thyroxine in group I was significantly higher than in group II (17.2 +/- 2.4 vs 14.9 +/- 1.9 pmol/l, p less than 0.003), but fell in both groups within the normal range. The evaluation of the psychomotoric and intellectual capacity of the children at different developmental stages showed no abnormalities detectable by our tests. Thus, in the children of the two groups we found no adverse effects of a maternal antithyroid drug treatment during pregnancy or of inactive maternal Graves' disease alone, neither on thyroid gland size and function nor on the physical or intellectual development, after the neonatal period.

Topics: Birth Weight; Carbimazole; Child; Drug Therapy, Combination; Female; Follow-Up Studies; Graves Disease; Growth; Humans; Infant, Newborn; Intelligence; Maternal-Fetal Exchange; Methimazole; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Propylthiouracil; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

Eighty-three patients with Graves' disease had been treated with methylmercaptoimidazole (MMI). They were prescribed a maintenance dose of antithyroid drug (MMI, 5 mg/day) at the time of a T3 suppression test. The 3-hour and 24-hour thyroidal 123I uptake after T3 administration (75 micrograms/day, 2 weeks) were measured (post T3 uptake). In 38 patients whose post T3 uptake was below 35% in post T3 24-hour uptake, treatment was stopped. The T3 suppression test was then repeated 1 and 3 months later. During a one-year follow up, 26 remained well, while 12 relapsed within 6 to 12 months. We have observed a good correlation between 3-hour uptake and 24-hour uptake of 123I after T3 administration (r = 0.847, p less than 0.001). In 38 patients who showed positive T3 suppression, most patients with MMI withdrawal produced a marked overshoot of post T3 3-hour and 24-hour uptake at one month. Retrospective analysis indicated that there was no significant difference in circulating thyroid hormone levels between remission and relapse groups. The present study provides evidence that 3-hour uptake values are able to be substituted for 24-hour uptake values during a T3 suppression test. In addition, overshoot of thyroidal uptake after antithyroid drug withdrawal was observed in 3-hour values, similar to 24-hour values.

Topics: Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Predictive Value of Tests; Recurrence; Remission Induction; Retrospective Studies; Thyroid Function Tests; Time Factors; Triiodothyronine

Lipid metabolism was examined in patients with hyper- or hypothyroidism. Compared with corresponding age and sex matched controls, serum total cholesterol (T-chol), low density lipoprotein cholesterol (LDL-chol), phospholipid (PL) and LDL levels were significantly low and free fatty acid (FFA) levels were high with apparently normal triglyceride (TG), very low density lipoprotein (VLDL) and high density lipoprotein cholesterol (HDL-chol) levels in 61 hyperthyroid patients, while T-chol, LDL-chol, TG, PL, VLDL and LDL levels were high with normal FFA and HDL-chol levels in 31 hypothyroid patients. Serum lipid levels were then repeatedly measured in 7 men and 7 women with hyperthyroid Graves' disease before treatment (stage I), just after the patients became euthyroid with anti-thyroid drug (stage II) and more than 2 months after the patients remained euthyroid (stage III). Serum T-chol, LDL-chol, PL and LDL levels were low at stage I, significantly elevated at stage II and then normalized at stage III. Transient but significant elevation of serum TG, VLDL and HDL-chol levels at stage II were also observed in men. Accelerated catabolism and anabolism of lipid has been reported in hyperthyroidism. Transient elevation of serum lipid levels suggests a more rapid improvement in catabolism than in anabolism of lipid in an early stage of the medical treatment for hyperthyroidism.

Topics: Adult; Aged; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Female; Graves Disease; Humans; Lipoproteins, LDL; Methimazole; Phospholipids; Thyroxine; Time Factors; Triglycerides; Triiodothyronine

The outcome of radioiodine therapy of Graves' hyperthyroidism was retrospectively evaluated in 274 consecutive patients treated from 1975 to 1984. At 1-yr follow-up, permanent hypothyroidism occurred in 36.9% of patients and the cumulative incidence of hypothyroidism progressively increased up to 79.3% after 7-10 yr. At the end of the follow-up period, 148 patients (54%) were hypothyroid, 115 (42%) euthyroid and 11 (4%) still hyperthyroid. The prevalence of hypothyroidism was significantly higher in patients with small goiters (less than or equal to 50 g) than in those with large goiters (greater than 90 g). Moreover, hypothyroidism was more frequent in patients with high thyroglobulin antibodies titers (greater than or equal to 1:25,600) than in those with low titers or negative tests, and occurred earlier in the former group than in the latter ones Correction of thyrotoxicosis was obtained after the administration of a single dose of 131I in 187 patients (63.6%); 69 patients required two doses and 11 three or more doses. Seven patients refused further treatment with 131I after the first dose. In an effort to identify possible factors affecting the efficacy of 131I therapy, we evaluated the results obtained after the administration of the first dose of radioiodine. We found that large goiters, rapid iodide turnover and adjunctive therapy with methimazole shortly after radioiodine were associated with a higher rate of persistence of thyrotoxicosis, whereas an increased prevalence of hypothyroidism was observed in patients with small goiters and in those not treated with methimazole up to one week after 131I.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Combined Modality Therapy; Female; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Radiotherapy; Thyroid Gland; Thyrotoxicosis

Synthesis of "sex-hormone binding globulin" (SHBG) is influenced by thyroid hormones and its concentration in the serum of female subjects may be a marker of thyroid hormone effect at the peripheral tissue (liver) level. Compared to the levels found in euthyroid females (n = 46), the mean (+/- S.D.) serum SHBG concentration was found elevated in overt hyperthyroidism (Graves' disease: n = 56; 141.6 +/- 37.6 vs. 48.3 +/- 16.2; toxic nodular goiter: n = 16; 119.9 +/- 50.7 vs. 48.3 +/- 16.2 nmol/l; P less than 0.001). In contrast, it was decreased in manifest hypothyroidism (n = 25; 24.9 +/- 14.8 vs. 48.3 +/- 16.2; P less than 0.001). In the group of preclinical hyperthyroidism (n = 43), despite suppressed TSH secretion, the serum value of SHBG was normal (47.4 +/- 16.8), while its serum level approached the lower border of the normal range in subclinical hypothyroidism (n = 10; 33.6 +/- 6.1 vs 48.3 +/- 16.2 nmol/l; P less than 0.01). Data indicate that the pituitary responds more sensitively than the liver to a slight change of the serum thyroid hormone level. During thyroid hormone replacement for hypothyroidism, measurement of serum SHBG may provide help to assess the response of the target organ to the given therapy. In patients with generalized resistance to thyroid hormone, the serum SHBG level is within the normal range (51.3 +/- 9.8 nmol/l), thus, its determination supports the diagnosis of this disease.

Topics: Biomarkers; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Methimazole; Reference Values; Sex Hormone-Binding Globulin; Thyroidectomy; Thyrotropin; Thyroxine; Triiodothyronine

In vitro studies have demonstrated that thyroid hormones can enhance basal and stimulated growth hormone secretion by cultured pituitary cells. However, both in man and in the rat the effects of high thyroid hormone levels on GH secretion are unclear. The aim of our study was to test the GH response to human GHRH in hyperthyroid patients and to evaluate the effects on GH secretion of short- and long-term pharmacological decrease of circulating thyroid hormones. We examined 10 hyperthyroid patients with recent diagnosis of Graves' disease. Twelve healthy volunteers served as controls. All subjects received a bolus iv injection of GHRH(1-29)NH2, 100 micrograms. Hyperthyroid patients underwent a GHRH test one and three months after starting antithyroid therapy with methimazole, 10 mg/day po. GH levels at 15, 30, 45, 60 min and GH peak after stimulus were significantly lower in hyperthyroid patients than in normal subjects. The GH peak was also delayed in hyperthyroid patients. After one month of methimazole therapy, most of the hyperthyroid patients had thyroid hormone levels in the normal range, but they did not show significant changes in GH levels after GHRH, and the GH peak was again delayed. After three months of therapy with methimazole, the hyperthyroid patients did not show a further significant decrease in serum thyroid hormone levels. However, mean GH levels from 15 to 60 min were significantly increased compared with the control study. The GH peak after GHRH was also earlier than in the pre-treatment study.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Female; Graves Disease; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Kinetics; Male; Methimazole; Middle Aged; Thyrotropin; Thyroxine; Triiodothyronine

This study was aimed at establishing the importance of routine monitoring of white blood cell counts in patients with Graves' disease receiving antithyroid drug treatment. In the 12-year period from 1975 to 1987, 15,398 patients with Graves' disease receiving treatment with antithyroid drugs were seen at our clinic. Of these, 55 (0.4%) were found to have agranulocytosis. Agranulocytosis was defined as a granulocyte count of 0.5 x 10(9)/L or less. In only 12 of the 55 patients was agranulocytosis detected after the occurrence of infection (symptomatic; classic agranulocytosis). The remaining 43 patients were asymptomatic when agranulocytosis was detected during routine white blood cell count monitoring. However, 14 of these 43 patients became symptomatic several days after withdrawal of antithyroid drug treatment despite antimicrobial treatment (asymptomatic to symptomatic). Twenty-nine patients who were treated appropriately had no symptom of infection throughout the course of the disease, despite the absence of or an extremely small number of granulocytes in circulation (asymptomatic). These results suggest that a "routine monitoring" of the white blood cell count could be the most effective way of predicting and detecting agranulocytosis due to antithyroid drug treatment.

Topics: Adult; Agranulocytosis; Female; Granulocytes; Graves Disease; Humans; Leukocyte Count; Male; Methimazole; Propylthiouracil

In pregnancy hyperthyroidism occurs with a prevalence of 0.04-0.2%. It occurs even less frequently de novo in previously undiagnosed patients. Within a short period of time we treated 3 patients, who also developed signs of pre-eclampsia. Specific principles of the management during pregnancy are explained.

Topics: Adult; Cesarean Section; Female; Graves Disease; Humans; Hyperthyroidism; Infant, Newborn; Lithium; Male; Methimazole; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy, Multiple; Propylthiouracil; Thyroid Function Tests

Graves' disease is an autoimmune disease whose development involves immunogenetic and exogenous factors such as viruses, bacteria and iodine excess. In a number of patients the disease follows a chronic recurrent course. A recurrence rate of 50% can be expected one year after the end of therapy. Based on the preliminary results of the prospective study presented here, this recurrence rate does not differ in groups where patients underwent long-term treatment with 10 or 40 mg thiamazole. Retrospectively obtained data suggest that the time at which euthyroidism occurs under low-dose treatment is dependent on the alimentary iodine supply. A number of groups have attempted to develop clinically applicable methods to identify patients at risk for recurrence at the end of treatment. All the studies yielded controversial results. A prospective multicenter study was undertaken to reinvestigate the importance of measuring TSH receptor antibodies and performing the TRH test and the suppression test at the end of therapy in connection with this problem. In 451 patients the recurrence rate was 50.3% one year after the end of treatment. The patients in the recurrence group had a significantly higher rate of persistent antibody activity, no increase in TSH after TRH (negative TRH test), no normal suppressibility of thyroid 123 iodine uptake (negative suppression test) and larger goiter. The calculation of sensitivities and specificities shows, however, that these differences are not large enough to be of clinical importance for the individual patient.

Topics: Autoantibodies; Diet; Graves Disease; Humans; Iodine; Methimazole; Prospective Studies; Receptors, Thyrotropin; Recurrence; Risk Factors

One hundred and twelve new cases with Graves' disease were treated by tapazole for 6 months and followed-up for another 12 months in a prospective study. One hundred and eleven cases completed the whole course of study, and only one failed to be followed up. The results of the follow-up for 12 mon showed that the remission rate was 41.4% (46/111) and relapse rate was 58.6% (65/111). The present study indicated that the remission or relapse was related with serum levels of T3 before treatment, shrank goiter and disappearance of goiter bruit during the treatment as well as thyroid suppression rate, but not related to sex, age, period of illness before therapy or severity of the disease. It is suggested that a 6-mon antithyroid drug therapy instead of traditional long term therapy may be suitable for those patients who are with a reduced goiter and disappeared goiter bruit during the antithyroid therapy, and suppressible thyroid up-take by T3 and whose serum levels of T3 before treatment are not very high. So the patients may benefit from the short-term therapy. They are not only able to obtain a prolonged remission but also save time and money.

Topics: Adolescent; Adult; Child; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Prospective Studies; Recurrence; Triiodothyronine

In patients with Graves' disease, thyrostatic drug treatment may induce definitive remission without the need of more aggressive measures such as surgery or radioiodine. Following drug therapy, however, relapses often occur. In the present study, a multivariate analysis of pretreatment variables was performed, in order to identify individuals running a high risk of an unfavourable outcome of thyrostatic drug therapy. We studied 109 consecutive patients with a mean age of 38 years, range 20-70, over a mean follow-up period of 5.3 years after cessation of therapy. The analysis showed that goitre size, age, thyroid hormone levels, HLA-DR 3 haplotype, and TSH receptor antibody levels were of prognostic significance, whereas HLA-B8 haplotype, a lymphocytic infiltrate at fine needle biopsy, thyroglobulin, and microsomal antibodies had no such value. In particular, patients characterized by young age, large goitre and high hormone values were found to be associated with an unfavourable course.

Topics: Adult; Age Factors; Aged; Drug Therapy, Combination; Female; Goiter; Graves Disease; HLA Antigens; Humans; Male; Methimazole; Middle Aged; Multivariate Analysis; Receptors, Thyrotropin; Thyroglobulin; Thyroxine; Triiodothyronine

The presence of serum antithyroglobulin (TGHA) and antithyroidal microsomal (MCHA) antibodies in Graves' disease patients is associated with lymphocytic infiltration of the thyroid. The aim of this study was to determine the clinical significance of TGHA and MCHA during and after treatment of hyperthyroidism due to Graves' disease. One hundred and seventeen such patients were treated for 2 yr with methimazole and then followed for an additional year or more (mean, 30 months). The patients were classified into the following three groups: group I, patients negative for TGHA and MCHA before and during the 2 yr of treatment; group II, patients positive for MCHA but negative for TGHA before and during the 2 yr of treatment; and group III, patients who were positive for both TGHA and MCHA before and during treatment. The relapse rates after discontinuation of treatment in these groups were 39% (13 of 33), 27% (13 of 48), and 11% (4 of 36), respectively; the value in group I was significantly higher than that in group III (P less than 0.01). The results suggest that the presence of TGHA and MCHA may influence the prognosis of Graves' disease in patients treated with methimazole. Those patients who had neither antibody before and during treatment were most likely to have a relapse of hyperthyroidism, and those who had both antibodies were least likely to have a relapse.

Topics: Adolescent; Adult; Antibodies; Antithyroid Agents; Female; Graves Disease; Humans; Hyperthyroidism; Immune Sera; Male; Methimazole; Microsomes; Middle Aged; Thyroglobulin; Thyroid Function Tests; Thyroid Gland

In 153 patients, who from 1978 to 1982 were under treatment for clinically and radiochemically proven hyperthyroidism, thyroid function was re-examined at an observation interval of 5-10 years. Overall, the remission rate after initial treatment was 75%; after 5-10 years, 123 patients (80%) showed an euthyroid metabolic condition. Following conservative therapy alone, euthyroidism was seen unexpectedly often in patients with supposed autonomy. This is probably due to a transitory iodine contamination and a heterogeneous case material, as the differentiation from Basedow's hyperthyroidism may be difficult. The conservative initial therapy with thyrostatic drugs is indicated for both forms of hyperthyroidism. Based on the hitherto known prognostic criteria, a reliable prediction of the clinical course of a given case cannot be provided.

Topics: Adenoma; Adolescent; Adult; Aged; Antithyroid Agents; Combined Modality Therapy; Female; Follow-Up Studies; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Thyroid Function Tests; Thyroid Neoplasms; Thyroiditis, Autoimmune

On the basis of clinico-laboratory and radioimmunologic investigations in 139 patients with thyrotoxicosis, it is shown that in prescription of lithium carbonate with mercazol, more rapid decrease in the blood level of thyroid hormones, incidence of complications before and after the operation, cost expenditure is noted when compared to the other methods.

Topics: Graves Disease; Humans; Lithium; Lithium Carbonate; Methimazole; Postoperative Complications; Preoperative Care; Thyroid Hormones; Thyroidectomy

The authors studied 389 Graves' hyperthyroid patients receiving either high propylthiouracil (PTU) or methimazole (MMI) daily doses or low doses to evaluate whether adverse effects were related to the thionamide drugs or its daily dose regimen. Group 1 patients (n = 286) received high PTU (728 +/- 216 mg/day, n = 92) or MMI (60 +/- 19 mg/day, n = 94) doses, and group 2 patients (n = 103) were treated with low PTU (255 +/- 85 mg/day, n = 39) or MMI (23 +/- 10 mg/day, n = 64) doses. Major adverse effects were observed in 11 (2.8%) patients. Of these, four (1.0%) had agranulocytosis, two (0.5%) were granulocytopenic and five (1.3%) had hepatotoxicity. Agranulocytosis occurred in two patients from each group, 0.7% and 1.9%, respectively from group 1 and group 2. There was no significant difference between the groups or the types of thionamide. There also was no correlation with the patients' age. All of the patients were hyperthyroid, and its onset occurred in the first to third month of treatment. Full recovery was achieved in all cases after drug withdrawal. Four of 5 patients with hepatotoxicity were treated with high PTU doses, and one patient received low MMI doses (p less than .05). All patients were euthyroid. Arthralgias, skin rash and gastric intolerance, the minor adverse effects of thionamides studied, were observed in 52 (13.4%) of the patients. Although no significant differences were found, most of the patients experiencing side effects were from group 1 an received MMI therapy. These adverse effects did not demand drug withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Agranulocytosis; Chemical and Drug Induced Liver Injury; Child; Dose-Response Relationship, Drug; Drug Eruptions; Graves Disease; Humans; Hyperthyroidism; Joints; Methimazole; Middle Aged; Pain; Propylthiouracil; Stomach Diseases

In this brief report we describe a case of juvenile Basedow disease associated which exophthalmus and treated with deflazacort and methimazole on the basis of its immune origin (as confirmed by the presence of high levels of antimicrosomal antibodies). After only two months of therapy, we already noted a definite reduction of the exophthalmus and normalization of the thyroid hormone parameters with disappearance of the antimicrosomal antibodies.

Topics: Adolescent; Anti-Inflammatory Agents; Drug Evaluation; Drug Therapy, Combination; Female; Graves Disease; Humans; Male; Methimazole; Pregnenediones; Thyroid Hormones

Plasma atrial natriuretic peptide (ANP), plasma renin activity (PRA) and aldosterone were consecutively measured during methimazole treatment in patients with hyperthyroidism due to Graves' disease. ANP values of untreated hyperthyroid patients varied greatly from patient to patient, but decreased progressively with a decrease of serum thyroid hormone concentration during methimazole treatment. PRA was elevated in hyperthyroid patients but less aldosterone was secreted as evidenced by lower aldosterone/PRA ratio in these patients than in normal subjects and in hypertensive patients treated with thiazide. In addition, aldosterone/PRA ratio increased progressively with a decrease of ANP during methimazole treatment. The data indicated that ANP secretion was increased and ANP thus secreted depressed aldosterone secretion in hyperthyroid patients. Propranolol depressed pulse rate but failed to affect ANP secretion. It is suggested that thyroid hormone specifically acts on myocytes to stimulate ANP secretion but physiologic significance of such increased ANP secretion remains to be solved.

Topics: Adolescent; Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Female; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Propranolol; Pulse; Renin; Thiazines; Thyroid Gland

The direct effect of methimazole (MMI) on FRTL-5 cell growth was examined. TSH, (Bu)2cAMP, calf serum, insulin-like growth factor I, and Graves' immunoglobulin (IgG) increased [3H]thymidine incorporation into DNA during 72-h incubation. MMI (10(-3) M), which does not damage cell viability, significantly enhanced the increase in [3H]thymidine incorporation induced by TSH and (Bu)2cAMP. In contrast, MMI suppressed the increase in [3H]thymidine incorporation induced by calf serum, insulin-like growth factor I, and Graves' IgG. MMI had no effect on the production of cAMP by TSH. Accordingly, we concluded that MMI has opposite effects on cAMP- and non-cAMP-dependent cell growth pathways. Moreover, Graves' IgG, which has a modest effect on cAMP production, is believed to induce cell growth via the non-cAMP dependent cell growth pathway.

Topics: Animals; Biomechanical Phenomena; Bucladesine; Cell Division; Clone Cells; Cyclic AMP; Dose-Response Relationship, Drug; Graves Disease; Immunoglobulin G; Insulin-Like Growth Factor I; Methimazole; Rats; Somatomedins; Thymidine; Thyroid Gland; Thyrotropin

The prognostic value of determination of different antibodies in Graves' disease patients is questionable. The authors simultaneously assessed the generation of cAMP, the TSH-receptor binding inhibitory assay and the detectability of anti-microsomal antibodies by indirect immuno-fluorescence. The tests were performed before, during and after methimazole treatment. During a 12 months' medication all 22 patients became euthyroid. Six months after withdrawal of the drug, 15 patients were still euthyroid (Group A); 7 relapsed (Group B). Patients showing enhanced activities by all three methods, relapsed (5 out of 7 cases of Group B). The results indicate that simultaneous determination of TSI, TBII and anti-microsomal antibodies are of high prognostic value for relapses. These data should be taken into consideration for the further therapy.

Topics: Autoantibodies; Euthyroid Sick Syndromes; Graves Disease; Humans; Hyperthyroidism; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Methimazole; Time Factors

The study investigated whether ciclosporin (C) affected the thyroid-stimulating immunoglobulins (TSI) in serum of patients with endocrine orbitopathy (EO). The effect of C was compared with that of prednisone (P). Fifteen patients with EO classes III-V received C (n = 7) or P (n = 8). In addition to the immunosuppressants, five patients with Graves' disease in each group received methimazole (MMI). The stimulation of the cAMP levels in the medium of thyrocyte cultures was determined as a parameter of TSI. The TSI levels were markedly lowered in both groups during and after therapy. C group: before therapy 6.2 pmol/ml +/- 1.63 (100%, mean +/- SEM), during treatment 4.6 pmol/ml +/- 2.28 (74%), after treatment 4.1 pmol/ml +/- 1.33 (66%). P group: before treatment 9.1 pmol/ml +/- 3.42 (100%), during treatment 5.9 pmol/ml +/- 2.90 (65%), after treatment 3.7 pmol/ml +/- 1.20 (41%). There is neither a significant difference between the two groups nor between the patients who received the combined therapy (MMI + immunosuppressants) or only received immunosuppressants (P more than 0.05). The mean cAMP value of the healthy reference group (n = 19) is 0.4 pmol/ml +/- 0.03. There is a significant difference between this value and the cAMP values of the patients both before and after therapy (P less than 0.01). Thus, both C and P markedly lower the TSI titers of patients with EO.

Topics: Adult; Aged; Cyclic AMP; Cyclosporins; Exophthalmos; Female; Graves Disease; Humans; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Prednisone; Thyroid Gland; Triiodothyronine

It is a well-known fact that a thyroid stimulation blocking antibody (TSBAb) may play an important role in primary hypothyroidism. However, it has rarely been reported that TSBAb appears in only a few cases of Graves' disease which became hypothyroidism in their clinical courses. We examined TSBAb in 120 sera from 79 cases with Graves' disease before or while under methimazole (MMI)-treatment. TSBAb value was expressed as the percentage inhibition of TSH-stimulated cAMP response of porcine thyroid cells by the patient's IgG. TSBAb was positive in 9 cases (11.4%) of 79 cases of Graves' disease. In 6 of the 9 cases, TSBAb was detected at the untreated period. In the other 2 of the 9 cases, it was detected during the exacerbation related with their pregnancy. It was difficult to control Graves' disease in all 9 cases. These results suggest that TSBAb appears not only in primary hypothyroidism but also even in the hyperthyroid state of Graves' disease, and that the combination of TSAb and TSBAb may regulate the pathogenesis of Graves' disease.

Topics: Adult; Aged; Autoantibodies; Autoimmune Diseases; Binding, Competitive; Female; Graves Disease; Humans; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Receptors, Thyrotropin; Thyroid Diseases; Thyroiditis, Autoimmune

We studied 4 cases of Graves' disease with anti-thyroid hormone antibodies. Changes in the serum levels of triiodothyronine(T3), thyroxine(T4), free T4, thyrotropin(TSH), and thyroglobulin(Tg), as well as titers of anti-Tg antibodies, anti-thyroid hormone antibodies, anti-TSH receptor antibodies(TRAb) and anti-microsomal antibodies(MCHA) during 2 10 years' treatment periods were examined in each case. Case 1; A woman, who was diagnosed as having Graves' disease when she was 10 years old, had been treated with methimazole(MMI) or propylthiouracil(PTU). Treatment with the antithyroid drug had been discontinued by herself when she was 19 years old until she was 24 years old, when she was pregnant and consulted our hospital. Since her serum levels of T3 were unusually high, examination of her serum for the presence of anti-T3 antibodies was done. The presence of anti-T3 antibodies in her serum was confirmed. Case 2; A woman, who was diagnosed as having Graves' disease at the age of 41, had been treated with MMI or PTU. Presence of serum anti-T3 antibodies was found in a screening test for the antibodies. Serial sera were obtained during the 5 year observation period when she was treated with MMI, PTU, and subtotal thyroidectomy. Titers of anti-Tg antibodies in her sera were in the normal range. Case 3; A woman, who was diagnosed as having Graves' disease at the age of 11, had been treated with MMI or PTU. Presence of anti-T3 and anti-T4 antibodies were found in her sera in a screening test. Serial sera obtained during the 4 year treatment period were tested. Case 4; A woman, who was diagnosed as having Graves' disease at the age of 14, had been treated with MMI. Presence of anti-T3 and anti-T4 antibodies was found in her sera in a screening test. Serial sera obtained during the 2 year treatment period were tested. Titers of anti-Tg were increased when the levels of TSH or titers of TRAb were increased. The results suggested that TSH and TRAb, which are thyroid stimulating substances, increased serum levels of Tg, which resulted in the increase of titers of anti-Tg. Because of the possibility that administration of PSL could modify B lymphocyte functions, periods during which PSL was administered were excluded from the examination of the correlation between Tg concentrations or titers of anti-Tg and titers of anti-thyroid hormone antibodies, as in Cases 2 and 4, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adolescent; Adult; Autoantibodies; Autoantigens; Child; Female; Graves Disease; Humans; Methimazole; Middle Aged; Propylthiouracil; Receptors, Thyrotropin; Thyroglobulin; Thyroid Hormones; Thyrotropin

We reviewed the records of approximately 7000 Japanese patients whose hyperthyroidism was treated with methimazole (MMI) alone. Four patients (Group I) developed agranulocytosis during a second course of MMI therapy and eight patients (Group II) during an initial course. Six patients (three in each group) received less than 30 mg MMI daily. Agranulocytosis occurred after more than 2 months of therapy (12 weeks-1 year) in five patients. Seven patients were less than 40 years of age. One patient displayed a gradual protracted development of agranulocytosis. These results indicate that agranulocytosis after MMI may occur irrespective of dose, age, duration of treatment, and with a second exposure.

Topics: Adult; Agranulocytosis; Female; Graves Disease; Humans; Japan; Leukocyte Count; Male; Methimazole; Middle Aged; Thyroid Function Tests

The authors describe a case of successful treatment of medicamentous agranulocytosis (induced by mercasolyl) using hemoperfusion, an extracorporeal method for the treatment of intoxications. In the severe total intoxication syndrome, application of hemoperfusion in multimodality therapy of myelotoxic agranulocytosis improves the disease prognosis.

Topics: Acute Disease; Agranulocytosis; Combined Modality Therapy; Critical Care; Female; Graves Disease; Hemoperfusion; Humans; Methimazole; Middle Aged; Thyroidectomy

A 47-year-old man with Graves' disease suffered from a feeling of hunger and sweating in the night, polyarthralgia and fever one month after the start of treatment with methimazole. The above symptoms were ascribed to the side effects of methimazole; insulin autoimmune syndrome and lupus-like syndrome. The change in the antithyroid drug to propylthiouracil caused an amelioration of the symptoms. In addition to an anti-insulin antibody with a high binding capacity, hyperglucagonemia (260 pg/ml with a plasma glucose level of 61 mg/dl) was observed, which returned to normal in parallel with the decrease in the insulin binding capacity of the plasma one month after beginning the treatment with propylthiouracil. A normal decrease in the plasma glucagon level due to exogenous insulin (2 mU/kg/min) was observed with the euglycemic clamp. However, the plasma glucagon level was not suppressed by the oral glucose loading and elicited a poor response to the arginine infusion. Taking previous reports into account, this basal hyperglucagonemia seems to be a characteristic finding in the insulin autoimmune syndrome, while a sluggish response of glucagon to oral glucose or arginine infusion might be ascribed to hyperthyroidism. This is the first case report concerning a kinetical study of the glucagon secretion in insulin autoimmune syndrome with Graves' disease.

Topics: Arginine; Autoimmune Diseases; Blood Glucose; Glucagon; Glucose Tolerance Test; Graves Disease; Humans; Insulin; Kinetics; Male; Methimazole; Middle Aged

The results are presented of a 3-17 years' prolongation of the usual one-year "long-term" drug treatment applied to patients with Graves' disease. Most of the 87 patients with an average age of 34.3 years were on the maintenance dose of 10 mg methimazole daily. This mono-drug therapy was well tolerated and accepted by the patients, the toxic state disappeared, glandular consistency and the size remained almost unchanged. Thirty-six patients of this group (41.4%) were in a "permanent" remission lasting over three years. The remaining 51 patients continued their maintenance dose which kept a balanced euthyroid state. The authors support the convenience of a considerable extension of the traditional long-term methimazole treatment of Graves' disease. This extended scheme of the drug suppression of euthyroid functions is reversible in contrast to radical surgical or radioiodine treatments which increase the cumulative rate of irreversible hypothyroidism over decades.

Topics: Adolescent; Adult; Aged; Child; Graves Disease; Humans; Methimazole; Middle Aged; Time Factors

The present study was undertaken to examine whether thyrocytes possess phagocytic activity and whether the phagocytic activity is influenced by cytokines, such as interleukin 1, 2 (IL 1, IL 2) and interferon-alpha, -beta, and -gamma (IFN-alpha, beta, and gamma), and drugs, such as methimazole and dexamethasone. Thyroid glands were obtained from patients with Graves' disease. Thyrocytes were prepared by collagenase digestion. Thyrocytes were pre-incubated in the presence or absence of cytokines and drugs at 37 degrees C for 20 h and were further incubated with fluoresceinated latex beads at 37 degrees C for 60 min. The number of phagocytic thyrocytes was determined by FACS IV. Phagocytosis of latex beads was indeed seen within thyrocytes and gradually increased in a time-dependent manner. The rate of phagocytosis in thyrocytes was extremely slow as compared with that in macrophages. Phagocytic activity was detected in thyrocytes from patients with Graves' disease and from normal thyroid tissue adjacent to thyroid cancer. Phagocytosis was inhibited by IL 1, but was enhanced by IL 2. Although the enhanced phagocytosis with IFN-beta was consistently seen, little effect was detected with IFN-alpha and -gamma. Both methimazole and dexamethasone markedly inhibited phagocytosis. These results indicated that thyrocytes had phagocytic properties and that their phagocytic activity was modulated by cytokines, antithyroidal drugs and dexamethasone.

Topics: Antithyroid Agents; Biological Factors; Cytokines; Dexamethasone; Glucocorticoids; Graves Disease; Humans; Interferon Type I; Interferon-gamma; Interleukin-1; Interleukin-2; Methimazole; Microscopy, Fluorescence; Phagocytosis; Thyroid Gland

This study examined the abilities of methimazole, propylthiouracil (PTU) and propranolol to exert an immunosuppressive effect in vitro. Incubation of peripheral blood lymphocytes (PBL) with propranolol showed the drug to have no effect on either B- or T-cell activity. Methimazole or PTU at concentrations of greater than or equal to 10(-5)M resulted in significantly lower amounts of IgG and IgM being released into the culture medium. Both drugs were also found to have a direct effect on T-cell function as they caused the percentage of total and suppressor cells to increase towards normal levels. The three drugs were all found to have some free radical scavenging ability. These ranked PTU greater than methimazole greater than propranolol. These in-vitro findings would suggest that both methimazole and PTU have some direct effect on the immune system. It would seem more likely however that these effects are mediated via interleukin 2 rather than by their ability to act as free radical scavengers.

Topics: Antithyroid Agents; B-Lymphocytes; Culture Media; Free Radicals; Graves Disease; Humans; Immunoglobulin G; Immunoglobulin M; Immunosuppression Therapy; In Vitro Techniques; Methimazole; Propranolol; Propylthiouracil; T-Lymphocytes

Cultures of human thyroid follicles embedded in collagen gel were performed to investigate certain functional properties under bovine thyrotropin (TSH) stimulation. Follicles obtained from normal glands responded to increasing concentrations of TSH administered on day 4 in culture and for 3 days by increased amounts of cyclic AMP (cAMP), thyroglobulin (Tg) and triiodothyronine (T3) and by decreased levels of thyroxine (T4). Effect was maximal at 2000 microU/ml TSH (cAMP) or 200 microU/ml (Tg, T3, T4). When methimazole or propylthiouracil (PTU) were added, the T3 levels decreased. Follicle lumens contained a periodic acid-Schiff substance which was identified by immunoreaction as Tg. Thyroid follicles obtained from Graves' disease glands gave modified results with an earlier and intensified T3 response and no increase in Tg. These data show that (1) Tg and T3 are secretory products of functional follicles giving a cAMP-mediated response to TSH. (2) The detected T3 also derives from T4 5'-deiodination inhibited by PTU. (3) Intensified T3 response in Graves' follicles is probably due to enhanced conversion of T4 to T3.

Topics: Cells, Cultured; Collagen; Cyclic AMP; Graves Disease; Humans; Kinetics; Methimazole; Propylthiouracil; Thyroglobulin; Thyroid Gland; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine

A 52-year-old woman developed a toxic, solitary, autonomously functioning thyroid nodule four years after antithyroid drug treatment for Graves' disease. When she was initially seen, a thyroid scan showed the homogeneous enlargement of both lobes with increased uptake. Graves' disease was diagnosed and the patient was treated with methimazole. Thyroid function was well-controlled with medication for 18 months, after which the patient stopped taking the drug for three years. Four years after Graves' disease was diagnosed, the patient again showed symptoms of hyperthyroidism. The etiology was a toxic, autonomously functioning nodule.

Topics: Female; Graves Disease; Humans; Methimazole; Middle Aged; Sodium Pertechnetate Tc 99m; Thyroid Diseases; Time Factors; Ultrasonography

In patients with Graves' disease, initiation of thyrostatic therapy with methimazole causes a selective reduction of thyroid but not other autoantibody levels. The mechanism of this immunosuppressive effect is unknown. In the present study, methimazole (20 mg daily) induced very rapid changes in the surface antigen expression of several circulating lymphocyte subpopulations in six patients with Graves' disease. Within 1 to 3 days of therapy, the proportions of HLA-DR+ cells within the CD8+(Leu 2+) subset (activated 'suppressor/cytotoxic' T cells), CD11+(Leu 15+) cells out of CD8+ cells ('suppressor' T cells), and CD45+R (Leu 18+) cells out of CD4+(LEU 3+) cells ('suppressor/inducer' T cells) increased significantly from 4.7 +/- 3.9% to 9.5 +/- 6.0%, from 7.5 +/- 1.5% to 17 +/- 5.8% and from 49 +/- 17% to 73 +/- 19%, respectively. In parallel, the percentages of DR+ cells within the CD4+(Leu 3+) subset (activated 'helper' T cells), 4F2+ cells out of CD19+(Leu 12+) cells (activated B cells) and 4F2+ cells out of CD16+(Leu 11+) cells (activated 'natural killer'-like cells) declined significantly from 7.2 +/- 5.6% to 2.8 +/- 2.1%, from 7.2 +/- 1.5% to 4.0 +/- 2.8% and from 5.5 +/- 3.5% to 2.8 +/- 4.9% at 3 days, respectively. In contrast, no consistent phenotypic changes occurred in lymphocytes drawn from six healthy subjects during 7 days of methimazole medication. Direct in vitro effects of methimazole on lymphocyte markers were not observed when blood mononuclear cells from untreated patients were incubated with either the drug (10(-4) and 10(-6)M) or with autologous pre/post treatment serum for 1 to 4 days. Methimazole thus induces rapid alterations in the subclass and activation marker expression of circulating lymphocyte populations in Graves' disease. These alterations are compatible with a down-regulation of B cell activity. Indirect evidence suggests that the thyroid gland is the source of secondary signals for these changes to take place.

Topics: Adolescent; Adult; Antigens, Differentiation, T-Lymphocyte; Antigens, Surface; B-Lymphocytes; Female; Graves Disease; HLA-DR Antigens; Humans; Killer Cells, Natural; Leukocyte Count; Lymphocyte Activation; Male; Methimazole; Middle Aged; T-Lymphocytes; T-Lymphocytes, Cytotoxic; T-Lymphocytes, Regulatory

Interleukin-2 is a lymphokine which is believed to play a central role in the regulation of the immune response. The production of and response to interleukin-2 were determined in hyperthyroid Graves' patients together with thyroid function and serum thyrotropin receptor antibody, a marker of autoimmune activity. Interleukin-2 production by mitogen-induced peripheral blood mononuclears was markedly low in 24 of 29 patients when compared to controls. Five patients in remission had normal values. In nine patients followed during antithyroid drug therapy, interleukin-2 production returned gradually to normal levels within 4-6 months. This rise and the concomitant decrease in serum thyrotropin receptor antibody correlated with the decline in the free thyroxin index. Antithyroid drugs and triiodothyronine had no effect on interleukin-2 production in vitro. Mitogen-activated mononuclears from hyperthyroid Graves' patients did not proliferate as well as the controls in response to interleukin-2. However, seven patients treated with antithyroid drugs and three in remission responded normally. Flow cytometry using anti-Tac antibody revealed that the interleukin-2 receptor density on mononuclears from five patients was low. This parameter was normal in treated patients and those in remission. We conclude that the production of and response to interleukin-2 by peripheral blood mononuclears from hyperthyroid Graves' patients are poor, the latter being due to impaired receptor expression. Both aberrations are restored to normal by antithyroid drug therapy or in remission. The relative roles of the autoimmune process and thyroid function in modulating the interleukin-2 pathway and the question of whether antithyroid drugs act directly or through thyroid inhibition remain to be clarified.

Topics: Adult; Antibody Formation; Cell Line; Cell Line, Transformed; Female; Graves Disease; Humans; Interleukin-2; Male; Methimazole; Middle Aged; Propylthiouracil; Receptors, Thyrotropin; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory; Thyroxine

The natural course of hyperthyroidism due to Graves' disease after discontinuation of antithyroid drug therapy was studied in 184 patients who had been treated with methimazole and whose thyroid function was suppressible with T3 when methimazole was discontinued. The patients were followed after discontinuation of therapy for up to 60 months. Serum T4, free T4 (FT4) and T3 levels, TSH receptor antibody (TRab) and anti-DNA antibody titers, and the percentage of HLA-DR positive lymphocytes in peripheral blood were measured serially. TRab and anti-DNA antibody tests were positive in the majority of patients before treatment and were negative in most at the end of treatment. Twenty-three (12.5%) patients had a recurrence of their hyperthyroidism, which occurred a mean of 20 months after withdrawal of methimazole; they are designated as having overt recurrent hyperthyroidism (group A). In these patients, serum T4, FT4 and T3 concentrations increased rather abruptly to markedly elevated levels in a several-month period and the TRab and anti-DNA antibody titers increased markedly at or shortly after recurrence in the majority. In 9 patients (4.1%), TRH-induced TSH secretion became totally suppressed, indicating the reappearance of thyroidal autonomy; however, the patients did not have any hyperthyroid signs and symptoms (subclinical hyperthyroidism; group B). Their serum T4 and FT4 concentrations fluctuated in the upper normal to slightly supra-normal range, and their serum T3 concentrations remained within the normal range throughout the follow-up period, but their TRab and anti-DNA antibody titers did not appreciably increase. Thus, the time of recurrence could not be precisely determined in group B. In the remainder (152 patients; 83.4%), serum thyroid hormone levels and TRH-induced TSH secretion remained normal, TRab and anti-DNA antibody titers remained negative, and hyperthyroidism did not recur (euthyroid remission; group C). At the time of final examination (in groups B and C) or at the time of recurrence (in group A), the percentage of HLA-DR positive peripheral lymphocytes was 17.9% in group A, 15.9% in group B, and 12.1% in group C. Retrospective analysis of the data indicated that the mean pretreatment TRab titer (percent inhibition of TSH binding) was slightly but not significantly lower in group C (37.8%) compared to those in group A (53.9%) and group B (54.8%). The 3 groups were indistinguishable by all other laboratory data both before treatment

Topics: Adult; Autoantibodies; DNA; Female; Graves Disease; HLA-DR Antigens; Humans; Lymphocytes; Male; Methimazole; Middle Aged; Receptors, Thyrotropin; Recurrence; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Time Factors; Triiodothyronine

We have expanded our early observation that a potent Graves' IgG preparation induces HLA-DR expression on thyroid cells, by showing that four randomly-selected Graves' IgG's were also capable of inducing DR antigens on thyroid cells. The effect of Graves' IgG was specific to thyroid cells, as it did not induce MHC Class II molecule expression on endothelial cells whereas interferon-gamma and immune complexes did so. The anti-thyroid drug methimazole was capable of rapidly reducing Graves' IgG-induced DR expression but to a much lesser extent than brought about by interferon-gamma. We conclude that Graves' IgG propagates thyroid-specific autoaggression by continued induction of DR antigens and than an important means whereby methimazole brings about remission is by reducing this induction.

Topics: Graves Disease; HLA-DR Antigens; Humans; Immunoglobulin G; In Vitro Techniques; Interferon-gamma; Methimazole; Thyroid Gland

To investigate the natural killer (NK) cell mediated immunity in Graves' disease (GD) and the effect of antithyroid drugs upon NK cell activity, 51Cr release assay for NK cytotoxicity against K562 cells was examined in patients with GD before and during antithyroid medication and after drug withdrawal. Fifty-eight patients were divided into three groups: the untreated thyrotoxic patients (n = 33), the euthyroid patients under antithyroid treatment (n = 19) and the euthyroid patients after drug withdrawal (n = 6). The results of the three groups were compared to 23, 15 and 5 sex- and age-matched controls, respectively. The data revealed a significant NK dysfunction in the untreated hyperthyroid patients, although the number of the NK cells was not decreased. NK function was normal when patients were no longer taking antithyroid medication and in euthyroid state. However, euthyroid patients under antithyroid medication had markedly depressed NK activity, suggesting an immunosuppressive effect of the antithyroid drugs. This study demonstrated that both the hyperthyroid state and the antithyroid drugs exerted immunosuppressive effects upon the NK cells. Since such an immunosuppressive effect on NK cells might be associated with a decreased immune surveillance against tumour growth, this study implies that a long-term follow up of GD patients treated with antithyroid drugs may be indicated to guard against a possible increased incidence of malignancy.

Topics: Adolescent; Adult; Female; Graves Disease; Humans; Killer Cells, Natural; Male; Methimazole; Middle Aged; Propylthiouracil; Thyroid Hormones; Time Factors

Topics: Echocardiography; Electrocardiography; Female; Graves Disease; Heart Diseases; Humans; Methimazole; Middle Aged

Topics: Adult; Autoantibodies; Autoimmune Diseases; Carbimazole; Cross-Sectional Studies; Female; Graves Disease; Humans; Hypoglycemia; Insulin Antibodies; Male; Methimazole; Syndrome; Taiwan

This study was undertaken to determine the effect of methimazole on the pharmacokinetics of iv prednisolone in patients with Graves' disease. Twenty women were studied, including eight with severe infiltrative ophthalmopathy who had taken methimazole and T4 for at least 4 months, six with severe infiltrative ophthalmopathy who had undergone subtotal thyroidectomy and, therefore, required no antithyroid treatment, and six age-matched normal women. All were euthyroid. Each women received 0.54 mg/kg prednisolone as an iv bolus dose. Plasma total and unbound prednisolone concentrations were measured at multiple times during a 10-h study period by high pressure liquid chromatography and equilibrium dialysis. The clearance of both total and unbound prednisolone was increased significantly in the women receiving methimazole therapy compared to values in both control groups. The volume of distribution at steady state was similar in all groups. These results suggest that patients receiving methimazole have enhanced prednisolone metabolism and, therefore, they may require higher prednisolone doses.

Topics: Adult; Eye Diseases; Female; Graves Disease; Humans; Metabolic Clearance Rate; Methimazole; Middle Aged; Prednisolone

The mechanism for agranulocytosis induced by antithyroid drugs is not established. The few available studies have proposed an immune-mediated process against mature granulocytes. We investigated the effect of methimazole and propylthiouracil and serum from a patient with methimazole-induced agranulocytosis on marrow myeloid colony growth. In the presence of normal serum or patient's recovery serum, antithyroid drugs had no effect on the growth of CFU-GM colonies from normal or patient's marrow. However, the patient's serum obtained during agranulocytosis inhibited the in vitro myeloid colony growth from both autologous and allogeneic bone marrow. These results are compatible with an immune-mediated mechanism for methimazole-induced agranulocytosis rather than a direct toxic effect of the drug on abnormally sensitive cells.

Topics: Adult; Agranulocytosis; Bone Marrow; Colony-Forming Units Assay; Female; Graves Disease; Humans; Methimazole; Propylthiouracil; Stem Cells

FRTL-5 thyroid epithelial cells in culture were used to study the possible inhibitory effects of iodine on thyroid growth. NaI exerted a dose-dependent, thyroid epithelial cell-specific inhibitory effect on [methyl-3H]thymidine incorporation into DNA, reduced the DNA content in the cell layer, and limited the increase in cell number mediated by TSH. The inhibitory effects of sodium iodide applied to growth stimulated by TSH-, cAMP-, and non-cAMP-dependent mechanisms and were prevented by 1-methylimidazole-2-thiol (methimazole) and 2-ethylthioisonicotinamide (ethionamide). The latter findings indicate that the inhibitory effects of NaI are mediated by some iodine-containing organic compound. The inhibitory effects of organic iodine on growth subsided 24-48 h after removal of excess NaI from the culture medium. In contrast, NaI had no effect on normal rat kidney fibroblast or thyroid fibroblast [methyl-3H]thymidine incorporation stimulated by epidermal growth factor or serum. These data demonstrate a specific inhibitory effect of organic iodine on thyroid epithelial cell growth.

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Animals; Cell Division; Cell Line; Colforsin; DNA Replication; Ethionamide; Fibroblasts; Graves Disease; Humans; Immunoglobulin G; Iodides; Methimazole; Sodium Iodide; Thyroid Gland

In an attempt to study the effects of methimazole treatment on immunologic abnormality of hyperthyroidism of Graves' disease, TSH receptor antibody (TRab), anti-DNA antibody and HLA-DR were measured in untreated patients with hyperthyroidism of Graves' disease and treated patients with methimazole for 2 years, using peripheral blood. In untreated patients, all 3 parameters elevated above normal. Three parameters decreased 2 years after methimazole treatment, but the magnitude of decrease was more in T3-suppressible patients than in T3-unsuppressible patients. However, both anti-DNA antibody and HLA-DR were significantly more in T3-suppressible patients than in normal subjects. It is suggested that immunologic abnormalities should largely be improved before remission of Graves' disease can be obtained.

Topics: Adolescent; Adult; DNA; Female; Graves Disease; HLA Antigens; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Receptors, Thyroid Hormone; Thyrotropin; Triiodothyronine

The pregnancy of a women with diabetes mellitus was complicated by Graves' disease and maternal allergies to propylthiouracil and methimazole. Preparations for surgical removal of the thyroid gland were being made until pregnancy intervened. Several well-documented mechanisms of hyperthyroidism, including increased intestinal absorption of glucose, decreased insulin responsiveness, and increased glucose production may exacerbate glucose intolerance; the daily insulin requirement of this patient rose 80% from her pregestational dosage. When large doses of propranolol failed to control her thyrotoxic symptoms and led to severe, recurrent hypoglycemic episodes, subtotal thyroidectomy was performed. A 42% decrease in insulin requirements was observed postoperatively, with return to the euthyroid state. A propensity for symptomatic postoperative hypoglycemia should be anticipated in diabetic patients undergoing thyroidectomy.

Topics: Adult; Drug Hypersensitivity; Female; Graves Disease; Humans; Insulin Coma; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics; Propranolol; Propylthiouracil; Thyroidectomy

In order to investigate the influence of near total thyroidectomy on the course of endocrine ophthalmopathy (E.O.) in patients with Graves' disease, 29 patients with goitre and E.O. were classified before and after (up to 18 months) operation by use of a special ophthalmopathy index. 14 patients without goitre served as controls; they get only antithyroid drug treatment (ADT) (E.O. I and II, n = 7) or additional retoorbital irradiation (E.O. III and IV, n = 7, linear accelerator, 20 Gray). 20 out of 29 operated patients showed an improvement in the E.O., 4 a deterioration, 5 were unchanged. 3 out of 7 not operated patients with mild E.O. showed an amelioration during ADT, 4 no change. Additional radiotherapy in 7 patients with severe E.O. caused an improvement in the clinical condition of 3 patients, 3 patients deteriorated and 1 patient showed no change. It is concluded that adequate near total thyroidectomy has a positive effect on the clinical course of E.O. in patients with Graves' disease and E.O.

Topics: Follow-Up Studies; Graves Disease; Humans; Methimazole; Orbit; Thyroidectomy

Two patients with hyperthyroidism and Graves' ophthalmopathy were treated with cyclosporin A (CyA), in addition to methimazole, after failure of steroid therapy. Eye disease showed favorable responses and TSH receptor antibody concentration showed precipitous decline in concentrations compared to a gradual linear decline in antibody concentrations observed in 10 patients not treated with CyA. These results prompted us to investigate the in vitro influence of CyA on the synthesis of TSH receptor antibody by a patient's lymphocytes (with highest antibody concentration) in response to thyroid membrane antigen. CyA caused a dose-dependent reduction of TSH receptor antibody synthesis compared to control cultures. The effect of CyA was more marked when added to lymphocyte culture at the same time rather than 24 h after addition of antigen, consistent with CyA's interference of early T cell triggering by antigen. This study emphasizes the importance of helper T cells in synthesis of TSH-receptor antibody by cells and suggests that the drug may be therapeutically beneficial in severe Graves' ophthalmopathy and/or Graves' hyperthyroidism resistant to conventional treatment.

Topics: Adult; Antibody Formation; Cyclosporins; Eye Diseases; Female; Graves Disease; Humans; Methimazole; Middle Aged; Receptors, Thyrotropin; Time Factors

Topics: Antithyroid Agents; Graves Disease; Humans; Methimazole; Models, Biological; Thyroid Gland; Thyroiditis, Autoimmune

The iodine organification in thyroid gland was inhibited by application of Thyrostatic (Methimazole, Carbimazole) and consequently, thyroid hormone production and excretion were diminished. Carbimazole is converted to Methimazole in vivo and in vitro. Equivalent doses of Carbimazole and Methimazole are 0.6 to 1.0. Methimazole penetrates through the placenta, therefore established therapy with Methimazole (or Carbimazole) and thyroid hormone are contradicted in states of gravidity. In hyperthyroidism, preferred therapy strategy is accepted as Methimazole and/or Carbimazole only and in low doses, respectively (40-60 mg Methimazole as first step, consequently to doses down to 5-10 mg daily); accompaning rates of hematopoetic damage are dose responded.

Topics: Antithyroid Agents; Carbimazole; Dose-Response Relationship, Drug; Graves Disease; Humans; Methimazole; Propylthiouracil

Many reports of thyroid stimulating immunoglobulins (TSI) in relation to treatment of Graves' disease have been published and with variable results concerning prediction of permanent remission or relapse after therapy. A range of methods has been used and little has been published measuring TSI by using their ability to stimulate cyclic AMP production in human thyroid cells in monolayer culture. We therefore conducted a prospective study of the predictive value of such an assay in patients with hyperthyroid Graves' disease before, during and after treatment of one year with methimazole and thyroid hormone substitution. Furthermore, the possible relationship between activated suppressor T lymphocytes and TSI in patients followed before, during and after medical therapy has been studied. Patients were divided into two groups; group I, 15 patients, who stayed in remission and group II, 14, who relapsed during the first year after discontinuation of therapy. Mean TSI activity did not differ between the two groups before and during the first half year of medication. In the second half year of treatment, however, mean TSI activity was significantly lower in group I. TSI activity at the end of treatment appeared to have no value in predicting final outcome. Increased TSI activity in group II during treatment was reflected in an increased pertechnetate thyroidal uptake as compared to that in group I. There was no relationship between changes in TSI activity and T cell subsets (Leu 1, 2a, 3a). We found no difference in T lymphocytes between the two groups at any time during observation. Subsets of T lymphocytes in both patient groups did not differ from normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Female; Graves Disease; Humans; Immunity, Cellular; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Prospective Studies; Thyroxine; Time Factors; Triiodothyronine

In 38 patients with immunogenic hyperthyroidism a follow-up was performed to estimate the value of TBII before, during and after methimazole therapy. Before therapy increased TBII were detectable in 37 patients (94.4%). After 12 months methimazole therapy 25 patients had TSH-receptor antibodies (66%) within the normal range. In 13 patients positive antibody titres were found. In most cases persistence of increased TBII-values during drug treatment was an indicator of the persistence of active hyperthyroidism (10 of 13 patients). In the rule a disappearance of TBII-activity was combined with a functional remission (22 of 25 patients). Prolonged demonstration of TBII-activity in conjunction with persistence of hyperthyroidism should lead to ablative measures. In contrast to this medical therapy should be finished in patients with immunological and functional remission. Though in the further follow-up a recurrence of the immunological base of the disease with a functional and clinical relapse is possible.

Topics: Autoantibodies; Follow-Up Studies; Graves Disease; Humans; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Methimazole; Radioligand Assay; Receptors, Thyrotropin; Thyroid Gland; Thyrotropin-Releasing Hormone

Thyrostatic drug treatment of Graves' disease suppresses excessive thyroid hormone synthesis and causes a parallel decrease in serum thyroid autoantibody levels. The mechanism of this immunosuppression is unknown. We studied methimazole-induced immunoregulatory effects prospectively in 14 patients with Graves' disease treated for up to six months. The numbers of circulating activated, HLA-DR-positive T helper/inducer cells decreased gradually, from 8.3+1.7 percent (+SD) to 1.0+1.7 percent (P less than 0.001). HLA-DR-positive T suppressor/cytotoxic cells increased transiently at one month, from 2.0+1.9 percent to 12.6+6.4 percent (P less than 0.001), and returned to 2.9+3.7 percent at six months. Methimazole did not alter the HLA-DR expression of T cells in vitro. In two patients, the helper activity of T cells in inducing autoantibody secretion in vitro was substantially reduced after one month of methimazole treatment. Before treatment, large proportions of thyroid-infiltrating T-cell subsets expressed the activation markers HLA-DR, interferon-gamma, and interleukin-2 receptors, which were partially lost during therapy. Methimazole treatment was accompanied by a gradual reduction in circulating levels of thyrotropin-receptor, microsomal, and thyroglobulin autoantibodies. These results are compatible with the view that methimazole-induced immunoregulation in Graves' disease is mediated by a direct inhibitory effect on thyrocytes. This inhibition is in turn accompanied by marked changes in the proportions of activated T helper-like and T suppressor-like cells. This altered T-cell activation profile reflects, at least in part, the functional suppression of autoantibody production observed in methimazole-treated patients with Graves' disease.

Topics: Adult; Autoantibodies; Cells, Cultured; Female; Graves Disease; HLA-DR Antigens; Humans; Leukocyte Count; Lymphocyte Activation; Male; Methimazole; Middle Aged; Receptors, Thyrotropin; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory; Thyroid Gland

Up to now the results of drug treatment are unsatisfying. Treatment of more than 1-2 years did not decrease the occurrence of relapses. Thyroid suppression test and TRH test give the same indications concerning the outcome in cases with Graves' disease and disseminated autonomy (short-time prognosis). The relapse rate is distinctly higher in Graves' disease than in cases with disseminated autonomy (goitre class 3 excluded).

Topics: Follow-Up Studies; Graves Disease; Humans; Hyperthyroidism; Methimazole; Thyroid Function Tests; Thyrotropin; Thyrotropin-Releasing Hormone

Topics: Adolescent; Autoantibodies; C-Peptide; Female; Glucose Tolerance Test; Graves Disease; Humans; Insulin Antibodies; Methimazole; Syndrome

Topics: Autoimmune Diseases; Graves Disease; Humans; Methimazole; T-Lymphocytes; Thyroid Diseases

In 16 untreated patients with hyperthyroidism due to Graves' disease, serum antidouble stranded DNA antibody, measured by RIA, was positive (greater than 20 U/ml) in 14. In methimazole-treated patients with T3-suppressible thyroid uptake, anti-DNA antibody was found in 9% (3 of 35). The frequency of positive tests in methimazole-treated patients with T3-nonsuppressible thyroid uptake and in surgically treated patients was 24% (5 of 21) and 57% (4 of 7), respectively. Among anti-DNA antibody-negative (less than 9 U/ml) and weakly positive (10-19 U/ml) patients, those with T3-suppressible thyroid uptake had lower anti-DNA antibody titers than those with T3-nonsuppressible thyroid uptake. Among 32 patients with Hashimoto's thyroiditis, anti-DNA antibody was positive in 7. None of the patients with simple goiter had positive or weakly positive anti-DNA antibody results. Although the quantity of antibodies did not correlate well in individual patients, the rates of positive TSH binding-inhibiting immunoglobulin and anti-DNA antibody tests were roughly comparable in these patient groups. None of these patients with thyroid disease associated with anti-DNA antibody had clinical or other serological evidence suggestive of systemic lupus erythematosus or related collagen vascular disorders. The finding of anti-DNA antibody provides a new aspect of immunological abnormality associated with hyperthyroidism of Graves' disease.

Topics: Antibodies, Antinuclear; Autoimmune Diseases; Female; Goiter; Graves Disease; Humans; Lupus Erythematosus, Systemic; Male; Methimazole; Thyroiditis, Autoimmune; Thyroxine; Triiodothyronine

Topics: Graves Disease; Humans; Interleukin-1; Lymphocyte Activation; Methimazole; T-Lymphocytes

We use an antithyroid drug for the treatment of hyperthyroidism due to Graves' disease in children and adolescents for as long as the patients are willing to comply and/or tolerate the drug. In more than 60 patients treated since 1961, the remission rate was 25% in the first 2 yr. This report looks at these same patients again, followed for an additional 5 yr. Survival analysis methods applied to the follow-up data on 63 children confirm our original statistical findings and suggest a continuing remission rate of 25% every 2.1 +/- 0.4 (+/- SE) yr regardless of the duration of previous therapy. The median time to remission was 4.3 +/- 1.5 yr, and 75% of patients are predicted to be in remission in 10.9 +/- 2.3 yr. Of 36 patients who went into remission, defined by their being euthyroid for 1 yr after cessation of therapy, 1 relapsed, and 2 developed spontaneous hypothyroidism; the remainder are euthyroid 1-11.7 yr after therapy was discontinued. Of 14 who switched from medical therapy, 2 of 7 treated surgically and 4 of 7 treated with 131I are hypothyroid. Only 1 patient had a significant adverse reaction to both methimazole and propylthiouracil. While medical therapy may have some direct effect on the autoimmune response in hyperthyroidism, its role in affecting the time to ultimate remission is unknown. These data, however, describe the course of children so treated and allow us to present therapeutic options initially or during treatment based on statistically derived probabilities of outcome.

Topics: Child; Female; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Propylthiouracil; Statistics as Topic; Time Factors

Methimazole concentrations in plasma and in the thyroid glands were measured by means of high-performance liquid chromatography. Pharmacokinetics of methimazole were studied after a single oral dose (175 mumol/m2) in nine children and adolescent who were in the thyrotoxic state. Plasma levels of methimazole showed peak concentrations of 4.4 to 12.6 (median 9.2) mumol/l at 0.5 to 4 h after drug administration. Plasma half-life, area under the curve, and distribution volume ranged from 2.73 to 6.04 h, 32.8 to 77.9 mumol X l-1 X h-1, and 0.516 to 0.913 l/kg, respectively. These pharmacokinetic parameters showed a wide variation among the patients, but were quite reproducible in the same subject. Intrathyroidal concentrations of methimazole were measured in another nine subjects including four adolescents and five adults who underwent thyroidectomy. The drug concentrations in the thyroid glands ranged between 3.5 and 23.8 mumol/kg tissue and were far higher than those in the plasma obtained at the time of surgery. In this series of experiments, the dose of the drug varied from 76 to 319 mumol/m2, time after the last dose to surgery from 5 to 24 h, and the mode of drug administration from a single to three divided doses. Among these variable factors, only the daily dose of methimazole corrected by body surface area showed significant correlation with the intrathyroidal concentration, whereas the time after the last dose of the drug and the mode of drug administration did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adolescent; Child; Chromatography, High Pressure Liquid; Female; Graves Disease; Humans; Kinetics; Male; Methimazole; Thyroid Gland

The effects of methylmercaptoimidazole (MMI) and propylthiouracil (PTU) were compared in patients with Graves' hyperthyroidism. Firstly, the duration of action of the drugs was studied by the perchlorate discharge test, which was performed 2, 12, or 24 h after administering a single dose of 15 mg MMI or 300 mg PTU. After 2 h, the 9 MMI-treated patients who were tested had marked discharge (mean +/- SD, 65.0 +/- 15.8%), as did the 6 patients treated with PTU (57.6 +/- 26.6%). The mean values for the percent discharge 12 and 24 h after drug administration were 34.9 +/- 31.9% (4 patients) and 36.5 +/- 26.9% (69 patients), respectively, in the MMI group and 19.1 +/- 11.7% (11 patients) and 8.6 +/- 10.5% (7 patients) in the PTU group, indicating that the effect of MMI lasted longer. Secondly, the clinical effects of long term administration of the drugs were compared in a different group of patients with Graves' hyperthyroidism. Within 5 weeks after the onset of treatment, 34 (52%) of 66 patients treated with MMI (10 mg, 3 times daily) were euthyroid, while only 1 of 17 patients treated with PTU (100 mg, 3 times daily) was euthyroid. The average time required to achieve euthyroidism, namely normal serum T3 and T4 levels, was significantly shorter in the MMI group [6.7 +/- 4.6 (+/-SD) weeks] than in the PTU group (16.8 +/- 13.7). In spite of the well known effect of PTU on the extrathyroidal conversion of iodothyronines, the serum T3 level normalized much faster with MMI than with PTU. These results indicate that in our patient population 15 mg MMI had a longer inhibitory effect on the organification of iodide than did 300 mg PTU, and that MMI was more rapidly effective in the treatment of Graves' hyperthyroidism.

Topics: Adult; Female; Graves Disease; Humans; Male; Methimazole; Propylthiouracil; Thyroid Hormones; Time Factors

Topics: Adolescent; Child; Female; Graves Disease; Humans; Menstrual Cycle; Methimazole; Thyroidectomy

Sequential changes in thyroid-stimulating antibodies (TSAb) and TSH-binding inhibitor immunoglobulins (TBII) during antithyroid drug treatment were studied in 17 patients with Graves' disease. Before treatment, TSAb and TBII were detected in 17 (100%) and 13 (76.5%) patients, respectively, with a significant correlation between the two activities (r = 0.600, n = 17, P less than 0.02). In 9 patients who became euthyroid as early as after 1-4 months of treatment, the TSAb and TBII activities both gradually decreased, and there was a good correlation between the changes of these activities during treatment. Among the 7 patients in whom small changes in TSAb and TBII activities were observed, 4 showed poor control of the thyrotoxicosis during the whole observation period (7 months-2 years). One patient who showed a marked dissociation between the changes in TSAb and TBII activities developed hypothyroidism, when his TBII became remarkably high. These potent TBII inhibited cAMP production induced by bTSH. These findings indicate that 1) changes in TSAb and TBII activities reflect the clinical course of hyperthyroidism in most patients with Graves' disease, and 2) development of a blocking-type of TBII may induce hypothyroidism in some patients after the treatment.

Topics: Adolescent; Adult; Antithyroid Agents; Female; Graves Disease; Humans; Hypothyroidism; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Propylthiouracil

Topics: Antithyroid Agents; Female; Graves Disease; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil

We studied the effects of high doses of methimazole (MMI) or propylthiouracil (PTU) on thyroid-stimulating antibody (TSAb), antithyroid microsomal (MCHA) and antithyroglobulin (TGHA) levels in Graves' disease and Hashimoto's thyroiditis. Thirty Graves' hyperthyroid patients were treated for 14 +/- 8 months (mean +/- SD) with MMI, 60-80 mg daily or PTU, 900-1200 mg daily plus T3, 50-75 micrograms daily. Fifteen Hashimoto's thyroiditis patients (4 of whom hypothyroid) received 100-200 micrograms of T4 daily for 4-8 weeks prior to MMI, 60-90 mg daily or PTU, 900 mg daily for 12-16 weeks. In Graves' disease a decrease (p less than 0.001) in TSAb activity (20/25 patients) was observed: before therapy, 0.424 +/- 0.506 pmoles/mg wet wt and at the end of treatment, 0.189 +/- 0.23 pmoles/mg wet wt. The MCHA titers also fell (18/26 patients) from 1:10,403 +/- 20,197 to 1:3,476 +/- 5,252 (p less than 0.01) and was associated with a decrease in free T4 values (1.23 +/- 0.69 vs. 0.51 +/- 0.36 ng/dl; p less than 0.01). A fall of MCHA titers in T4-treated Hashimoto's thyroiditis patients (1:10,416 +/- 25,576) was found when compared with the value before T4 (1:25,920 +/- 39,973; p less than 0.001). However, the titers of MCHA (1:13,280 +/- 25,992) did not change on MMI or PTU plus T4 treatment. The TGHA titers fell in a single patient. No alterations were observed in serum immunoglobulins. Serum concentrations of the complement factor C'3 remained higher (p less than 0.01) than normal values in both Graves' disease and Hashimoto's thyroiditis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Isoantibodies; Male; Methimazole; Microsomes; Middle Aged; Propylthiouracil; Thyroiditis, Autoimmune

The insensitivity of Graves' thyroid to stimulation of cAMP formation by TSH as well as Graves' immunoglobulins in vitro is well known. The present study was performed to find out Graves' sera which may induce a final activation i.e. stimulation of T3 release in Graves' thyroid slices despite this insensitivity of tissue and to characterize determinants responsible for the efficiency of those sera. Out of 20 sera from patients with active untreated Graves' disease 6 were found to stimulate T3 release from Graves' thyroid in vitro. These 6 sera were effective in stimulating different Graves' glands, irrespective of pretreatment with propranolol, thiamazole (methimazole) or thiamazole plus iodine. In contrast, a significant response to bTSH was not observed in any Graves' gland. For comparison, 17/20 of the same sera were able to stimulate T3 release when tested on human goitrous thyroid. Sera which stimulated Graves' slices revealed no higher stimulating activities in goitrous tissue than serum samples which did not. All sera were additionally assessed for TSH binding inhibiting immunoglobulins in a radioreceptor assay. Remarkably, Graves' thyroid stimulating sera had a low or absent TSH binding inhibiting activity. Thus, hormone release from Graves' thyroid in vitro - in contrast to that from goitrous tissue - could only be activated by a minority of Graves' sera. These Graves' thyroid stimulating sera could be characterized to contain a selected spectrum of biologically active antibodies with a high TSH agonistic potency stimulating in the presence of a negligible TSH binding inhibiting activity.

Topics: Adult; Biological Assay; Graves Disease; Humans; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Iodine; Methimazole; Middle Aged; Propranolol; Radioligand Assay; Thyroid Gland; Triiodothyronine

One hundred and twenty-one patients with hyperthyroidism of Graves' disease were treated with antithyroid drugs for 3 years and thyroidal response to an increase or decrease of TSH and the serum thyroid stimulating immunoglobulin (TSI) activity were studied in relation to the presence or absence of TSH binding inhibiting immunoglobulin (TBII). TBII activity was positive in 83% of untreated patients but decreased gradually with time during antithyroid drug therapy. Thyroidal radioactive iodine uptake (RAIU) was suppressed by T3 in 86 of 121 treated patients but 16% of suppressible patients had TBII activity. Thyroidal RAIU was not suppressed by T3 in 35 treated patients, and 19 of 35 unsuppressible patients had TBII activity but other 16 patients did not. When suppressible and unsuppressible patients were combined, suppression of serum T4 and thyroidal RAIU by T3 tended to be less in the presence of TBII activity. TSI activity was detected in the sera of untreated patients but did not correlate with TBII activity. TSI activity was undetectable after treatment for 3 years irrespective of presence or absence of TBII activity and T3-suppressibility. TSH, T4 and T3 elevation in response to 500 micrograms thyrotropin releasing hormone (TRH) was normal in all treated patients irrespective of presence or absence of TBII activity and T3-suppressibility. It is suggested that in vivo thyroidal responsiveness to an increase or decrease of endogenous TSH did not correlate with the presence or absence of TBII activity after long-term therapy with antithyroid drugs.

Topics: Adolescent; Adult; Female; Graves Disease; Humans; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

A 37-year-old male with total thyroxine-binding globulin (TBG) deficiency associated with Graves' disease is described. Both TBG immunoreactivity and TBG capacity were not detectable in his serum. Serum concentrations of thyroxine-binding prealbumin and albumin were normal. He was initially hyperthyroid. During methimazole-treatment he was maintained in an euthyroid state except for two short hypothyroid periods. His plasma triiodothyronine/thyroxine (T3/T4) ratios during both the untreated hyperthyroid and the methimazole-induced hypothyroid states were higher than those during his methimazole-induced euthyroid state. These findings on changes in his T3/T4 ratio accompanying thyroidal dysfunction were qualitatively comparable with those in patients with Graves' disease with normal TBG levels: that both untreated hyperthyroid and methimazole-induced hypothyroid patients showed higher T3/T4 ratios than methimazole-induced euthyroid patients. These results may provide indirect evidence that changes in hormonal secretion and conversion that raise T3/T4 ratio can occur in thyroidal dysfunctions even in the complete absence of TBG.

Topics: Adult; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Thyroid Hormones; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine

Insulin autoimmune syndrome is characterized by spontaneous hypoglycemia, glucose intolerance, hyperinsulinemia and insulin-binding antibodies in serum without previous immunization. A 31-year-old man with Graves' disease developed insulin autoantibodies after therapy with methimazole. The patient was unique in that persistent hyperglycemia with polyuria and polydipsia had continued for several days before frequent hypoglycemic attacks appeared. We were able to extract a huge amount of immunoreactive insulin (116,000 microU/ml) with acid-ethanol from his serum obtained in the diabetic stage, and serum C-peptide immunoreactivity was as high as 268 ng/ml. The insulin-binding activity of his serum was quite potent, and when 1:5,000 diluted serum was incubated with 125I-porcine insulin, 71.2% of the label could be precipitated by polyethylene glycol. The insulin-binding protein was identified as mainly IgG with kappa light chains. Insulin-binding activity was not detected in serum obtained before methimazole therapy, suggesting that the drug was responsible for the induction of antibodies in this patient. The antibodies recognized porcine, sheep, bovine and horse insulins as well as human insulin. The mechanisms by which the antibodies produced hyper- and hypoglycemia have also been discussed.

Topics: Adult; Autoantibodies; Glucose Tolerance Test; Graves Disease; Humans; Hypoglycemia; Insulin Antibodies; Insulin Resistance; Male; Methimazole

Changes in titers of serum thyroid hormone autoantibodies (THAA) and anti-thyroglobulin (Tg) antibodies during treatment with antithyroid drugs (methimazole and propylthiouracil) were examined in two cases of Graves' disease. Effects of prednisolone and subtotal thyroidectomy were also investigated in one case (case 1). Initially both cases had only anti-T4 autoantibodies in their serum. During methimazole therapy, the titer of anti-T4 autoantibodies increased in both cases, and anti-T3 autoantibodies became detectable and their titer increased in case 2. The influence of propylthiouracil on the titer of THAA was not clear. Both prednisolone plus methimazole therapy and subtotal thyroidectomy decreased the level of anti-T4 autoantibodies in case 1. There was a significant correlation between titers of THAA and anti-Tg antibodies in both cases, although titers of anti-Tg antibodies in case 1 stayed within the normal range throughout the investigation period. These results indicate that methimazole treatment could induce and/or enhance the production of THAA and THAA are antibodies against thyroid hormone-containing Tg molecule.

Topics: Autoantibodies; Child; Female; Graves Disease; Humans; Methimazole; Middle Aged; Prednisolone; Propylthiouracil; Thyroglobulin; Thyroid Hormones; Thyroidectomy; Thyroxine; Triiodothyronine

One hundred and twenty-four patients with newly diagnosed hyperthyroidism received a combined thionamid-thyroxine medical therapy for approximately 2 years. According to the estimated goitre size before therapy and the type of goitre the patients were divided into 4 groups: Graves' disease no goitre (n = 19), Graves' disease small goitre (n = 57), Graves' disease medium or large goitre (n = 23), multinodular goitre (n = 25). The median follow-up period after cessation of medication was 64 (range 11-141) months. The remission rates in the different groups during follow-up were calculated using life table analysis. Graves' patients with no goitre or a small goitre had a significantly better outcome (remission % after 5 years 82.5 +/- 15.4 (SE) and 71.5 +/- 7.8, respectively) than Graves' patients with a medium size or large goitre (remission % after 5 years 37.0 +/- 11.1)(P less than 0.025). Most patients with multinodular goitre had a relapse within the first year after stop of medication (remission % after 5 years 15.5 +/- 10.1). Hence patients with Graves' disease having a small thyroid gland should be treated medically while surgery or radioiodine may be a more reasonable choice in Graves' patients with medium size or large goitres. Medically treated patients with toxic multinodular goitres have a very small chance of prolonged remission if medication is stopped.

Topics: Adult; Aged; Female; Follow-Up Studies; Goiter, Nodular; Graves Disease; Humans; Male; Methimazole; Middle Aged; Prognosis; Thyroxine; Triiodothyronine

Peroxidase activity in thyroid tissue from 25 patients with Graves' disease was measured by Mini assay method (J. Biochem. 98, 637-647, 1985) employing guaiacol or iodide as a second substrate. The mean values of protein-based specific activity were 0.496 guaiacol unit/mg protein and 0.187 iodide unit/mg protein, reaching 16 fold and 28 fold those of normal thyroids, respectively. The mean value of ratio of iodide unit to guaiacol unit in each thyroid, 0.68, was also much higher than that of normal human thyroid, 0.16. No significant difference in peroxidase activity was observed between patients treated with methylmercaptoimidazole and those with propylthiouracil, but the activities of those groups were significantly higher than those of patients treated with potassium iodide, suggesting that inorganic iodine therapy plays some role in suppressing the synthesis of thyroid peroxidase in vivo.

Topics: Adolescent; Adult; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Peroxidases; Potassium Iodide; Propylthiouracil; Thyroid Gland

Anti-thyroid drugs are widely used to treat diffuse toxic goiter (Graves' disease). Of the two drugs currently available in the United States, propylthiouracil is prescribed far more often than is methimazole (Tapazole). However, compared with propylthiouracil, methimazole can be given as a single daily dose, is cheaper, and, at low doses, is associated with less major toxicity; for these reasons, methimazole should be used for the routine management of Graves' disease when anti-thyroid drugs are selected as primary therapy. On the other hand, because of certain pharmacologic factors, propylthiouracil should be used in selected situations, particularly in patients with "thyroid storm" and in pregnant or lactating women.

Topics: Drug Administration Schedule; Female; Graves Disease; Humans; Metabolic Clearance Rate; Methimazole; Pregnancy; Propylthiouracil

Aplasia cutis congenita, the localized absence of skin at birth, usually is an isolated scalp defect. We examined an infant with aplasia cutis congenita associated with maternal Grave's disease and the use of methimazole during pregnancy. This association was reported twice before. It has certain implications with respect to therapy of pregnant hyperthyroid women.

Topics: Abnormalities, Drug-Induced; Adult; Female; Graves Disease; Humans; Infant, Newborn; Male; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Skin Abnormalities

Topics: Female; Graves Disease; Humans; Hypothyroidism; Infant, Newborn; Maternal-Fetal Exchange; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil

To re-evaluate the clinical utility of the prolonged management of hyperthyroidism with sodium tyropanoate (TP), an oral cholecystographic agent, we studied the changes in the scoring of thyrotoxic signs and symptoms (thyrotoxic index; TI), serum concentrations and binding of thyroid hormone, and circulating TSH receptor antibodies (TRAb) in two groups of patients with Graves' disease; seven patients (TP group) received TP (1.5 g daily) alone for 14 weeks, and six patients (TP + MMI group) received methimazole (MMI; 30 mg daily) in addition to TP for 8 weeks and MMI alone thereafter. In the TP group, the TI reduced significantly, but it failed to reach a euthyroid level in all except one. Serum total T4 (TT4), free T4 (FT4), and T3 uptake (T3U) values declined by the third week of treatment, but an 'escape' occurred thereafter. Serum rT3 and T4 binding globulin (TBG) levels were increased. The TRAb titres were increased slightly but significantly. Serum T3 levels fell within a week but remained higher than normal during the treatment. In the TP + MMI group, all patients achieved a normal TI by the end of the treatment. Serum TT4, FT4 and T3U fell more significantly than those in the TP group, indicating no escape from the effect of TP. The serum TRAb decreased significantly. Serum T3 levels showed a greater reduction than those in the TP group, and remained decreased even after withdrawal of TP. In a further 9 patients receiving TP alone for 4-14 weeks (7.3 +/- 5.0 weeks on the average), TP was withdrawn and replaced by MMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Drug Therapy, Combination; Female; Graves Disease; Humans; Iodobenzenes; Male; Methimazole; Middle Aged; Thyroid Hormones; Tyropanoate

Topics: Adult; Agranulocytosis; Female; Graves Disease; Humans; Methimazole

Topics: Animals; Antithyroid Agents; Autoantibodies; Autoimmune Diseases; Carbimazole; Graves Disease; Humans; Hyperthyroidism; Immunity, Cellular; Immunosuppressive Agents; Methimazole; Propylthiouracil; Thiourea; Thyroid Hormones

The course of thyrotoxicosis in 33 patients with Graves' disease was evaluated clinically and biochemically (free thyroxine index, serum triiodothyronine, thyroid stimulating antibodies, (TSAb), thyroid stimulating hormone binding inhibiting immunoglobulins (TBII)). Relapse of the disease was found to be correlated to anamnestic information of thyrotoxicosis among first degree relatives (predictive value 90%) and to concomitantly raised levels of TSAb and TBII at the start of treatment (predictive value 71%). Mean duration of treatment of patients with long-lasting remission was 16.8 months. When comparing various information used to predict relapse of Graves' disease, anamnestic information of familial predisposition to thyrotoxicosis carries the highest predictive value.

Topics: Adolescent; Adult; Aged; Antibodies; Female; Graves Disease; Humans; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Prognosis; Recurrence; Thyroxine; Triiodothyronine

In a patient with active Graves' disease an infiltrative ophthalmopathy developed during antithyroid drug therapy. Her eye symptoms were effectively treated with a large dose of prednisolone (PD), plasma exchanges (PE), cyclophosphamide, orbital irradiation, antithyroid drug and a supplemental dose of triiodothyronine. Before, during and after these treatments thyrotropin binding inhibitor immunoglobulin (TBII) activities in a unit serum immunoglobulin (IgG) were measured after adjusting the IgG concentration by adding normal IgG. Relative TBII concentrations were calculated by extrapolating individual data on a standard curve constructed from serial dilutions of the most potent IgG. Approximately a 5 fold increase in the TBII concentration was observed during the 2 months of progression of the ophthalmopathy, while TBII activity revealed only a 13.3% increase. After treatment TBII concentrations decreased gradually showing a close relation with the severity of the eye symptoms. Every PE was found to remove 48.5 +/- 7.9 (s.e.m.) % of TBII. After PE TBII returned to the preexchange level very rapidly and then overshot it in 2 to 3 weeks. Sixty mg of PD failed to prevent the overshoot but a 100 mg initial dose of PD after 5 PEs inhibited it to some extent. The effectiveness of combined therapy with PE, PD and cyclophosphamide appeared to confirm a role of humoral factors in the pathogenesis of Graves' ophthalmopathy. Serial determinations of TBII in a relative concentration were considered quite useful in analyzing the effectiveness of treatment in Graves' ophthalmopathy.

Topics: Eye Diseases; Female; Graves Disease; Humans; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Methimazole; Middle Aged; Plasmapheresis; Propylthiouracil; Radiography; Skull

Topics: Autoantibodies; Graves Disease; Humans; Hyperthyroidism; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Methimazole; Receptors, Cell Surface; Receptors, Thyrotropin; Thyroid Gland; Thyroidectomy

The prognostic value of the determinations of autoantibodies in Graves' disease is still questionable. So far, the role of different assay procedures used has not been intensively investigated. We simultaneously applied two different techniques, a radioreceptor assay and a T3 releasing in vitro assay, in the follow-up of patients with Graves' disease to directly compare the course of the antibody activities determined by these assays and to find out a prognostic significance of the composition of the antibody spectrum present. The initial activities of thyroid stimulating antibodies (TSAb) and TSH-binding inhibiting immunoglobulins (TBII) were not significantly correlated in patients before treatment. During a 12-month antithyroid medication antibody titres showed a concordant course in the majority of patients. In 6 of 25 patients, however, a discordant behaviour was clearly documented including dose-response curves. At the end of treatment, the patients could be divided into three groups: group I included 5 patients positive for both TSAb and TBII, group II 6 patients positive for TBII and negative for TSAb and group III 14 patients negative for both of them. During the following survey of 18 months all patients of group I, 2 patients of group II and 6 patients of group III experienced a relapse of hyperthyroidism. In conclusion, TSAb and TBII activities dissociate in some patients during antithyroid drug therapy. For the individual patient, the disappearance of both TSAb and TBII was no certain indicator for a longstanding remission of Graves' hyperthyroidism. The persistence of TSAb seems to be more reliably associated with persisting or rapidly relapsing disease than the persistence of TBII.

Topics: Adult; Aged; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Graves Disease; Humans; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Radioligand Assay; Thyroid Gland; Thyroxine; Triiodothyronine

Patients with Graves disease were prospectively followed by means of three 99mtechnetium thyroid uptake ratios. These three ratios were greater than 90% sensitive and specific for the detection of hyperthyroidism in the patient with untreated Graves disease. Twelve of 15 patients experienced prolonged remission after normalization of the ratios. These ratios exhibit significant linear correlation with serum thyroxine and triiodothyronine concentrations (r = 0.4-0.6, P less than 0.01) and are a very sensitive index of medical oversuppression of thyroid function.

Topics: Adolescent; Child; Child, Preschool; Female; Follow-Up Studies; Graves Disease; Humans; Male; Methimazole; Propylthiouracil; Prospective Studies; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Thyroid Gland; Time Factors

Two groups of patients with newly diagnosed thyrotoxicosis were treated with propylthiouracil (PTU) 400 mg every 6 h for 4 days followed by methimazol (MMI) 40 mg every 6 h for 4 days or by MMI for 4 days followed by PTU for 4 days. The shift from MMI to PTU induced a considerable decrease in serum T3 while shift from PTU to MMI led to an increase in serum T3. Serum T4 decreased gradually during the whole treatment period. The opposite variations in serum T3 were accompanied by similar opposite variations in basal metabolic rate (BMR) (P less than 0.001). Hence the rapid variations in serum T3 which can be induced by PTU in thyrotoxic patients, are followed by rapid alterations in the thyrotoxic state as evaluated by BMR.

Topics: Achilles Tendon; Adult; Basal Metabolism; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Propylthiouracil; Pulse; Reflex; Thyroid Hormones; Thyroxine; Triiodothyronine

In the sera of patients with Graves' disease have been demonstrated the immunoglobulins able to inhibit the binding of TSH to the human thyroid membrane (TBI-Ab) and the immunoglobulins stimulating the thyroid adenylate cyclase (TS-Ab). The present study was performed in 75 hyperthyroid Graves' patients to ascertain the pathophysiological significance of these immunoglobulins. TS-Ab and TBI-Ab prevalence appeared to be much higher in the untreated and in relapsing patients than in subjects in remission. When the results of TBI-Ab and TS-Ab were compared in each group of patients no correlation was found between the two activities. We conclude that the TBI-Ab and the TS-Ab are the markers of hyperthyroidism in Graves' disease but the two activities are not equivalent and probably reflect a different phenomenon concomitantly produced.

Topics: Adenylyl Cyclases; Adult; Autoantibodies; Graves Disease; Humans; Immunoglobulin G; Methimazole; Middle Aged; Thyroid Gland; Thyrotropin

The coupling of iodotyrosine (coupling reaction) is one of the least studied in the formation of thyroid hormone, particularly in human thyroid diseases. This paper describes a method of measuring iodotyrosine coupling catalyzed by human thyroid peroxidase (TPO) in vitro. There were two important requirements to demonstrate the coupling reaction: 1) thyroglobulin with a low thyroid hormone content, and 2) partially purified TPO. Thyroglobulin with low thyroid hormone content was obtained from Grave's and follicular adenoma tissues after propylthiouracil (PTU) therapy and L-T4 therapy, respectively. TPO was prepared from Graves' thyroid by solubilizing the 100,000 X g pellet of thyroid homogenate with sodium deoxycholate and trypsin, followed by Sephacryl S-300 gel filtration. Before the coupling reaction, thyroglobulin was iodinated with chloramine-T and potassium iodide, followed by dialysis. The coupling reaction was carried out by incubating newly iodinated thyroglobulin with TPO, diiodotyrosine, a coupling stimulator, and a H2O2-generating system (glucose and glucose oxidase) for 20 min at 37 C. After thyroglobulin was digested with Pronase, the thyroid hormone content of the thyroid digest was measured by RIA. Coupling activity was measured by the amount of newly formed T3 (nanograms of T3 per mg thyroglobulin). The time course of coupling reaction showed a progressive increase in coupling activity up to 30 min, and the reaction was temperature and pH dependent, with a pH optimum of 7.0. Coupling activity in the presence of H2O2 and TPO was 43 +/- 5.0 ng T3/mg thyroglobulin (mean +/- SD of triplicate samples), and addition of diiodotyrosine to the H2O2-TPO system caused a nearly 3-fold increase in coupling activity. This method has potential utilization for measurement of peroxidase coupling activity, since there was a linear relationship between the measured coupling activity and the amount of added TPO when the TPO concentration was over 3 micrograms/300 microliter. Methimazole (MMI) and PTU had similar potencies in inhibiting the TPO-catalyzed coupling reaction, whereas MMI was distinctly more potent than PTU as an inhibitor of TPO-mediated iodination in vitro. The different potencies of MMI in the two reactions suggest that different inhibitory mechanisms may be involved in iodination and coupling. The reducing agent, sodium metabisulfite, was also found to be a more potent inhibitor of the TPO-mediated coupling reaction than of the TPO-mediated

Topics: Catalysis; Chemical Phenomena; Chemistry; Chromatography, Gel; Graves Disease; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Iodide Peroxidase; Methimazole; Monoiodotyrosine; Peroxidases; Propylthiouracil; Sulfites; Temperature; Thyroglobulin; Thyroxine; Triiodothyronine

The response to methimazole [1-methyl-2-mercaptoimidazole (MMI)] therapy was evaluated in 18 patients with diffuse toxic goiter residing in an area of iodine deficiency (Tehran) and in 18 patients residing in an area of iodine sufficiency (Boston). The mean free T4 index (FT4I) decreased from 22.9 +/- 4.8 (+/- SD) to 4.9 +/- 4.3 in Tehran and from 23.8 +/- 5.2 to 17.0 +/- 4.1 in Boston after 4 weeks of MMI administration (10 mg, three times daily). The mean free T3 index (FT3I) decreased from 489 +/- 124 to 117 +/- 58 in Tehran and from 512 +/- 250 to 368 +/- 152 in Boston. In patients residing in Tehran, the FT4I was normal in 9 (less than 6.3 in 6), above normal in 1, and subnormal in 8 (44%) after 4 weeks of MMI treatment. In 4 of 8 patients with subnormal FT4I, serum TSH was also above normal, and clinical findings of hypothyroidism were evident. MMI (10 mg, twice daily) was then given to 15 additional patients with diffuse toxic goiter in Tehran. Mean FT4I values were 22.7 +/- 6.8, 12.1 +/- 2.5, 10.8 +/- 2.8, and 6.0 +/- 4.3 before and 8, 14, and 28 days after treatment, respectively. Corresponding mean FT3I values were 415 +/- 90, 196 +/- 36, 162 +/- 44, and 117 +/- 46. At 28 days, FT4I was subnormal in 7 (46%) patients, of whom 1 had increased TSH. These results indicate that treatment with recommended doses of MMI rapidly causes hypothyroidism in patients residing in Tehran, an area of iodine deficiency. Furthermore, they support the hypothesis that the dosage of thionamide compounds and the duration of therapy with the initial doses necessary to induce euthyroidism may vary in various parts of the world.

Topics: Adult; Boston; Dose-Response Relationship, Drug; Environment; Female; Graves Disease; Humans; Hypothyroidism; Iodine; Iran; Male; Methimazole; Middle Aged; Thyroxine; Triiodothyronine

Topics: Adolescent; Adult; Autoantibodies; Female; Graves Disease; Hemagglutination Tests; Humans; Male; Methimazole; Prognosis; Thyroglobulin; Thyroid Gland

A newly developed method for extracting and measuring methimazole in biological fluids was used to study the pharmacokinetics of methimazole in two euthyroid and eight hyperthyroid subjects. The volume of distribution approximated total body water; the biological half-life was 2-3 h in euthyroid and about 6 h in hyperthyroid patients. Total clearance was lower in hyperthyroid patients than in euthyroid subjects, and it did not increase after thyroid function was normalized. Bioavailability in euthyroid subjects was greater than 1 but only 0.5 in hyperthyroid subjects. The reasons for these observed differences are not known.

Topics: Biological Availability; Chromatography, High Pressure Liquid; Graves Disease; Half-Life; Humans; Hyperthyroidism; Infusions, Parenteral; Kinetics; Metabolic Clearance Rate; Methimazole

Peripheral T-Lymphocyte subsets were analyzed with monolateral antibodies in 40 patients with Graves' ophthalmopathy. The 20 patients with untreated hyperthyroid exophthalmos showed a slight statistically not significant decrease in the percentage of total T-Lymphocytes and a statistically significant decrease with percentage of the OK T8 cells. No significant changes were observed in the percentage of OK T3 and OK T4 and OK T8 cells in patients with euthyroid exophthalmos under the drug treatment. These findings indicate the significant association of quantitative abnormality of suppressor-cytotoxic cells with untreated hyperthyroid exophthalmos.

Topics: Exophthalmos; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; T-Lymphocytes

Pancreatic alpha and beta cell hormone secretion was studied in 11 patients with thyrotoxicosis before and in 7 patients after thyroid function was normalized with either prophylthiouracil or methimazole and propranolol (R). All had IV arginine and IV glucose infusions. Forty control subjects had IV arginine; 21 had IV glucose tests. After arginine, untreated patient had blunted serum insulin at both 15 and 30 minutes (p less than 0.05, p less than 0.001) compared to control subjects, blunted glucagon at 30 minutes (p less than 0.05) and blunted glucose at both 15 and 30 minutes (p less than 0.001, p less than 0.01) compared to control subjects. After glucose, untreated patients had lower nadir glucagon than in the studies with both arginine and glucose infusions. These data document blunted glucagon, suppressed glucose and insulin peaks after arginine in thyrotoxicosis, indicate that both alpha and beta cell hormone secretion may be abnormal, and that the preferential abnormality follows protein rather than carbohydrate loading.

Topics: Adolescent; Adult; Aged; Arginine; Blood Glucose; Child; Child, Preschool; Female; Glucagon; Glucose; Graves Disease; Growth Hormone; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Methimazole; Middle Aged; Propranolol; Propylthiouracil

Topics: Adult; Drug Therapy, Combination; Female; Graves Disease; Humans; Lithium; Lithium Carbonate; Male; Methimazole; Middle Aged; Premedication

Topics: Cytochrome Reductases; Goiter, Nodular; Graves Disease; Humans; Iodide Peroxidase; Lactates; Lactic Acid; Lithium; Lithium Carbonate; Methimazole; NADH Dehydrogenase; Oxidation-Reduction; Preoperative Care; Pyruvates; Pyruvic Acid; Succinate Dehydrogenase; Thyroid Gland; Thyroidectomy

A study was made of the antithyroid effect of lithium carbonate in 163 patients with diffuse toxic goiter. In addition to clinical monitoring a radioimmunoassay was used to determine the level of serum thyroxine, triiodothyronine and thyrotropin. The most important indicators of the activities of the cardiovascular system were analysed by RCG and polycardiography findings. Data on a rapid and stable antithyroid effect of lithium carbonate were obtained. With the concentration of lithium ion within 0.4-0.8 meq/l the basal level of thyroxine and triiodothyronine decreased by 40 and 35% respectively. Reducing the level of circulating thyronines in hemocirculation lithium did not cause a sharp rise of blood thyrostimulating activity. In combined application of lithium and mercasolil the thyrostatic effect of both drugs was summarized. Lithium did not block iodine accumulating function of the thyroid permitting, if necessary, its combination with iodine drugs. Possible mechanisms of the effect of lithium on the thyroid in hyperthyroidism and its role in multimodality therapy of the diffuse toxic goiter were discussed.

Topics: Adult; Drug Therapy, Combination; Female; Follow-Up Studies; Graves Disease; Humans; Lithium; Lithium Carbonate; Male; Methimazole; Middle Aged; Thyroid Function Tests

Suppressor T cell function induced by concanavalin A (con A) was evaluated in patients with Graves' disease and Hashimoto's thyroiditis. Patients with Graves' disease were divided into the following two groups: (1) untreated, and (2) euthyroid during antithyroid drug (methylmercaptoimidazole) therapy. T cells (2 X 10(5)), activated by con A for 48 hours, were added to preincubated responder cells (2 X 10(5)) and re-incubated for 7 days in the presence of pokeweed mitogen (PWM). IgG produced in the culture medium was measured by radioimmunoassay and then % suppressions (IgG) were calculated. Thyroid stimulating activity (TSA) in serum was measured by McKenzie's method by means of normal human thyroid slices, and % suppressions (c-AMP) were calculated. IgG produced in lymphocyte culture medium was suppressed by added con A-activated cells in untreated and euthyroid groups of Graves' disease, Hashimoto's thyroiditis and normal controls. The value of % suppression (IgG) was reduced in each group of Graves' disease compared to normal controls. No significant relation was observed between TSA in serum and % suppression (IgG), but three cases with high serum TSA showed low % suppressions (IgG). In 12 cases of Graves' disease, % suppression (IgG) had a positive relation with % suppression (c-AMP) in same medium. The amount of c-AMP produced in thyroid slices incubated in medium, in which responder cells (8 X 10(5)), was elevated in all 7 untreated cases of Graves' disease, while not elevated in 7 euthyroid cases. The value of % suppression (c-AMP) in euthyroid cases with Graves' disease was significantly higher than that in untreated cases. The value of % suppression (IgG) was reduced and had a significant negative relation with logarithm of serum antimicrosomal antibody titer in patients with Hashimoto's thyroiditis. These results indicate that low activity of suppressor T cell had a role on antibody production, including thyroid stimulating antibody, and pathogenesis of autoimmune thyroid diseases.

Topics: Adult; Autoimmune Diseases; Concanavalin A; Cyclic AMP; Female; Graves Disease; Humans; Immunoglobulin G; Male; Methimazole; T-Lymphocytes, Regulatory; Thyroiditis, Autoimmune; Triiodothyronine

Previous studies have shown that serum titers of thyroid-specific antibodies such as thyroid-stimulating immunoglobulins (TSI), TSH-displacing antibodies (TDA), or microsomal antibodies (MAb) decrease in patients with Graves' disease during therapy with thionamide drugs (TD). In keeping with some in vitro results it was postulated that TD have an immunosuppressive action which may be partly responsible for the beneficial effects. To further elucidate this theory, we compared the changes in TSI during treatment with TD such as methimazole (MMI) and propylthiouracil (PTU) as well as with perchlorate (PC), an unrelated compound with a different mode of therapeutic action. Of 69 patients with hyperthyroidism due to Graves' disease, serum from 62 (90%) was positive for TSI, as measured by cAMP accumulation in a thyroid tissue culture assay. Six patients had to be excluded due to noncompliance. Of the remaining 56 patients, those 41 subjects (73%) with good control of the disease were followed up to 24 months during dose-adjusted antithyroid treatment. All patients with an uncomplicated course of treatment had a decline in the initially increased TSI values on either drug regimen. Five of 10 patients receiving PTU and 8 of 13 patients receiving MMI reached normal TSI levels; so did 11 of 18 patients receiving PC. There was no individual correlation between TSI decrease and drug dosages or the serum T4 and T3 levels. In all 3 groups, however, a decrease in mean T4 and T3 levels preceded the fall in TSI. By grouping the patients according to whether they had more than a 20% decrease in the initial TSI values after either 2 months or more than 4 months of treatment, it could be shown that the late responders had significantly higher T4 and T3 levels after 2 months of treatment. The similar patterns of change in TSI during treatment with TD and PC are strong evidence against an immunosuppressive effect of TD. If any direct interference occurs, a toxic effect on intrathyroidal lymphocytes by intrathyroidal drug accumulation could be the cause of the disappearance of TSI with both drug types. On the other hand, the data provide indirect evidence for the theory that the restoration of the euthyroid state is the cause of decreasing TSI levels and normalization of the immune regulation in many patients during treatment with antithyroid drugs.

Topics: Adult; Antithyroid Agents; Graves Disease; Humans; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Methimazole; Middle Aged; Perchlorates; Propylthiouracil; Thyroxine; Time Factors; Triiodothyronine

Studies of in vitro immunoreactivity to propylthiouracil (PTU), methimazole (MMI), and carbimazole (CARB), as assessed by peripheral blood lymphocyte transformation and 2 antibody tests, were carried out in 12 patients with Graves' hyperthyroidism who had developed agranulocytosis during treatment with PTU (11 patients) or CARB (1 patient) from 1 week to 10 yr earlier. Significant lymphocyte transformation responses to antithyroid drugs (stimulation indices greater than mean +/- 2 SD for normal subjects) were found in 5 of 6 patients tested, in 1 patient to PTU only, in 3 patients to MMI only, and in 1 patient to both PTU and MMI, but in none of 10 patients currently being treated with PTU who did not develop agranulocytosis. Circulating antibodies causing neutrophil agglutination in the presence of antithyroid drugs were demonstrated, using the indirect Coombs test, in 5 of 7 patients tested, in 2 patients to PTU only, in 3 patients to CARB only and in 1 patient (the only one tested with MMI) to PTU and MMI. Lymphocyte transformation and antibody tests to PTU were both carried out in 6 patients. Of these, both tests were positive in one patient, both negative in 3 patients, and 1 negative and 1 positive in 2 patients. In the 1 patient in whom both tests were carried out with CARB (patient 3), tests were negative, whereas in the 1 patient in whom both tests were carried out with MMI (patient 3), 1 test was positive, whereas the other was negative. Thus, in patients in whom both tests were carried out using the same drug, correlation between lymphocyte transformation responses and the detection of neutrophil antibodies was found in 5 of 6 cases. Antibodies reactive with neutrophils were also detected in 2 of the 5 patients tested using an enzyme-linked immunosorbent assay. In this test antibodies to PTU or MMI were not demonstrated. Possible mechanisms for the neutrophil depression in relation to these findings are discussed. It is concluded that patients with Graves' disease may be prone to develop this complication of antithyroid drug therapy because of underlying immunological abnormalities.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Antithyroid Agents; Autoantibodies; Carbimazole; Female; Graves Disease; Humans; In Vitro Techniques; Lymphocyte Activation; Male; Methimazole; Middle Aged; Neutrophils; Propylthiouracil

Topics: Adult; B-Lymphocytes; Female; Graves Disease; Humans; Lymphocyte Activation; Male; Methimazole; Middle Aged; Rosette Formation; T-Lymphocytes

Thyroidal suppressibility by exogenous T3 in terms of both radioiodine uptake (RAIU) and serum T4 was evaluated in 115 hyperthyroid patients treated with methimazole for 2 yr and followed for an additional 2 yr to study the rate of recurrence. Various other serum parameters including serum thyroglobulin concentrations, thyroid autoantibody, and TSH receptor antibody titers, and thyroidal responses to TRH-induced TSH elevation were also determined. After 2 yr of methimazole therapy, thyroidal RAIU was not suppressible (RAIU less than 12%/4 h was defined as suppressible) in 50 of 115 patients (group I). Of 65 patients with suppressible thyroid RAIU, serum T4 was significantly reduced (less than 60% of pre-T3 level) by T3 administration in only 43 patients (group III) but not in the remainder (group II). Antithyroid drug therapy was discontinued in the group II and III patients, and 7 of the patients had recurrence of hyperthyroidism within 2 yr of follow-up. All of them were from group II. The thyroidal response to TSH was greater in group III patients than in group II patients. During antithyroid drug therapy, decrease of microsomal antibody titer was more likely to occur in group III patients than in those of group II. Serum thyroglobulin concentrations were uniformly normal in treated patients irrespective of T3 suppressibility. TSH receptor antibody was positive in all 13 untreated patients with Graves' disease but was negative in treated patients regardless of their T3 suppressibility. Measurement of both thyroidal RAIU and serum T4 after administration of T3 improves the reliability of T3-suppression testing as a predictor of the remission of Graves' disease.

Topics: Adolescent; Adult; Aged; Autoantibodies; Child; Evaluation Studies as Topic; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Prognosis; Thyroglobulin; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

Urine samples from 8 healthy subjects, from 16 patients with primary hypothyroidism and 8 patients with Graves' hyperthyroidism were pre-purified in SP-Sephadex-C-25 cation-exchange-chromatography, subjected to reverse phase high-pressure liquid chromatography (HPLC) with 0.01 M ammonium acetate pH 4 as a polar and propanol as a non-polar solvent with a 1%/min gradient and assayed in our TRH radioimmunoassay. Urine TRH-immunoreactivity levels were measured before and after 3 months of treatment with thyroxine or methimazole. The urine TRH-levels in healthy subjects were 5.5 +/- 1.4 ng/1 (mean +/- SEM, n = 8). In the hypothyroid patients, the urine TRH levels were 50.6 +/- 40 ng/1 before and 71.7 +/- 45.3 ng/1 after 3 months of treatment with thyroxine. These values did not significantly differ from those in healthy subjects. The large variations were due to highly elevated values in 3 patients. In 2 hypothyroid patients with initially high urine TRH values, 67 and 657 ng/1, urine TRH was measured 5 and 18 months later and was found to have decreased to 5 and 11 ng/1. In the hyperthyroid patients, urine TRH levels were 10.3 +/- 3.9 ng/1 before and 8.9 +/- 3.3 ng/1 after the treatment with methimazole and did not differ significantly from the levels in healthy subjects. After 3 months of treatment, the hyper- and the hypothyroid patients were euthyroid. Our results show, that, except in 2 hypothyroid patients, there does not appear to be any relationship between urine TRH levels and serum TSH or thyroid hormone levels in hypothyroid and hyperthyroid patients.

Topics: Chromatography, Gel; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Methimazole; Thyrotropin-Releasing Hormone; Thyroxine

A RIA for the antithyroid drug methimazole [1-methyl-2-mercaptoimidazole (MMI)] has been developed. A MMI derivative, 5-COOH-MMI, was conjugated to porcine thyroglobulin, and antibodies to the conjugate were raised in rabbits. [35S]MMI was used as the tracer. At a final antibody dilution of 1:100, the assay could detect MMI in amounts as low as 2.5 ng. The putative MMI metabolites 3-methyl-2-thiohydantoin and 1-methylimidazole had minor cross-reactivities of 2.1% and 0.5%, respectively. There was no effect of serum proteins on MMI immunoactivity. MMI was given orally to normal subjects (n = 6), hyperthyroid patients (n = 5), patients with hepatic cirrhosis (n = 4), and normal lactating women (n = 4). After a single dose of 60 mg, peak MMI levels were similar in the normal subjects and the hyperthyroid patients (approximately 1.5 micrograms/ml). Patients with hepatic cirrhosis had similar peak MMI serum levels [1.31 +/- 0.3 (+/- SEM) micrograms/ml], but the half-time of MMI disappearance from serum was significantly prolonged compared with the normal value (21.2 vs. 6.0 h; P less than 0.001). The lactating women received 40 mg MMI as a single dose. Over the next 8 h, mean MMI levels in serum and milk were nearly identical, with a mean serum to milk ratio of 1.03 +/- 0.16. A total of 70.0 +/- 6.0 micrograms MMI was excreted in the milk over the 8-h time period. This amount of MMI could affect neonatal thyroid function.

Topics: Adolescent; Adult; Female; Graves Disease; Humans; Kinetics; Lactation; Liver Cirrhosis; Male; Methimazole; Middle Aged; Milk, Human; Pregnancy; Radioimmunoassay

Triiodothyronine (T3)-predominant Graves' disease is characterized by persistently high serum T3 level, normal serum thyroxine (T4) level, and high (greater than 20) serum T3/T4 ratio (nanograms/micrograms) during thionamide drug therapy. We studied the clinical course of 30 patients with T3-predominant Graves' disease. After receiving drug therapy for 1 to 4 years, 27 patients with T3-predominant Graves' disease had relapses, whereas only 9 control patients with Graves' disease whose serum T3/T4 ratio had become persistently normal (less than 20) had relapses. The T3-predominant patients had greater serum TSH receptor antibody activity, thyroid T4 5'-deiodinase activity, and decreased T3 content of thyroglobulin when compared with the control patients. Our findings show that patients with T3-predominant Graves' disease are unlikely to have a long-term remission with drug therapy. The cause of high serum T3/T4 ratio is due, in part, to the more active thyroid T4 5'-deiodinase that may be mediated by high levels of Graves' immunoglobulin.

Topics: Adolescent; Adult; Female; Graves Disease; Humans; Male; Methimazole; Prognosis; Propylthiouracil; Recurrence; Thyroxine; Time Factors; Triiodothyronine

We asked 54 thyroidologists how they would treat each of four patients having moderate hyperthyroidism of Graves' disease and a thyroid gland weighing 70 g (three to four times normal). For a 19-year-old woman, 67% of thyroidologists recommended an initial course of therapy with antithyroid drugs, usually for 1 year; 24% favored radioiodine treatments; and 9%, surgery. Choices for treating a 19-year-old man were similar. For a 29-year-old man, 44% of thyroidologists preferred drug therapy; 50%, radioiodine; and 6%, surgery. For a 29-year-old woman, choices were similar to those for the 29-year-old man, except for a slight preference for drugs over radioiodine. If hyperthyroidism recurred after a first course of antithyroid drugs, the consultants favored radioiodine treatments and surgery about equally, except in the 29-year-old man, in whom radioiodine was preferred. This survey shows considerable variation among experts in treating hyperthyroidism in young adults.

Topics: Adult; Drug Administration Schedule; Female; Genes; Graves Disease; Humans; Internal Medicine; Iodine Radioisotopes; Male; Medicine; Methimazole; Propylthiouracil; Specialization

A T4 suppression test involving 24-h thyroidal 131I uptake was carried out on patients with Graves' disease during therapy with an antithyroid drug. Thirty-three patients received propylthiouracil (PTU) for at least 1 year. Each patient was given 75 micrograms L-T3 daily for 8 days in conjunction with PTU (50 mg/day) at the time of the experiment and then the 24-h thyroidal 131I uptake (post T3 uptake was measured). Twenty-two patients had normal levels of serum T3 and T4-I before L-T3 administration and were divided into 2 groups, positive T3 suppression (post T3 uptake less than or equal to 35%, group I) and negative T3 suppression (post T3 uptake greater than 35%, group II). Eleven patients showed elevated serum T3 or T4-I concentrations before L-T3 administration (group III). The T4 suppression test was then performed on the same patients. Each patient was given 300 micrograms L-T4 daily for 8 days in conjunction with PTU and the 24-h thyroidal 131I uptake (post T4 uptake) was measured. Some patients receiving PTU (50 mg/day) were switched to MMI (5 mg/day) and the T4 suppression test was done one month later. A significant correlation between the two suppression tests during PTU therapy was observed (r = 0.961, p less than 0.01). None of the patients complained of side effects during the T4 suppression test. The mean post T4 uptake in group I was 18.8 +/- 3.3% during PTU therapy and 5.4 +/- 1.3% during MMI therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Thyroid Function Tests; Thyroxine; Triiodothyronine

Topics: Autoimmune Diseases; Graves Disease; Humans; Hypoglycemia; Insulin Antibodies; Methimazole; Syndrome

Topics: Adult; Agranulocytosis; Antithyroid Agents; Female; Graves Disease; Humans; Iodine; Methimazole; Propranolol; Thyroidectomy

Topics: Adolescent; Adult; Antithyroid Agents; Child; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Prognosis; Propylthiouracil; Recurrence; Thyroxine; Triiodothyronine

The T3 suppression test by the 24-hr thyroidal 131I uptake was reevaluated in patients with Graves' disease before and after withdrawal of antithyroid drug. Fifty patients had been treated with propylthiouracil (PTU) or methylmercaptoimidazole (MMI) for 12 to 70 months. They were prescribed a maintenance dose of antithyroid drug (PTU, 50 mg/day; MMI, 5 mg/day) at the time of investigation and regarded as euthyroid on the basis of serum T3, T4 and TSH levels. Each patient was given 75 micrograms T3 daily for 8 days in conjunction with PTU or MMI. The 24-hr thyroidal 131I uptake was then measured (post T3 uptake). In 30 patients whose post T3 uptake was below 35%, treatment was stopped and the T3 suppression test was repeated at one and 3 months later. During the two-year follow up, 24 remained well, while 6 relapsed within 4 to 12 months. In patients with sustained remission, the post T3 uptake was significantly lower in the MMI-treated group (13 cases, 7.7 +/- 1.0%) than in the PTU-treated group (11 cases, 18.6 +/- 1.9%). MMI withdrawal produced a marked rebound in the post T3 uptake, whereas none of the patients showed the rebound after PTU withdrawal. In patients who relapsed later, there was no difference in the post T3 uptake during treatment and the rebound occurred in the both groups following goitrogen withdrawal. Serum T3, T4 and TSH levels were within normal ranges at one and 3 months after cessation of antithyroid drug. From the results of the present study, it is concluded that criteria for T3 suppressibility by the 24-hr uptake should be determined by the antithyroid drug employed and by the time of investigation. There is a dissociation in the post T3 uptake values following withdrawal of the two different antithyroid drugs.

Topics: Antithyroid Agents; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Propylthiouracil; Thyroid Gland; Time Factors; Triiodothyronine

Although the activity of lysosomal protease in Graves' thyroid is considered to be increased, there has been no quantitative method to estimate the protease activity in the thyroid tissue due to the contamination of thyroglobulin (Tg) which varies in susceptibility to the protease. In the present study, the proteolytic activity (PA) of thyroid lysosomal protease preparation (P25) separated from Tg was assayed using 125I labeled rat Tg. More than 95% of 125I-Tg was hydrolyzed at pH 4.0 without deiodination, and the pattern of liberated iodoamino acids resembled that of pronase digest except for a higher T3/T4 ratio. Thirty-seven Graves' thyroids and 15 paranodular thyroid tissues were assayed. PA, the specific PA (SPA; calculated as PA per mg P25 protein) and PA per DNA content in Graves' thyroids were significantly higher than those in controls. There were good correlations among PA, SPA and PA per DNA content of the thyroid tissue. PA and SPA in the thyroid from 29 patients with Graves' disease treated with propylthiouracil or methimazole did not correlate with serum thyroid hormone level immediately before surgery. In 8 patients treated with KI, PA from 5 patients whose serum thyroid hormone levels had been normalized were significantly lower than those from 3 patients who were still thyrotoxic.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Aspartic Acid Endopeptidases; Endopeptidases; Graves Disease; Humans; Hydrolysis; In Vitro Techniques; Lysosomes; Male; Methimazole; Potassium Iodide; Propylthiouracil; Rats; Rats, Inbred Strains; Thyroglobulin; Thyroid Gland

The records of all patients with antithyroid drug-related agranulocytosis at two Boston hospitals (Group 1, 14 patients), as well as the published case reports of 36 patients with this syndrome (Group 2) were reviewed. The clinical characteristics of these patients were then compared with those of 50 hyperthyroid patients who had taken antithyroid medication without untoward hematologic reactions (Group 3). The mean ages of patients in Group 1 and Group 2 were significantly greater than that of Group 3 (50.6 +/- 16 years versus 35.7 +/- 13.7 years, p less than 0.001; 46.3 +/- 18.7 years versus 35.7 +/-- 13.7 years, p less than 0.02). By chi-square analysis, the relative risk of developing agranulocytosis in patients over age 40 was 6.4 times that among younger patients (p less than 0.001). The mean doses of methimazole in Group 1 and Group 2 were significantly higher than that in Group 3 (43.8 +/- 9.9 mg/d versus 29.5 +/- 10.4 mg/d, p less than 0.001; 40.7 +/- 15.7 mg/d versus 29.5 +/- 10.4 mg/d, p less than 0.02), with and 8.6-fold increased risk of agranulocytosis with doses greater than 40 mg/d (p less than 0.01). In contrast, the mean doses of propylthiouracil did not differ among the three groups. These data suggest that antithyroid drugs should be administered cautiously to patients over age 40. Because no cases of agranulocytosis were seen with methimazole doses less than 30 mg/d, low-dose methimazole therapy may be safer than high-dose therapy or treatment with conventional doses of propylthiouracil.

Topics: Adolescent; Adult; Age Factors; Aged; Agranulocytosis; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Propylthiouracil; Sex Factors

The accumulation of 35S labelled methimazole (MMI) was examined in lymphocytes. No uptake of label was found in peripheral blood lymphocytes (PBL) from normal control subjects after in vitro incubation with the drug. Following administration of [35S]MMI to patients with Graves' hyperthyroidism PBL cell to plasma (C/P) 35S activity was greater than 1 in 4 of 11 patients and only in 1 of 7 other patients undergoing thyroidectomy. Thyroid lymphocytes from 2 of these patients showed some accumulation of activity. Following administration of [35S]MMI to normal rats C/P 35S ratios ranged from 1-5.6 but no 35S accumulation was found in PBL or thyroid lymphocytes from August strain rats in which experimental autoimmune thyroiditis had been produced. It is concluded that there is minimal, if any, significant accumulation of MMI in lymphocytes of patients with Graves' disease. The immunosuppressive action of MMI on lymphocyte antibody production must therefore by indirect.

Topics: Animals; Autoimmune Diseases; Graves Disease; Humans; Immunosuppression Therapy; Lymphocyte Activation; Lymphocytes; Methimazole; Rats; Rats, Inbred Strains; Thyroiditis

A sensitive gas chromatographic-mass spectrometric method enabled us to study intrathyroidal concentrations of methimazole in 20 euthyroid patients with Graves' disease on treatment with carbimazole and T4. There was no difference between patients receiving a final dose of carbimazole (10 mg), known to be totally bioactivated to methimazole (6.1 mg), 3-6 h before thyroid excision (518 ng/g thyroid tissue +/- 90 SEM) and patients who received the same dose 17-20 h before excision (727 ng/g thyroid tissue +/- 157 SEM), indicating a slow intrathyroidal turnover of the drug. On the other hand, the serum concentrations were much higher in the first group (102 ng/ml +/- 5 SEM vs. 16 ng/ml +/- 3 SEM), reflecting a short plasma half-life of the drug. The intrathyroidal concentrations of methimazole ranged from 230-1895 ng/g among individual glands but were similar in pieces from different parts of a single gland. These methimazole concentrations are lower than the concentrations reported by others to have an immunosuppressive action on lymphocytes in vitro.

Topics: Adult; Carbimazole; Female; Gas Chromatography-Mass Spectrometry; Graves Disease; Humans; Male; Methimazole; Middle Aged; Thyroid Gland; Thyroidectomy

Topics: Adult; Autoimmune Diseases; Female; Graves Disease; Humans; Insulin Antibodies; Methimazole

In order to investigate the incidence of side effects of antithyroid drugs and to study if there were any factors related to the onset of the side effects, clinical and laboratory findings were examined in 71 untreated Graves' patients. The overall incidence was 28.2% among 71 cases who were initially administered methimazole or propylthiouracil. The incidences were 23.2% (13 of 56 cases) for methimazole and 46.7% (7 of 15 cases) for propylthiouracil, respectively, which were significantly higher than those previously reported. Seventeen of 20 cases with side effects under the drug of first choice were administered the another antithyroid drug. Four of 17 (23.5%) cases successively had side effects. The side effects were observed within 1.5 months of administration of less than 150 tablets in total in most of the cases. The serum concentration of Ig-E and peripheral eosinophils(/mm3) at the onset of the side effects were significantly higher than those before treatment. These results suggest that allergic mechanism rather than accumulating may concern the onset of side effects. Since in cases without the side effects the peripheral eosinophils at 3 to 4 weeks after administration were significantly higher than those before treatment and 19 of 51 (38.0%) cases without side effects had a high concentration of Ig-E of more than 500 u/ml, it is suggested that allergic mechanism may be triggered in most of Graves' patients who were administered methimazole or propylthiouracil. Thus, immunological disturbances in Graves' disease seems to be the cause of the side effects of antithyroid drugs, although there was no correlation between antithyroid autoantibodies and development of the side effects.

Topics: Adolescent; Adult; Chemical and Drug Induced Liver Injury; Eosinophils; Female; Graves Disease; Humans; Immunoglobulin E; Leukocyte Count; Male; Methimazole; Middle Aged; Propylthiouracil

Using peripheral blood lymphocytes from 8 healthy individuals and 5 patients with untreated Graves' disease, direct effects of methimazole (MMI) and propylthiouracil (PTU) on lectin-induced lymphocyte proliferative response were studied. Lymphocytes were cultured for 72 hr in the presence of lectins and antithyroid drugs. Lymphocyte DNA synthesis was counted by incorporation of 3H-thymidine. MMI at 1,000 microM enhanced lectin-induced lymphoproliferation of peripheral blood lymphocytes from both patients with Graves' disease and healthy individuals, at every point of culture time, while PTU showed a tendency toward suppression. These results suggest that this lympho-stimulation by MMI may be a causative factor related to insulin autoimmune syndrome, as deduced from the clinical reports that insulin autoimmune syndrome is, sometimes, found in patients with Graves' disease treated with MMI. This lympho-stimulation was evident regardless of the time of MMI addition, thus indicating that MMI is, by its action, a lymphoid stimulator and may lead to the insulin autoimmune syndrome in predisposed subjects with underlying Graves' disease.

Topics: Autoimmune Diseases; Concanavalin A; Graves Disease; Humans; Insulin Antibodies; Lymphocyte Activation; Methimazole; Phytohemagglutinins; Pokeweed Mitogens; Propylthiouracil; Syndrome

Appropriate dosage of levothyroxine for the treatment of hypothyroidism is assessed by determining the serum thyroxine (T4) concentration in secondary and tertiary types. In primary hypothyroidism, the optimal thyroid replacement is that which induces a normal thyroid-stimulating hormone level and a normal TSH response to administration of thyrotropin-releasing hormone. Hypothyroidism often occurs in the management of hyperthyroidism. Serial serum TSH measurements help in the early detection of hypothyroidism, whereas serum triiodothyronine (T3) aids in prompt recognition of recurrence of hyperthyroidism.

Topics: Antithyroid Agents; Drug Evaluation; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Methimazole; Propylthiouracil; Thyroid Function Tests; Thyroid Hormones; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine