methimazole and Hyperthyroidism

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

The purpose of this meta-analysis was to assess the safety of the anti-thyroid drugs (ATDs) propylthiouracil (PTU) and methimazole (MMI) in the treatment of hyperthyroidism during pregnancy.. From inception until June 2, 2022, all available studies were searched in PubMed, Web of Science, Cochrane, EBSCO, Embase, Scopus, and CNKI.. Thirteen articles satisfying the inclusion criteria were examined. Our meta-analysis indicated that pregnant women treated with MMI had a higher risk of congenital anomalies than those treated with PTU (OR 0.80, 95%CI 0.69-0.92, P = 0.002, I2 = 41.9%). Shifting between MMI and PTU during pregnancy did not reduce the risk of birth defects compared to PTU alone (OR 1.18, CI 1.00 to 1.40, P = 0.061, I2 = 0.0%). There were no statistically significant differences in hepatotoxicity (OR 1.54, 95%CI 0.77-3.09, P = 0.221, I2 = 0.0%) or miscarriage (OR 0.89, 95%CI 0.72-1.11, P = 0.310, I2 = 0.0%) between PTU and MMI exposure.. The study confirmed propylthiouracil is a safer alternative to methimazole for treating hyperthyroidism in pregnant women, and it is appropriate to treat maternal thyroid disease with PTU during the first trimester of pregnancy. However, it is not clear whether switching between propylthiouracil and methimazole is a better option than treating PTU alone during pregnancy. Further studies on this matter may be needed to develop new evidence-based guidelines for the treatment of pregnant women with hyperthyroidism.

Topics: Abortion, Spontaneous; Antithyroid Agents; Female; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil

The risk of congenital anomalies following in utero exposure to thionamide antithyroid drugs (ATDs) is unresolved. Observational studies are contradictory and existing meta-analyses predate and preclude more recent studies. We undertook an updated meta-analysis of congenital anomaly risk in women exposed to carbimazole or methimazole (CMZ/MMI), propylthiouracil (PTU), or untreated hyperthyroidism in pregnancy.. We searched Medline, Embase, and the Cochrane database for articles published up till August 2021. We pooled separate crude and adjusted risk estimates using random effects models and subgroup analyses to address heterogeneity.. We identified 16 cohort studies comprising 5957, 15,785, and 15,666 exposures to CMZ/MMI, PTU, and untreated hyperthyroidism, respectively. Compared to nondisease controls, adjusted risk ratio (RR) and 95% confidence intervals (95% CIs) for congenital anomalies was increased for CMZ/MMI (RR, 1.28; 95% CI, 1.06-1.54) and PTU (RR, 1.16; 95% CI, 1.08-1.25). Crude risk for CMZ/MMI was increased relative to PTU (RR, 1.20; 95% CI, 1.01-1.43). Increased risk was also seen with exposure to both CMZ/MMI and PTU, that is, women who switched ATDs in pregnancy (RR, 1.51; 95% CI, 1.14-1.99). However, the timing of ATD switch was highly variable and included prepregnancy switches in some studies. The excess number of anomalies per 1000 live births was 17.2 for patients exposed to CMZ/MMI, 9.8, for PTU exposure, and 31.4 for exposure to both CMZ/MMI and PTU. Risk in the untreated group did not differ from control or ATD groups. The untreated group was however highly heterogeneous in terms of thyroid status. Subgroup analysis showed more positive associations in studies with >500 exposures and up to 1-year follow-up.. ATD therapy carries a small risk of congenital anomalies which is higher for CMZ/MMI than for PTU and does not appear to be reduced by switching ATDs in pregnancy. Due to key limitations in the available data, further studies will be required to clarify the risks associated with untreated hyperthyroidism and with switching ATDs in pregnancy.

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

Hyperthyroidism affects about 0.2%-2.7% of all pregnancies, and is generally treated with propylthiouracil (PTU). However, previous studies about the effects of propylthiouracil on maternal or foetal are contentious.. This meta-analysis was carried out to investigate the safety and efficacy of propylthiouracil during pregnancy.. PubMed, EBSCO, Embase, Scopus, Web of Science, Cochrane, CNKI, Wanfang and VIP database were searched from inception until August 31, 2021 for all available randomized controlled trials (RCTs) or cohort studies that evaluated the efficacy of propylthiouracil and its effects on pregnancy outcomes. Odds ratio (OR) and 95% confidence interval (CI) were used for binary variables, weighted mean difference (WMD) and 95% confidence interval (CI) were used for continuous variables. RevMan5.4 and Stata 16.0 were used for performing the meta-analysis.. The researchers examined data from 13 randomized controlled trials and cohort studies involving 18948 infants. Congenital anomalies were not significantly associated with PTU in the pooled results (OR = 1.03, 95%CI: 0.84-1.25, P = 0.80, I2 = 40.3%). There were no statistically significant differences in neonatal hypothyroidism (OR = 0.55, 95%CI: 0.06-4.92, P = 0.593, I2 = 57.0%) or hepatotoxicity (OR = 0.34, 95%CI: 0.08-1.48, P = 0.151, I2 = 0.0%) exposed to PTU compared to the control group. The serum levels of FT3, FT4, TT3, and TT4 were significantly lower in the propylthiouracil group compared to the control group.. This meta-analysis confirmed the beneficial effects of propylthiouracil treatment, namely the risks of adverse pregnancy outcomes were not increased, and it also proved PTU's efficacy in the treatment of pregnant women with hyperthyroidism. The findings supported the use of propylthiouracil during pregnancy with hyperthyroidism in order to improve clinical pregnancy outcomes in patients with thyroid dysfunction.

Topics: Antithyroid Agents; Female; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil

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

Atrial fibrillation is exceedingly rare in children with structurally and functionally normal hearts. We present a novel case of a 15-year-old female with known hyperthyroidism who subsequently developed atrial fibrillation. She had been suffering from fatigue, heat intolerance and myalgias for 6 months. Her initial TSH was 0.01mU/L, and free T4 was 75.4 pmol/L, with a free T3 of >30.8 pmol/L. An electrocardiogram showed atrial fibrillation with a ventricular rate of 141 beats per minute. An echocardiogram demonstrated an enlarged left atrium and ventricle, with mild mitral regurgitation. She was treated with methimazole and underwent synchronized cardioversion. She subsequently returned to a euthyroid state and remained in normal sinus rhythm. In this case, we discuss the physiologic and arrhythmogenic properties of thyroid hormone, with a summary of the existing literature on atrial fibrillation in hyperthyroidism in children. Current guidelines for treatment of atrial fibrillation are also outlined.

Topics: Adolescent; Antithyroid Agents; Atrial Fibrillation; Electrocardiography; Female; Humans; Hyperthyroidism; Methimazole; Thyroid Function Tests; Treatment Outcome

Maternal antithyroid drug (ATD) use during pregnancy has been associated with an increased risk of birth defects in offspring. Uncertainty remains on the size of this risk and how it compares to untreated hyperthyroidism due to methodological limitations of previous studies.. Systematic review of MEDLINE and EMBASE identifying observational studies examining ATD use during pregnancy and risk of birth defects by 28 August 2020. Data were extracted on study characteristics, effect estimates and comparator groups. Adjusted effect estimates were pooled using a random-effects generic inverse variance method and absolute risk calculated.. Seven cohort studies and 1 case-control study involving 6 212 322 pregnancies and 388 976 birth defects were identified reporting regression effect estimates. Compared to an unexposed population comparison, the association between ATD use during pregnancy and birth defects in offspring was: adjusted risk ratio (aRR) 1.16 95% confidence interval (CI) 1.08-1.25 for propylthiouracil (PTU); aRR 1.28 95%CI 1.06-1.54 for methimazole/carbimazole (MMI/CMZ); aRR 1.51, 95%CI 1.16-1.97 for both MMI/CMZ and PTU; and aRR 1.15 95%CI 1.02-1.29 for untreated hyperthyroidism. The excess risk of any and major birth defects per 1000, respectively, was: 10.2 and 1.3 for PTU; 17.8 and 2.3 for MMI/CMZ; 32.5 and 4.1 for both MMI/CMZ and PTU; and 9.6 and 1.2 for untreated hyperthyroidism.. When appropriately analysed the risk of birth defects associated with ATD use in pregnancy is attenuated. Although still elevated, the risk of birth defects is smallest with PTU compared to MMI/CMZ and may be similar to that of untreated hyperthyroidism.

Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Case-Control Studies; Female; Humans; Hyperthyroidism; Methimazole; Observational Studies as Topic; Pregnancy; Pregnancy Complications; Propylthiouracil

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

Early identification of the causes of cholestasis is important for appropriate management of patients with hyperthyroidism. We report a patient who had hyperthyroidism and severe cholestasis after methimazole (MMI) treatment. The patient was diagnosed as having MMI-induced cholestatic hepatitis. Treatment with MMI was stopped at admission to hospital. However, his serum total bilirubin (TBil) level rose from 410.5 µmol/L to 519.9 µmol/L and prothrombin time activity (PTA) dropped from 81.0% to 52.2% in 10 days. To prevent further deterioration of his liver function, plasma exchange was performed three times, and dexamethasone (10 mg, intravenously) was used each time. His PTA rose to 101% and his TBil continued to increase to 669.8 µmol/L after plasma exchange. He was subsequently diagnosed as having thyrotoxicosis-induced cholestasis and treated with radioactive iodine (380 MBq) 2 weeks after admission. His hyperthyroidism was significantly relieved, but the TBil level further increased to 776.8 µmol/L. Three weeks after admission, oral prednisone (30 mg/day) was used in this patient. Subsequently, his TBil levels gradually decreased and his liver function almost normalized within 3 months. We discuss the literature on cholestasis in the context of hyperthyroidism.

Topics: Cholestasis; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Thyroid Neoplasms

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

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

Hyperthyroidism is a condition in which the thyroid gland is overreactive and produces excess amounts of thyroid hormone. Tripterygium glycosides, traditional Chinese medicine has been widely used in the treatment of rheumatoid arthritis, nephrotic syndrome, hyperthyroidism and other diseases due to its anti-inflammatory and immunosuppressive effects. Evidence-based research is becoming popular especially with the application of Chinese traditional medicine. This paper systematically reviews and evaluates existing clinical data on the efficacy and safety of Tripterygium glycosides in the treatment of hyperthyroidism.. PubMed, Cochrane library and EMBase, Chinese biomedical literature database (CBM), Chinese journal full-text database (CNKI), Wan fang digital periodical full-text database and China Science and Technology Journal Database (VIP) were searched based on the defined inclusion and exclusion criteria. Data extraction, research quality assessment and meta-analysis were conducted with RevMan5.3 software. Trial sequential analysis (TSA) was used to evaluate information size and treatment benefits.. Seventeen randomized controlled clinical trials with 1536 participants were included in the systematic review. In the meta-analysis, there were two subgroups: Tripterygium glycosides combined with thiamazole and prednisone group; Tripterygium glycosides combined with thiamazole group. The study results revealed that the degree of exophthalmos, FT3, FT4, BGP, and AKP decreased while TSH, SOD, GSH-PX increased after the addition of Tripterygium glycosides. This study results suggested that Tripterygium glycosides combined with western medicine are an effective therapy for hyperthyroidism.. This study indicates that Tripterygium glycosides enhances the effect of thiamazole and prednisone in the treatment of hyperthyroidism and without increasing the risk of adverse events.

Topics: Anti-Inflammatory Agents; Drug Therapy, Combination; Drugs, Chinese Herbal; Glycosides; Humans; Hyperthyroidism; Methimazole; Prednisone; Tripterygium

This study investigated the aberrant connectivity of the salience network (SN) and default mode network (DMN) and the relevance between these abnormalities and symptom improvement in hyperthyroid patients using resting-state functional magnetic resonance imaging (rs-fMRI). Seed-based functional connectivity (FC) analyses were performed on state fMRI data to reveal possible differences in critical node connectivity in the SN and DMN between 41 new-onset, untreated hyperthyroid patients and 41 healthy controls. Subsequently, follow-up data were available for 25 patients treated with methimazole for one month. Compared with the healthy controls, the patients exhibited abnormal internetwork FC from the SN to the DMN and the executive control network (ECN) and decreased intra-network FC within the SN. Relative to the hyperthyroid state, the antithyroid therapy induced reversible connectivity of the left insula to the dorsal anterior cingulate cortex(dACC)and ECN, and persistently increased connectivity between the SN and DMN in patients with improved thyroid function. Finally, Pearson's correlation analyses were performed among the abnormal FC, neuropsychological assessment and serum free triiodothyronine(FT3)level data. The results indicated that aberrant intra- and internetwork FC in the SN and DMN might underlie the pathogenesis of hyperthyroidism, and antithyroid treatment could regulate the FC of certain key brain regions within the SN and DMN in hyperthyroid patients.

Topics: Adolescent; Adult; Brain; Brain Mapping; Cerebral Cortex; Executive Function; Female; Follow-Up Studies; Gyrus Cinguli; Humans; Hyperthyroidism; Magnetic Resonance Imaging; Male; Methimazole; Middle Aged; Nerve Net; Neural Pathways; Neuropsychological Tests; Rest

Many conditions that require frequent medication use are common during pregnancy. The purpose of this article is to list some of the most common of these disorders and to discuss the risk to the developing fetus of the medications used most frequently to treat them. Included are drugs used for the treatment of asthma, nausea and vomiting, hyperthyroidism, pain and fever, and depression during pregnancy.

Topics: Abnormalities, Drug-Induced; Acetaminophen; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Analgesics, Non-Narcotic; Anti-Asthmatic Agents; Antidepressive Agents; Antiemetics; Antithyroid Agents; Asthma; Congenital Abnormalities; Depressive Disorder; Female; Humans; Hyperthyroidism; Leukotriene Antagonists; Maternal-Fetal Exchange; Methimazole; Morning Sickness; Ondansetron; Pregnancy; Pregnancy Complications; Propylthiouracil; Teratogens

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

Topics: Aged; Antithyroid Agents; Disease Progression; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Reference Values; Thyroid Hormones; Thyrotropin; Thyroxine

Hyperthyroidism in pregnant women should be adequately treated to prevent maternal and fetal complications. The treatment of choice in pregnancy is antithyroidal medications (ATDs). The risk of embryopathies associated with the use of Methimazole (MMI) and Propylthiouracil (PTU) in early pregnancy is a matter of clinical attention and concern. This review describes current evidence and how scientific findings are reflected in current clinical guidelines.. Embryopathies after the use of ATDs were previously mainly described in case reports and considered rare. Recent large observational studies, including nonexposed control groups, have quantified an increased risk of embryopathies associated with use of ATDs during pregnancy. Findings suggest a risk of embryopathies with the use of both MMI and PTU, but the pattern of embryopathies differs, and embryopathies with the use of PTU appear less severe.. Current guidelines highlight the need for clinical attention on the use of ATDs in early pregnancy. Patients managed on ATDs for the treatment of hyperthyroidism should be counseled to report a pregnancy as early as possible. PTU is the recommended treatment in early pregnancy, but if the risk of relapse or worsening of hyperthyroidism is considered low, it is suggested that ATD treatment can be withdrawn followed by frequent monitoring of thyroid function.

Topics: Antithyroid Agents; Female; Fetal Diseases; Gestational Age; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Risk Factors

Thionamides, such as methimazole and propylthiouracil, are used for the management of hyperthyroidism. Agranulocytosis is a rare adverse effect of thionamides and elderly patients are especially vulnerable. Here we discuss a case of an 80-year-old woman who developed agranulocytosis and pneumonia approximately 4 weeks after starting low dose methimazole therapy. Despite aggressive treatment with broad-spectrum antibiotics and granulocyte colony stimulating factor, she developed multiorgan failure and died. Our goals are to identify risk factors common to elderly patients and hopefully improve outcomes in this population when prescribed thionamides.

Topics: Age Factors; Aged, 80 and over; Agranulocytosis; Anti-Bacterial Agents; Antithyroid Agents; Fatal Outcome; Female; Granulocyte Colony-Stimulating Factor; Humans; Hyperthyroidism; Methimazole; Propylthiouracil; Risk Factors

Antithyroid drugs (ATDs) are widely used for the treatment of Graves' disease (GD) in the general population. Over the past decade, there has been an increasing awareness that several disturbances of thyroid function may occur in mothers after delivery which may be more prevalent than previously appreciated. Exacerbation of immune reactions occurs 3-12 month following delivery. Management of hyperthyroidism during lactation requires special considerations and should be implemented to prevent any adverse outcomes in mother and neonate. Continuation of breastfeeding is safe and should be encouraged in hyperthyroid mothers taking ATDs, whether these are ATDs being continued after gestation or indeed ATD treatment initiated in the postpartum period. Given PTU hepatotoxicity concerns, experts currently recommend using low-to-moderate MMI doses as a first-line therapy in lactating mothers. PTU should be reserved only as a second-line agent for cases of severe hyperthyroidism (thyroid storm) and allergic reactions to previous MMI treatment. ATD should be administered in divided doses immediately following each feeding. Evaluation of thyroid function tests is advisable at least 3-4 weeks after the initiation of breastfeeding.

Topics: Adult; Antithyroid Agents; Breast Feeding; Drug Hypersensitivity; Female; Humans; Hyperthyroidism; Infant, Newborn; Methimazole; Mothers; Propylthiouracil

Hyperthyroidism can occur during pregnancy and the postpartum period, and the treatment of hyperthyroidism should be considered in the preconception phase. Pregnancy has multiple normal physiologic effects on thyroid hormone, which is a separate process distinct from syndromes such as transient hyperthyroidism of hyperemesis gravidarum. The rationale regarding antithyroid drug use during different stages of pregnancy is reviewed, including the literature regarding adverse neonatal outcomes such as aplasia cutis and methimazole embryopathy in the setting of first trimester maternal methimazole use. The use of treatment modalities for hyperthyroidism during pregnancy such as surgery is also discussed. Studies of maternal, fetal, and neonatal complications of hyperthyroidism are examined in this article. Moreover, the evidence regarding antithyroid drugs, specifically methimazole and propylthiouracil, during lactation is considered. Other disease conditions that can take place during pregnancy and the postpartum period such as hyperemesis gravidarum, subclinical hyperthyroidism, gestational trophoblastic disease, and postpartum thyroiditis and their treatments are also presented.

Topics: Antithyroid Agents; Birth Weight; Female; Humans; Hyperthyroidism; Infant, Newborn; Methimazole; Postpartum Period; Preconception Care; Pregnancy; Pregnancy Complications; Premature Birth; Propylthiouracil; Risk; Thyroid Hormones

Hyperthyroidism affects about 0.2%-2.7% of all pregnancies, and is commonly managed with antithyroid drugs (ATDs). However, previous studies about the effects of ATDs on congenital anomalies are controversial. Therefore, the present meta-analysis was performed to explore the risk of congenital anomalies in children exposed to ATDs in-utero.. Embase, Pubmed, Web of Knowledge, and BIOSIS Citation Index were searched to find out studies about congenital anomalies in children exposed to ATDs in-utero reported up to May 2014. The references cited by the retrieved articles were also searched. The relative risks (RRs) and confidence intervals (CIs) for the individual studies were pooled by fixed effects models, and heterogeneity was analyzed by chi-square and I2 tests.. Eight studies met the inclusion criteria. Exposure to propylthiouracil (PTU), methimazole/carbimazole (MMI/CMZ), and PTU & MMI/CMZ was investigated in 7, 7 and 2 studies, respectively. The pooled RR was 1.20 (95%CI: 1.02-1.42), 1.64 (95%CI: 1.39-1.92), and 1.83 (95%CI: 1.30-2.56) for congenital anomalies after exposure to PTU, MMI/CMZ, and PTU & MMI/CMZ, respectively.. The meta-analysis suggests that exposure to ATDs in-utero increases the risk of congenital anomalies. The use of ATDs in pregnancy should be limited when possible. Further research is needed to delineate the exact teratogenic risk for particular congenital anomaly.

Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Carbimazole; Cohort Studies; Databases, Factual; Female; Humans; Hyperthyroidism; Infant, Newborn; Methimazole; Pregnancy; Prenatal Exposure Delayed Effects; Propylthiouracil; Risk

To evaluate the association of either propylthiouracil or methimazole treatment for hyperthyroidism during pregnancy with congenital malformations, relevant studies were identified by searching Medline, PubMed, the Cochrane Library and EMBASE. We intended to include randomized controlled trials, but no such trials were identified. Thus, we included cohort studies and case-control studies in this meta-analysis. A total of 7 studies were included in the meta-analyses. The results revealed an increased risk of birth defects among the group of pregnant women with hyperthyroidism treated with methimazole compared with the control group (odds ratio 1.76, 95% confidence interval 1.47-2.10) or the non-exposed group (odds ratio 1.71, 95% confidence interval 1.39-2.10). A maternal shift between methimazole and propylthiouracil was associated with an increased odds ratio of birth defects (odds ratio 1.88, 95% confidence interval 1.27-2.77). An equal risk of birth defects was observed between the group of pregnant women with hyperthyroidism treated with propylthiouracil and the non-exposed group (odds ratio 1.18, 95% confidence interval 0.97-1.42). There was only a slight trend towards an increased risk of congenital malformations in infants whose mothers were treated with propylthiouracil compared with in infants whose mothers were healthy controls (odds ratio 1.29, 95% confidence interval 1.07-1.55). The children of women receiving methimazole treatment showed an increased risk of adverse fetal outcomes relative to those of mothers receiving propylthiouracil treatment. We found that propylthiouracil was a safer choice for treating pregnant women with hyperthyroidism according to the risk of birth defects but that a shift between methimazole and propylthiouracil failed to provide protection against birth defects.

Topics: Abnormalities, Drug-Induced; Adult; Antithyroid Agents; Case-Control Studies; Cohort Studies; Confidence Intervals; Female; Humans; Hyperthyroidism; Infant, Newborn; Male; Methimazole; Odds Ratio; Pregnancy; Pregnancy Complications; Propylthiouracil; Risk

The aim of this review was to delineate the characteristics of antineutrophil cytoplasmic antibody (ANCA)-associated small-vessel vasculitis associated with antithyroid drugs (ATD). A PubMed search was made for English language articles using the search terms antithyroid drugs AND ANCA OR ANCA-associated vasculitis.. The literature includes approximately 260 case reports of ANCA-associated small-vessel vasculitis related to ATD, with 75% of these associated with thiouracil derivatives (propylthiouracil [PTU]) and 25% with methyl-mercapto-imidazole derivatives (MMI/TMZ). The prevalence of ANCA-positive cases caused by ATD varied between 4% and 64% with PTU (median 30%), and 0% and 16% with MMI/TMZ (median 6%). Young age and the duration of ATD therapy were the main factors contributing to the emergence of ANCA positivity. Before ATD therapy initiation, the prevalence of ANCA-positive patients was 0-13%. During ATD administration, 20% of patients were found to be positive for ANCA. Only 15% of ANCA-positive patients treated with ATD exhibited clinical evidence of vasculitis, corresponding to 3% of all patients who received ATD. Clinical manifestations of ANCA-associated vasculitis related to ATD were extremely heterogeneous. When vasculitis occurred, ATD withdrawal was usually followed by rapid clinical improvement and a favorable prognosis.. ANCA screening is not systematically recommended for individuals on ATD therapy, particularly given the decreasing use of PTU in favor of TMZ/MMI. Particular attention should be given to the pediatric population with Graves' disease who receive ATD, as well as patients treated with thiouracil derivatives and those on long-term ATD therapy.

Topics: Age Factors; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antithyroid Agents; Humans; Hyperthyroidism; Methimazole; Prevalence; Propylthiouracil; Time Factors

Functional thyropathies present significant health risks for patients. Advanced functional thyropathies are always treated while indications for therapy of subclinical thyropathies are individual and often controversial. It is widely agreed that these disorders should be diagnosed and individuals should be followed. The drug of choice in substitution therapy of hypothyroidism is levothyroxine, in the treatment of hyperthyroidism it is methimazole. Administration of propylthiouracil should be limited to the first trimester of pregnancy, because its serious hepatotoxicity has been described. Hyperthyroidism based on thyroid nodules and immunogenic hyperthyroidism not reaching long-term remission, need to be treated radically: by surgery or radioiodine treatment. When radiation protection requirements are met, radioiodine can also be administered on an outpatient basis. Exceptionally, small doses of methimazole can be administered over an extended period of time in individual cases.

Topics: Female; Humans; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Function Tests; Thyroidectomy; Thyroxine

Pharmacological management of feline hyperthyroidism offers a practical treatment option for many hyperthyroid cats. Two drugs have been licensed for cats in the last decade: methimazole and its pro-drug carbimazole. On the basis of current evidence and available tablet sizes, starting doses of 2·5 mg methimazole twice a day and 10 to 15 mg once a day for the sustained release formulation of carbimazole are recommended. These doses should then be titrated to effect in order to obtain circulating total thyroxine (TT4) concentrations in the lower half of the reference interval. Treated cases should be monitored for side-effects, especially during the first months of treatment. Some side-effects may require discontinuation of treatment. At each monitoring visit, clinical condition and quality of life should also be evaluated, with special attention to possible development of azotaemia, hypertension and iatrogenic hypothyroidism. When euthyroidism has been achieved, monitoring visits are recommended after 1 month, 3 months and biannually thereafter. Cats with pre-existing azotaemia have shorter survival times. However, development of mild azotaemia during the initial course of treatment, unless associated with hypothyroidism, does not appear to decrease survival time. The long-term effects of chronic medical management require further study.

Topics: Animals; Antithyroid Agents; Carbimazole; Cat Diseases; Cats; Hyperthyroidism; Methimazole; Veterinary Medicine

Propylthiouracil (PTU) has been used for the treatment of hyperthyroidism since the 1940s, but over the years reports of significant hepatotoxicity have come forth, particularly in children. This led to a black box warning being issued by the US FDA in 2009, followed by a similar warning by the European Medicines Agency and the United Kingdom Medicines and Healthcare Regulatory Agency later that year.. This article provides a concise review of the data on hepatotoxicity associated with the currently available antithyroid drugs: PTU, methimazole (MMI) and carbimazole. The differences in mechanism are examined in detail, as well as clinical presentation, management and monitoring. Use in special populations and trends in use of antithyroid medication are also discussed.. PTU is known to cause severe hepatic failure, particularly in children. Its use in children should be avoided. In adults, it is beneficial to use in the first trimester of pregnancy and thyroid storm. In the rest of the adult population, it should be used with caution. Carbimazole and MMI are associated with less severe hepatic injury and should be preferred when choosing thionamides as a treatment option.

Topics: Adult; Antithyroid Agents; Carbimazole; Chemical and Drug Induced Liver Injury; Child; Drug Labeling; Female; Humans; Hyperthyroidism; Methimazole; Pregnancy; Propylthiouracil; Severity of Illness Index

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

The treatment of choice for hyperthyroidism in pregnancy is antithyroid drugs, but the potential risk of birth defects is of major concern. For the use of thiamazole and carbimazole, there is consistent evidence of an increased risk of birth defects, which are often severe. For the use of propylthiouracil, the evidence is less clear. These birth defects may be less severe, and a Danish study which included all birth defects diagnosed before the age of two years showed an increased risk of birth defects in the face and neck region and in the urinary system after the use of propylthouracil.

Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Carbimazole; Female; Humans; Hyperthyroidism; Infant, Newborn; Methimazole; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Propylthiouracil; Risk Factors

Antithyroid drugs are relatively simple molecules known as thionamides, which contain a sulfhydryl group and a thiourea moiety within a heterocyclic structure. Propylthiouracil (6- propyl 2- sulfanylidene 1,2,3,4- tetrahydropyrimidin4- one) and methimazole (1- metyl 2,3- dihydro1H imidazole 2- thione) are the antithyroid drugs used in the United States. Methimazole is used in most of Europe and Asia, and carbimazole -  methimazole analogue, is used in the United Kingdom and parts of the former British Commonwealth. Their primary effect is to inhibit thyroid hormone synthesis by interfering with thyroid peroxidase mediated iodination of tyrosine residues in thyroglobulin and is an important step in the synthesis of thyroxine and triiodothyronine. Propylthiouracil (but not methimazole or carbimazole), can block the conversion of thyroxine to triiodothyronine within the thyroid and in peripheral tissues. Antithyroid drugs may have clinically important immunosuppressive effects. Side effects of thionamides are usually mild, serious untoward effects are observed in < 5% of cases, more frequently during the initial phases of treatment, when the drug daily dose is higher.

Topics: Antithyroid Agents; Carbimazole; Europe; Humans; Hyperthyroidism; Methimazole; Propylthiouracil; Structure-Activity Relationship; Thyroglobulin; Thyroid Hormones; Thyroxine; Triiodothyronine

Clinical hyperthyroidism has been associated with an increased risk of maternal, fetal, and neonatal complications. The available antithyroid drugs are methimazole/carbimazole and propylthiouracil. Several case reports and some epidemiologic studies suggest that methimazole/carbimazole exposure during the first trimester of pregnancy is associated with an increased risk of congenital malformations, including ectodermal anomalies, choanal atresia, esophageal atresia, and omphalocele. However, the absolute risk appears to be very small, and it remains unclear whether the association is driven by the maternal disease, the medication, or the combination of both factors. Propylthiouracil exposure has not been associated with an increased risk of congenital malformations and is the recommended drug during the first trimester of pregnancy. Since propylthiouracil-induced hepatotoxicity has been reported in approximately 0.1% of exposed adults and the number of case-reports of severe liver injury is increasing, treatment with low dose methimazole during the second and third trimesters should be considered. Until now, there has been no evidence that children prenatally exposed to methimazole/carbimazole or propylthiouracil have an increased risk of neurodevelopmental delay.

Topics: Antithyroid Agents; Carbimazole; Choanal Atresia; Drug Administration Schedule; Esophageal Atresia; Female; Hernia, Umbilical; Humans; Hyperthyroidism; Infant, Newborn; Maternal Exposure; Methimazole; Pregnancy; Pregnancy Trimester, First; Propylthiouracil

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

A 63-year-old woman suddenly developed central retinal artery occlusion following a slight fever while being treated with methimazole (MMI) for hyperthyroidism. She was diagnosed to have anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) based on increased inflammatory reactions with positive myeloperoxidase-ANCA in the serum. Her visual acuity remained low despite immediate treatment with corticosteroids and cyclophosphamide after cessation of MMI, which may have played a role in the pathogenesis of AAV. Central retinal artery occlusion is a rare manifestation of AAV; however, it is important with regard to the possibility of serious sequelae.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Anticoagulants; Antithyroid Agents; Dalteparin; Female; Humans; Hyperthyroidism; Immunosuppressive Agents; Methimazole; Middle Aged; Retinal Artery Occlusion

Hypothyroidism and hyperthyroidism are associated with maternal and neonatal pregnancy complications. Hypothyroidism should be treated with levothyroxine. Hyperthyroidism requires treatment with propylthiouracil or thiamazole. Subclinical hypothyroidism and thyroid auto-immunity are also associated with maternal and neonatal pregnancy complications. For both subclinical hypothyroidism and thyroid auto-immunity, treatment with levothyroxine has not yet been proven to be effective in preventing complications during pregnancy. For the Dutch population the following reference values for TSH levels during pregnancy may be used: 0.01-4.00 mU/l in the first and second trimesters. Reference values for the third trimester have not reported for this population, but are probably comparable with those of the second trimester.

Topics: Antithyroid Agents; Congenital Hypothyroidism; Female; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Maternal-Fetal Exchange; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Reference Values; Thyroid Function Tests; Thyrotropin; Thyroxine

Hyperthyroidism is one of the most common endocrine disorders in pregnant women, and it can severely complicate the course and outcome of pregnancy. Methimazole (MMI) and propylthiouracil (PTU) are the standard anti-thyroid drugs used in the treatment of hyperthyroidism in pregnancy. Traditionally, MMI has been considered to have clearer evidence of teratogenicity than PTU. Recent studies suggest that PTU can be hepatotoxic, leading to a United States Food and Drug Administration "black box alert." We wished to systematically review the effects of PTU and MMI during pregnancy, and to compare maternal and fetal safety.. We conducted a systematic search of PubMed, EMBASE, TOXNET, TOXLINK, DART, Medscape, EBSCO, and Google. Both English and non-English publications were included. We excluded studies using anti-thyroid therapies other than PTU and MMI, studies not allowing interpretation of results, and abstracts of meetings.. Overall, insufficient statistical power precluded determination of accurate rates of either MMI teratogenicity or PTU hepatotoxicity in cohort studies. However, a case-control study helped identify the relative risk of MMI-induced choanal atresia. A second case-control study failed to show that aplasia cutis congenita is associated with MMI. PTU has been associated with a rare but serious form of hepatic failure.. MMI causes a specific pattern of rare teratogenic effects after first trimester exposure, while PTU therapy may be followed by rare but severe hepatotoxic sequelae. It is therefore appropriate to use PTU to treat maternal hyperthyroidism during the first trimester of pregnancy, and to switch to MMI for the remainder of the pregnancy.

Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Case-Control Studies; Chemical and Drug Induced Liver Injury; Female; Gestational Age; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Propylthiouracil

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

Poorly treated or untreated maternal overt hyperthyroidism may affect pregnancy outcome. Fetal and neonatal hypo- or hyper-thyroidism and neonatal central hypothyroidism may complicate health issues during intrauterine and neonatal periods.. To review articles related to appropriate management of hyperthyroidism during pregnancy and lactation.. A literature review was performed using MEDLINE with the terms 'hyperthyroidism and pregnancy', 'antithyroid drugs and pregnancy', 'radioiodine and pregnancy', 'hyperthyroidism and lactation', and 'antithyroid drugs and lactation', both separately and in conjunction with the terms 'fetus' and 'maternal.'. Antithyroid drugs are the main therapy for maternal hyperthyroidism. Both methimazole (MMI) and propylthiouracil (PTU) may be used during pregnancy; however, PTU is preferred in the first trimester and should be replaced by MMI after this trimester. Choanal and esophageal atresia of fetus in MMI-treated and maternal hepatotoxicity in PTU-treated pregnancies are of utmost concern. Maintaining free thyroxine concentration in the upper one-third of each trimester-specific reference interval denotes success of therapy. MMI is the mainstay of the treatment of post partum hyperthyroidism, in particular during lactation.. Management of hyperthyroidism during pregnancy and lactation requires special considerations and should be carefully implemented to avoid any adverse effects on the mother, fetus, and neonate.

Topics: Adult; Antithyroid Agents; Child Development; Female; Gestational Age; Humans; Hyperthyroidism; Infant, Low Birth Weight; Infant, Newborn; Lactation; Maternal-Fetal Exchange; Methimazole; Postpartum Thyroiditis; Pregnancy; Pregnancy Complications; Propylthiouracil; Risk; Thyroid Function Tests; Thyroid Gland

Methimazole (MMI) and propylthiouracil (PTU) are the main antithyroid drugs used for hyperthyroidism. They inhibit the synthesis of thyroid hormone at various levels and are used as the primary treatment for hyperthyroidism or as a preparation before radioiodine therapy or thyroidectomy. MMI is the drug of choice because of its widespread availability, longer half-life and small number of severe side effects. Drugs of second choice are potassium perchlorate, beta blockers, iodine, lithium carbonate and glucocorticoids. Rituximab, a monoclonal antibody directed against human CD20, was recently proposed as a biological therapy for cases of Graves' disease unresponsive to traditional drugs.

Topics: Antithyroid Agents; Drug Monitoring; Humans; Hyperthyroidism; Methimazole; Secondary Prevention

Hyperthyroidism is a common endocrine disorder affecting 2% of females and 0.5% of males worldwide and antithyroid drugs constitute the first line of treatment in the majority of cases. These agents may cause severe adverse effects and among them liver failure, although rare, is a potential lethal one. This case illustrates the sudden and abrupt deterioration of hepatic function due to antithyroid drug administration. This case along with a concise literature review is presented aiming to increase the awareness of endocrinologists of possible fatal complications from the everyday use of common agents such as antithyroid drugs.

Topics: Adult; Antithyroid Agents; Female; Humans; Hyperthyroidism; Liver Failure; Methimazole; Propylthiouracil; Thyroidectomy

Antithyroid drugs (ATD) are used as a first line treatment in thyrotoxicosis. Propylthiouracil (PTU), carbimazole (CMZ) and methimazole (MMI) are available. During absorption CMZ is bioactivated to MMI. Initially, mothers were not allowed to breastfeed during treatment with ATD. Newer studies minimized the risk for mother and infant. PTU should be preferred over MMI due to its lower milk concentration. Recent studies have shown severe hepatic dysfunction for both ATD, but especially for PTU, in hyperthyroid patients. Most of those cases were idiosyncratic, not-dose related and presented a latent period of occurrence. No biomarkers could predict hepatic damage. The American Thyroid Association (ATA) has recommended that PTU should not be prescribed as the first line agent in children and adolescents. Its use might be accepted in the first trimester of pregnancy for severe thyrotoxicosis or for patients with previous MMI adverse reactions. Considering the potential harmful effects of PTU, MMI should be used instead during lactation.

Topics: Adult; Antithyroid Agents; Breast Feeding; Carbimazole; Child Development; Female; Humans; Hyperthyroidism; Infant; Lactation; Methimazole; Milk, Human; Mothers; 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

Thyroxine (T4), the main secretory hormone of the thyroid gland, is produced on thyroglobulin by thyroid peroxidase (TPO)/H(2)O(2)/iodide system and deiodinated to its active form (T3) by a selenocysteine-containing enzyme, iodothyronine deiodinase (ID). The activation of thyroid-stimulating hormone (TSH) receptor by auto-antibodies leads to 'hyperthyroidism', a life-threatening disease which is treated by antithyroid drugs such as 6-propyl-2-thiouracil (PTU) and methimazole (MMI). The present review describes the biological activities of a number of S/Se derivatives bearing the methimazole pharmacophore. It is shown that the isosteric substitutions in the existing drugs lead to compounds that can effectively and reversibly inhibit the heme-containing lactoperoxidase (LPO). In contrast to methimazole, the selenium analogue, MSeI, does not interfere with the enzyme directly, but it inhibits LPO by reducing the H(2)O(2) that is required for the oxidation of the Fe-center in LPO. These studies reveal that the degradation of the intracellular H(2)O(2) by the Se analogues of antithyroid drugs may be beneficial to the thyroid gland, as these compounds may act as antioxidants and protect thyroid cells from oxidative damage. Because the drugs with an action essentially on H(2)O(2) can reversibly inhibit the thyroid peroxidase, such drugs could be of great importance in the treatment of hyperthyroidism.

Topics: Antithyroid Agents; Humans; Hyperthyroidism; Iodide Peroxidase; Lactoperoxidase; Methimazole; Selenium Compounds; Thyroid Gland

Radioiodine is considered the treatment of choice for hyperthyroidism, but in some situations, methimazole therapy is preferred, such as in cats with preexisting renal insufficiency. Unfavorable outcomes from methimazole are usually attributable to side effects, such as gastrointestinal upset, facial excoriation, thrombocytopenia, neutropenia, or liver enzyme elevations. Because restoration of euthyroidism can lead to a drop in glomerular filtration rate, all cats treated with methimazole should be monitored with blood urea nitrogen and creatinine levels in addition to serum thyroxine (T(4)) and a complete blood cell count. Transdermal methimazole is associated with fewer gastrointestinal side effects and can be used in cats with simple vomiting or inappetence from oral methimazole. Hypertension may not resolve immediately when serum T(4) is normalized, and moderate to severe hypertension should be treated concurrently with atenolol, amlodipine, or an angiotensin-converting enzyme inhibitor.

Topics: Animals; Antithyroid Agents; Cat Diseases; Cats; Hyperthyroidism; Methimazole

Radioiodine is considered the treatment of choice for hyperthyroidism, but in some situations, methimazole therapy is preferred, such as in cats with pre-existing renal insufficiency. Methimazole blocks thyroid hormone synthesis, and controls hyperthyroidism in more than 90% of cats that tolerate the drug. Unfavorable outcomes are usually due to side effects such as gastrointestinal (GI) upset, facial excoriation, thrombocytopenia, neutropenia, or liver enzyme elevations; warfarin-like coagulopathy or myasthenia gravis have been reported but are rare. Because restoration of euthyroidism can lead to a drop in glomerular filtration rate, all cats treated with methimazole should be monitored with BUN and creatinine, in addition to serum T4, complete blood count, and liver enzymes. Transdermal methimazole is associated with fewer GI side effects, and can be used in cats with simple vomiting or inappetance from oral methimazole. Hypertension may not resolve immediately when serum T4 is normalized, and moderate to severe hypertension should be treated concurrently with-atenolol, amlodipine, or an ACE inhibitor. Alternatives to methimazole include carbimazole, propylthiouracil, or iodinated contrast agents.

Topics: Adrenergic beta-Antagonists; Animals; Antithyroid Agents; Carbimazole; Cat Diseases; Cats; Contrast Media; Hyperthyroidism; Iodine Radioisotopes; Iodobenzenes; Methimazole; Propylthiouracil; Treatment Outcome

Topics: Antithyroid Agents; Autoantibodies; Diagnosis, Differential; Female; Humans; Hyperthyroidism; Immunoglobulins, Thyroid-Stimulating; Infant, Newborn; Iodides; Maternal-Fetal Exchange; Methimazole; Mutation; Pregnancy; Receptors, Thyrotropin; Thyroiditis, Autoimmune; Thyrotoxicosis; Thyroxine

Hyperthyroidism occurs in approximately 1 in every 1000 to 2000 pregnancies. Although the signs and symptoms of the disease are similar in the pregnant and nonpregnant patient, the complications of hyperthyroidism can have even more profound consequences for the mother and fetus during gestation. These include maternal heart failure, preeclampsia, miscarriage, and preterm labor; as well as fetal loss and low birth weight. Furthermore, thyroid function and laboratory testing for hyperthyroidism are altered in pregnancy. The gestational increase in thyroid size, increased thyroid-binding globulin levels, increased serum total T4 and total T3 levels, and decreased thyroid stimulating hormone levels often confuses the evaluation of the thyroid status in pregnancy. Worldwide, the thionamides-propylthiouracil, methimazole, and carbimazole-have been used in pregnancy for the treatment of hyperthyroidism. However, propylthiouracil has been the drug of choice in the United States because it is believed to have less potential to induce fetal/neonatal hypothyrodism, to cross the placenta and into breast milk to a lesser degree, and to be less teratogenic than methimazole or carbimazole. None of the above have been substantiated in more recent studies. The pharmacokinetics of the thionamides in the pregnant and nonpregnant states, as well as the pharmacotherapeutic recommendation for hyperthyroidism will be reviewed.

Topics: Antithyroid Agents; Carbimazole; Female; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Sulfhydryl Compounds; Thiones

Drug therapy for the endocrine system is implemented to replace a hormone deficiency or to prevent or reduce the formation or effects of excess hormone. Treatment of endocrine disorders covers diseases of the pituitary, adrenal, parathyroid, and thyroid glands as well as the endocrine pancreas. This article focuses on new therapies currently available for specific diseases. Administration of trilostane for treatment of hyperadrenocorticism and use of insulin glargine, protamine zinc insulin (PZI), and porcine Lente insulin for diabetes mellitus are discussed. In addition, transdermal methimazole therapy for treatment of feline hyperthyroidism and administration of progestins for pituitary dwarfism are considered.

Topics: Adrenocortical Hyperfunction; Animals; Antithyroid Agents; Cat Diseases; Cats; Diabetes Mellitus; Dihydrotestosterone; Dog Diseases; Dogs; Enzyme Inhibitors; Hyperthyroidism; Hypoglycemic Agents; Insulin, Long-Acting; Methimazole

Topics: Antithyroid Agents; Humans; Hyperthyroidism; Iodine Radioisotopes; Lithium Carbonate; Methimazole; Propylthiouracil; Treatment Outcome

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

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

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

Topics: Aged; Anticoagulants; Antithyroid Agents; Atrial Fibrillation; Female; Humans; Hyperthyroidism; Methimazole; Osteoporosis; Practice Guidelines as Topic; Risk Factors; Thyroid Function Tests; Thyrotropin; Thyroxine

Topics: Aged; Antithyroid Agents; Cholestasis, Intrahepatic; Humans; Hyperthyroidism; Male; Methimazole

Therapy of thyroid dysfunction needs a close cooperation between endocrinologist and gynecologist. In addition to a number of metabolic changes during pregnancy, the diaplacentar transfer of different substances (thionamides, antibodies) has to be considered. Pregnant women with overt and subclinical hypothyroidism should be treated using L-Thyroxine with the bTSH between 1 and 2 mU/l. Many of the women need an increase of the L-Thyroxine dose during pregnancy. Overt hyperthyroidism (mostly due to Graves' disease) has to be treated immediately after diagnosis using thionamides. Because thionamides cross the placenta, the dose should be as low as possible with the fT4 in upper level and bTSH in the lower level of normal range. Most studies show, that both methimazole (MI) and propylthiouracil (PTU) can be used in pregnancy. Although PTU is preferred especially in the USA, an advantage of PTU over MI is not proven. Surgery is necessary in only few cases of hyperthyroidism during pregnancy with the optimal time for surgery during the second trimester. In case of subclinical hyperthyroidism and HCG induced hyperthyroidism several controls of thyroid function should be performed to decide whether treatment is necessary.

Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Dose-Response Relationship, Drug; Female; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Risk Factors; Thyroid Function Tests; Thyroxine

The frequency, predisposing factors and course of agranulocytosis (granulocytes < 250/microliter) secondary to antithyroid drugs were studied in a cohort of 1256 continuously treated outpatients with hyperthyroidism during the 15 year period from 1973 to 1987. Two cases of agranulocytosis were detected; the frequency was 0.18% (95%-confidence intervals, 0.0-0.44%). This prevalence appears to be lower than reported in previous studies (up to 1.8%). For other adverse drug reactions, there was a clear-cut relationship to initial thionamide dose and to the body mass index; most reactions occurred during the first weeks of treatment. In addition, eight patients referred for thionamide drug- induced agranulocytosis were studied, and the following results obtained: Methimazole dose in patients with agranulocytosis was almost twice as in other patients (63.3 +/- 19.7 vs 34.3 +/- 29.7 mg daily) suggesting that this complication was related to dose. The interval between start of antithyroid drug treatment and first symptoms of agranulocytosis was 33 days (median; range, 23-55 days); hence, prolonged treatment beyond this period would appear relatively safe. Withdrawal of the causative agent and treatment of infection led to recovery of leukocyte counts within 15 days (median; range, 5-31 days). Two fatal outcomes were seen in referred patients. In one severely hyperthyroid patient with methimazole-induced agranulocytosis, recombinant human granulocyte/macrophage colony stimulating factor induced clinical and hematologic recovery within a few days of administration. In conclusion, agranulocytosis is the most severe side effect of antithyroid drugs. According to our results and a literature review, it occurs almost exclusively during the first ten weeks of treatment and is probably related to the drug dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Agranulocytosis; Antithyroid Agents; Cohort Studies; Dose-Response Relationship, Drug; Female; Germany; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Hyperthyroidism; Leukocyte Count; Male; Methimazole; Middle Aged; Prevalence; Recombinant Proteins; Time Factors

Thioamide therapy has improved the outcome of pregnancies complicated by maternal hyperthyroidism, without long-term effects on cognitive and somatic development. However, there remain questions concerning whether these drugs, especially methimazole (MMI), may be associated with aplasia cutis congenita (ACC) and how best to avoid impairment of fetal thyroid function during their use. We report an example of ACC and review the relevant literature. We conclude that there is insufficient evidence either to establish or eliminate a direct causal relationship between ACC and MMI use. Since propylthiouracil is an equally effective antithyroid agent and has not been associated with ACC, it is the preferred thioamide for hyperthyroidism during pregnancy. Our review also indicates that impairment of neonatal thyroid function may be minimized by using a thioamide dose that is just sufficient to maintain the maternal serum free thyroxine concentration in the high normal or slightly thyrotoxic range.

Topics: Abnormalities, Drug-Induced; Adult; Antithyroid Agents; Child Development; Female; Humans; Hyperthyroidism; Infant, Newborn; Maternal-Fetal Exchange; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Skin Abnormalities; Teratogens; Thyroid Diseases; Thyroxine

A 57-yr-old male with atrial septal defect (ASD) was scheduled for the patch closure operation. The patient had a history of hyperthyroidism due to giant adenoma of the thyroid gland. The patient was controlled under euthyroid state by thiamazole for four years. With this treatment, his thyroid function became normal and he was doing well for over the last seven years. On the morning of the day of operation, thiamazole was given orally to this patient. When the ASD patch closure was performed, the examination of his thyroid gland revealed hypothyroidism, but the operation could be performed without any thyroidal trouble. After the operation thiamazole was given intramuscularly to this patient and from the next day it was continued orally. Thyroid storm did not occur after the operation until discharge. We conclude that in a case of heart disease with hyperthyroidism, it is important to keep the patient's thyroid function under normal for a long time before surgery.

Topics: Administration, Oral; Anesthesia; Fentanyl; Heart Septal Defects, Atrial; Humans; Hyperthyroidism; Injections, Intramuscular; Male; Methimazole; Middle Aged

The authors review the current knowledge of fetus and woman thyroid physiology during pregnancy. They analyze the abnormalities related to hyperthyroidism, and clinical and therapeutic aspects of thyrotoxicosis; in detail possible fetal complications. They suggest the practical management of thyrotoxicosis during pregnancy.

Topics: Adolescent; Adult; Embryonic and Fetal Development; Female; Humans; Hyperthyroidism; Maternal-Fetal Exchange; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyrotoxicosis; Thyrotropin

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

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

Topics: Animals; Cat Diseases; Cats; Clinical Enzyme Tests; Female; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Propylthiouracil; Thyroid Hormones; Thyroid Neoplasms; Thyroidectomy

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: Adult; Aminoglutethimide; Animals; Antithyroid Agents; Carbimazole; Cobalt; Ethionamide; Female; Fetal Diseases; Goiter; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Iodides; Lithium; Male; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Rats; Sulfonamides; Sulfonylurea Compounds; Vegetables

Topics: Carbimazole; Child; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Lithium; Methimazole; Pregnancy; Pregnancy Complications; Propranolol; Thyroid Function Tests; Thyroidectomy; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

Topics: Age Factors; Animals; Animals, Newborn; Behavior, Animal; Biogenic Amines; Brain; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Lithium; Methimazole; Triiodothyronine; Tryptophan Hydroxylase; Tyrosine 3-Monooxygenase

Topics: Animals; Antithyroid Agents; Dogs; Humans; Hyperthyroidism; Iodine; Methimazole; Methylthiouracil; Propylthiouracil; Radioimmunoassay; Rats; Thyroidectomy; Thyroxine; Triiodothyronine

Topics: Depression, Chemical; Humans; Hyperthyroidism; Iodine; Iodine Radioisotopes; Lithium; Methimazole; Propranolol; Propylthiouracil; Reserpine; Thyroid Hormones

Topics: Abortion, Spontaneous; Female; Fetal Diseases; Humans; Hyperthyroidism; Hypothyroidism; Maternal-Fetal Exchange; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Diseases; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones; Thyroidectomy; Thyrotropin-Releasing Hormone; Thyroxine

Topics: Biological Transport; Female; Humans; Hyperthyroidism; Hypothyroidism; Iodides; Kinetics; Methimazole; Pregnancy; Propylthiouracil; Thyroid Gland; Thyrotropin; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Umbilical Cord

Topics: Agranulocytosis; Antithyroid Agents; Carbimazole; Eye Manifestations; Female; Follow-Up Studies; Goiter; Humans; Hyperthyroidism; Imidazoles; Methimazole; Pregnancy; Propylthiouracil; Thyroxine; Time Factors; Triiodothyronine

Topics: Abortion, Spontaneous; Congenital Hypothyroidism; Female; Fetal Death; Humans; Hyperthyroidism; Infant, Newborn; Infant, Newborn, Diseases; Intellectual Disability; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroidectomy; Triiodothyronine

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

This study compared the degree of sustained control of hyperthyroidism in patients with toxic multinodular goiter (TMNG) treated with long-term methimazole (LT-MMI) or radioactive iodine (RAI).. In this clinical trial, 130 untreated patients with TMNG were randomized to either LT-MMI or RAI treatment. Both groups were followed for 108 to 148 months, with median follow-up durations of 120 and 132 months in the LT-MMI and RAI groups, respectively. Both groups of patients were followed every 1 to 3 months in the first year and every 6 months thereafter.. After excluding patients in whom the treatment modality was changed and those who were lost to follow-up, 53 patients in the LT-MMI group and 54 in the RAI group completed the study. At the end of the study period, 50 (96%) and 25 (46%) patients were euthyroid, and two (4%) and 25 (46%) were hypothyroid in LT-MMI and RAI groups, respectively. In the RAI group, four (8%) patients had subclinical hyperthyroidism. The mean time to euthyroidism was 4.3±1.3 months in LT-MMI patients and 16.3± 15.0 months in RAI recipients (P<0.001). Patients treated with LT-MMI spent 95.8%±5.9% of the 12-year study period in a euthyroid state, whereas this proportion was 72.4%±14.8% in the RAI-treated patients (P<0.001). No major treatment-related adverse events were observed in either group.. In patients with TMNG, LT-MMI therapy is superior to RAI treatment, as shown by the earlier achievement of euthyroidism and the longer duration of sustained normal serum thyrotropin.

Topics: Goiter, Nodular; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Thyroid Neoplasms

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

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

Hyperthyroidism is a common endocrinopathy of middle-aged and elderly cats. Dietary treatment has been proposed as an alternative to traditional therapies.. The aim of this prospective study was to compare the efficacy of iodine-restricted food versus pharmacological therapy with methimazole in client-owned cats with hyperthyroidism.. Indoor cats with newly diagnosed hyperthyroidism (consistent clinical signs and serum total thyroxine concentration greater than 50 nmol/l) were assigned to one of three groups: (A) received an iodine-restricted food as a single therapy; (B) received transdermal methimazole in pluronic lecithin organogel; and (C) received oral methimazole. In all groups, clinical parameters, biochemistry, and serum total thyroxine were evaluated at baseline and 10, 30, 60, and 90 days after treatment began.. Thirty-four cats were enrolled in the study (group A:. These results suggest that iodine-restricted food is effective at reducing the total thyroxine concentration in the serum of hyperthyroid cats. Moreover, the iodine-restricted food did not cause any increase in serum creatinine concentrations and failed to improve liver enzymes abnormalities. These findings could indicate a persistent hyperthyroid state in cats treated with iodine-restricted food despite normalization of serum total thyroxine concentrations.

Topics: Administration, Cutaneous; Administration, Oral; Animals; Antithyroid Agents; Cat Diseases; Cats; Female; Hyperthyroidism; Iodine; Male; Methimazole; Non-Randomized Controlled Trials as Topic; Prospective Studies; 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

Feline hyperthyroidism is a common endocrine disorder in older cats for which homeopathic treatment has been advocated. A double-blinded, placebo-controlled randomised trial was performed to look for evidence of efficacy for the use of individualised homeopathy in the treatment of this disease. Using a case definition of a concentration of the thyroid hormone T4 >66 nmol/l, cats were randomised into two treatment arms. Either a placebo or a homeopathic treatment was given to each cat blindly. After 21 days, the T4 levels, weight (Wt) and heart rate (HR) were compared with pretreatment values. There were no statistically significant differences in the changes seen between the two treatment arms following placebo or homeopathic treatment (T4 P=0.96, Wt P=0.16, HR P=0.36) or between the means of each parameter for either treatment arm before and after placebo or homeopathic treatment (all P values >0.13). In a second phase of the study, patients in both treatment arms were given methimazole treatment for 21 days and T4, Wt and HR determined again. Again there were no statistically significant differences between the groups, but there were statistically significant reductions in T4 (P<0.0001) and HR (P=0.02), and a statistically significant increase in Wt (P=0.004) in both groups compared with their pre-methimazole treatment levels. The results of this study failed to provide any evidence of the efficacy of homeopathic treatment of feline hyperthyroidism.

Topics: Animals; Antithyroid Agents; Cat Diseases; Cats; Double-Blind Method; Homeopathy; Hyperthyroidism; Methimazole; Thyroxine; Treatment Outcome

Relatively low radioiodine uptake (RAIU) represents a common obstacle for radioiodine ((131)I) therapy in patients with multinodular goiter complicated by hyperthyroidism.. To evaluate whether thiamazole (MTZ) pretreatment can increase (131)I therapeutic efficacy.. Twenty-two patients with multinodular goiter, subclinical hyperthyroidism, and RAIU < 50% were randomized to receive either a low-iodine diet (LID; n = 10) or MTZ 30 mg/d (n = 12) for 42 days. Thyroid function and 24-hour RAIU were measured before and after treatment. Thyroid volume was evaluated by either magnetic resonance imaging or single photon emission computed tomography.. Mean 24-hour RAIU increased significantly from 32 ± 10% to 63 ± 18% in the MTZ group (P < .001). Consequently, there was a 31% decrease in the calculated median therapeutic (131)I activity after MTZ (P < .05). No significant changes in 24-hour RAIU were observed after diet. In the MTZ group, median serum TSH levels increased significantly by 9% and mean serum free T4 and free T3 concentrations decreased by 22% and 15%, respectively, whereas no changes in thyroid function were observed in the LID group. Thyroid volume did not significantly change in either of the two groups. At 12 months after radioiodine treatment, median serum TSH was within the normal range in both groups.. MTZ treatment before (131)I therapy resulted in an average 2-fold increase in thyroid RAIU and enhanced the efficiency of radioiodine therapy assessed at 12 months. MTZ pretreatment is therefore a safe, easily accessible alternative to recombinant human TSH stimulation and a more effective option than LID.

Topics: Aged; Aged, 80 and over; Antithyroid Agents; Case-Control Studies; Combined Modality Therapy; Drug Administration Schedule; Female; Goiter, Nodular; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Organ Size; Radiotherapy Dosage; Thyroid Function Tests; Thyroid Gland

Investigate the differences in cardiopulmonary (CP) capacity and Quality of Life (QOL) between healthy elderly (≥ 65 years) with different TSH levels (< 1.0 and ≥ 1.0 μIU/mL) both within the normal range. Also, evaluate the effects of TSH elevation on CP test and QOL, by administering methimazole to subjects with initial lower-normal TSH, in order to elevate it to superior-normal limit.. Initially, a cross-sectional study was performed to compare CP capacity at peak exercise and QOL (using WHOQOL-OLD questionnaire) between healthy seniors (age ≥ 65 years) with TSH < 1.0 μIU/mL vs. TSH ≥1.0 μIU/mL. In the second phase, participants with TSH < 1.0 μIU/mL were included in a non-controlled-prospective-interventional study to investigate the effect of TSH elevation, using methimazole, on QOL and CP capacity at peak exercise.. From 89 elderly evaluated, 75 had TSH ≥ 1 μIU/mL and 14 TSH < 1 μIU/mL. The two groups had similar basal clinical characteristics. No difference in WHOQOL-OLD scores was observed between groups and they did not differ in terms of CP function at peak exercise. QOL and CP variables were not correlated with TSH levels. Twelve of 14 participants with TSH < 1.0 μIU/mL entered in the prospective study. After one year, no significant differences in clinical caracteristics, QOL, and CP variables were detected in paired analysis before and after methimazole intervention.. We found no differences in CP capacity and QOL between health elderly with different TSH levels within normal range and no impact after one year of methimazole treatment. More prospective-controlled-randomized studies are necessary to confirm or not the possible harm effect in normal low TSH.

Topics: Age Factors; Aged; Aging; Antithyroid Agents; Cross-Sectional Studies; Exercise Tolerance; Female; Heart Rate; Humans; Hyperthyroidism; Male; Methimazole; Oxygen Consumption; Prospective Studies; Quality of Life; Reference Values; Statistics, Nonparametric; Surveys and Questionnaires; Thyrotropin; Thyroxine

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

Oral methimazole has been widely used to treat hyperthyroidism, but its usage is restricted by its adverse systemic effects. The aim of this study was to investigate the efficacy and safety of methimazole ointment for the treatment of hyperthyroidism. One hundred forty-four subjects with hyperthyroidism were initially enrolled. These patients were initially divided into two groups and given the following treatments for 12 weeks: patients in group A received 5% methimazole ointment applied to the skin around the thyroid and an oral placebo; and patients in group B received methimazole tablets and placebo ointment. One hundred thirty-one subjects were included in the final analysis. Therapeutic efficacy was assessed via the levels of free triiodothyronine and thyroxine in the serum and by biweekly monitoring of the symptoms of thyrotoxicosis. Adverse effects were recorded. Fifty-nine (89.40%) patients in group A and 57 (87.69%) patients in group B were euthyroid and experienced alleviation of thyrotoxicosis symptoms (complete control; p>0.05). The median times required to achieve complete control for the patients in the two groups were 6.5 weeks and 6.4 weeks for groups A and B, respectively (p>0.05). Systemic adverse effects (e.g., rash, liver dysfunction, leucopenia, etc.) were significantly less common in group A (1.5%) than in group B (12.3%; p<0.05). This study showed that methimazole ointment has a clinical efficacy similar to that of oral tablets, but methimazole ointment caused fewer systemic adverse effects in patients with hyperthyroidism.

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

There is no general agreement as to which treatment is best for hyperthyroidism. The objective of this study is to investigate the effectiveness of continuous methimazole (MMI) treatment and to compare the results of neuropsychological testing in patients receiving long-term continuous MMI to those on replacement thyroxine following radioiodine-induced (RAI) hypothyroidism.. We enrolled 239 patients with diffuse toxic goiter who had recurrences of hyperthyroidism. Of these, 104 patients were randomized into two groups, MMI and treatment with thyroxine following RAI hypothyroidism. The remaining 135 patients voluntarily enrolled into either of the two groups. From all patients, 59 MMI-treated patients and 73 patients in the RAI group completed follow up. Thyroid function tests, serum lipids and lipoproteins, echocardiography, bone mineral density (BMD) and seven neuropsychology tests were performed at the final visit.. In the RAI group compared to the MMI-treated group during a mean of 14 years follow up, there were more incidences of elevated TSH [> 5 mU/L; adjusted relative risk (RR) 1.23; 95% confidence interval (CI) 1.04-1.47), increased triglycerides (> 150 mg/dL; RR 2.20; 95% CI 1.34-3.62), HDL-C (< 40 mg/dL; RR 3.46; 95% CI 1.40 - 8.53), and early diastolic annular velocity (< 12.2 cm; RR 3.91; 95% CI 1.42-10.74), in addition to a decreased early diastolic to annular velocity ratio (< 6.7; RR 7.14; 95% CI 1.38-34.48). The MMI group scored better in neuropsychology tests that included mood, direction, logical memory, repeated numbers, and intelligence quotient (IQ).. Long-term MMI treatment was superior to RAI therapy in patients with diffuse toxic goiter when mood, cognition, cardiac function and occurrence of thyroid dysfunction were compared.. Iranian Registry of Clinical Trials: IRCT 201009224794N1.

Topics: Antithyroid Agents; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Time Factors

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

Structural myocardial abnormalities have been extensively documented in hypothyroidism. Experimental studies in animal models have also shown involvement of thyroid hormones in gene expression of myocardial collagen. This study was planned to investigate the ability of ultrasonic tissue characterization, as evaluated by integrated backscatter (IBS), to early identify myocardial involvement in thyroid dysfunction.. We studied 15 patients with hyperthyroidism (HYPER), 8 patients with hypothyroidism (HYPO), 14 patients with subclinical hypothyroidism (SCH) and 19 normal (N) subjects, who had normal LV systolic function. After treatment, 10 HYPER, 6 HYPO, and 8 SCH patients were reevaluated. IBS images were obtained and analyzed in parasternal short axis (papillary muscle level) view, at left ventricular (LV) posterior wall. The following IBS variables were analyzed: 1) the corrected coefficient (CC) of IBS, obtained by dividing IBS intensity by IBS intensity measured in a rubber phantom, using the same equipment adjustments, at the same depth; 2) cardiac cyclic variation (CV) of IBS--peak-to-peak difference between maximal and minimal values of IBS during cardiac cycle; 3) cardiac cyclic variation index (CVI) of IBS--percentual relationship between the cyclic variation (CV) and the mean value of IBS intensity.. CC of IBS was significantly larger (p < 0.05) in HYPER (1.57 +/- 0.6) and HYPO (1.53 +/- 0.3) as compared to SCH (1.32 +/- 0.3) or N (1.15 +/- 0.27). The CV (dB) (HYPO: 7.5 +/- 2.4; SCH: 8.2 +/- 3.1; HYPER: 8.2 +/- 2.0) and the CVI (HYPO: 35.6 +/- 19.7%; SCH: 34.7 +/- 17.5%; HYPER: 37.8 +/- 11.6%) were not significantly different in patients with thyroid dysfunction as compared to N (7.0 +/- 2.0 and 44.5 +/- 15.1%).. CC of IBS was able to differentiate cardiac involvement in patients with overt HYPO and HYPER who had normal LV systolic function. These early myocardial structural abnormalities were partially reversed by drug therapy in HYPER group. On the other hand, although mean IBS intensity tended to be slightly larger in patients with SCH as compared to N, this difference was not statistical significant.

Topics: Adult; Antithyroid Agents; Diagnosis, Differential; Echocardiography, Doppler; Female; Heart Diseases; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Middle Aged; Severity of Illness Index; Systole; Thyroxine; Ventricular Function, Left

Cardiovascular abnormalities may be the only manifestations of overt hyperthyroidism. In patients with heart failure and atrial fibrillation digoxin can be beneficial in controlling the symptoms and signs, but hyperthyroid patients show an impaired response or even resistance to digoxin treatment. The aim of the study is to establish: 1. Are there any differences in the pharmacokinetics of a single oral dose of digoxin between hypertyroid and euthyroid patients? 2. Does simultaneous administration of digoxin and methimazole affect the pharmacokinetics of a single oral dose of dogoxin? 3. Does methimazole-induced euthyroidism change the pharmacokinetics of a single oral dose of digoxin?. The subject of the study were 28 patients with hyperthyroidism and 15 healthy persons. We evaluated the pharmacokinetics of a single oral dose of digoxin. Moreover we evaluated pharmacokinetics of a single dose of digoxin after simultaneous administration of digoxin and methimazole in 12 patients and 12 methimazole treated patients werere-assessed once they had become euthyroid.. Hyperthyroid patients showed significantly lower serum digoxin concentrations, shorter T1/2 beta and a significantly smaller area under the concentration curve (AUC) that the control group. Administration of methimazole did not affect digoxin pharmacokinetics.. In hyperthyroid patients: 1. the pharmacokinetics of a single oral dose of digoxin does differ from that observed in healthy subjects. 2.methimazole do not alter digoxin pharmacokinetics.

Topics: Administration, Oral; Adult; Anti-Arrhythmia Agents; Antithyroid Agents; Area Under Curve; Digoxin; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hyperthyroidism; Male; Methimazole

There are potentially complex interrelationships between thyroid function, leptin, ghrelin, body mass index (BMI), and percentage of body fat (%BF). The goal of this study was to determine if normalization of thyroid status in premenopausal women with hyperthyroidism and hypothyroidism would be associated with changes in serum leptin and ghrelin in the absence of thyroid dysfunction treatment-associated changes in BMI and %BF.. The study was carried out in 47 selected premenopausal women: 17 with hyperthyroidism, 11 with hypothyroidism, and 19 healthy individuals who constituted the control group. Patients with thyroid dysfunction were selected for study if their BMI and %BF did not change after treatment of thyroid dysfunction. Subjects in the control group were selected on the basis of the age, BMI, and the %BF characteristics of the patients with thyroid dysfunction. Concentrations of free thyroxine (fT4), free triiodothyronine (fT3), thyrotropin, leptin, and ghrelin in serum were determined before and after treatment of thyroid dysfunction and in the control group.. Serum leptin concentrations were similar in patients with hyperthyroidism and hypothyroidism before treatment and in normal subjects and did not change significantly after treatment of hyperthyroidism or hypothyroidism. Serum ghrelin concentrations were lower in patients with hyperthyroidism, and higher in patients with hypothyroidism than in the control group (hypothyroidism = 2345 (1157-7015) [median (range)], hyperthyroidism = 1205 (438-2914), control = 2398 (1542-4920), p < 0.05).. In premenopausal women with hyperthyroidism or hypothyroidism, treatment of thyroid dysfunction that is not associated with changes in BMI or %BF does not influence serum leptin but does affect serum ghrelin. Thyroid status itself, in the absence of alterations in the BMI and %BF, has an important influence on circulating ghrelin but not leptin.

Topics: Adolescent; Adult; Antithyroid Agents; Blood Pressure; Body Mass Index; Female; Ghrelin; Humans; Hyperthyroidism; Hypothyroidism; Leptin; Methimazole; Middle Aged; Postmenopause; Thyroxine; Triiodothyronine

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

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

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

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

To investigate the long-term effects of continuous methimazole (MMI) therapy.. Five hundred and four patients over 40 years of age with diffuse toxic goiter were treated with MMI for 18 months. Within one year after discontinuation of MMI, hyperthyroidism recurred in 104 patients. They were randomized into 2 groups for continuous antithyroid and radioiodine treatment. Numbers of occurrences of thyroid dysfunction and total costs of management were assessed during 10 years of follow-up. At the end of the study, 26 patients were still on continuous MMI (group 1), and of 41 radioiodine-treated patients (group 2), 16 were euthyroid and 25 became hypothyroid. Serum thyroid and lipid profiles, bone mineral density, and echocardiography data were obtained.. There was no significant difference in age, sex, duration of symptoms and thyroid function between the two groups. No serious complications occurred in any of the patients. The cost of treatment was lower in group 1 than in group 2. At the end of 10 years, goiter rate was greater and antithyroperoxidase antibody concentration was higher in group 1 than in group 2. Serum cholesterol and low density lipoprotein-cholesterol concentrations were increased in group 2 as compared with group 1; relative risks were 1.8 (1.12-2.95, P<0.02) and 1.6 (1.09-2.34, P<0.02) respectively. Bone mineral density and echocardiographic measurements were not different between the two groups.. Long-term continuous treatment of hyperthyroidism with MMI is safe. The complications and the expense of the treatment do not exceed those of radioactive iodine therapy.

Topics: Adult; Antithyroid Agents; Female; Follow-Up Studies; Goiter; Health Care Costs; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Risk Factors; Treatment Outcome

It is well-know that hyperthyroidism is one of the key causes of secondary osteoporosis. High values of thyroid hormones increase the bone mineral turnover speed by promoting osteoclastic and osteoblastic activities. The aim of our study is to evaluate the increase of bone mineral density (BMD) in osteoporotic and hyperthyroid patients treated with only antithyroid drugs versus patients treated with antithyroid drugs and diphosphonates.. Twenty-six elderly male patients, 65-75 years, were selected. In all these patients, thyroid function (FT3, FT4, TSH, Tg, AbTg, AbTPO) was evaluated at baseline and after 6 and 12 months from the start of medical treatment; the following were evaluated: BMD, calcium serum, phosphorus serum, alkaline phosphatase, PTH and 24 hours urinary calcium, phosphorus and hydroxyprolin. Thirteen patients (group 1) were treated with antithyroid drugs (methimazole 5-20 mg/die/os) and diphosphonates (alendronate 10 mg/die/os). The control group of 13 patients (group 2) was treated with antithyroid drugs only.. After 6 months of treatment, the patients of group 1 showed a mean increase of 2.5% in lumbar spine BMD compared with a mean increase of 0.3% in group 2 (p<0.01). After 12 months, group 1 showed a mean increase of 6.2% in lumbar spine BMD, compared with a mean increase of 2% in group (p<0.001).. The combination of antithyroid and diphosphonates drugs appears to be more efficacious than antithyroid therapy alone for the treatment of osteoporosis in male hyperthyroid patients.

Topics: Aged; Alendronate; Alkaline Phosphatase; Antithyroid Agents; Bone Density; Calcium; Case-Control Studies; Drug Therapy, Combination; Humans; Hyperthyroidism; Male; Methimazole; Osteoporosis; Parathyroid Hormone; Phosphorus; Treatment Outcome

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

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

To determine whether once daily administration of methimazole was as effective and safe as twice daily administration in cats with hyperthyroidism.. Randomized, nonblinded, clinical trial.. 40 cats with newly diagnosed hyperthyroidism.. Cats were randomly assigned to receive 5 mg of methimazole, PO, once daily (n = 25) or 2.5 mg of methimazole, PO, twice daily (15). A complete physical examination, including measurement of body weight; CBC; serum biochemical analyses, including measurement of serum thyroxine concentration; and urinalysis were performed, and blood pressure was measured before and 2 and 4 weeks after initiation of treatment.. Serum thyroxine concentration was significantly higher in cats given methimazole once daily, compared with cats given methimazole twice daily, 2 weeks (3.7 vs 2.0 micro +/- g/dL) and 4 weeks (3.2 vs 1.7 microg/dL) after initiation of treatment. In addition, the proportion of cats that were euthyroid after 2 weeks of treatment was lower for cats receiving methimazole once daily (54%) than for cats receiving methimazole twice daily (87%). Percentages of cats with adverse effects (primarily gastrointestinal tract upset and facial pruritus) were not significantly different between groups.. Results suggest that once daily administration of methimazole was not as effective as twice daily administration in cats with hyperthyroidism and cannot be recommended for routine use.

Topics: Administration, Oral; Animals; Antithyroid Agents; Cat Diseases; Cats; Drug Administration Schedule; Hyperthyroidism; Methimazole; Safety; Thyroxine; 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

Topics: Aged; Alendronate; Antithyroid Agents; Bone Density; Drug Therapy, Combination; Femur Neck; Humans; Hyperthyroidism; Lumbar Vertebrae; Male; Methimazole; Osteoporosis

Topics: Climacteric; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Humans; Hyperthyroidism; Methimazole; Middle Aged; Phytotherapy

To evaluate randomly the effect of thyrostatic treatment (tiamazole) versus selective (metoprolol) and nonselective beta-blockade (propranolol) on whole-body energy metabolism in women with hyperthyroidism.. beta-blockade is used as an alternative to thyrostatic drugs in the preoperative treatment of patients with hyperthyroidism. beta-blockers have well-established symptomatic effects, but in contrast to antithyroid drugs beta-blockade is thought to lack direct effects on the increased metabolism in hyperthyroidism.. Whole-body oxygen consumption and carbon dioxide production was measured in a semiopen canopy system with paramagnetic O2 and infrared CO2 sensors. A constant flow generator and the gas-dilution method for calculation of gas flow were used. Anabolic parameters were body weight, triceps skinfold, and arm muscle circumference.. Tiamazole normalized oxygen consumption and induced signs of anabolism with improved nutritional state. Metroprolol did not affect oxygen consumption. Propranolol reduced elevated oxygen consumption by 54%. Body weight and other anthropometric assessments were stable after specific and nonspecific beta-blockade, which also led to symptomatic relief in approximately 90% of the patients.. Tiamazole was the most effective drug to oppose the adverse effects of hyperthyroidism. Therefore, thyrostatic agents are recommended for preoperative treatments of patients with severe catabolic hyperthyroidism. Whenever beta-blockers are chosen for treatment of hyperthyroidism, propranolol (beta 1 + beta 2) has an advantage because it reduces the metabolic rate, whereas selective beta 1-blockade seemed to provide only symptomatic relief, related to the normalization of heart rate.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Analysis of Variance; Antithyroid Agents; Carbon Dioxide; Female; Humans; Hyperthyroidism; Methimazole; Metoprolol; Middle Aged; Oxygen Consumption; Preoperative Care; Propranolol; Prospective Studies; Treatment Outcome

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

Insulin-like growth factor binding-protein-1 (IGFBP-1) has a role in glucose homeostasis and is present at high concentrations in hyperthyroidism. We have investigated the relationship between IGFBP-1 concentration and glucose homeostasis in hyperthyroidism.. Patients and controls had intravenous glucose tolerance tests (IVGTT) and/or oral glucose tolerance tests (OGTT). Patients were tested when hyperthyroid and when euthyroid whilst the controls were tested once. The IVGTT was used to assess insulin sensitivity and the OGTT to establish that the study group had abnormal glucose tolerance. The hyperthyroid patients were treated with methimazole to restore euthyroidism.. Ten patients (9 females) and 13 healthy controls (9 females) consented to the study. Ten patients and nine controls (7 females) had IVGTT. Six patients (5 females) and six controls (4 females) had OGTT.. Glucose, insulin, glucagon, GH and IGFBP-1 were measured during GTT. IGF-I, free thyroid hormones, and TSH concentrations were measured basally.. Hyperthyroid subjects were insulin resistant and 67% had impaired glucose tolerance. Fasting IGFBP-1 levels were doubled in hyperthyroid subjects compared to healthy controls and correlated positively with free T4 (r = 0.84, P < 0.0001), with peak glucose during the OGTT (r = 0.68, P < 0.005) with peak insulin during the IVGTT (r = 0.51, P < 0.005) and negatively with glucose disappearance constant (r = - 0.52, P < 0.005). IGFBP-1 was highly phosphorylated in hyperthyroid and control subjects. Fasting insulin and IGFBP-1 levels were unrelated but IGFBP-1 suppressed acutely during GTT in all groups. GH levels fell less in patients with hyperthyroidism than in normals during GTTs.. We conclude that in hyperthyroidism thyroid hormones directly increase fasting IGFBP-1 concentration but acute regulation of IGFBP-1 by insulin is normal and that elevated fasting phosphorylated IGFBP-1 concentration is associated with insulin resistance.

Topics: Adult; Antithyroid Agents; Area Under Curve; Blood Glucose; Case-Control Studies; Female; Glucose Tolerance Test; Human Growth Hormone; Humans; Hyperthyroidism; Insulin; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Male; Methimazole; Thyroxine

Hyperthyroid patients have high bone turnover and negative calcium and phosphorus balance often associated with mild osteopenia. Early during antithyroid treatment bone turnover decreases, the mineral balance is converted to positive, and sometimes hypocalcemia occurs. The aim of this investigation was to study the mechanisms of the changes in some parameters of bone and mineral metabolism after treatment of thyrotoxicosis. Thirteen newly diagnosed patients with Graves' disease (seven postmenopausal women, four premenopausal women, and two men) were studied longitudinally, every 6 weeks, for 1 yr after commencing antithyroid treatment with methimazole. Mean serum calcium and phosphorus were both slightly above the normal mean at week 0 and decreased significantly (by 10% and 24%, respectively) during treatment. Fasting urinary calcium was 236 +/- 4 (mean +/- SEM) mg/g creatinine, and the fractional excretion of Ca was 2.0 +/- 0.33% before treatment; both fell significantly to minimums of 61 +/- 20 mg/g and 0.6 +/- 0.16%, respectively. Urinary phosphorus was 282 +/- 60 mg/g creatinine, and the fractional excretion of phosphorus was 3.3 +/- 0.6% before treatment; both increased significantly to 452 +/- 40 mg/g and 8.4 +/- 1.0%, respectively, during treatment. The z-scores were calculated from the mean and SD ofthe respective control groups. The z-score of urinary N-telopeptides of type I collagen (U.NTx) was 9.3 +/- 1.3 at week 0 and declined exponentially, but failed to normalize after 1 yr of antithyroid treatment. The serum alkaline phosphatase (ALP) z-score was initially 2.2 +/- 0.2, increased to 6.0 +/- 1.0 at week 6, and declined slowly there after to 1.0 +/- 1.1 at week 54. The serum osteocalcin (OC) z-score showed a temporal pattern similar to that of ALP. It was initially 2.2 +/- 0.2, increased to 4.0 +/- 0.6 at week 6, and later declined slowly to 0.7 +/- 0.5 at week 54. The failure of the markers of bone turnover to normalize after 1 yr of therapy indicates an on-going high rate of bone turnover despite the attained euthyroidism. The uncoupling index (UI = z-score of U.NTx minus z-score of OC) was 7.1 +/- 1.2 before treatment, indicating unbalanced bone turnover in favor of bone resorption, and fell close to zero at week 30 of treatment. Pretreatment plasma PTH was suppressed slightly to 2.17 +/- 0.47 pmol/L and rose significantly during treatment, reaching a plateau of 5.27 +/- 0.78 at week 12. In all postmenopausal women PTH increased above the

Topics: Adult; Aged; Antithyroid Agents; Bone and Bones; Bone Density; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Minerals; Thyroid Function Tests; Thyroxine; Time Factors; Triiodothyronine

For many years, breast-feeding was forbidden if antithyroid drugs were being used. Recently, limited studies have shown the relative safety of propylthiouracil and methimazole (MMI). It is not known whether MMI therapy of lactating mothers for 1 yr is safe for breast-fed infants and does not cause alterations in thyroid function and intellectual development. Between 1988 and 1998, 139 thyrotoxic lactating mothers and their infants were studied. Fifty-one thyrotoxic lactating mothers were treated with MMI during pregnancy, and MMI was continued during breast-feeding. Eighty-eight mothers were given 10 mg MMI (n 46) or 20 mg MMI (n = 42) daily for 1 month, 10 mg daily for the second month, and 5-10 mg daily thereafter. Serum T4, T3, and TSH concentrations were measured in thyrotoxic lactating mothers and their infants, before and at 1, 2, 4, 8, and 12 months. Serum MMI was measured in the infants of thyrotoxic lactating mothers taking 20 mg MMI. Thyroid function, urinary iodine, thyroid antibodies, intelligence quotient (IQ), verbal and functional components (Wechsler and Goodenough tests) were performed on 14 children of thyrotoxic lactating mothers between 48 and 74 months of age and on 17 controls. Mean +/- SD of FT4I in thyrotoxic lactating mothers treated with 10 mg MMI for 1 month decreased from 19.4 +/- 4.1 to 11.6 +/- 4.4 and from 20.5 +/- 4.7 to 9.8 +/- 1.5 when treated with 20 mg MMI. Values for FT3I decreased from 462 +/- 52 to 194 +/- 52 with 10 mg MMI and from 481 +/- 92 to 171 +/- 38 with 20 mg MMI. FT4I and FT3I were normal from the third to the twelfth months. In all infants FT4I, FT3I, and TSH concentrations were normal before and up to 12 months of MMI therapy in their lactating mothers. The lowest T4 and T3 values were 108 and 1.87 nmol/L, and the highest TSH value was 4.0 mU/L. Serum MMI levels in infants were less than 0.03 microg/mL. Six mothers receiving 20 mg MMI had increased serum TSH concentrations ranging from 26-135 mU/L after 1 month of treatment. Their infants were euthyroid with serum TSH values less than 2.6 mU/L. At 48-74 months of age, height, weight, FT4I, FT3I, TSH, and antithyroid antibody titers were not different than controls. The mean IQ was 107 +/- 14 vs. 106 +/- 16 (Goodenough test) and 103 +/- 10 vs. 103 +/- 16 (Wechsler test) for infants of thyrotoxic lactating mothers and control infants, respectively. Similarly, there was no difference in verbal and performance IQ and their components between infants of thyrot

Topics: Adult; Antithyroid Agents; Breast Feeding; Female; Humans; Hyperthyroidism; Infant, Newborn; Intelligence; Intelligence Tests; Methimazole; Thyroid Function Tests; Thyroid Gland; Thyrotoxicosis; Thyrotropin; Thyroxine; Triiodothyronine

Low bone mineral density (BMD) and increased bone turnover are common features of untreated hyperthyroidism in adult patients. The effect of treatment on BMD is still controversial. BMD and bone metabolism in hyperthyroid children have not been thoroughly investigated. In the present study, we measured spinal and whole body BMD by dual-energy X-ray absorptiometry in a group of 13 girls (aged 5.0-14.9 years) at diagnosis of hyperthyroidism. The bone resorption rate was assessed by urine measurement of N-terminal telopeptide of type I collagen (NTX). Hyperthyroid patients have been studied longitudinally during treatment. BMD values and NTX urine concentrations have been also determined in 155 healthy Caucasian girls (aged 2.4-24.2 years). Spinal and whole body bone density measurements were significantly lower compared with healthy controls in untreated hyperthyroid girls, after correction for differences in age and anthropometric measurements (p

Topics: Adolescent; Adult; Antithyroid Agents; Biomarkers; Bone Density; Bone Resorption; Child; Child, Preschool; Collagen; Collagen Type I; Creatinine; Female; Humans; Hyperthyroidism; Longitudinal Studies; Methimazole; Peptides; Thyrotoxicosis; Thyroxine

To investigate the effect of Jiakang Ning (JKN) capsule on hyperthyroidism.. Eighty-five cases of hyperthyroidism were divided into JKN group (24 cases), JKN with low dose Tapazol group (35 cases) and Tapazol control group (26 cases) at random. The effects were evaluated by total effective rate, using principal symptoms, body weight, EKG, thyroid hormone and atrial natriuretic peptide (ANP) after 6 months.. The total effective rates of three groups were 83.8%, 97.1%, 88.5% respectively, and there were insignificant difference among them statistically (P > 0.05). The first two groups had better effect in principal symptoms than Tapazol control group (P < 0.05). There were similar results in adjusting thyroid dysfunction and abnormal EKG, decreasing ANP and increasing body weight among those three groups (P > 0.05).. The effect on hyperthyroidism treatment by JKN capsule was satisfactory. The combination of Chinese herbs with western medicine could enhance the curative effect of hyperthyroidism without obvious side-effects.

Topics: Adolescent; Adult; Antithyroid Agents; Capsules; Diagnosis, Differential; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Humans; Hyperthyroidism; Male; Medicine, Chinese Traditional; Methimazole; Middle Aged; Phytotherapy; Yin Deficiency

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

In a prospective, randomized study we examined the influence of prophylactic short-term thyrostatic therapy on thyroid iodine metabolism in patients with euthyroid autonomy undergoing elective coronary angiography. From a total of 1177 patients, 51 fulfilled the criteria of euthyroid autonomy before coronary angiography (negative thyrotropin-releasing hormone test, 10-min uptake of at least 1.2%, 99mTc and no elevation of free thyroxine and free triiodothyronine indices) and were randomized into three groups: group 1 (N = 17) received 20mg/day of thiamazole and group 2 (N = 17) received 900 mg/day of sodium perchlorate; thyrostatic therapy was begun on the day before angiography and continued for 14 days; group 3 (N = 17) served as controls without treatment. Parameters of thyroid function-free thyroxine (FT4) index and free triiodothyronine (FT3) index, thyrotropin (TSH) and delta-TSH urine iodine excretion and 99mTc uptake were determined before and 30 days after coronary angiography. At the end of the study the mean FT4 index and FT3 index were elevated significantly in the control group compared with baseline values, but were still within the normal range. In contrast, the mean FT4 index and FT3 index remained unchanged in the treated groups. Four mild cases of hyperthyroidism were observed at the end of the study: two cases in the control group and one case in each of the treated groups. Thyrotropin suppression, urine iodine excretion and 99mTc uptake differed significantly between the treated groups and the control group. In the treated groups TSH suppression, urine iodine excretion and 99mTC uptake remained unchanged 30 days after coronary angiography compared with baseline values. In the control group the degree of TSH suppression and the level of urine iodine excretion increased (about twofold) significantly after coronary angiography, whereas 99mTc uptake decreased significantly (ca. 50%). In conclusion, short-term prophylactic thyrostatic therapy seems to have a protective effect against iodine excess in patients with euthyroid autonomy. However, mild hyperthyroidism could not be prevented in some cases. Probably a combination therapy of thiamazole and perchlorate would be more effective.

Topics: Aged; Antithyroid Agents; Contrast Media; Coronary Angiography; Female; Humans; Hyperthyroidism; Iodine; Male; Methimazole; Middle Aged; Perchlorates; Pilot Projects; Prospective Studies; Sodium Compounds; Thyroid Function Tests; Thyroid Gland

To determine whether increases in BUN and serum creatinine (SCr) concentrations, which have been reported to develop after surgical bilateral thyroidectomy in hyperthyroid cats, also develop after treatment of hyperthyroidism with radioactive iodine and methimazole.. Prospective, clinical trial.. 58 hyperthyroid cats.. Urine specific gravity, SCr, BUN, and serum thyroxine (T4) concentrations were determined before and 30 and 90 days after treatment of hyperthyroidism with radioactive iodine, methimazole, or surgical bilateral thyroidectomy.. Mean SCr and BUN concentrations determined 30 and 90 days after treatment were significantly higher than those measured before treatment. Mean SCr, BUN, and T4 concentrations were not different among groups before treatment or 30 and 90 days after treatment.. Reduction of serum T4 concentrations after treatment of hyperthyroidism may result in azotemia in older cats with chronic renal disease. Treating azotemic hyperthyroid cats with methimazole until it can be determined whether correction of the hyperthyroid state will exacerbate the azotemia may be prudent.

Topics: Animals; Antithyroid Agents; Blood Urea Nitrogen; Cat Diseases; Cats; Creatinine; Hyperthyroidism; Iodine Radioisotopes; Kidney; Methimazole; Prospective Studies; Specific Gravity; Thyroidectomy; Thyroxine; Urine

The entero-hepatic circulation of thyroid hormones is increased in thyrotoxic states. Based on this observation, the use of ionic exchange resins to bind thyroid hormones in the intestine has been tried. The present study evaluates the effectiveness of cholestyramine as an adjunctive therapy in the management of hyperthyroid Graves' disease. Thirty patients with newly diagnosed hyperthyroid Graves' disease were randomly assigned to one of the following treatment groups: methimazole, propranolol and cholestyramine for 4 weeks (group I); methimazole and propranolol for 4 weeks (group II); methimazole, propranolol, and cholestyramine for 2 weeks, followed by 2 weeks of methimazole and propranolol (group III). At the end of the study, total and free T4 as well as T3 levels had decreased more in group I compared with group II: 61%, 78%, 68% in group I compared with 43%, 65%, 50% in group II (P = 0.037 for T4, P = 0.038 for free T4, P = 0.012 for T3). Group III behaved like group I while patients were receiving cholestyramine, but once the drug was discontinued, the rate of decline of thyroid hormones slowed down. We conclude that cholestyramine represents an effective and well-tolerated adjunctive therapy in patients with hyperthyroid Graves' disease, and it produces a more rapid and complete decline in thyroid hormone levels in these patients.

Topics: Cholestyramine Resin; Drug Therapy, Combination; Humans; Hyperthyroidism; Methimazole; Propranolol; Thyroxine; Triiodothyronine

The study aimed at the evaluation of the kinetics of gastric emptying (GE) of a solid meal in hyperthyroid patients during a pharmacological treatment with thiamazole until the moment of euthyroid restoration. Fourteen female patients ((33.4 +/- 2.6 y, mean +/- SE) with recently diagnosed hyperthyreosis took part in the study. Twelve age matched healthy women (34.5 +/- 2.3 y) constituted a control group (C). Every patient underwent the GE examination before treatment (I). In 12 patients the GE was reexamined on the 3rd treatment week (II). After the achievement of euthyroid, which happened after 4.5 mo (median; interquartile range 2.0 to 7.3 mo), a third GE measurement was taken in 13 patients (III). The GE of a 99mTc-labelled solid meal was measured with the use of a gamma camera. Time-activity curves from the gastric region of interest were used, after subjection to appropriate corrective procedures, to calculate the mean gastric transit time (MTT 90) and the fraction of the test meal retained in the stomach after 90 min (F90). Before the treatment and on the third week of management the GE of hyperthyroidism was not statistically significantly different from that of healthy controls (MTT90:39.44 +/- 0.30 min [I] 39.31 +/- 0.64 min [II] and 40.06 +/- 0.29 [C]; F90:46.6 +/- 1.9% [I], 47.9 +/- 3.7% [II] and 50.8 +/- 2.4% [C]). The restoration of euthyreosis was accompanied by a slight but statistically significant increase in the GE -p < 0.05 in the case of F90 vs the pre-treatment situation. Also the patients' GE was found then to be slightly but statistically faster than in healthy controls (MTT90:38.72 +/- 0.39 min [III], and F90: 42.2 +/- 2.3% [III] -p < 0.05 vs [C] for both parameters). We conclude that in hyperthyreotic women the GE of solids does not differ significantly from age-matched healthy female controls and remains unchanged during a pharmacological treatment. After achievement of euthyreosis a slightly but statistically significantly faster GE is observed in the patients when compared to healthy controls.

Topics: Adult; Female; Gastric Emptying; Humans; Hyperthyroidism; Methimazole

This study to compare single-dose and multiple-dose antithyroid therapy was prompted by a perceived lack of compliance in our University Medical Clinics by those patients using multidose regimens. Twenty-two hyperthyroid patients were randomly assigned to two therapy groups. Twelve received methimazole (Tapazole) 30 mg once daily in the morning; 10 received propylthiouracil 100 mg every 8 hours. Patients were seen every 4 weeks for 3 months and assessed clinically, as well as having the appropriate thyroid tests done. Univariate analysis revealed no difference in the two groups at baseline. Posttreatment assessment revealed the once-a-day methimazole therapy to be just as effective as propylthiouracil in improving thyroid indices and clinical markers. Compliance with methimazole was 83.3% compared to 53.3% with propylthiouracil. In conclusion, once-a-day methimazole was just as effective as propylthiouracil every 8 hours in this population. Compliance was also improved with the once-a-day therapy.

Topics: Drug Administration Schedule; Female; Humans; Hyperthyroidism; Male; Methimazole; Patient Compliance; Propylthiouracil; Thyrotropin; Thyroxine; Triiodothyronine

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

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

To assess the value of antithyroid drugs as an adjunct to radioactive iodine for the treatment of hyperthyroidism the incidence of relapse or hypothyroidism after a mean follow-up of 5 1/2 years (range 2-7 years) was reviewed retrospectively for 206 patients, some treated with and others without antithyroid drugs after radioiodine therapy. Allocation to treatment group had been random, and both groups were similar in all respects except for the adjunctive treatment with antithyroid drugs. All doses of 131I had been calculated by one physician. Compared with those who received 131I alone, those starting on antithyroid drugs within 8 days after 131I had a lower incidence of hypothyroidism but a higher incidence of early post-treatment recurrence or persistence of hyperthyroidism, and a considerably lower incidence of remission.

Topics: Adult; Aged; Aged, 80 and over; Antithyroid Agents; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Recurrence; Retrospective Studies; Thyroid Hormones

Despite the increasing use of beta-blocking agents alone as preoperative treatment of patients with hyperthyroidism, there are no controlled clinical studies in which this regimen has been compared with a more conventional preoperative treatment. Thirty patients with newly diagnosed and untreated hyperthyroidism were randomized to preoperative treatment with methimazole in combination with thyroxine (Group I) or the beta 1-blocking agent metoprolol (Group II). Metoprolol was used since it has been demonstrated that the beneficial effect of beta-blockade in hyperthyroidism is mainly due to beta 1-blockade. The preoperative, intraoperative, and postoperative courses in the two groups were compared, and patients were followed up for 1 year after thyroidectomy. At the time of diagnosis, serum concentration of triiodothyronine (T3) was 6.1 +/- 0.59 nmol/L in Group I and 5.7 +/- 0.66 nmol/L in Group II (reference interval 1.5-3.0 nmol/L). Clinical improvement during preoperative treatment was similar in the two groups of patients, but serum T3 was normalized only in Group I. The median length of preoperative treatment was 12 weeks in Group I and 5 weeks in Group II (p less than 0.01). There were no serious adverse effects of the drugs during preoperative preparation in either treatment group. Operating time, consistency and vascularity of the thyroid gland, and intraoperative blood loss were similar in the two groups. No anesthesiologic or cardiovascular complications occurred during operation in either group. One patient in Group I (7%) and three patients in Group II (20%) had clinical signs of hyperthyroid function during the first postoperative day. These symptoms were abolished by the administration of small doses of metoprolol, and no case of thyroid storm occurred. Postoperative hypocalcemia or recurrent laryngeal nerve paralysis did not occur in either group. During the first postoperative year, hypothyroidism developed in two patients in Group I (13%) and in six patients in Group II (40%). No patient had recurrent hyperthyroidism. The results suggest that metoprolol can be used as sole preoperative treatment of patients with hyperthyroidism without serious intra- or postoperative complications. Although the data indicate that the risk of postoperative hypothyroidism is higher after preoperative treatment with metoprolol than with an antithyroid drug, a longer follow-up period than 1 year is needed to draw conclusions regarding late results.

Topics: Adult; Clinical Trials as Topic; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hyperthyroidism; Male; Methimazole; Metoprolol; Middle Aged; Preoperative Care; Prospective Studies; Random Allocation; Thyroidectomy; Thyroxine

The aim of this investigation was to compare the effects of a beta 1-selective adrenoceptor blocking agent and an antithyroid drug on urinary excretion of creatinine (Cr) and 3-methylhistidine (3-MH) and plasma concentrations of amino acids in hyperthyroid patients. beta-adrenoceptor blocking agents are increasingly used in the treatment of hyperthyroid patients, and the effects on clinical signs and symptoms mainly reflect beta 1-adrenoceptor blockade. The consequences of this treatment on metabolic alterations in hyperthyroidism are not fully known. In the present study, 30 hyperthyroid patients were randomized to preoperative treatment with the antithyroid drug methimazole + thyroxine (group I) or the beta 1-selective adrenoceptor blocking agent metoprolol (group II). Urinary excretion of Cr and 3-MH and plasma concentrations of amino acids were measured at the time of diagnosis, following preoperative treatment and 6 months postoperatively. Serum triiodothyronine (T3) was comparably elevated in the two groups of patients at the time of diagnosis and was normalized during preoperative treatment in group I but remained elevated during preoperative treatment in group II. Urinary excretion of creatinine was lower at the time of diagnosis than postoperatively, suggesting reduced muscle mass during hyperthyroidism. Urinary excretion of Cr increased during preoperative treatment in group I but was not significantly altered during treatment with metoprolol. The 3-MH/Cr ratio, which was higher at the time of diagnosis than postoperatively, indicating accelerated protein breakdown in skeletal muscle during hyperthyroidism, was reduced during preoperative treatment in group I but not in group II.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Amino Acids; Creatinine; Female; Humans; Hyperthyroidism; Male; Methimazole; Methylhistidines; Metoprolol; Middle Aged; Preoperative Care; Prospective Studies; Proteins; Random Allocation; Thyroxine; Triiodothyronine

Up to the present time lithium therapy is under discussion in patients with severe, particularly of contrast remedy induced hyperthyroidism. The aim of our presentation was to investigate if the short term combined methimazole-lithium therapy in the initial phase will be advantageous in contrast to the monotherapy of methimazole. The examination in our material showed a good effectiveness and tolerance of the combined therapy. At present the precise mechanism of action of lithium has not been elucidated. There is evidence that lithium inhibits the thyreoglobulin hydrolysis and the peripheral conversion of thyroxin to triiodothyronin. Other actions are under discussion. In our opinion only the combined methimazole-lithium therapy will be advantageous. Through this procedure an earlier drug effect could be expected and the increase of thyroid hormones after finishing lithium therapy will be suppressed. In the own material severe side effects are not demonstrable.

Topics: Contrast Media; Drug Therapy, Combination; Humans; Hyperthyroidism; Lithium; Lithium Carbonate; Methimazole; Thyroid Crisis; Thyroid Hormones

Twenty-five patients with newly diagnosed thyrotoxicosis participated in a double-blind study of the added effect of propranolol during tiamazol treatment. During the trial, the effect of treatment was ascertained by estimation at regular intervals of the clinical score (Crooks-Wayne index), free thyroxine index, serum triiodothyronine, serum reverse triiodothyronine, serum thyroglobulin and serum thyroglobulin antibodies. Both groups became euthyroid within two weeks. No statistically significant difference in the values for the clinical score or for any of the laboratory parameters measured was found between propranolol- and the placebo-treated patients. It is concluded that propranolol has no beneficial effect on tiamazol-treated hyperthyroid patients.

Topics: Adult; Aged; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Propranolol; Random Allocation; Thyroid Hormones

Even nowadays the therapy of severe, particularly of contrast remedy-induced hyperthyroidism is not without any problems. According to reports in literature the application of lithium salts seems to be an expedient from this dilemma. We controlled the effect of a short-term lithium therapy of 7 days in combination with methimazole in comparison to a group with methimazole monotherapy. The examination showed a good effectiveness and tolerability of the lithium methimazole therapy. While the decrease of the thyroxin concentration in the two groups was not different, in the group with combined therapy a more rapid per cent decrease of the triiodothyronine concentration appeared. In primarily strict selection of the therapy severe side-effects are not to be expected. According to the results yielded up to now the described form of therapy is an actual enrichment for selected forms of hyperthyreosis.

Topics: Adult; Aged; Drug Therapy, Combination; Female; Humans; Hyperthyroidism; Lithium; Male; Methimazole; Middle Aged; Thyroxine; Time Factors; Triiodothyronine

The examinations were performed on 3 groups of altogether 65 persons with thyreotoxicosis, the cause of which was either Basedow's disease or struma nodosa. The first group received metizol (thiamazol) in a daily dosage of 60 mg, the second group lithium carbonate (1.0 up to 1.5 g/a day), the third group metizol together with lithium carbonate. The groups were of the same value, concerning the degree of the symptoms of hyperthyroidism. The examinations showed that when lithium carbonate is used alone at the earliest a significant decrease of the serum T4 and T3 concentration as well as of the T3 binding index appears. After a treatment of seven days the therapeutic effects even up. Under the lithium therapy an essential improvement of the clinical findings was achieved. The combined therapy with lithium and metizol did not exhibit any advantages in this respect. The side-effects observed under the lithium therapy are no essential clinical problem.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Female; Humans; Hyperthyroidism; Lithium; Male; Methimazole; Middle Aged; Thyroxine; Time Factors; Triiodothyronine

Topics: Adolescent; Adult; Carbimazole; Clinical Trials as Topic; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Preoperative Care; Propranolol; Thyroidectomy

Of 24 patients with newly diagnosed thyrotoxicosis, 13 were randomly selected for treatment with methimazole 40 mg per day, and 11 for treatment with lithium carbonate in such doses that the serum lithium lay between 0-5 and 1-3 meq. per litre. The lithium treatment brought about a fall in serum-thyroxine iodine (T4I) of 27.0%, and in the free-thyroxine index (F.T.I.) of 38.1% after 10 days. A comparison of the two patient groups with regard to the fall in F.T.I. after 3 and 10 days showed no statistically significant difference; similarly the calculated confidence limits appeared to exclude any difference of clinical importance. 8 of the 11 patients subjected to lithium treatment had side-effects, so that the general condition, which was already affected by the hyperthyroidism, was worsened. It is concluded that lithium cannot be considered superior to thiocarbamides for the rapid control of thyrotoxicosis.

Topics: Clinical Trials as Topic; Drug Evaluation; Female; Humans; Hyperthyroidism; Iodine; Iodine Radioisotopes; Lithium; Male; Methimazole; Middle Aged; Thyroid Function Tests; 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

The accumulation of 131J in the thyroid gland was investigate in dynamics in 31 patients with thyrotoxicosis, treated with mercaptoimidazol (timidazol) for an average of 16 months. The patients were clinically euthyroid, with normal values of the basal metabolism, PBI, PBI131 AND TOTAL THYROXIN IN SERUM. The 131J captation, investigated in the course of a maintaining treatment without discontinuation of thyrostatics, show elevated percentages (55.4 per cent by the 6th hour, 61.3 per cent by the 24th hour), being within the norm only in eight patients. Its average values are significantly lower up to the 6th month post treatment discontinuation and closrm, with only 13 above the norm. Only three of them (10 per cent) developed recidivations till the end of the 9th month after e treatment. The authors concluded that thyrostatics, in maintaining doses, do not block thyroid gland 131J cumulation which in the majority of the cases persisted to be elevated a long time after the discontinuation. Its complete normalization in the later stages speak, most probably, for the development of a lasting remission of thyrotoxicosis.

Topics: Adult; Aged; Clinical Trials as Topic; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Hyperthyroidism; Hypnotics and Sedatives; Iodine; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propranolol; Remission, Spontaneous; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones; Time Factors

Topics: Adolescent; Adult; Birth Weight; Female; Fetal Death; Humans; Hyperthyroidism; Infant; Infant Mortality; Infant, Newborn; Infant, Premature; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Function Tests; Thyroid Hormones

Topics: Administration, Oral; Adolescent; Adult; Antithyroid Agents; Basal Metabolism; Dose-Response Relationship, Drug; Humans; Hyperthyroidism; Imidazoles; Iodine; Lead; Methimazole; Middle Aged; Radioisotopes; Thyroid Function Tests

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

Topics: Adolescent; Adult; Clinical Trials as Topic; Female; Growth Hormone; Humans; Hydrocortisone; Hyperthyroidism; Hypoglycemia; Insulin; Male; Methimazole; Thyroidectomy

Topics: Antithyroid Agents; Clinical Trials as Topic; Follow-Up Studies; Humans; Hyperthyroidism; Imidazoles; Iodine Radioisotopes; Methimazole; Prognosis; Propylthiouracil; Thyroid Function Tests; Triiodothyronine

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

Despite the requirement of routine blood tests during thiamazole treatment in Japan, granulocytopenia among patients treated with thiamazole has been occasionally reported to the Pharmaceuticals and Medical Devices Agency (PMDA). To characterize granulocytopenia in patients with thiamazole in Japan, the effects of routine blood tests were examined in a cohort of new users of thiamazole or propylthiouracil utilizing the MID-NET. The occurrence of granulocytopenia (neutrophil count ≤ 1,500/μL) in a given period was compared between patients with and without blood test results prior to the period. The trend in neutrophil count during thiamazole treatment was also compared between patients with and without granulocytopenia. A nested case-control study based on the cohort was conducted to identify potential risk factors for granulocytopenia during thiamazole treatment. In the new user cohort including 4,371 patients treated with thiamazole, the occurrence of granulocytopenia in patients who had undergone blood tests at all previous periods was similar or higher than that among those who had not undergone blood test in all previous periods (e.g., adjusted odds ratio in period 2 was 1.63). The neutrophil count was relatively lower in the group of patients with granulocytopenia even before the occurrence of granulocytopenia. In a nested case-control study, an upward tendency of the risk was observed when a patient was co-prescribed anti-arrhythmic drugs or antiulcer drugs with thiamazole. The characteristics of granulocytopenia during thiamazole treatment elucidated in this study should be recognized in clinical practice for the proper use of thiamazole.

Topics: Agranulocytosis; Antithyroid Agents; Case-Control Studies; Humans; Hyperthyroidism; Japan; Methimazole

Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as Drug-induced hypersensitivity syndrome (DiHS), is a severe adverse drug reaction. Propylthiouracil, a member of thiouracils group, is widely used in medical treatment of hyperthyroidism. Propylthiouracil is associated with multiple adverse effects such as rash, agranulocytosis hepatitis and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, but rarely triggers DRESS/DiHS syndrome. Here, we describe a severe case of propylthiouracil-induced DRESS/DiHS syndrome.. A 38-year-old female was treated with methimazole for hyperthyroidism at first. 4 weeks later, the patient developed elevated liver transaminase so methimazole was stopped. After liver function improved in 2 weeks, medication was switched to propylthiouracil therapy. The patient subsequently developed nausea and rash followed by a high fever, acute toxic hepatitis and multiple organ dysfunction (liver, lung and heart), which lasted for 1 month after propylthiouracil was started. According to the diagnostic criteria, the patient was diagnosed of DRESS/DiHS syndrome which was induced by propylthiouracil. As a result, propylthiouracil was immediately withdrawn. And patient was then treated with adalimumab, systematic corticosteroids and plasmapheresis in sequence. Symptoms were finally resolved 4 weeks later.. Propylthiouracil is a rare cause of the DRESS/DiHS syndrome, which typically consists of severe dermatitis and various degrees of internal organ involvement. We want to emphasize through this severe case that DRESS/DiHS syndrome should be promptly recognized to hasten recovery.

Topics: Adult; Drug Hypersensitivity Syndrome; Eosinophilia; Exanthema; Female; Humans; Hyperthyroidism; Methimazole; Propylthiouracil

Methimazole is the most commonly used medication for hyperthyroidism with good effects and little adverse reactions. However, improper selection of initial dose will affect the efficacy, such as excessive dose is proven to various adverse reactions; insufficient dose can hardly achieve desired efficacy. Based on the literature and personal clinical experience, the author discusses the following clinical issues related to methimazole in the treatment of hyperthyroidism, including the selection of initial dose, dose adjustment and withdrawal of methimazole, drug therapy for patients with liver function injury, and management strategies for methimazole-related adverse reactions.. 甲巯咪唑是治疗甲状腺功能亢进症（甲亢）最常用的药物，其效果良好，不良反应少。初始剂量选择不当将影响疗效，如剂量过大易发生各种不良反应；剂量过小，达不到预期疗效。本文笔者根据文献及个人临床经验，对甲巯咪唑治疗甲亢的以下临床问题进行探讨，包括甲巯咪唑的起始剂量选择、剂量调整和停药、伴肝功能损伤者药物治疗及甲巯咪唑相关不良反应的应对策略等。.

Topics: Antithyroid Agents; Humans; Hyperthyroidism; Methimazole

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; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; East Asian People; Female; Humans; Hyperthyroidism; Methimazole; Propylthiouracil

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

We present a case of a 43-year-old female patient diagnosed with hyperthyroidism. This study aims to demonstrate the rare association between hyperthyroidism and severe cholestatic jaundice, and the effectiveness of methimazole treatment.. The patient developed severe jaundice, a typically mild symptom in most hyperthyroidism cases.. The severe jaundice was suspected to be a result of cholestasis induced by hyperthyroidism, with other potential causes such as drug-induced or autoimmune liver dysfunction being ruled out.. The patient was effectively treated with methimazole. Outcomes: Treatment with methimazole alleviated the severe cholestatic jaundice and restored normal thyroid function.. The specific mechanism of cholestasis as a secondary complication of hyperthyroidism remains unclear, and there are no specific biochemical markers for cholestasis caused by this hormonal disease. This case underscores the possibility of severe jaundice as a clinical manifestation of hyperthyroidism, and highlights antithyroid drug treatment as an effective strategy for managing severe cholestatic jaundice.

Topics: Adult; Antithyroid Agents; Cholestasis; Female; Humans; Hyperthyroidism; Jaundice, Obstructive; Methimazole

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

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

To investigate the effects of levothyroxine combined with methimazole on the clinical efficacy of hyperthyroidism treatment. A total of 102 patients with hyperthyroidism admitted to our hospital from January 2018 to June 2020 were selected and randomly assigned into the combination group (levothyroxine combined with methimazole) and the control group (methimazole treatment alone). 3 months after treatment, the two groups were compared with regard to clinical efficacy, changes in ultrasound findings, the thyroid hormones, and serum indexes and the adverse reactions rate. The combination group (98.04%) outperformed the control group (86.27%) in total effective rate, and the overall efficacy garnered the similar result. After treatment, the combination group showed advantages in thyroid hormone level, serum index level, thyroid volume, superior thyroid artery diameter, and maximum blood flow rate when compared with those of the control group (P<0.05). As for the adverse reactions rate, the combination group was superior to the control group (3.92%vs15.69%) (P<0.05). Levothyroxine combined with methimazole promotes the clinical efficacy of hyperthyroidism treating, reduces thyroid volume and the diameter of superior thyroid artery, enhances the patient's thyroid function and serum index, with higher safety profile.

Topics: Adult; Aged; Antithyroid Agents; Drug Therapy, Combination; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Thyroxine; 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

Extragonadal choriocarcinoma is rare and can be associated with hyperthyroidism when producing very high levels of human chorionic gonadotropin.. Severe thyrotoxicosis can represent an unusual initial presentation of metastatic choriocarcinoma in the setting of extreme elevation of beta-human chorionic gonadotropin. Primary gastric choriocarcinoma is an aggressive malignancy with very poor outcomes. The co-occurrence of severe thyrotoxicosis with advanced primary gastric choriocarcinoma and imminent liver failure complicates management options.

Topics: Choriocarcinoma; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Female; Hepatomegaly; Humans; Hyperthyroidism; Liver Failure; Male; Methimazole; Middle Aged; Neoplasms, Germ Cell and Embryonal; Pregnancy; Stomach Neoplasms; Testicular Neoplasms; Thyrotoxicosis; Tomography, X-Ray Computed

The objective of this study was to evaluate the presence of traces of thiamazole in the urine of owners of hyperthyroid cats treated with antithyroid drugs.. Urine was collected from 24 owners of hyperthyroid cats, five human patients treated with thiamazole and five healthy humans without any contact with antithyroid drugs. All owners of hyperthyroid cats were asked to fill out a questionnaire. Urine of hyperthyroid cats was collected by spontaneous micturition. All urine samples were stored at -20°C until analysis by ultra-high-performance liquid chromatography coupled to high-resolution quadrupole Orbitrap mass spectrometry.. These owners were assessed to have a lot of contact with their cat. Adherence to antithyroid medication handling guidelines was rather poor. High concentrations of thiamazole were detected in all feline samples (median concentration 2818 ng/ml; range 104-15,127) and in the urine of all human patients treated with thiamazole (median concentration 4153 ng/ml; range 1826-5009). No thiamazole was detected in the urine of owners of hyperthyroid cats (limit of detection 3.88 ng/ml; limit of quantification 11.75 ng/ml).. The results regarding the potential exposure of owners of hyperthyroid cats to antithyroid drugs are reassuring. Nevertheless, prudence is still warranted when administering antithyroid drugs. Whether these results can be extrapolated to the use of transdermal application requires further investigation.

Topics: Administration, Cutaneous; Animals; Antithyroid Agents; Cat Diseases; Cats; Humans; Hyperthyroidism; Methimazole; Surveys and Questionnaires

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

Hyperthyroidism after total thyroidectomy is extremely rare. No studies have investigated hyperthyroidism during multiple kinase inhibitor treatment for advanced thyroid carcinoma.. A 57-year-old man with a history of radioactive iodine refracted thyroid follicular carcinoma presented to our hospital with back pain. Computed tomography (CT) showed a huge tumor at the left ilium and multiple metastases in the lung, liver, and bone. His serum thyroglobulin was 322,000 ng/mL and bone biopsy revealed thyroid carcinoma metastasis. After left iliac tumor decompression surgery, lenvatinib and denosumab treatment were initiated. Serum thyroglobulin decreased to 88,600 ng/mL, and no progression was observed on CT. Although thyrotropin (TSH) was suppressed at 125 µg of levothyroxine sodium, serum free T3 started to increase at 70 weeks after lenvatinib initiation. Levothyroxine sodium was gradually reduced to 25 µg. At 83 weeks after initiation, the patient was hospitalized due to nausea, diarrhea, and anorexia. Serum free T3 increased to 13.98 pg/mL, whereas CT showed progression of lung and liver metastasis. Given the patient's positivity for anti-thyrotropin receptor antibody (TRAb), levothyroxine sodium and lenvatinib were discontinued and methimazole was administered at the dose of 15 mg/day. Lenvatinib was restarted after 2 weeks withdrawal. Methimazole was gradually reduced to 5 mg/day as thyroid function normalized. However, CT showed pleural effusion and enlargement of the lung, liver, and adrenal metastases. The patient died at 100 weeks after lenvatinib initiation due to disease progression.. The patient developed Graves' disease after lenvatinib treatment for radioactive iodine refracted thyroid follicular carcinoma. Persistent TSH stimulation caused by TRAb can be involved in tumor growth and thyroid hormone secretion from metastases.

Topics: Carcinoma; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Thyroglobulin; Thyroid Neoplasms; Thyrotropin; 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

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

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

To investigate the incidence rate of adverse reactions of methimazole in children with hyperthyroidism.. A retrospective analysis was performed on the medical data of 304 children with hyperthyroidism who were hospitalized in Shengjing Hospital of China Medical University from January 2015 to May 2021. The incidence rate of methimazole-related adverse reactions was analyzed. The risk factors for common adverse reactions were evaluated.. Among the 304 children, 87 (28.6%) experienced adverse reactions, among whom there were 20 boys (23%) and 67 girls (77%). Common adverse reactions included neutropenia (12.8%), rash (11.8%), elevated alanine aminotransferase (9.5%), and joint pain (3.0%), and some children experienced multiple adverse reactions simultaneously or intermittently. Neutropenia often occurred within 3 months after administration (25/39, 64%), elevated alanine aminotransferase often occurred within 1 month after administration (17/29, 59%), and rash often occurred within 3 months after administration (30/36, 83%). Most of the above adverse reactions returned to normal after symptomatic treatment. The multivariate logistic regression analysis showed that younger age and lower absolute neutrophil count before treatment were risk factors for neutropenia after methimazole treatment (. The adverse reactions of methimazole are common in children with hyperthyroidism, and most adverse reactions occur within 3 months after administration and can be relieved after symptomatic treatment. Children with a younger age or a lower baseline absolute neutrophil count may have a higher risk of neutropenia.

Topics: Alanine Transaminase; Antithyroid Agents; Child; Exanthema; Female; Humans; Hyperthyroidism; Male; Methimazole; Neutropenia; Retrospective Studies

Here, we reported two cases with hyperthyroidism who complained of myalgia and muscle cramps during treatment with methimazole tablets (or Thyrozol, the brand name). One case experienced muscle cramps after taking Thyrozol for 6 months, and by this time the patient's thyroid function had returned to normal. In the other case, pain caused by muscular cramps began after the patient took Thyrozol for two weeks and the patient's thyroid function had not returned to normal yet at the time. In both cases, pain caused by muscle cramps appeared while the patients were taking Thyrozol. The myalgia persisted in spite of a reduction in the Thyrozol dose, but was significantly relieved with the discontinuation of Thyrozol. Myalgia and muscle cramps did not recur after the patients were switched to methimazole ointment. There was a strong temporal association between oral administration of Thyrozol and pain caused by muscle cramps, which may indicate that myalgia and muscle cramps are adverse reactions of Thyrozol. Looking into the relevant literature on the topic, we explored in this report the possible mechanisms of the onset of muscle cramps associated with Thyrozol, and compared the adverse reactions of two different formulations of methimazole, intending to provide more clinical experience for the treatment of hyperthyroidism and the management of rare adverse reactions related to antithyroid drugs.

Topics: Humans; Hyperthyroidism; Methimazole; Muscle Cramp; Myalgia; Tablets

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

To clarify the actual administration of thiamazole (MMI), the first choice of antithyroid drugs, the actual therapy provided by the Japan Thyroid Association (JTA) members for the following conditions was surveyed. The subjects included adult patients, pregnant women, and pediatric patients with Graves' disease who visited each medical institution from September 2019 to February 2020. Initial doses, frequency of administration, maintenance doses, maximum doses, consultation intervals for pregnant women, and dosages administrated to breastfeeding mothers were surveyed. The total number of cases collected was 11,663. Administration of 15 mg once a day was the most common initial therapy, constituted 74.4% (2,526/3,397 cases) of adults, 33.8% (44/130) of pregnant women, and 50.8% (61/120) of children. The maintenance dose before discontinuation was equivalent to 2.5 mg/day in 52.3% (3,147/6,015). The most common maximum dose for adults and children was 30 mg/day, administrated to 57.5% of adults (223/388) and 59.6% (28/47) of children; for pregnant women, it was 15 mg/day, administrated to 71.1% (27/38). The most common consultation interval for pregnant women was every four weeks (32.1%, 341/1,063). In lactating mothers, the dose was 10 mg/day or less in 366 of 465 cases (78.7%). Breastfeeding was also allowed 4-6 hours after the administration of 15-20 mg/day in 69 patients (14.8%). Breastfeeding was prohibited in 26 patients (5.6%). In conclusion, initial MMI therapy was started with 15 mg once a day in most patients, and MMI was also administrated to lactating mothers following the Graves' disease treatment guidelines by the JTA.

Topics: Adult; Antithyroid Agents; Child; Female; Humans; Hyperthyroidism; Japan; Lactation; Methimazole; Pregnancy

Topics: Abdominal Pain; Antithyroid Agents; Ascites; Atrial Fibrillation; Diagnosis, Differential; Echocardiography, Transesophageal; Electrocardiography; Female; Heart Failure; Humans; Hyperthyroidism; Magnetic Resonance Imaging, Cine; Medication Adherence; Methimazole; Metoprolol; Middle Aged; Paracentesis; Thyroid Function Tests

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

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

Összefoglaló. Bevezetés: A tudományos szakirodalomban számos kérdés fogalmazódik meg a pajzsmirigybetegségeket befolyásoló pszichológiai tényezőkről. Kevés tanulmány készült a pajzsmirigybetegségek és a megküzdési stratégiák kapcsolatáról. Célkitűzés: Jelen tanulmányunk célja felmérni a megküzdési stratégiák, a depresszió és a szorongás szintjének változásait a pajzsmirigybetegek (hyperthyreosis és hypothyreosis) esetében a gyógyszeres kezelés (Thyrozol és Euthyrox) hatására. Módszer: A betegeket a szakorvos diagnózisa, illetve a TSH- és fT4-szint alapján hyperthyreosis- (n = 10) és hypothyreosis- (n = 21) csoportba soroltuk. Mindkét csoport tagjait az endokrinológiai kezelés előtt és után pszichológiai felmérésnek vetettük alá. A felmérés során a megküzdési stratégiák felméréséhez a következő skálákat alkalmaztuk: Kognitív Érzelem Szabályozás Kérdőív (Cognitive Emotion Regulation Questionnaire - CERQ), Hobfoll-féle Megküzdési Stratégia Kérdőív (Strategic Approach to Coping Scale - SACS). A Beck Depresszió Kérdőívet (Beck Depression Inventory - BDI-II) alkalmaztuk a depresszió felmérésére, az Állapot- és Vonásszorongás Kérdőívet (State-Trait Anxiety Inventory, Form Y - STAI-Y) a szorongás szintjének felmérésére. Eredmények: A két csoport pszichológiai és laboreredményeit összehasonlítottuk a gyógyszeres kezelés előtt és után. Mind a hyperthyreosisban, mind a hypothyreosisban szenvedő betegeknél magas volt a depresszió és a szorongás szintje. A hyperthyreosisban szenvedő betegeknél a depresszió magasabb. A gyógyszeres kezelés után a depresszió és a szorongás szintje csökkent mindkét csoportban, a megküzdési stratégiák többnyire változatlanok maradtak. Következtetések: Pajzsmirigybetegeknél a kognitív viselkedésbeli pszichoterápiás beavatkozás a gyógyszeres kezelés kiegészítő alternatívája lehet a szorongás és a depresszió szintjének csökkentése és a diszfunkcionális megküzdési stratégiák módosítása szempontjából. Orv Hetil. 2021; 162(7): 262-268.. There is a high interest in the scientific literature in psychological factors that influence the course of thyroid disease. There are a few studies on the link between thyroid disease and coping strategies.. In the present study, we aimed to evaluate the manifestation of depression, anxiety and coping strategies in people with thyroid disease and the impact of endocrinological medication on these psychologic items.. The patients were grouped into two groups, hyperthyroid (n = 10) and hypothyroid (n = 21), according to the diagnosis established by the attending physician, TSH and fT4 level. Patients with hyperthyroidism and hypothyroidism were evaluated before and after endocrinological treatment with the Cognitive Emotion Regulation Questionnaire (CERQ), Strategic Approach to Coping Scale (SACS) for the evaluation of coping strategies, Beck Depression Inventory (BDI-II) for assessing the level of depression, State-Trait Anxiety Inventory, Form Y (STAI-Y) for assessing anxiety. These two groups have been compared.. The psychological and laboratory results of the two groups were compared before and after drug treatment. Both patients with hyperthyroidism and with hypothyroidism had high levels of depression and anxiety. In hyperthyroidism, depression is more severe. Following treatment with Thyrozol and Euthyrox, the level of depression and anxiety decreases in patients with hyper- and hypothyroidism; the coping strategies remained almost unchanged.. Cognitive-behavioral psychotherapeutic intervention could be supplementary to drug treatment in terms of reducing anxiety, depression, and modifying dysfunctional coping strategies for patients with thyroid diseases. Orv Hetil. 2021; 162(7): 262-268.

Topics: Adaptation, Psychological; Antithyroid Agents; Anxiety; Depression; Humans; Hyperthyroidism; Hypothyroidism; Methimazole; Thyroid Diseases; Thyroxine

Thionamides (methimazole and propylthiouracil) have been associated with common side effects, such as rash and pruritus, and rare but serious adverse effects, such as agranulocytosis and hepatotoxicity. Methimazole is usually the preferred thionamide for the treatment of hyperthyroidism if the patient is not planning to conceive or not in the first trimester of pregnancy, given the less frequent dosing and lower risk of hepatotoxicity. In patients who experience rash or itching when treated with methimazole, switching them to propylthiouracil is one treatment option. Here we report our experience regarding desensitization to methimazole to allow continued treatment with methimazole as an alternative management option.. We conducted a retrospective chart review of patients at a single institution who had side effects to methimazole and who were desensitized to methimazole under the supervision of an allergist. A total of 7 patients were included who experienced side effects to methimazole that did not include agranulocytosis or hepatotoxicity.. All 7 patients were able to take methimazole for treatment of their hyperthyroidism, either for continued medical therapy or as a bridge to definitive therapy, with either surgery or radioactive iodine treatment.. Under the supervision of an allergist, desensitization to methimazole is an option for treating patients who experience side effects to methimazole (excluding agranulocytosis and hepatotoxicity).

Topics: Antithyroid Agents; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Pregnancy; Propylthiouracil; Retrospective Studies; Thyroid Neoplasms

Methimazole (MMI) is the treatment of choice for patients with Graves' disease. The major drawback of this treatment is the relapse of hyperthyroidism in half of the patients after discontinuation of the recommended conventional 12-18 months of MMI treatment. TSH receptor antibody (TRAb) concentration is recognized as the strongest predictor of hyperthyroidism relapse. In this case report, efficacy of low-dose MMI to control hyperthyroidism even after multiple recurrences in the setting of normal TRAb concentrations is shown.. An 80-year-old Iranian woman with Graves' disease was treated with MMI for 31 years. While receiving treatment, she always had a normal serum TRAb concentration; however, three times during the 31 years she decided to stop MMI therapy, and each time the disease recurred 16-21 months after MMI withdrawal. It is noteworthy that she maintained euthyroidism with the low-dose 1.25-2.5 mg MMI daily without any adverse events during three decades of treatment.. Normal serum TRAb is not a sufficiently strong marker to predict relapse of Graves' hyperthyroidism. Long-term therapy with low-dose MMI is an effective and safe treatment to sustain euthyroidism.

Topics: Aged, 80 and over; Antithyroid Agents; Female; Humans; Hyperthyroidism; Iran; Methimazole; Recurrence

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

Hyperthyroidism is a common disease mainly manifested by hyperexcitability of multiple systems and hypermetabolism. Currently, antithyroid drugs (ATDs), radioiodine therapy (RIT), and surgery are mainly used in the clinical treatment for primary hyperthyroidism. We reported a case of a 28-year-old female who received a novel treatment for primary hyperthyroidism. This patient had poor control of thyroid function while taking ATD, and her oral Methimazole (MMI) dose varied repeatedly between 20 mg qd and 15 mg qd, failing to maintain a stable status. To minimize the possible complication and to achieve drug reduction or withdrawal, she refused RIT and surgery and showed up in our department. The patient, diagnosed with Graves' disease (GD) and met the surgical indication after systematic clinical evaluation, was subject to ultrasound-guided percutaneous microwave ablation (MWA) of the partial thyroid gland with continuous oral administration of 20 mg qd MMI. The post-ablation condition was stable and the patient was discharged 2 days after the operation. Thyroid ultrasound and serum thyroid function test were examined regularly after ablation and the MMI dosage was gradually reduced according to the results of the biochemical examination. Five weeks after the operation, the patient completely discontinued the medication. Ultrasound-guided percutaneous microwave ablation is minimally invasive, safe, and effective, and has potential to be an alternative treatment besides the 3 classical treatments of hyperthyroidism.

Topics: Adult; Antithyroid Agents; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Microwaves; Treatment Outcome

The aim of this study was to evaluate the efficiency and safety of methimazole (MMI) and propylthiouracil (PTU) in the treatment of hyperthyroidism.. Articles were searched through the PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang, and QVIP. The primary outcomes were clinical efficacy and thyroid hormone levels in MMI and PTU groups. The secondary outcomes were liver function indexes and adverse reactions in MMI and PTU groups. Results were expressed as weighted mean difference (WMD) or odds ratio (OR) with 95% confidence intervals (CIs). The Begg test was applied to assess the publication bias.. Totally, 16 randomized controlled trials were retained in this meta-analysis with 973 patients receiving MMI and 933 receiving PTU. The levels of triiodothyronine (T3) (WMD = -1.321, 95% CI: -2.271 to -0.372, P = .006), thyroxine (T4) (WMD = -37.311, 95% CI: -61.012 to -13.610, P = .002), Free T3 (FT3) (WMD = -1.388, 95% CI: -2.543 to -0.233, P = .019), Free T4 (FT4) (WMD = -3.613, 95% CI: -5.972 to -1.255, P = .003), and the risk of liver function damage (OR = 0.208, 95% CI: 0.146-0.296, P < .001) in the MMI group were lower than those in the PTU group. The thyroid-stimulating hormone level (WMD = 0.787, 95% CI: 0.380-1.194, P < .001) and the risk of hypothyroidism (OR = 2.738, 95% CI: 1.444-5.193, P = .002) were higher in the MMI group than those in the PTU group.. Although MMI might have higher risk of hypothyroidism than PTU, the efficacy of MMI may be better than PTU in patients with hyperthyroidism regarding reducing T3, T4, FT3, and FT4 levels, decreasing the risk of liver function damage and increasing the level of thyroid-stimulating hormone.. osf.io/ds637 (https://osf.io/search/).

Topics: Antithyroid Agents; Humans; Hyperthyroidism; Methimazole; Propylthiouracil; Randomized Controlled Trials as Topic

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

Topics: Antithyroid Agents; Critical Illness; Humans; Hyperthyroidism; Methimazole

Topics: Adult; Alkaline Phosphatase; Antithyroid Agents; Body Mass Index; Bone Density; Calcium; Drug Administration Schedule; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Parathyroid Hormone; Phosphates; Thyroid Gland; Vitamin D; Vitamin D Deficiency

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

Topics: Adult; Aged; Antithyroid Agents; Carbimazole; Case-Control Studies; Comorbidity; Databases, Factual; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Multivariate Analysis; Odds Ratio; Pancreatitis; Pharmacovigilance; Propylthiouracil; Retrospective Studies; Risk; Taiwan; Thioamides

Agranulocytosis is a rare but very serious complication of thyrostatic therapy. In severe hyperthyroidism, the removal of circulating thyroid hormones by plasmapheresis may be an effective therapeutic option. This report describes the therapeutic difficulties and successful preoperative treatment with plasmapheresis in a 63-year-old patient admitted to the Endocrinology Clinic with severe hyperthyroidism, during the course of giant toxic nodular goiter and agranulocytosis, which occurred after 2 weeks of taking methimazole. During hospitalization, methimazole treatment was discontinued and therapy with steroids, a beta blocker, propylthiouracil, Lugol's solution, lithium carbonate, and antibiotics were initiated. Granulocyte colony growth stimulating factor was also used to resolve agranulocytosis. Due to the failure to achieve euthyreosis using this approach, we decided to conduct thyroid surgery, as a life-saving action, after preparation of the patient by plasmapheresis. Two plasmapheresis procedures were performed, resulting in a decrease in the concentration of free thyroid hormones. Total thyroidectomy was performed and there were no complications during surgery. We conclude that plasmapheresis may be considered as an effective alternative treatment option for the preparation of patients with hyperthyroidism for surgery, when the clinical situations prevent the use of conventional treatments for hyperthyroidism and when immediate life-saving surgery is necessary.

Topics: Agranulocytosis; Antithyroid Agents; Electrocardiography; Female; Goiter, Nodular; Humans; Hyperthyroidism; Methimazole; Middle Aged; Plasmapheresis; Preoperative Care; Thyroidectomy; Treatment Outcome

A warning has been recently issued by the European Medicine Agency (EMA) regarding a potential increased risk of acute pancreatitis (AP) in methimazole (MMI) users.. To investigate the association between MMI and the diagnosis of AP in a population-based study.. A retrospective analysis of administrative health databases was conducted (2013-2018). Relevant data were obtained from: (1) inhabitants registry, (2) hospital discharge records (ICD-9-CM 577.0), and (3) drug claims registry (ATC H03BB02). We evaluated AP risk in MMI users in 18 months of treatment, stratifying results by trimester. Poisson regression was used to estimate the age- and sex-adjusted rate ratios (RR), and the relative 95% confidence intervals (CI), comparing rates of AP between MMI users and nonusers. The absolute risk of AP in MMI users was also calculated.. A total of 23 087 new users of MMI were identified. Among them, 61 hospitalizations occurred during the study period. An increase in AP risk was evident during the first 3 trimesters of therapy (RR 3.40 [95% CI: 2.12-5.48]; RR 2.40 [95% CI: 1.36-4.23]; RR 2.80 [95% CI: 1.66-4.73]), but disappeared thereafter. The AP absolute risk in MMI users during the first 18 months of treatment was less than 0.4% in all sex and age classes.. Our results support the EMA warning, suggesting an increased risk of AP associated with MMI use. However, such an increase seems limited to the first months of MMI treatment. Moreover, in absolute terms, the probability of AP is low among patients, well below 1%.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antithyroid Agents; Cohort Studies; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Pancreatitis; Retrospective Studies; Risk Factors; Young Adult

BACKGROUND Methimazole embryopathy is caused by maternal methimazole intake during early pregnancy. It causes fetal malformations such as choanal atresia, esophageal atresia, aplasia cutis, omphalomesenteric duct remnants, urachal remnants, and omphalocele. Gallbladder agenesis is sometimes complicated with other malformations, but there have been no reports of gallbladder agenesis due to methimazole or concomitant methimazole embryopathy with gallbladder agenesis. CASE REPORT The mother of a male neonate had taken methimazole for hyperthyroidism until pregnancy was recognized at 7 weeks of gestation. Ultrasonography at 12 weeks and 4 days of gestation showed the fetus had a cystic lesion in the umbilical region. The child was born at the gestational age of 38 weeks and 5 days. At birth there was omphalocele, omphalomesenteric fistula, and a scalp defect, and the child was diagnosed with methimazole embryopathy. Ultrasonography could not identify the gallbladder. Emergency surgery was performed for omphalocele with omphalomesenteric fistula on day 0. The intestine, including the omphalomesenteric fistula, was resected. Postoperative blood testing revealed hypothyroidism, so the patient was administered levothyroxine. Although MRI did not detect the gallbladder, it showed dilatation of the biliary duct. Hypothyroidism was well controlled by levothyroxine, so the patient was discharged with outpatient follow-up for the gallbladder agenesis. Six months later, the patient is asymptomatic. CONCLUSIONS Concomitant gallbladder agenesis with methimazole embryopathy has not been previously reported. In the case of a dilated common bile duct, even when asymptomatic in the neonatal period, gallbladder agenesis demands long-term follow-up because of possible manifestation of choledocholithiasis or biliary malignant tumors.

Topics: Antithyroid Agents; Child; Female; Fetal Diseases; Gallbladder; Humans; Hyperthyroidism; Infant; Infant, Newborn; Male; Methimazole; Pregnancy

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

Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Drug Administration Schedule; Female; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil

Zinc-α2-glycoprotein (ZAG) is a recently novel lipolytic adipokine implicated in regulation of glucose and lipid metabolism in many metabolic disorders. In vitro and animal studies suggest that thyroid hormones (TH) up-regulates ZAG production in hepatocytes. However, there is no data evaluating the possible relationship between ZAG and TH in a human model of hyperthyroidism. The objective of the present study is to assess the association of serum ZAG levels with TH and lipid profile in patients with hyperthyroidism before and after methimazole treatment.. A total of 120 newly diagnosed overt hyperthyroidism and 122 healthy control subjects were recruited. Of them, 39 hyperthyroidism patients were assigned to receive methimazole treatment as follow-up study for 2 months.. The clinical consequence showed that serum ZAG levels were elevated in patients with hyperthyroidism (P < 0.01). Adjust for age, gender and BMI, serum ZAG levels were positively related with serum free T3 (FT3), free T4 (FT4) levels and negatively correlated with serum total cholesterol (TC), low density lipoprotein cholesterol (LDLC) levels in hyperthyroidism subjects (all P < 0.01). After methimazole treatment, serum ZAG levels were decreased and the decline was associated with decreased FT3, FT4 and increased TC levels (all P < 0.001).. We conclude that ZAG may be involved in the pathogenesis of lipid metabolism disorder in patients with hyperthyroidism.. ChiCTR-ROC-17012943 . Registered 11 October 2017, retrospectively registered.

Topics: Adult; Antithyroid Agents; Biomarkers; Female; Follow-Up Studies; Humans; Hyperthyroidism; Male; Methimazole; Prognosis; Prospective Studies; Seminal Plasma Proteins; Thyroid Hormones; Zn-Alpha-2-Glycoprotein

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: Administration, Cutaneous; Adult; Betamethasone; Biopsy; Drug Therapy, Combination; Humans; Hyperthyroidism; Leg Dermatoses; Male; Methimazole; Myxedema; Occlusive Dressings; Propranolol; Skin; Treatment Outcome

Objectives The aim of this study was to evaluate changes in circulating insulin-like growth factor type 1 (IGF-1) concentrations in hyperthyroid cats, before and after thiamazole treatment. Methods Thirty-four hyperthyroid cats were retrospectively included. Plasma free thyroxine (fT4) and IGF-1 concentrations were measured at diagnosis and 3 months after initiating antithyroid drug therapy. Results Median fT4 significantly decreased ( P <0.001) after treatment (from 78 pmol/l [range 43-122 pmol/l] to 31 pmol/l [range below assay limit of detection to 88 pmol/l]), whereas IGF-1 values significantly increased ( P <0.001) after treatment (from 117 ng/ml [33-341 ng/ml] to 221 ng/ml [36-865 ng/ml]). fT4 and IGF-1 concentrations were significantly negatively correlated both at diagnosis (r = -0.43, P = 0.01) and after treatment (r = -0.51, P = 0.002). Conclusions and relevance In cats, IGF-1 concentrations appear to be inversely proportional to the severity of hyperthyroidism and significantly increase after treatment with thiamazole.

Topics: Animals; Antithyroid Agents; Cat Diseases; Cats; Female; Hyperthyroidism; Insulin-Like Growth Factor I; Male; Methimazole

Topics: Agranulocytosis; Anti-Bacterial Agents; Antithyroid Agents; Drug Substitution; Emergencies; Female; Humans; Hyperthyroidism; Lung Abscess; Methimazole; Middle Aged; Propylthiouracil; Tomography, X-Ray Computed

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

The purinergic system has an important role in the regulation of vascular functions. The interference of thyroid hormones in this system and in cardiovascular events has been studied in recent years. However, the mechanisms involved in vascular, purinergic, and oxidative changes in thyroid disorders are not completely understood. Therefore, the present study aimed to assess purinergic enzyme activity in platelets from rats with hypothyroidism and hyperthyroidism induced, respectively, by continuous exposure to methimazole (MMI) at 20 mg/100 mL or L-thyroxine at 1.2 mg/100 mL in drinking water for 1 month. Results showed that rats exposed to L-thyroxine had a significant decrease in NTPDase activity, wherein ATP hydrolysis was 53% lower and ADP hydrolysis was 40% lower. Moreover, ecto-5'-nucleotidase activity was decreased in both groups, by 39% in the hypothyroidism group and by 52% in the hyperthyroidism group. On the other hand, adenosine deaminase (ADA) activity was increased in hyperthyroidism (75%), and nucleotide pyrophosphatase/phosphodiesterase (NPP) activity was increased in animals with hypothyroidism (127%) and those with hyperthyroidism (128%). Our findings suggest that changes in purinergic enzyme and purine levels could contribute to the undesirable effects of thyroid disturbances. Moreover, oxidative stress and, in particular, a high level of ROS production, showed a causal relation with changes in ectonucleotidase activity and nucleotide and nucleoside levels.

Topics: 5'-Nucleotidase; Adenosine Deaminase; Adenosine Triphosphate; Animals; Antigens, CD; Apyrase; Blood Platelets; Hydrolysis; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Nucleotides; Oxidative Stress; Rats; Rats, Wistar

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

Amiodarone-induced hyperthyroidism is a known side effect of amiodarone treatment. In the pediatric population, long-term amiodarone treatment is rarely indicated because of its severe side effects including thyroid function impairment. Treatment is therefore restricted to therapy-resistant arrhythmias. In the literature, scarce data are available on the management and therapy of amiodarone-induced thyroid dysfunction at a young age. We present three adolescent patients developing amiodarone-induced thyrotoxicosis in the months after amiodarone therapy. A latency period for thyroid dysfunction has been described in adulthood but was not previously reported in pediatric patients. The gap between amiodarone treatment and the development of symptoms and the diagnosis of hyperthyroidism was between 3 and 10 months. In two patients, hyperthyroidism was transient and resolved without treatment. These two patients, one boy and on girl, were almost asymptomatic. In contrast, in one male patient overt and severe hyperthyroidism developed. We began treatment with thiamazole without benefit. Control of hyperthyroidism was achieved under prednisone treatment, which was continued for 9 months. Clinical evaluation proved an amiodarone-induced destructive thyroiditis in this patient. Amiodarone-induced thyroid dysfunction is frequent also in pediatric patients with long-term amiodarone treatment. Patients and clinicians should be aware of the impact of amiodarone on thyroid function during and also in the months and maybe years after treatment. Careful follow-up is needed, as symptoms might be associated with the underlying cardiac disease in these patients. Amiodarone-induced thyrotoxicosis often resolves without treatment but can be challenging in some cases.

Topics: Adolescent; Amiodarone; Anti-Arrhythmia Agents; Antithyroid Agents; Arrhythmias, Cardiac; Female; Glucocorticoids; Humans; Hyperthyroidism; Male; Methimazole; Prednisolone; Thyroid Function Tests; Thyroid Gland

Topics: Antithyroid Agents; Coronary Vasospasm; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; ST Elevation Myocardial Infarction

Topics: Administration, Intravenous; Adult; Antithyroid Agents; Brain; Female; Humans; Hyperemesis Gravidarum; Hyperthyroidism; Magnetic Resonance Imaging; Methimazole; Pregnancy; Thiamine; Thiamine Deficiency; Vitamin B Complex; Wernicke Encephalopathy

Methimazole is an antithyroid drug that is widely used for the treatment of hyperthyroidism. As an inhibitor of the enzyme thyroperoxidase, methimazole is generally well-tolerated. However, there have been increasing reports of methimazole-induced liver damage, although this effect of methimazole has been limited by the absence of objective diagnosis of the liver condition or the inappropriate use of the Naranjo scale. We present the case of an elderly man with hyperthyroidism, gastritis, and epilepsy who developed liver damage after administration of multiple drugs.. Considering the low sensitivity of the Naranjo scale in detecting rare reactions associated with liver damage, we used the Roussel-Uclaf Causality Assessment Method scale, with a finding of cholestatic jaundice hepatitis induced by methimazole. The patient's liver enzyme levels improved after discontinuation of methimazole.. Our case underlines the possible hepatoxicity associated with the use of methimazole. A review of the literature confirmed a selective hepatoxicity risk in individuals of Asian ethnicity, which has not been identified in Caucasian or Black populations. Physicians should be aware of the risk of hepatoxicity when prescribing oral methimazole to patients of Asian ethnicity.

Topics: Aged; Antithyroid Agents; Asian People; Chemical and Drug Induced Liver Injury; Humans; Hyperthyroidism; Jaundice, Obstructive; Liver Function Tests; Male; Methimazole

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

Insufficient or excessive thyroid hormone (TH) levels during fetal development can cause long-term neurological and cognitive problems. Studies in animal models of perinatal hypo- and hyperthyroidism suggest that these problems may be a consequence of the formation of maladaptive circuitry in the cerebral cortex, which can persist into adulthood. Here we used mouse models of maternal hypo- and hyperthyroidism to investigate the long-term effects of altering thyroxine (T4) levels during pregnancy (corresponding to embryonic days 6.5-18.5) on thalamocortical (TC) axon dynamics in adult offspring. Because perinatal hypothyroidism has been linked to visual processing deficits in humans, we performed chronic two-photon imaging of TC axons and boutons in primary visual cortex (V1). We found that a decrease or increase in maternal serum T4 levels was associated with atypical steady-state dynamics of TC axons and boutons in V1 of adult offspring. Hypothyroid offspring exhibited axonal branch and bouton dynamics indicative of an abnormal increase in TC connectivity, whereas changes in hyperthyroid offspring were indicative of an abnormal decrease in TC connectivity. Collectively, our data suggest that alterations to prenatal T4 levels can cause long-term synaptic instability in TC circuits, which could impair early stages of visual processing.

Topics: Adult; Animals; Animals, Newborn; Antithyroid Agents; Brain Mapping; Disease Models, Animal; Female; Gestational Age; Green Fluorescent Proteins; Humans; Hyperthyroidism; Hypothyroidism; Image Processing, Computer-Assisted; Male; Methimazole; Mice; Mice, Inbred C57BL; Neuroimaging; Pregnancy; Prenatal Exposure Delayed Effects; Synapses; Synapsins; Thalamus; Thyroxine; Time Factors; Transduction, Genetic; Visual Cortex

Topics: Adult; Antibodies, Heterophile; Antithyroid Agents; Biomarkers; Biotin; False Positive Reactions; Humans; Hyperthyroidism; Immunoassay; Male; Methimazole; Thyrotropin; Thyroxine

Hyperthyroidism is the most common feline endocrinopathy; thyroid computed tomography (CT) may improve disease detection and methimazole dose selection. Objectives of this experimental pre-post with historical case-control study were to perform thyroid CT imaging in awake or mildly sedated hyperthyroid cats, compare thyroid gland CT appearance in euthyroid and hyperthyroid cats pre- and postmethimazole treatment, and determine whether thyroid size or attenuation correlate with methimazole dose needed for euthyroidism. Premethimazole treatment, eight hyperthyroid cats received CT scans from the head to heart, which were compared to CT of seven euthyroid cats. Total thyroxine levels were monitored every 3-4 weeks. Postmethimazole CT was performed 30 days after achieving euthyroid status. Computed tomography parameters recorded included thyroid length, width, height, attenuation, and heterogeneity. Median time between CT was 70 days (53-213 days). Mild sedation was needed in five hyperthyroid cats premethimazole, and none postmethimazole. Thyroid volume was significantly larger in hyperthyroid cats compared to euthyroid cats (785.0 mm

Topics: Animals; Antithyroid Agents; Case-Control Studies; Cat Diseases; Cats; Female; Hyperthyroidism; Male; Methimazole; Tomography, X-Ray Computed

Topics: Abortion, Therapeutic; Adult; Antithyroid Agents; Cardiopulmonary Resuscitation; Female; Heart Arrest; Humans; Hyperemesis Gravidarum; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Thyrotoxicosis; Thyrotropin; Thyroxine; Triiodothyronine; Ventricular Fibrillation

Dome-and-dart T waves (or bifid T waves) are a rare phenomenon in the surface electrocardiogram. These wave forms are mainly observed in patients with congenital heart disease such as atrial septal defect and ventricular septal defect. And hyperthyroidism who presented with an electrocardiogram that had dome-and-dart T waves in a precordial lead is never been reported.. The patient presented with continuous tachycardia, palpitations, chest tightness, and headache for 4 days, and aggravated for 1 day.. Hyperthyroidism.. Methimazole.. All symptoms were alleviated.. Dome-and-dart or bifid T waves have been reported in the conventional 12-lead electrocardiograms in some patients with congenital heart disease. The case illustrated here, to the best of our knowledge, dome-and-dart or bifid T waves may associate with hyperthyroidism patients.

Topics: Adolescent; Antithyroid Agents; Arrhythmias, Cardiac; Electrocardiography; Humans; Hyperthyroidism; Male; Methimazole

A 22-year-old woman presented to the emergency department (ED) with a 24-hour history of nausea, vomiting, diarrhea, generalized abdominal pain, and mild headache. She denied shortness of breath, chest pain, or anxiety, and didn't have a history of cardiac problems. The physical examination revealed tachycardia (heart rate, 135 beats/min) and a respiratory rate of 24 breaths per minute.

Topics: Adult; Antithyroid Agents; Atenolol; Female; Humans; Hyperthyroidism; Methimazole; Nausea; Pulmonary Edema; Tachycardia; Treatment Outcome; Vomiting; Weight Loss; Young Adult

Antithyroid arthritis syndrome is a constellation of symptoms of myalgia, arthralgia, arthritis, fever and rash associated with the use of antithyroid medications. We report a case of a patient with severe hyperthyroidism likely secondary to Graves' disease who presented with the abovementioned symptoms after being treated with methimazole (antithyroid medication). Our aim is to increase awareness regarding this uncommon but disabilitating and life-threatening adverse effect of antithyroid medications among clinicians. We also discuss the proposed pathophysiology for this immunological reaction as well as management options in these patients.

Topics: Antithyroid Agents; Arthralgia; Arthritis; Drug Eruptions; Female; Fever; Humans; Hyperthyroidism; Methimazole; Middle Aged; Syndrome

Hyperthyroidism is common in cats, but there are no reports that evaluate its severity or underlying thyroid tumor disease based on disease duration (ie, time from original diagnosis). The objective of this study was to compare serum thyroxine (T4) concentrations and thyroid scintigraphic characteristics of cats referred for radioiodine treatment based on disease duration.. This was a cross-sectional study of 2096 cats with hyperthyroidism. Cats were divided into five groups based on time from diagnosis: ⩽1 year (n = 1773); >1-2 years (n = 169); >2-3 years (n = 88); >3-4 years (n = 35); and >4-6.1 years (n = 31). Methimazole, administered to 996 (47.5%) cats, was stopped at least 1 week prior to examination to allow for serum T4 testing. Each thyroid scintiscan was evaluated for pattern (unilateral, bilateral, multifocal), location (cervical, thoracic inlet, chest) and size (small, medium, large, huge) of the thyroid tumor, as well as features suggesting malignancy.. Median serum T4 concentration increased with increasing disease duration from 100 nmol/l (⩽1 year) to 315 nmol/l (>4-6.1 years) (P <0.001). Prevalence of unilateral thyroid disease decreased, whereas multifocal disease (three or more tumor nodules) increased (P <0.001) with increasing disease duration. Median tumor volume in the five groups increased from 1.6 cm(3) (⩽1 year) to 6.4 cm(3) (>4-6.1 years). Prevalence of large (4-8 cm(3)) and huge (>8 cm(3)) thyroid tumors increased from 5.1% (⩽1 year) to 88.6% (>4-6.1 years), while the prevalence of intrathoracic tumor tissue increased from 3.4% (⩽1 year) to 32.3% (>4-6.1 years). Prevalence of suspected thyroid carcinoma (characterized by severe hyperthyroidism; huge, intrathoracic, multifocal tumors; refractory to methimazole treatment) increased with increasing disease duration from 0.4% (⩽1 year) to 19.3% (>4-6.1 years).. Our results indicate that the prevalence of severe hyperthyroidism, large thyroid tumors, multifocal disease, intrathoracic thyroid masses and suspected malignant disease all increase with disease duration in cats referred for radioiodine therapy.

Topics: Animals; Antithyroid Agents; Cat Diseases; Cats; Cross-Sectional Studies; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Prevalence; Thyroid Function Tests

The objective of this work is to report our experience with (131)I therapy without recent antithyroid drug (ATD) pretreatment for refractory severe hyperthyroidism complicated by hyperbilirubinemia due to hepatic dysfunction.. Five patients with refractory severe hyperthyroidism were treated with (131)I at 90 to 120 μCi/g-thyroid (total activity, 6.2 to 10.1 mCi). The patients previously had received ATD treatment from 2 months to 12 years and discontinued ATDs from 2 months to 4 years before (131)I treatment due to treatment failure or severe jaundice. Prior to (131)I therapy, the patients were asked to take a low-iodine diet and were treated with bisoprolol fumarate, digoxin, furosemide, S-adenosylmethionine, polyene phosphatidylcholine, and plasma exchange as supportive treatment for related clinical conditions. Four of the patients also received lithium carbonate in conjunction with their (131)I treatment. The patients were followed for 4 to 9 years after (131)I therapy.. After (131)I treatment, jaundice disappeared completely within 3 to 4 months in all patients, and liver function tests returned to normal. Concurrent atrial fibrillation and heart failure, leukopenia and thrombocytopenia, or thrombocytopenia and left cardiac enlargement improved remarkably in 3 patients during the follow-up period. Three to 45 months after (131)I treatment, hypothyroidism was noted in the patients and they were treated with L-thyroxine replacement therapy.. (131)I therapy without recent ATD pretreatment for refractory severe hyperthyroidism complicated by serious jaundice appears to be safe and effective, with good long-term results. It may be the preferred therapy for such patients and should be used as early as possible.

Topics: Adult; Antithyroid Agents; Chemical and Drug Induced Liver Injury; China; Female; Humans; Hyperbilirubinemia; Hyperthyroidism; Iodine Radioisotopes; Jaundice; Liver Diseases; Male; Methimazole; Middle Aged; Propylthiouracil; Retrospective Studies; Severity of Illness Index

Methimazole is commonly prescribed for patients who are thyrotoxic. Cholestatic hepatitis is a rare but serious adverse event which may be associated with interventional therapy. In this case report, we present two Chinese women with cholestatic jaundice due to methimazole treatment. Both patients had a history of hyperthyroidism; initial laboratory studies of liver function were normal and cholestatic hepatitis occurred after treatment with methimazole. Concomitant liver disease, such as viral hepatitis (A, B, C, D, E), autoimmune hepatitis, primary biliary cirrhosis and calculus of bile duct, were excluded. Liver enzyme levels in both patients returned to normal after stopping methimazole therapy and taking hepatoprotective drugs. It is essential that patients are informed about the earliest symptoms of serious adverse effects of antithyroid drugs, such as hepatic toxicity, and that they are advised to stop taking the drug immediately and contact their physician if such symptoms occur.

Topics: Adult; Anti-Inflammatory Agents; Antithyroid Agents; Drug-Related Side Effects and Adverse Reactions; Female; Hepatitis; Humans; Hyperthyroidism; Jaundice, Obstructive; Methimazole; Methylprednisolone; Middle Aged; Prognosis

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

Antithyroid drug (ATD)-induced agranulocytosis is a rare but life-threatening disease. Clinical features of ATD-induced agranulocytosis and outcomes remain incompletely understood.. Patients with clinically diagnosed ATD-induced agranulocytosis were retrospectively studied, involving 9690 patients who were referred for radioiodine treatment during a 15-year period (2000-2015) in China. There were 114 cases of agranulocytosis attributable to ATD included, and their clinical characteristics and therapy outcomes were analyzed.. The female-to-male ratio of ATD-induced agranulocytosis was 10.4:1. The mean age (±standard deviation) of the patients with ATD-induced agranulocytosis was 41.7 ± 12.3 years. The methimazole and propylthiouracil doses given at the onset were 22.9 ± 8.0 mg/day and 253.6 ± 177.5 mg/day, respectively. ATD-induced agranulocytosis occurred in 45.1%, 74.3%, and 88.5% of patients within 4, 8, and 12 weeks of the onset of ATD therapy, respectively. Fever (78.9%) and sore throat (72.8%) were the most common symptoms when agranulocytosis was diagnosed. The mean recovery time of agranulocytosis was 13.41 ± 7.14 days. Recovery time in the granulocyte colony-stimulating factor (G-CSF)-treated group (12.7 ± 6.0 days) did not differ from that in the group not treated with G-CSF (16.4 ± 10.6 days; p = 0.144). Treatment with (131)I was successful in 87/98 patients (88.8%). The success rate of (131)I was equivalent (p = 1.000) between the groups receiving methimazole (88.2%, 75/85) and propylthiouracil (92.3%, 12/13).. This largest single-institution study in China shows that ATD-induced agranulocytosis tends to occur within the first 12 weeks after the onset of ATD therapy. For patients with ATD-induced agranulocytosis, G-CSF does not improve the recovery time of agranulocytosis, and (131)I is an optimal treatment approach.

Topics: Adult; Agranulocytosis; Antithyroid Agents; China; Female; Granulocyte Colony-Stimulating Factor; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Propylthiouracil; Retrospective Studies; Treatment Outcome

Trisomia 21 pary chromosomów (Zespół Downa, DS) jest jednym z częściej występujących zaburzeń chromosomalnych w praktyce pediatrycznej. Zaburzenia funkcji tarczycy często występują u tych pacjentów. Niedoczynność tarczycy jest rozpoznawana u blisko 50% pacjentów z ZD, a liczba ta wzrasta wraz z wiekiem. Nadczynność tarczycy jest rozpoznawana znaczniej rzadziej u dzieci z ZD. Odpowiednia strategia leczenia nadczynności tarczycy jest bardzo istotna ze względu na możliwość zaburzenia rozwoju dzieci. Przedstawiamy dwa przypadki dzieci z zespołem Downa i nadczynnością tarczycy. Proces leczenia tych pacjentów był odmienny.

Topics: Child; Down Syndrome; Female; Humans; Hyperthyroidism; Male; Methimazole; Thyroxine; Treatment Outcome

Overt hyperthyroidism and methimazole (MMI) treatment are frequently associated with abnormal liver function tests (LFTs). We describe the serial changes of LFTs in MMI-treated hyperthyroid patients.. We retrospectively analyzed all 77 patients presenting with newly diagnosed overt hyperthyroidism (59 Graves diseases, 11 toxic nodular goiters, 4 toxic adenomas, 3 amiodarone-induced thyrotoxicosis) between 2012 and 2014. All patients started MMI at 10 to 60 mg/day that was gradually tapered. We measured thyroid-stimulating hormone, free thyroxine, alanine aminotransferase (ALT) and aspartate aminotrasnferase (AST) at baseline and at 6 weeks, 4.5 months and 10 months after starting the MMI treatment. The concomitant medication was stable during MMI treatment.. At baseline, 25 patients (32.5%) had abnormal LFT, of which 5 had ALT or AST levels >2× the upper limit of normal (ULN). In most patients with baseline abnormal LFT, MMI treatment resulted in a normalization of serum ALT and AST. Thirteen patients with normal baseline LFT had <2× the ULN elevations of LFT sometime during treatment. There was a case of significant hepatotoxicity. During treatment, there were no significant differences in LFT levels between patients with initially normal or abnormal LFT. In a Cox proportional hazard regression model, abnormal LFT at baseline, abnormal thyroid function at the last evaluation, and MMI dose were not predictors of abnormal LFT at the final evaluation.. MMI treatment can induce insignificant LFT elevation, <2× the ULN. MMI can be safely administered in hyperthyroid patients with abnormal LFT, and normalization of increased AST and ALT levels should be anticipated.. ALT = alanine aminotransferase AST = aspartate aminotransferase fT4 = free thyroxine HCV = hepatitis C virus LFT = liver function test LOCF = last observation carried forward MMI = methimazole PTU = propylthiouracil TSH = thyroid-stimulating hormone ULN = upper limit of normal.

Topics: Adult; Aged; Alanine Transaminase; Antithyroid Agents; Aspartate Aminotransferases; Female; Humans; Hyperthyroidism; Liver; Liver Function Tests; Male; Methimazole; Middle Aged; Thyrotoxicosis

Thyroid scintigraphy is commonly used for evaluation of cats with hyperthyroidism, with the thyroid-to-salivary ratio (T/S) being the most common method to quantify the degree of thyroid activity and disease. Calculation of thyroid-to-background ratios (T/B) or percent thyroidal uptake of (99m) TcO(-) 4 (TcTU) has only been reported in a few studies. The purpose of this prospective, cross-sectional study was to evaluate a number of quantitative scintigraphic indices as diagnostic tests for hyperthyroidism, including the T/S, three different T/B, TcTU, and estimated thyroid volume. Of 524 cats referred to our clinic for evaluation of suspected hyperthyroidism, the diagnosis was confirmed (n = 504) or excluded (n = 20) based on results of a serum thyroid panel consisting of thyroxine (T4 ), triiodothyronine (T3 ), free T4 (fT4 ), and thyroid-stimulating hormone (TSH) concentrations. In the hyperthyroid cats, median values for TcTU, T/S, and three T/B ratios were all significantly higher (P < 0.001) than values in euthyroid suspect cats or clinically normal cats. All scintigraphic parameters were relatively sensitive and specific as diagnostic tests for hyperthyroidism, but the T/S ratio had the highest test accuracy. The T/S ratio correlated strongly with the TcTU (r = 0.85). However, the TcTU had a higher and more significant correlation (P < 0.01) with serum T4 (r = 0.76 vs. 0.64), T3 (r = 0.77 vs. 0.64), and estimated thyroid volume (r = 0.62 vs. 0.38). Overall, calculation of TcTU is an accurate diagnostic test, but also appears to be the best parameter to predict the functional volume and metabolic activity of the feline adenomatous thyroid gland.

Topics: Animals; Antithyroid Agents; Cat Diseases; Cats; Female; Hyperthyroidism; Male; Methimazole; Radionuclide Imaging; Saliva; Sodium Pertechnetate Tc 99m; Thyroid Gland

A 23-year-old woman with preexisting Graves' disease who received thiamazole treatment presented with fever, dysphagia, hyperthyroidism and leukopenia. With suspicion of thyreotoxicosis accompanied by drug-induced agranulocytosis she was successfully managed by plasmapheresis, G‑CSF administration and inhibition of periphereal conversion of thyroid hormones. In due course she underwent thyroidectomy. Thiamazole is frequently associated with drug-induced agranulocytosis. Long-term therapy with thiamazole requires critical evaluation and alternatives should be considered early. Plasmapheresis is an adequate treatment option to achieve normal thyroid hormonal status.

Topics: Acute Disease; Adult; Antithyroid Agents; Combined Modality Therapy; Diagnosis, Differential; Female; Granulocyte Colony-Stimulating Factor; Humans; Hyperthyroidism; Methimazole; Plasmapheresis; Tonsillitis; Treatment Outcome

The authors present the case history of a patient suffering from hyperthyroidism. The diagnostic procedures revealed the presence of propylthiouracyl induced vasculitis with renal involvement, that recovered completely after the withdrawal of propylthiouracyl and corticosteroid treatment. Thereafter, the patient was treated with thiamasol, that caused agranulocytosis with fever. After transient litium carbonate therapy a succesful thyreoidectomy was performed. Cumulative serious side effects of antithyroid drugs are rare. This case highlights some of the challenges and complications encountered in the management of hyperthyroidism.

Topics: Adult; Antithyroid Agents; Febrile Neutropenia; Female; Humans; Hyperthyroidism; Methimazole; Propylthiouracil; Thyroidectomy; Vasculitis

Concurrent thyroid cancer (TC) and hyperthyroidism (HT) is rare though increasingly being reported. HT due to TC is much rarer and more challenging especially in Africa where TC and HT have significant case fatality rates.. We present a 37-year-old Cameroonian female who had been on irregular regimens of propranolol and digoxin as treatment for worsening palpitations for 12 months. She came to our district hospital for her propranolol medication refill. We fortuitously identified features of HT and found a left uninodular goiter with no cervical lymphadenopathy. She was referred for thyroid assessment which suggested primary HT and an enlarged heterogeneous left lobe with a well-defined homogenous solid mass. We restarted her on propranolol and referred her for a course of methimazole. At the referral hospital, she also underwent a left thyroid lobectomy. The resected lobe was sent for histopathology which revealed a neoplastic nodule with features suggestive of a papillary thyroid cancer (PTC) causing HT. The patient's clinical progress postoperatively was good and there was regression of hyperthyroid symptoms.. The historical, clinical, and laboratory findings were suggestive of HT due to PTC. A high index of suspicion, prompt referral and counter-referral lead to a positive outcome of such a rare case in a resource poor setting. We advocate for systematic and careful evaluation of all thyroid nodules.

Topics: Adult; Anti-Arrhythmia Agents; Antithyroid Agents; Cameroon; Carcinoma; Carcinoma, Papillary; Developing Countries; Female; Humans; Hyperthyroidism; Incidental Findings; Methimazole; Propranolol; Thyroid Cancer, Papillary; Thyroid Gland; Thyroid Neoplasms; Thyroidectomy

A 51-year-old woman with a personal history of vitiligo, normal thyroid hormone studies, a simple hysterectomy for multiple uterine myomas at age 35 years, and childhood adenotonsillectomy was seen for progressive hearing loss. She reported mild asthenia, cold intolerance, mild dysphagia with frequent choking while eating and drinking, and a progressive increase in inspiratory effort, especially in the supine position. Her partner described a progressively worsening history of snoring and witnessed apneic episodes, mostly in the supine position. Mild to moderate daytime sleepiness was also present.

Topics: Antithyroid Agents; Female; Goiter, Nodular; Hearing Loss; Humans; Hyperthyroidism; Lingual Thyroid; Magnetic Resonance Imaging; Methimazole; Middle Aged; Radionuclide Imaging; Radiopharmaceuticals; Sleep Apnea, Obstructive; Sodium Pertechnetate Tc 99m; Supine Position; Tomography, X-Ray Computed

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Antithyroid Agents; Cholestasis; Humans; Hyperthyroidism; Male; Methimazole

Topics: Adrenergic beta-Antagonists; Antithyroid Agents; Humans; Hyperthyroidism; Hypokalemia; Hypophosphatemia; Lower Extremity; Male; Methimazole; Muscle Weakness; Propranolol; Young Adult

Topics: Animals; Antithyroid Agents; Arrhythmias, Cardiac; Cat Diseases; Cats; Electrocardiography; Female; Hyperthyroidism; Methimazole; Pacemaker, Artificial

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; Female; Humans; Hyperthyroidism; Methimazole; Physical Exertion; Rhabdomyolysis

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

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

Hyperthyroidism is much less common in children <7 years vs. older children and less well studied. It was our impression that the youngest patients needed a higher weight-based dose of methimazole (MMI) to achieve euthyroidism.. To compare the mean MMI dose needed to normalize free T4 in younger (<7 years) vs. older children and the time taken to normalize free T4.. Based on chart review (2004-2012), patients were divided into groups based on age at diagnosis: <7 years (n=13), 7-12 years (n=30) and >12 years (n=40). Follow-up visits were reviewed until free T4 normalized.. The mean dose of MMI (mg/kg/day) needed to normalize free T4 was 0.71 (±0.29) in the <7 group, significantly higher vs. the two older groups: 0.50 (±0.22) and 0.44 (±0.24). Months taken to achieve a euthyroid state was significantly longer in children <7 (6.23±3.91) vs. the older groups (3.10±2.12 and 3.18±2.86 months).. Hyperthyroid children diagnosed before age 7 required higher initial doses of MMI and took a longer time to become euthyroid than older patients. Clinicians should consider starting with higher weight-based MMI doses when treating younger patients to more rapidly normalize free T4.

Topics: Adolescent; Age Factors; Antithyroid Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Humans; Hyperthyroidism; Male; Methimazole; Thyroid Function Tests; Thyroxine; Treatment Outcome

Abdominal pain is a common chief complaint that encompasses a broad differential diagnosis at emergency department (ED), ranging from general discomfort to life-threatening disease. Abdominal pain induced by a metabolic disorder should also be considered. Diabetic ketoacidosis (DKA) is a common complication of new-onset type 1 diabetes mellitus in young patients. Although DKA that presented to the ED with complaint of abdominal pain is not uncommon, it is precipitated by hyperthyroidism, which is rare and more complicated. Herein, we present a case of a 20-year-old women who came to our ED with the chief complaint of abdominal pain, which was actually the result of DKA caused by hyperthyroidism without underlying disease.

Topics: Antithyroid Agents; Biomarkers; Diabetic Ketoacidosis; Diagnosis, Differential; Diagnostic Imaging; Electrocardiography; Emergency Service, Hospital; Female; Humans; Hyperthyroidism; Insulin Resistance; Methimazole; Young Adult

Available data from in vitro studies show that thyroid hormones (THs) regulate herpes simplex virus (HSV) gene expression and may modulate latency/reactivation of the virus. Whether infectivity of the virus is also affected by THs is not known. Using animal models (in vivo study) and Vero cell culture (in vitro study), we examined the effects of alterations in THs level on HSV-1 infectivity.. Rats were rendered hypo- and hyperthyroid by daily addition of methimazole and l-thyroxine into their drinking water, respectively. Euthyroid animals served as control. All animals were given a single dose of HSV-1 (10(7)TCID50, ip) and sacrificed 3 d later. The spleen of the animals was then removed and viral particles were recovered from the tissue extract through aseptic procedures. Serial dilution of the extracts was prepared and added to Vero cell culture. For the in vitro study, the cultures were pretreated with l-thyroxine and the viral particles were then added. Virus titration was determined by Reed-Muench quantal assay.. The viral load of spleen in hyperthyroid rats was significantly lower (1000-fold) than that of the euthyroid rats. Similarly, in vitro presence of supraphysiologic levels of l-thyroxine in the culture media of Vero cells decreased virus infectivity. Interestingly, hypothyroid animals showed a significant increase (10-fold) in spleen viral load as compared to that of their euthyroid counterparts.. These data clearly show that the HSV-1 infectivity is affected by THs, and suggest that THs or their analogs may have a potential application in prevention and/or treatment of viral infections.

Topics: Animals; Antithyroid Agents; Chlorocebus aethiops; Disease Models, Animal; Herpes Simplex; Herpesvirus 1, Human; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Rats, Sprague-Dawley; Thyroid Gland; Thyroxine; Vero Cells

An 11-year-old spayed female domestic shorthair cat was presented for polydipsia, hyperactivity and bilateral thyroid gland enlargement. Total T4 (TT4) was in the upper interval range; therefore, an early hyperthyroidism was suspected. A treatment trial with methimazole was started, as the owner refused further tests. Six months later the owner stopped the treatment. One year later, clinical signs persisted and TT4 was still in the upper interval range. Methimazole was re-introduced but 48 h later the cat presented non-pruritic alopecia with erythema, scales and perilesional yellowish crusts. Pyogranulomatous mural folliculitis was diagnosed by histopatological examination of the skin biopsies. Methimazole was withdrawn and macroscopic lesions healed and disappeared histologically in 15 days. An idiosyncratic drug reaction to methimazole was suspected. To the best of our knowledge, this is the first report of feline pyogranulomatous mural folliculitis likely secondary to an adverse drug reaction to methimazole administration.

Topics: Animals; Antithyroid Agents; Cat Diseases; Cats; Female; Folliculitis; Hyperthyroidism; Methimazole; Thyroid Function Tests

Transdermal methimazole is suggested as an alternative to oral therapy for hyperthyroid cats that are difficult to pill. However, no information on long-term management with this treatment is available. Our objective was therefore to retrospectively evaluate the efficacy and safety of long-term transdermal methimazole treatment in hyperthyroid cats. Sixty cats with newly diagnosed hyperthyroidism and available long-term follow-up information were included. Methimazole was formulated in a pluronic lecithin organogel-based vehicle and was applied to the pinna of the inner ear. Cats were re-evaluated at regular intervals. Median (range) follow-up was 22.6 months (3.6-88.4 months). Clinical improvement was observed in all cats and side effects were rare (mild transient gastrointestinal signs: n = 3; erythema of the pinna: n = 2, necessitating a switch to oral medication). Despite a significant decrease, with median T4 concentrations within the reference interval during the follow-up period, several cats repeatedly had T4 concentrations in the thyrotoxic and hypothyroid range. Maximal and minimal daily doses during the follow-up period were 15.0 and 1.0 mg, respectively; they were significantly higher than the starting dose after 24-36 months of therapy. Although the majority of owners were highly satisfied with the treatment, several admitted not treating their cat regularly. Transdermal methimazole is a safe option for the long-term management of feline hyperthyroidism. However, it seems difficult to keep the T4 concentrations constantly within the reference interval. Higher doses can be expected after prolonged treatment and, despite the convenience of transdermal application, owner compliance should be assessed regularly.

Topics: Administration, Cutaneous; Animals; Antithyroid Agents; Cat Diseases; Cats; Ear Auricle; Female; Follow-Up Studies; Hyperthyroidism; Male; Methimazole; 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

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

Hyperthyroidism is one of the most frequent endocrine disorders and its current treatment is based on drugs, surgery and radioactive iodine. Methimazole is the antithyroid drug of choice because of its potency and infrequent side effects, usuaIly mild. This medication is rarely associated with liver toxicity, usually manifested as cholestatic jaundice. Here we report the case of a 33-year-old woman treated at the University Hospital Fundación Santa Fe de Bogota, with hepatotoxicity induced by a methimazole-based treatment for Graves' disease. The pruritus and jaundice appeared after three weeks of therapy, viral hepatitis markers were negative, hepatobiliary ultrasonography was normal, and an increase of the levels of alkaline phosphatase, total bilirubin and aminotransferases was found The causal diagnosis of methimazole-induced hepatotoxicity was supported by the results of a liver biopsy. According to the CIOMS scale the score was 10, and the causal relationship of the hepatic adverse reaction by methimazole is highly probable. The clinical course was satisfactory when the medication was suspended, with clinical improvement at 5 days, and normalization of liver tests at 5 weeks. We discuss this case from a diagnostic and therapeutic approach.

Topics: Adult; Antithyroid Agents; Female; Humans; Hyperthyroidism; Jaundice, Obstructive; Methimazole

Topics: Animals; Antithyroid Agents; Arrhythmias, Cardiac; Cat Diseases; Cats; Electrocardiography; Hyperthyroidism; Methimazole

Propylthiouracil (PTU) and methimazole (MMI) are antithyroid drugs used to treat hyperthyroidism. Despite the widespread use of PTU and MMI during pregnancy, modest clinical data and less animal data are available on the teratogenic potential of these drugs.. We evaluated the teratogenicity of in utero exposure to PTU or MMI in mice and rats. First, pregnant C57Bl/6 mice were treated daily with PTU (10 or 100 mg/kg), MMI (2 or 20 mg/kg), or vehicle from gestation day (GD) 6 to 16. GD 18 fetuses were evaluated for gross and histopathological abnormalities. Next, pregnant Sprague-Dawley rats were treated daily with PTU (50 or 100 mg/kg), MMI (10 or 20 mg/kg), or vehicle from GD 6 to 19, followed by evaluation for gross and histopathological abnormalities at GD 20.. In mice treated with PTU or MMI, no significant histopathological abnormalities or external gross malformations, and no adverse effects on placental weight, litter size, resorption rates, or fetal weight were observed at GD 18. In rats, no adverse effects on litter size, placental weights, or maternal body weights were observed with either PTU or MMI treatment. PTU treatment (50 and 100 mg/kg) and MMI (10 mg/kg) treatment resulted in a decrease in crown-rump length in rat fetuses but no external gross malformations or histopathological abnormalities were observed.. We did not observe either gross external malformations or histopathological malformations in mice or rats treated long-term with high doses of PTU or MMI during pregnancy.

Topics: Animals; Antithyroid Agents; Female; Hyperthyroidism; Methimazole; Mice; Mice, Inbred C57BL; Pregnancy; Pregnancy Complications; Propylthiouracil; Rats; Rats, Sprague-Dawley; Teratogens

Topics: Amiodarone; Anti-Arrhythmia Agents; Antithyroid Agents; Cardiomyopathies; Cardiopulmonary Resuscitation; Catecholamines; Defibrillators, Implantable; Echocardiography; Electrocardiography; Female; Humans; Hyperthyroidism; Hypokinesia; Methimazole; Middle Aged; Multiple Organ Failure; Perchlorates; Sodium Compounds; Thyroidectomy; Thyrotropin; Ventricular Fibrillation

Radioactive Iodine therapy (RAIT) plays a major role in the treatment of hyperthyroidism. In addition to the thyroid gland, significant amounts of radioactive iodine are maintained in the stomach. The aim of this study was to determine if RAIT has any effect on Helicobacter pylori infection, based on the C urea breath test (UBT).. The study included 85 patients with hyperthyroidism scheduled to undergo RAIT and 69 hyperthyroid subjects in whom methimazole treatment was planned. All subjects had pretreatment-positive UBT results, and the test was repeated on the first and third months after RAIT and methimazole treatment.. After a mean RAIT dose of 15 mCi (range, 10-20 mCi), UBT became negative in 13 (15.3%) of 85 patients on the first month and 18 (21.2%) of 85 patients on the third month. All subjects treated with methimazole remained UBT positive on the first and third months of methimazole treatment (100%). Reduction in the number of UBT-positive patients on both the first and the third months after RAIT was statistically significant (P < 0.001). Distribution of hyperthyroidism etiologies and thyroid autoantibody levels in subjects with UBT that became negative and in subjects with UBT that remained positive were similar in the RAIT group (P > 0.05). Urea breath test negativity rates did not differ according to the radioiodine dose.. Our findings indirectly showed that RAIT might have an antimicrobial effect on H. pylori. Clinical applications of this beneficial effect of RAIT on H. pylori should be further evaluated.

Topics: Antithyroid Agents; Breath Tests; Carbon Radioisotopes; Female; Helicobacter Infections; Helicobacter pylori; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Prospective Studies; Urea

The evidence of hepatotoxicity of antithyroid drugs (ATDs) is limited to case reports or spontaneous reporting. This study aimed to quantify the incidence and comparative risks of hepatotoxicity for methimazole (MMI)/carbimazole (CBM) vs. propylthiouracil (PTU) in a population-based manner.. We conducted a cohort study of hyperthyroidism patients initially receiving MMI/CBM or PTU between 1 January 2004 and 31 December 2008 using the Taiwan National Health Insurance Research Database. The examined hepatotoxicity consisted of cholestasis, non-infectious hepatitis, acute liver failure and liver transplant, with the incidences and relative risks being quantified by Poisson exact methods and Cox proportional hazard models, respectively.. The study cohort comprised 71 379 ATD initiators, with a median follow-up of 196 days. MMI/CBM vs. PTU users had a higher hepatitis incidence rate (3.17/1000 vs. 1.19/1000 person-years) but a lower incidence of acute liver failure (0.32/1000 vs. 0.68/1000 person-years). The relative risk analysis indicated that any use of MMI/CBM was associated with a 2.89-fold (95% CI 1.81, 4.60) increased hepatitis risk compared with PTU, with the risk increasing to 5.08-fold for high dose MMI/CBM (95% CI 3.15, 8.18). However, any MMI/CBM use vs. PTU was not related to an increased risk of cholestasis (adjusted hazard ratio [HR] 1.14, 95% CI 0.40, 3.72) or acute liver failure (adjusted HR 0.54, 95% CI 0.24, 1.22).. MMI/CBM and PTU exert dissimilar incidence rates of hepatotoxicity. Compared to PTU, MMI/CBM are associated in a dose-dependent manner with an increased risk for hepatitis while the risks are similar for acute liver failure and cholestasis.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Carbimazole; Chemical and Drug Induced Liver Injury; Cohort Studies; Databases, Factual; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Hyperthyroidism; Incidence; Male; Methimazole; Middle Aged; Proportional Hazards Models; Propylthiouracil; Retrospective Studies; Taiwan; Young Adult

Atherogenic dyslipoproteinemia is one of the most important risk factor for atherosclerotic changes development. Hypothyroidism is one of the most common causes of secondary dyslipidemias which results from reduced LDL clearance and therefore raised levels of LDL and apoB. Association between small dense LDL (sdLDL) presentation and thyroid status has been examinated using polyacrylamide gel electrophoresis for lipoprotein subfractions evaluation.. 40 patients with diagnosed autoimmune hypothyroidism and 30 patients with autoimmune hyperthyroidism were treated with thyroxine replacement or thyreo-suppressive treatment. In both groups lipid profiles, LDL subractions, apolipoproteins (apoA1, apoB), apoA1/apoB ratio and atherogenic index of plazma (AIP) were examined before treatment and in state of euthyreosis.. Thyroxine replacement therapy significantly reduced levels of total cholesterol (TC), LDL, triglycerides (TG) and also decreased levels of sdLDL (8,55±11,671 vs 0,83±1,693mg/dl; p<0,001), apoB and AIP. For estimation of atherogenic lipoprotein profile existence an AIP evaluation seems to be better than apoB measurement because of the more evident relationship with sdLDL (r=0,538; p<0,01). Thyreo-suppressive therapy significantly increased levels of TC, LDL, TG and apoB. The sdLDL was not found in hyperthyroid patients.. Atherogenic lipoprotein profile was present in 52.5% of hypothyroid subjects, which is higher prevalence than in normal, age-related population. Substitution treatment leads to an improvement of the lipid levels, TG, apoB, AIP and LDL subclasses. It significantly changed the presentation of sdLDL - we noticed shift to large, less atherogenic LDL particles. Significantly positive correlation between sdLDL and TAG; sdLDL and VLDL alerts to hypertriglyceridemia as a major cardiovascular risk factor.

Topics: Adult; Aged; Aged, 80 and over; Antithyroid Agents; Apolipoprotein A-I; Apolipoprotein B-100; Cholesterol, LDL; Electrophoresis, Polyacrylamide Gel; Female; Hashimoto Disease; Humans; Hyperthyroidism; Lipoproteins, VLDL; Male; Methimazole; Middle Aged; Thyroiditis, Autoimmune; Thyroxine

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

We report a case of apathetic hyperthyroidism associated with unrecognized slowly growing functional thyroid adenoma (Plummer's disease), atrial fibrillation and heart failure. An 81-year-old woman with worsening thyroid dysfunction was admitted to our hospital for the treatment of heart failure. The patient had developed heart failure associated with chronic atrial fibrillation at 76 years of age, and one year later was found to have asymptomatic hyperthyroidism. Anti-thyroid autoantibodies were negative, but thyroid echography showed a 32-mm tumor devoid of internal blood flow in the left lower lobe. Free thyroxine 4 (FT4) decreased from 3.30 to 2.60 ng/dl without treatment. The patient was diagnosed with transient thyroiditis and was followed-up without treatment. However, a repeat thyroid echography showed growth of the tumor to 41 mm in 4 years. Thyroid scintigraphy showed uptake that matched the thyroid mass. Based on these findings, the established diagnosis was Plummer's disease complicated with heart failure. The patient was treated with anti-thyroid drugs, which resulted in improvement of FT4 and reduced the severity of heart failure. In this rare case of an elderly patient, Plummer's disease was associated with a slowly-growing functional thyroid adenoma, apathetic hyperthyroidism, repeated episodes of atrial fibrillation and heart failure. Since symptoms of thyrotoxicosis are likely to be missed in the elderly, it is necessary to include hyperthyroidism in the pathoetiology of heart failure and atrial fibrillation in this population.

Topics: Aged, 80 and over; Antithyroid Agents; Atrial Fibrillation; Female; Goiter, Nodular; Heart Failure; Humans; Hyperthyroidism; Methimazole; Receptors, Thyrotropin; Recurrence; Thyrotoxicosis; Treatment Outcome

Neonatal hyperthyroidism is usually a self-limited condition frequently associated with transplacental passage of thyroid stimulating antibodies secondary to maternal autoimmune disorders. To timely detect mothers with this medical antecedents decreases the risk for fetal adverse events.. To report a case of neonatal hyperthyroidism associated with intrauterine growth restriction and heart failure.. A 36 week-old newborn with birth weight of 1,240 g. Symptoms were tachycardia, distal coldness, exophthalmos, hepatomegaly and tremors. Echocardiogram ruled out structural heart disorders. Due to maternal symptoms suggestive of hyperthyroidism, TSH tests were performed showing 0.01 ulU/ml, free T4 7.7 ng/dl, so the diagnosis of neonatal hyperthyroidism was confirmed. It was treated with methimazole and propanol, alleviating the symptoms and decreasing the levels of free T4.. To know the maternal history helps identify and manage neonatal complications of hyperthyroidism. Heart failure and other cardiopulmonary disorders are determinants of mortality during early neonatal period. High-risk newborns should receive follow up assessments.

Topics: Adrenergic beta-Antagonists; Antithyroid Agents; Fetal Growth Retardation; Heart Failure; Humans; Hyperthyroidism; Infant, Newborn; Male; Methimazole; Propranolol; Thyroxine

Although most patients remain clinically euthyroid, some develop amiodarone-induced hyperthyroidism (HPEAI) or hypothyroidism (HPOAI). The authors present a retrospective analysis of ten patients with amiodarone-induced thyroid dysfunction. Six patients were female and mean amiodarone intake was 17.7 months. HPOIA was more common (six patients). From all the patients with HPEAI, two had type 2, one had type 1, and one had type 3 hyperthyroidism. Symptoms suggestive of thyroid dysfunction occurred in five patients, most of them with HPOAI. In HPEAI, the most frequent symptom was exacerbation of arrhythmia (three patients). Discontinuation of amiodarone and treatment with levothyroxine was chosen in 83.3% of the HPOAI cases, while thyonamide treatment with corticosteroids and without amiodarone was the option in 75% of the HPEAI cases. There were three deaths, all in patients with HPEAI. HPEAI is potentially fatal. The clinical picture may be vague, so the thyroid monitoring is mandatory.

Topics: Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Antithyroid Agents; Drug Combinations; Female; Glucocorticoids; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Middle Aged; Retrospective Studies; Thyroxine; Treatment Outcome; Withholding Treatment

Hyperthyroidism is the most common feline endocrinopathy. Treatment options comprise anti-thyroid medication, iodine-restricted diet, surgical thyroidectomy and radioiodine. One hundred and eleven owners of hyperthyroid cats completed a detailed survey asking about their experiences and views on the management of hyperthyroidism. Male cats were slightly over-represented (60 cats, 54%). Concurrent chronic kidney disease was reported in 27% of the cats. Oral anti-thyroid medication was offered to 92% of owners. The final treatment decision was usually based on the veterinarian's recommendation or joint decision-making between the owner and the veterinarian. Almost all of the cats (103, 93%) had received oral anti-thyroid medication at some point in the course of their disease. Sixty-nine cats (62%) were receiving oral anti-thyroid medication at the time of survey completion. Management of hyperthyroidism using UK veterinary-licensed oral anti-thyroid medication (Vidalta; MSD Animal Health, Felimazole; Dechra Veterinary Products) was associated with 72-75% success rates in terms of owner-assessed clinical outcome. The most important treatment priorities for owners were the prescription of the most accurate dose of medication and use of the lowest possible dose. None ranked once-daily treatment as most important to them, and 79% of owners said that they were, or would be, happy to dose their cat twice daily to control its hyperthyroidism. For 62% of owners, pilling their cat twice daily was not a problem. These results suggest that most cat owners are not a barrier to prescribing twice-daily anti-thyroid medication, if required.

Topics: Animals; Antithyroid Agents; Carbimazole; Cat Diseases; Cats; Data Collection; Female; Hyperthyroidism; Male; Methimazole; Ownership

Thyroid hormones have many effects on cardiovascular function, and deficiency or excess of thyroid hormones can result in cardiac dysfunction. Abnormalities of the cardiovascular system are often identified during examination of hyperthyroid and hypothyroid patients. This article addresses the effects of thyroid hormones on the cardiovascular system and the clinical relevance of the cardiovascular response to thyroid dysfunction. In addition, treatment recommendations are presented.

Topics: Animals; Antithyroid Agents; Cardiovascular Diseases; Cat Diseases; Cats; Dog Diseases; Dogs; Hyperthyroidism; Hypothyroidism; Methimazole; Thyroxine

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

Agranulocytosis is a rare but dreaded side-effect of thiamazole. A 61-year-old woman presented at the emergency department with fever and dyspnoea. Because she had recently started therapy with thiamazole for hyperthyroidism, a case of agranulocytosis was feared. Laboratory findings did indeed reveal an absolute neutrophil count of zero. Broad-spectrum antibiotics were given immediately, granulocyte-colony stimulating factor was started and she was admitted to the ICU for supportive care. Unfortunately, she died a day after admission. In this case report, we wanted to place the focus on the importance of this severe side-effect. We emphasize the value of warning the patient, preferably in writing, about the risk of agranulocytosis. We also draw attention to the fact that every doctor must know about agranulocytosis. In this case, the patient consulted her family doctor because she had a sore throat and fever, but was admitted to the hospital only three days after the onset of the symptoms. We believe the risk of agranulocytosis should be understood by every doctor and that the publication of many cases such as this could help heighten general awareness of possibly fatal side-effects like agranulocytosis.

Topics: Agranulocytosis; Anti-Bacterial Agents; Antithyroid Agents; Fatal Outcome; Female; Granulocyte Colony-Stimulating Factor; Humans; Hyperthyroidism; Leukocyte Count; Methimazole; Middle Aged

Agranulocytosis is a rare yet life-threatening complication of methimazole therapy for hyperthyroidism. We present the case of a 37-year-old female recently started on methimazole for hyperthyroidism who presented to our facility for evaluation of suspected thyroid storm. In addition to having abnormal thyroid indices, she was noted to have an odontogenic abscess, and was septic with profound neutropenia. Her symptoms resolved quickly following incision and drainage of her abscess and treatment with broad-spectrum antibiotics. Her neutrophil count improved significantly following cessation of methimazole and administration of granulocyte colony-stimulating factor. Diagnosis was initially confounded by the similarity between symptoms of early sepsis and those of thyroid storm. This case report discusses the factors leading to diagnostic delay and highlights the dangerous manifestations of neutropenia in patients on methimazole therapy.

Topics: Adult; Agranulocytosis; Antithyroid Agents; Diagnosis, Differential; Female; Humans; Hyperthyroidism; Methimazole; Sepsis; Thyroid Crisis

Agranulocytosis is known to be a rare side effect of thionamides. This complication puts pregnant patients at particular risk for infections. Obstetricians caring for such patients have the difficult task of deciding between conservative or surgical management.. The patient is a 37-year-old gravida 4 para 3 Hispanic woman at 11 weeks of gestation with recently diagnosed hyperthyroidism who presented with a neutropenic fever and ecthyma as a complication of thionamide use. She subsequently underwent a thyroidectomy and then had a spontaneous abortion on postoperative day 2.. This patient had life-threatening thyrotoxicosis complicated by neutropenic fever and infection, likely caused by a reaction to thionamides. She quickly recovered with broad-spectrum antibiotics. She could not be restarted on methimazole or propylthiouracil as a result of agranulocytosis and thus underwent thyroidectomy.

Topics: Adrenergic beta-1 Receptor Antagonists; Adult; Antithyroid Agents; Atenolol; Drug Eruptions; Ecthyma; Female; Humans; Hyperthyroidism; Methimazole; Neutropenia; Pregnancy; Pregnancy Complications; Propylthiouracil; Staphylococcal Skin Infections; Staphylococcus aureus

Hyperthyroidism was diagnosed in four guinea pigs by demonstration of an increased serum total thyroxine concentration. The main clinical signs were comparable with those observed in feline hyperthyroidism and included weight loss despite maintenance of appetite and a palpable mass in the ventral cervical region. Three animals were treated successfully with methimazole for between 13 and 28 months. Clinical signs and regular measurement of circulating total thyroxine concentrations appear to be convenient parameters for monitoring response to medical therapy.

Topics: Animals; Antithyroid Agents; Female; Guinea Pigs; Hyperthyroidism; Male; Methimazole; Rodent Diseases; Thyroxine; Weight Loss

Topics: Animals; Antithyroid Agents; Arrhythmias, Cardiac; Cat Diseases; Cats; Electrocardiography; Female; Hyperthyroidism; Methimazole

Hyperthyroidism in pregnant women should be adequately treated to prevent maternal and fetal complications, but teratogenic effects of antithyroid drug (ATD) treatment have been described. Evidence is still lacking in regard to the safety and choice of ATD in early pregnancy.. Our objective was to determine to which degree the use of methimazole (MMI)/carbimazole (CMZ) and propylthiouracil (PTU) in early pregnancy is associated with an increased prevalence of birth defects.. This Danish nationwide register-based cohort study included 817 093 children live-born from 1996 to 2008. Exposure groups were assigned according to maternal ATD use in early pregnancy: PTU (n = 564); MMI/CMZ (n = 1097); MMI/CMZ and PTU (shifted in early pregnancy [n = 159]); no ATD (ATD use, but not in pregnancy [n = 3543]); and nonexposed (never ATD use [n = 811 730]). Multivariate logistic regression was used to estimate adjusted odds ratio (OR) with 95% confidence interval (95% CI) for diagnosis of a birth defect before 2 years of age in exposed versus nonexposed children.. The prevalence of birth defects was high in children exposed to ATD in early pregnancy (PTU, 8.0%; MMI/CMZ, 9.1%; MMI/CMZ and PTU, 10.1%; no ATD, 5.4%; nonexposed, 5.7%; P < .001). Both maternal use of MMI/CMZ (adjusted OR = 1.66 [95% CI 1.35-2.04]) and PTU (1.41 [1.03-1.92]) and maternal shift between MMI/CMZ and PTU in early pregnancy (1.82 [1.08-3.07]) were associated with an increased OR of birth defects. MMI/CMZ and PTU were associated with urinary system malformation, and PTU with malformations in the face and neck region. Choanal atresia, esophageal atresia, omphalocele, omphalomesenteric duct anomalies, and aplasia cutis were common in MMI/CMZ-exposed children (combined, adjusted OR = 21.8 [13.4-35.4]).. Both MMI/CMZ and PTU were associated with birth defects, but the spectrum of malformations differed. More studies are needed to corroborate results in regard to early pregnancy shift from MMI/CMZ to PTU. New ATD with fewer side effects should be developed.

Topics: Abnormalities, Drug-Induced; Adult; Antithyroid Agents; Carbimazole; Denmark; Female; Humans; Hyperthyroidism; Infant, Newborn; Male; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Prevalence; Propylthiouracil

A 12-year-old neutered male domestic shorthair cat presented for chronic, localized, swelling and crusting of the left upper lip, weight loss, sporadic vomiting, and focal alopecia between the scapulae was diagnosed with hyperthyroidism and regional eosinophilic lymphadenitis. Treatment with methimazole exacerbated an underlying hypersensitivity disorder leading to marked generalized lymphadenopathy that histologically mimicked lymphoma.

Topics: Animals; Cat Diseases; Cats; Hyperthyroidism; Lymphatic Diseases; Male; Methimazole; Pruritus

Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Carbimazole; Female; Humans; Hyperthyroidism; Male; Methimazole; Pregnancy; Propylthiouracil

This study is aimed to explore the relationship between bone marrow characteristics and clinical prognosis of antithyroid drug (ATD) induced agranulocytosis. A retrospective study was conducted in the first affiliated hospital of the University of South China. A total of 33 hospitalized patients diagnosed with ATD-induced agranulocytosis were analyzed. The bone marrow characteristics were classified into two types. Type I was characterized by reduction or absence of granulocytic precursors and type II was recognized as hypercellular bone marrow with dysmaturity of granulocytic cells. Bone marrow of 20 cases (61%) were characterized with type I whereas 13 cases (39%) with type II. The median duration of neutrophil recovery and high-grade fever were 4.7 ± 1.0 days and 3.6 ± 2.5 days respectively for type II, compared to 8.0 ± 2.8 days and 8.6 ± 3.1 days for type I (p < 0.01 in both compared groups). However, there was no significant difference between the two types in terms of age, median duration of drug administration before the diagnosis of agranulocytosis, the amount of neutrophil count on admission and the total administration dose of granulocyte-colony stimulating factor (G-CSF) before bone marrow examination. Two cases of type I died of complications from infection. This study showed that the bone marrow characteristics of ATD-induced agranulocytosis could be classifed into two types. Also, the clinical prognosis was closely related to the bone marrow features. Type I is the dominant type which is usually associated with worse clinical prognosis compared to type II.

Topics: Adult; Agranulocytosis; Antithyroid Agents; Bone Marrow; Cell Differentiation; China; Female; Fever; Granulocyte Colony-Stimulating Factor; Granulocyte Precursor Cells; Hospitals, University; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Prognosis; Propylthiouracil; Retrospective Studies; Young Adult

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

Not much has been reported about the effects of hyperthyroidism and its correction on resistance vessels, and just two inconsistent studies have investigated the impacts of restored euthyroidism on vascular reactivity. In this regard, we designed the current study to evaluate the vascular reactivity of the mesenteric arteries of hyperthyroid and restore euthyroid rats. Hyperthyroidism was induced by administration of triiodothyronine (T3; 300μg/kg, i.p., for 12 weeks in T3 group). Euthyroidism was restored by administration of T3 for 8 weeks and then T3+Methimazole (0.003% in drinking water) for 4 weeks (T3+MMI group). According to the McGregor method, vascular relaxation and contractility response were measured in response to acetylcholine or phenylephrine respectively. We found that maximal contractility response (Emax) to phenylephrine in the T3 group was significantly decreased (P<0.001), and Emax to acetylcholine was significantly increased compared with the saline group (P<0.05). When N(G)-nitro-L-arginine methyl ester (L-NAME, 3×10(-4)M) was used, Emax to acetylcholine in the T3 group was still higher than the saline group (P<0.05). However, decrease in maximal response of the T3 group was significantly greater than the saline group (P<0.01). We also showed that when euthyroidism is restored by methimazole therapy, enhanced acetylcholine-induced vasorelaxation and impaired contractility response to phenylephrine were normalized, as there was no significant difference in Emax of the T3+MMI group versus the saline group (P>0.05). In conclusion, synthesis of both nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in mesenteric arteries significantly increased as a consequence of hyperthyroidism, and this abnormal vascular reactivity is corrected by methimazole therapy.

Topics: Animals; Chronic Disease; Endothelium, Vascular; Hyperthyroidism; Male; Mesenteric Arteries; Methimazole; Perfusion; Rats; Rats, Sprague-Dawley; Recovery of Function; Thyroid Gland; Vasoconstriction; Vasodilation

The aim of this study was to examine whether the relative gene expression of AdipoR1 and AdipoR2 in rat adipose tissue is altered by thyroid hormones, and whether this might relate to their circulating thyroid hormones and adiponectin levels. Hyper- and hypothyroidism were induced by daily oral administration of levothyroxine and methimazole in rats, respectively, over a 42 days period. Real-time PCR analysis was performed to evaluate the changes in AdipoR1 and AdipoR2 mRNA levels in the adipose tissue on days 15, 28, 42, and also 2 weeks after the cessation of treatment. In response to treatment with methimazole, mRNA levels of AdipoR1 and AdipoR2 decreased in the white adipose tissue compared to the euthyroid rats (p < 0.05). This decline was reversible 2 weeks after treatment cessation. The mRNA levels of AdipoR1 and AdipoR2 were increased in the hyperthyroid group of animals compared to euthyroid control (p < 0.05), and its changes were reversible 2 weeks after treatment cessation (P < 0.05). Adiponectin receptors gene expression levels in the adipose tissue of treated animals have positive correlations with thyroid hormones concentrations. Our results suggest that AdipoR1 and AdipoR2 gene expression is regulated by thyroid hormones in hypo- and hyperthyroidism.

Topics: Adiponectin; Animals; Female; Gene Expression Regulation; Hyperthyroidism; Hypothyroidism; Intra-Abdominal Fat; Methimazole; Organ Specificity; Rats; Rats, Sprague-Dawley; Receptors, Adiponectin; RNA, Messenger; Thyroxine; Triiodothyronine

Thyrotoxicosis is mainly caused by autonomous adenomas of the thyroid gland and by Graves' disease. A less frequent cause for thyrotoxicosis is Hashimoto's thyroiditis. Thyrotoxicosis in autonomous adenomas and Graves' disease is caused by an increased thyroid hormone production whereas hyperthyroidism in Hashimoto's thyroiditis results from destruction of the thyroid gland. Drug therapy depends on the cause of the disease. Autonomous adenomas and Graves' disease are treated with methimazole and potentially with β-blockers. Regarding thyroid ablative therapy, radioiodine is mostly preferred compared to thyroidectomy. Drug therapy of Hashimoto's thyroiditis is purely symptomatic using β-blockers and rarely corticosteroids. Hyperthyroidism in pregnancy is a major issue and pregnant women in the first trimester are treated with propylthiouracil (PTU) whereas women in the second and third trimesters are treated with methimazole. The aim is to maintain the serum fT4 levels within the upper normal range.

Topics: Adrenergic beta-Antagonists; Adult; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Pregnancy; Pregnancy Complications; Radiopharmaceuticals; Radiotherapy

Topics: Animals; Antithyroid Agents; Cat Diseases; Cats; Female; Hyperthyroidism; Leptin; Male; Methimazole; Thyroid Hormones; Thyroxine; Treatment Outcome

A 41-year-old man with a history of hyperthyroidism had been treated with methimazole and propranolol for the past 2 months. He developed multiorgan dysfunction with acute liver failure, severe lactic acidosis, disseminated intravascular coagulation, heart failure and acute pulmonary edema with rapid deterioration of renal function. The patient had no history of alcoholism, drug abuse, blood transfusion, or exposure to hepatitis A, B, or C. Extrahepatic obstruction was ruled out with an abdominal ultrasonogram. Serologic studies and immunologic tests were negative. This case illustrates the sudden and abrupt deterioration of multiorgan dysfunction due to antithyroid drug administration and thyroid storm. The thyroid storm score of Burch and Wartofsky was 90/140. The multiorgan dysfunction was reversed by discontinuation of the methimazole and treat with hemodialysis, steroids, cholestyramine, nonselective beta-blocker, fresh frozen plasma infusion and supportive management in the intensive care unit. The patient was discharged from the hospital with normal coagulation parameters, renal and liver function tests.

Topics: Adrenergic beta-Antagonists; Adult; Anticholesteremic Agents; Antithyroid Agents; Cholestyramine Resin; Humans; Hyperthyroidism; Male; Methimazole; Multiple Organ Failure; Propranolol; Renal Dialysis; Steroids; Thyroid Crisis

Agranulocytosis is a life-threatening disorder characterised by a greatly decreased number of circulating neutrophils below 500/μL. This article presents two cases of agranulocytosis in patients treated with pegylated interferon and ribavirin due to chronic hepatitis C. Interferon induced hyperthyroidism, which required the use of a tyreostatic. Anti-thyroid drugs (ATD) used to treat hyperthyroidism can cause agranulocytosis. The synergistic reaction of ATD and interferon on bone marrow cannot be excluded.

Topics: Adult; Agranulocytosis; Antithyroid Agents; Antiviral Agents; Drug Therapy, Combination; Female; Hepatitis C, Chronic; Humans; Hyperthyroidism; Interferon alpha-2; Interferon-alpha; Methimazole; Middle Aged; Polyethylene Glycols; Propylthiouracil; Recombinant Proteins; Ribavirin; Time Factors; Viral Load

Disrupted thyroid hormone function evokes severe physiological consequences in the immature brain. In adulthood, although clinical reports document an effect of thyroid hormone status on mood and cognition, the molecular and cellular changes underlying these behavioural effects are poorly understood. More recently, the subtle effects of thyroid hormone on structural plasticity in the mature brain, in particular on adult hippocampal neurogenesis, have come to be appreciated. However, the specific stages of adult hippocampal progenitor development that are sensitive to thyroid hormone are not defined. Using nestin-green fluorescent protein reporter mice, we demonstrate that thyroid hormone mediates its effects on hippocampal neurogenesis by influencing Type 2b and Type 3 progenitors, although it does not alter proliferation of either the Type 1 quiescent progenitor or the Type 2a amplifying neural progenitor. Thyroid hormone increases the number of doublecortin (DCX)-positive Type 3 progenitors, and accelerates neuronal differentiation into both DCX-positive immature neurones and neuronal nuclei-positive granule cell neurones. Furthermore, we show that this increase in neuronal differentiation is accompanied by a significant induction of specific transcription factors involved in hippocampal progenitor differentiation. In vitro studies using the neurosphere assay support a direct effect of thyroid hormone on progenitor development because neurospheres treated with thyroid hormone are shifted to a more differentiated state. Taken together, our results indicate that thyroid hormone mediates its neurogenic effects via targeting Type 2b and Type 3 hippocampal progenitors, and suggests a role for proneural transcription factors in contributing to the effects of thyroid hormone on neuronal differentiation of adult hippocampal progenitors.

Topics: Animals; Cell Count; Cells, Cultured; Disease Models, Animal; Doublecortin Protein; Gene Expression Regulation, Developmental; Hippocampus; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Mice; Mice, Inbred C57BL; Mice, Transgenic; Molecular Imaging; Neural Stem Cells; Neurogenesis; Promoter Regions, Genetic; Thyrotropin; Thyroxine; Transcription Factors; Triiodothyronine; Up-Regulation

We report here a case of a paediatric hyperthyroidism due to a micro-macro-follicular thyroid adenoma in the presence of heterozygous point mutation of TSH receptor (TSHr). We describe the case from the initial diagnosis, through laboratoristic examinations and imaging techniques, until the radical surgical treatment made by a mini-cervicotomic videoassisted technique. We also explained the genetic work-up from peripheral blood and thyroid adenoma tissue.

Topics: Adenoma; Amino Acid Substitution; Exons; Hormone Replacement Therapy; Humans; Hyperplasia; Hyperthyroidism; Infant, Newborn; Male; Methimazole; Mutation, Missense; Receptors, Thyrotropin; Thoracic Surgery, Video-Assisted; Thyroid Neoplasms; Thyroid Nodule; Thyroidectomy; Thyroxine

Topics: Anticoagulants; Antithyroid Agents; Coronary Thrombosis; Diagnosis, Differential; Diagnostic Imaging; Factor V; Female; Humans; Hyperthyroidism; Methimazole; Middle Aged; Mutation; Pleural Effusion

A 12-year-old girl presented signs and symptoms of hyperthyroidism. She had a firm goiter (II°) and she stated that she felt constant warmth, nervousness and experienced palpitations. Autoimmune hyperthyroidism was diagnosed (TSH 0.022 mIU/L↓; fT4 21.0 pmol/L; fT3 7.5 pmol/L↑; antithyroperoxidase antibodies 1148.0 U/mL↑; antithyroglobulin antibodies 41.4 U/mL; thyroid-stimulating hormone receptor antibodies 2.3 U/L↑). Thyroid ultrasound showed multiple hypoechogenic areas with increased vascular flow. During treatment with methimazole, a small hyperpigmented and moderately irritated region was found on the right side of the umbilicus. It was not an allergic skin reaction to methimazole but the classic contact allergic dermatitis, probably a result of nickel in her belt. Two years after stopping the treatment she returned to clinics. She was euthyroid but manifested a firm goiter and ultrasonographic features of autoimmune thyroid disease. The diagnostic work-up concerning antithyroid antibodies is mandatory to confirm the ongoing autoimmune process with a long-term significance.

Topics: Autoimmune Diseases; Child; Dermatitis, Allergic Contact; Female; Humans; Hyperthyroidism; Methimazole

The relationship between ischemia-modified albumin (IMA) and thyroid dysfunction remains uncertain. This study aimed to investigate the influence of overt hypothyroidism (Oho), overt hyperthyroidism (Ohe), and their treatments on serum IMA levels.. A total of 35 untreated patients with Ohe, 35 untreated patients with Oho, and 35 control subjects were enrolled in the study. C-reactive protein (CRP), homocysteine (Hcy), IMA, and lipid profiles were measured and evaluated before and after treatment.. CRP, Hcy, and IMA levels and lipid profiles were higher in patients with Oho than in euthyroid or Ohe subjects (p<0.05). Basal IMA levels were reduced after treatments in all patients (p<0.05). In Ohe patients, serum IMA levels were positively correlated with free triiodothyronine (r=0.424, p=0.011) and free thyroxine (r=0.567, p<0.001) levels. In Oho patients, serum IMA levels were inversely correlated with free triiodothyronine (r=-0.555, p=0.001) and free thyroxine (r=-0.457, p=0.006) but positively correlated with anti-thyroid peroxidase antibody, C-reactive protein, and homocysteine levels (p<0.05). Linear regression analyses showed that free triiodothyronine was the most important factor affecting serum IMA levels in Ohe (β=0.694, p=0.019) and in Oho (β=-0.512, p=0.025).. IMA levels are increased in patients with thyroid dysfunction, particularly in overt hypothyroidism. Thyroid dysfunction has a significant impact on the oxidative stress status.

Topics: Adult; Antithyroid Agents; Autoantibodies; Biomarkers; C-Reactive Protein; Case-Control Studies; Cholesterol, HDL; Cholesterol, LDL; Female; Homocysteine; Humans; Hyperthyroidism; Hypothyroidism; Iodide Peroxidase; Male; Methimazole; Middle Aged; Oxidative Stress; Serum Albumin; Serum Albumin, Human; Thyroxine; Triglycerides; Triiodothyronine

A 12-year-old female neutered ragdoll crossbred cat was presented for investigation of generalised weakness and regurgitation. The cat was being treated with transdermal methimazole for hyper-thyroidism, which had been diagnosed 10 weeks previously. An acetylcholine receptor antibody titre was consistent with acquired myasthenia gravis. Withdrawal of methimazole and treatment with pyridostigmine was followed by resolution of clinical signs and reduction of the acetylcholine -receptor antibody titre. Medical control of hyperthyroidism was subsequently achieved with carbimazole, administered in conjunction with pyridostigmine, and no recurrence of clinical signs was observed. Myasthenia gravis is an uncommon but clinically significant adverse effect of methimazole therapy in cats, and may be caused by immunomodulatory properties of this drug. An adverse drug reaction should be considered in cats receiving methimazole that develop myasthenia gravis, and potentially also other immune-mediated disorders.

Topics: Animals; Antithyroid Agents; Carbimazole; Cat Diseases; Cats; Female; Hyperthyroidism; Methimazole; Myasthenia Gravis; Pyridostigmine Bromide; Receptors, Cholinergic

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

The osteoporosis associated with human hyperthyroidism has traditionally been attributed to elevated thyroid hormone levels. There is evidence, however, that thyroid-stimulating hormone (TSH), which is low in most hyperthyroid states, directly affects the skeleton. Importantly, Tshr-knockout mice are osteopenic. In order to determine whether low TSH levels contribute to bone loss in hyperthyroidism, we compared the skeletal phenotypes of wild-type and Tshr-knockout mice that were rendered hyperthyroid. We found that hyperthyroid mice lacking TSHR had greater bone loss and resorption than hyperthyroid wild-type mice, thereby demonstrating that the absence of TSH signaling contributes to bone loss. Further, we identified a TSH-like factor that may confer osteoprotection. These studies suggest that therapeutic suppression of TSH to very low levels may contribute to bone loss in people.

Topics: Animals; Bone Density; Bone Diseases, Metabolic; Bone Resorption; Dose-Response Relationship, Drug; Drug Implants; Hormone Replacement Therapy; Hyperthyroidism; Hypothyroidism; Methimazole; Mice; Mice, Inbred C57BL; Mice, Knockout; Osteoporosis; Phenotype; Receptors, Thyrotropin; Signal Transduction; Thyrotropin; Thyroxine

Thyroid hormones are essential for normal brain development and very important in the normal functioning of the brain. Thyroid hormones action in the adult brain has not been widely studied. The effects of adult hyperthyroidism are not as well understood as adult hypothyroidism, mainly in hippocampal granular cells. The purpose of the present study is to assess the consequences of adult hormone dysthyroidism (excess/deficiency of TH) on the morphology of dentate granule cells in the hippocampus by performing a quantitative study of dendritic arborizations and dendritic spines using Golgi impregnated material. Hypo-and hyperthyroidism were induced in rats by adding 0.02 percent methimazole and 1 percent L-thyroxine, respectively, to drinking water from 40 days of age. At 89 days, the animals' brains were removed and stained by a modified Golgi method and blood samples were collected in order to measure T4 serum levels. Neurons were selected and drawn using a camera lucida. Our results show that both methimazole and thyroxine treatment affect granule cell morphology. Treatments provoke alterations in the same direction, namely, reduction of certain dendritic-branching parameters that are more evident in the methimazole than in the thyroxine group. We also observe a decrease in spine density in both the methimazole and thyroxine groups.

Topics: Analysis of Variance; Animals; Antithyroid Agents; Disease Models, Animal; Hippocampus; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Neurons; Rats; Rats, Wistar; Silver Staining; Statistics, Nonparametric; Thyroid Hormones; Thyroxine

To assess the influence of thyroid function on natriuretic peptide concentration in hyperthyroid cats before and after treatment.. Serum natriuretic peptide concentration was measured in 61 hyperthyroid cats recruited from first-opinion clinics before and after treatment.. Following successful treatment, total thyroxine, heart rate, systolic blood pressure and packed cell volume all decreased and bodyweight and creatinine concentrations increased. Furthermore, a significant (P < 0·001) decline in NT-proBNP concentration but not NT-proANP was identified.. Thyroid function has a modest but significant effect on NT-proBNP concentration. Thyroid status should be taken into account when interpreting NT-proBNP concentrations in cats.

Topics: Animals; Antithyroid Agents; Biomarkers; Blood Pressure; Case-Control Studies; Cat Diseases; Cats; Female; Heart Rate; Hyperthyroidism; Male; Methimazole; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Thyroxine; Treatment Outcome

Propylthiouracil (PTU) is a drug used to treat hyperthyroidism. A number of adverse effects have been reported with this drug, including fever, agranulocytosis, skin rash, and vasculitis. PTU-induced interstitial pneumonia is rare--only three cases have been reported--and PTU-induced nonspecific interstitial pneumonia (NSIP) has not been reported. We report a patient who developed NSIP after taking PTU for 1 year. She developed dyspnea, cough, and mild fever lasting 1 month, and a chest CT scan showed multifocal patchy consolidation in both lungs. She underwent a surgical lung biopsy, and NSIP was confirmed pathologically. The symptoms and abnormalities seen in the chest radiograph improved after withdrawal of PTU. To our knowledge, this is the first documented case of pathologically proven PTU-induced NSIP.

Topics: Antithyroid Agents; Female; Humans; Hyperthyroidism; Lung Diseases, Interstitial; Methimazole; Middle Aged; Propylthiouracil; Radiography, Thoracic; Tomography, X-Ray Computed

To compare, using two large nationwide population-based data sets, the risk of adverse pregnancy outcomes (low birthweight [LBW], preterm birth, small for gestational age [SGA] and congenital anomalies) among pregnant women with hyperthyroidism classified into three groups: receiving propylthiouracil (PTU) treatment during pregnancy, receiving methimazole/carbimazole (MMI) treatment, and no antithyroid treatment during pregnancy.. A matched case-control study.. Taiwan.. A total of 2830 mothers with hyperthyroidism and 14,150 age-matched randomly selected mothers without hyperthyroidism were included.. Conditional logistic regression analyses were performed to examine the risk of adverse pregnancy outcomes (LBW, preterm birth, SGA and major congenital anomalies) among these three groups.. LBW, preterm birth, SGA and major congenital anomalies.. Women receiving PTU treatment during pregnancy had a higher risk of giving birth to LBW infants than those not receiving antithyroid treatment (odds ratio = 1.40; 95% CI 1.00-1.96), after adjusting for maternal education, anaemia, hyperlipidaemia, pregestational diabetes, pregestational hypertension, hyperemesis gravidarum and infant's gender and birth order. However, children of women receiving MMI treatment did not have increased risks of any adverse fetal outcome relative to mothers not receiving antithyroid treatment.. Our study finds an increased risk of LBW among babies of mothers with hyperthyroidism receiving PTU treatment during pregnancy relative to untreated mothers with hyperthyroidism.

Topics: Adult; Antithyroid Agents; Carbimazole; Case-Control Studies; Congenital Abnormalities; Female; Humans; Hyperthyroidism; Infant, Low Birth Weight; Infant, Newborn; Infant, Small for Gestational Age; Logistic Models; Male; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Prevalence; Propylthiouracil; Taiwan; Young Adult

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

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

Topics: Antithyroid Agents; Atenolol; Chorea; Dibenzothiazepines; Female; Goiter, Nodular; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Patient Compliance; Prednisone; Propylthiouracil; Quetiapine Fumarate; Thyrotoxicosis; Thyrotropin; Thyroxine; Triiodothyronine; Young Adult

Topics: Aged; Agranulocytosis; Anti-Bacterial Agents; Antithyroid Agents; Debridement; Diagnosis, Differential; Fasciitis, Necrotizing; Female; Follow-Up Studies; Humans; Hyperthyroidism; Methimazole; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Animals; Antithyroid Agents; Cat Diseases; Cats; Combined Modality Therapy; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Prognosis

Movement disorders are known to be associated with hyperthyroidism. However, the association of Meige's syndrome and hemichorea with hyperthyroidism has not been reported. We describe a young Chinese woman with hyperthyroidism, who presented with a unique combination of Meige's syndrome and hemichorea in the left limbs. Both neurologic manifestations were preceded by symptoms of hyperthyroidism, and resolved following treatment with methimazole for hyperthyroidism. Nevertheless, the neurologic symptoms recurred when she stopped taking methimazole, but abated when she returned to a euthyroid state after additional treatment with methimazole. The evolution of her clinical course indicated that the involuntary movements were in association with hyperthyroidism. This case is the first report of Meige's syndrome and hemichorea in a patient with hyperthyroidism, which raises the likelihood that hyperthyroidism may be a cause of Meige's syndrome and hemichorea. Furthermore, it emphasizes the need for greater attention to thyroid function in those afflicted with involuntary movements in order to optimize clinical management.

Topics: Adult; Antithyroid Agents; Chorea; Female; Humans; Hyperthyroidism; Meige Syndrome; Methimazole; Thyroid Function Tests

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Biomarkers; Female; Hepatitis B; Hepatitis, Viral, Human; Humans; Hyperthyroidism; Liver Function Tests; Male; Methimazole; Middle Aged; Propylthiouracil; Retrospective Studies; Severity of Illness Index; Thyroid Function Tests; Young Adult

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

The thionamide antithyroid drugs methimazole and propylthiouracil are the mainstay of pharmacologic therapy for Graves' disease. However, little is known about the rate of use of these drugs and the prescribing practices of physicians treating hyperthyroidism.. The objective of the study was to examine the frequency of methimazole and propylthiouracil use from years 1991 to 2008.. The data were acquired by the U.S. Food and Drug Administration's Division of Epidemiology through two databases: IMS National Sales Perspectives and the Surveillance Data, Inc. Vector One: National database.. There was a 9-fold increase in the annual number of methimazole prescriptions during the study period, from 158,000 to 1.36 million per year. There was a 19% increase in the annual number of propylthiouracil prescriptions, from 348,000 to 415,000 per year. Propylthiouracil, which held two thirds of the market from 1991 to 1995, was surpassed by methimazole in 1996. Patient demographic data indicated that although 72% of methimazole prescriptions were for females, males were more likely to be on methimazole (82%) than females (74%) (P < 0.001, two tailed chi(2) test). The only demographic group in which methimazole use decreased was women of child-bearing age (5% decrease, P < 0.001, two tailed chi(2)). The incidence of hyperthyroidism in 2008 was estimated based on the number of new prescriptions of thionamides by age group and data from the 2008 U.S. census: 0.44 per 1000 for ages 0-11 yr, 0.26 per 1000 for ages 12-17 yr, 0.59 per 1000 for ages 18-44 yr, 0.78 per 1000 for ages 45-64 yr, and 1.01 per 1000 for ages 65+ yr.. Methimazole has become the most frequently prescribed antithyroid drug. The remarkable increase in the total number of dispensed thionamide prescriptions over the last 18 yr may indicate a trend toward pharmacological treatment as primary treatment of Graves' disease in the United States.

Topics: Adolescent; Adult; Age Factors; Aged; Antithyroid Agents; Child; Child, Preschool; Drug Prescriptions; Female; Humans; Hyperthyroidism; Incidence; Male; Methimazole; Middle Aged; Prescription Drugs; Propylthiouracil; Sex Characteristics; United States; United States Food and Drug Administration

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

Thyroid hormones (THs) play a crucial role in the development and physiological functioning of different body organs especially the brain. Therefore, the objective of this study was to show the histopathological effects of the different thyroid states on some brain regions (cerebrum and cerebellum) and the skeletal features of their newborns during the postnatal development from the 1st to 3rd week. The female white albino rats were allocated into 3 groups as follows: the experimental hypothyroidism group is induced by 0.02% methimazole (MMI) (w/v) in drinking water, while the experimental hyperthyroidism group is performed by exogenous T4 [from 50 to 200microg/kg body weight intragastric administration beside adding 0.002% T4 (w/v) to the drinking water] from the gestation day 1 to lactation day 21 and control group which received tap water. As well, both maternal hypo- and hyperthyroidism caused some malformation and developmental defects in the cerebellar and cerebral cortex of their newborns along the duration of the experiment. These degenerative symptoms became more prominent and widely spread at the 3rd postnatal week. Concomitantly, there were some degeneration, deformation and severe growth retardation in neurons of these regions in both treated groups throughout the experimental period. Moreover, the skeletal features of these newborns were accelerated in hyperthyroid group while these maturations were delayed partially in hypothyroid ones during the examined periods. These alterations, on both treated groups, were age and dose dependent. Thus, further studies need to be done to emphasize this concept.

Topics: Animals; Antithyroid Agents; Brain; Cell Differentiation; Disease Models, Animal; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Nerve Degeneration; Neurogenesis; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Thyroxine

Clinical hyperthyroidism is not uncommon in pregnancy, with a reported prevalence of 0.1 to 0.4%. The available antithyroid drugs are propylthiouracil and methimazole/carbimazole.. In this report we examined the association of both drugs with congenital malformations using data from the International Clearinghouse for Birth Defects Surveillance and Research.. The study used a case-affected control analysis and included 18,131 cases with malformations and reported first-trimester exposure to medication. A total of 127 subjects were born to mothers with known first-trimester antithyroid drug exposure.. Among the 52 groups of malformations that were analyzed, situs inversus ± dextrocardia, isolated unilateral kidney a/dysgenesis, and cardiac outflow tract defects were associated with prenatal exposure to propylthiouracil based on three, two, and five cases, respectively. Prenatal exposure to methimazole/carbimazole was significantly associated with choanal atresia, omphalocele, and total situs inversus ± dextrocardia (P < 0.01).. Further studies are required to exhaustively evaluate the associations between propylthiouracil and birth defects because of the low number, the lack of biological plausibility, and the possibility of underdiagnosis. Association between methimazole/carbimazole exposure and omphalocele and choanal atresia is consistent with previous reports and definitely suggests that these malformations could be part of a specific, even if rare, embryopathy.

Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Carbimazole; Case-Control Studies; Female; Humans; Hyperthyroidism; Incidence; Methimazole; Odds Ratio; Pregnancy; Pregnancy Complications; Propylthiouracil

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

Thiamazole is a widely used antithyroid agent that has been approved for the treatment of hyperthyroidism. Although thiamazole-induced hepatotoxicity is a main side effect, it may progress to liver failure in a very few cases.. We described a 24-year-old patient with hyperthyroidism and trilogy of Fallot, who developed liver failure due to thiamazole. Liver biopsy showed intrahepatic cholestasis, mild inflammatory infiltrates, as well as significant fibrosis, indicating both acute and chronic liver injuries. Although a series of potent therapies were given, the patient deceased due to severe liver decompensation.. This case suggests that thiamazole-induced hepatotoxicity in the setting of advanced fibrosis increases the risk of poor outcome. Regular liver function monitoring during thiamazole therapy is therefore important.

Topics: Antithyroid Agents; Fatal Outcome; Humans; Hyperthyroidism; Liver Failure; Male; Methimazole; Trilogy of Fallot; Young Adult

We report a case of a 67-year-old woman with stage IIIB locally advanced non-small cell lung cancer who had also suffered from hyperthyroidism with persistent atrial fibrillation (AF). Thiamazole provided euthyroid status, but medication failed to resolve AF. A computed tomography (CT)-scan revealed a 5×5-cm mass in the left hilar region that involved the left atrium (LA) and bifurcation of the pulmonary artery. Left pneumonectomy, LA partial resection and reconstruction of the bifurcation of the pulmonary artery were performed. In addition, a maze procedure was performed using cardiopulmonary bypass and cardiac arrest. We present the first case report of advanced lung cancer surgery with a maze procedure. Follow-up by CT-scan 34 months later did not show any recurrence and attacks of AF (no medication after surgery) were completely resolved after the operation.

Topics: Aged; Antithyroid Agents; Atrial Fibrillation; Blood Vessel Prosthesis Implantation; Carcinoma, Non-Small-Cell Lung; Cardiopulmonary Bypass; Catheter Ablation; Female; Heart Arrest, Induced; Heart Atria; Humans; Hyperthyroidism; Lung Neoplasms; Lymph Node Excision; Methimazole; Neoplasm Invasiveness; Neoplasm Staging; Pneumonectomy; Pulmonary Artery; Tomography, X-Ray Computed; Treatment Outcome

Most solitary hyperfunctiong regions on thyroid scan consist of benign tissue. Here we report a patient with a Burkitt-like lymphoma that was infilterated into a region containing a hyperfunctioning nodule.. A 56-year-old man was referred to our Endocrine Unit in May 2009 due to the incidental discovery of a large left thyroid lobe nodule by a computed tomography study. This had been performed to search for a primitive tumor in a patient with bone metastasis. He was clinically and biochemically thyrotoxic with no evidence of humoral thyroid autoimmunity. The nodule had a dyshomogenous appearance at neck ultrasonography, with multiple hypoechogenic areas and calcifications. (99m)-Technetium thyroid scintiscan revealed a hot nodule with suppression of the contralateral lobe. Fine-needle aspiration cytology indicated the presence of neoplastic cells not of thyroid origin. Remission of hyperthyroidism was obtained with methimazole, and the patient was submitted to left lobe thyroidectomy and istmectomy. Histological analysis of the surgical specimen led to a diagnosis of Burkitt-like large B-cell lymphoma harbored within a thyroid adenoma. After further staging, the final diagnosis was stage IV E Burkitt-like lymphoma with the involvement of the bone and the thyroid. This is the first description of an aggressive Burkitt-like lymphoma that infiltrated an hyperfunctioning thyroid adenoma, thus presenting as a hot nodule at thyroid scintiscan. In our patient there was no humoral or histological evidence of thyroid autoimmunity, thus suggesting a metastatic seeding of the lymphoma within the hyperfunctioning thyroid nodule.. Involvement of the thyroid gland by Burkitt-like lymphoma is extremely rare as is close localization of malignancy and a hyperfunctioning thyroid nodule. As highlighted by the present report, performing fine-needle aspiration cytology should be always considered in the clinical context of a metastatic disease of unknown origin or when there are ultrasonography signs suggesting malignancy, even when the nodule is hyperfunctioning.

Topics: Adenoma; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biopsy, Fine-Needle; Bone Neoplasms; Burkitt Lymphoma; Cyclophosphamide; Dexamethasone; Doxorubicin; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Neoplasm Staging; Technetium; Thyroid Neoplasms; Thyroid Nodule; Vincristine

Topics: Adult; Antihypertensive Agents; Antithyroid Agents; Female; Headache; Humans; Hyperthyroidism; Methimazole; Propranolol

Methimazole is a widely used antithyroid agent. Although methimazole is generally well tolerated, rare but severe cholestatic jaundice may occur. We described a 74-year-old woman who had a 10-year history of type 2 diabetes had developed severe jaundice and itching 1 month after receiving methimazole (10 mg tid) and propranolol (10 mg tid) for the treatment of hyperthyroidism. Clinical investigations revealed no evidence of any mechanical obstruction in the common bile duct or other obvious causes of hepatic injury, and the diagnosis methimazole-induced cholestasis was made on the basis of the temporal relationship between initiation of methimazole and onset of cholestasis. Methimazole was hence discontinued. However, the patient experienced a progressive worsening in cholestasis after receiving 2 weeks of ursodeoxycholic acid (UDCA) therapy. Prednisone therapy was then attempted. Liver function tests eventually improved with combination of glucocorticoids and ursodeoxycholic acid therapy. This case clearly showed that glucocorticoids could be a possible additional way of treatment for some cases of drug-induced cholestatic jaundice even in diabetic patients.

Topics: Aged; Antithyroid Agents; Diabetes Mellitus, Type 2; Female; Humans; Hyperthyroidism; Hypoglycemic Agents; Jaundice, Obstructive; Methimazole; Severity of Illness Index; Steroids

We aimed to compare the prevalence of antineutrophil cytoplasmic antibody (ANCA) and its subgroups between on-treatment (with anti-thyroid drugs; propylthiouracil, methimazole) and untreated patients with hyperthyroidism in our unit. Overall 78 consecutive patients were enrolled in the study; 45 patients were on-treatment (female/male 31:14) and 33 were newly diagnosed (female/male 20:13). We have studied ANCA, perinuclear-ANCA (p-ANCA), cytoplasmic-ANCA (c-ANCA), myeloperoxidase-ANCA (mpo-ANCA), and proteinase 3-ANCA (pr3-ANCA) in sera of all the patients. The data about clinical status, laboratory tests, and physical examination and mean duration of treatment in treated group were recorded. There was no statistically significant difference between the two groups for ANCA, c-ANCA, and pr3-ANCA (P=0.13, P=0.07, and P=0.63 respectively). p-ANCA and mpo-ANCA prevalences were significantly higher in on-treatment group than in untreated group (P=0.04 and P=0.01, respectively). The mean duration of treatment was 17 months in on-treatment group. The use of antithyroid drugs (propylthiouracil, methimazole) seems to be correlated with increased prevalence of ANCA. These drugs may especially increase p-ANCA and mpo-ANCA positivity.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Myeloblastin; Peroxidase; Propylthiouracil; Seroepidemiologic Studies

Typical presentations of hyperthyroidism are palpitation, nervousness, tremor, malaise, and weight loss. Hyperthyroidism affects nearly every system in the body, and some patients may manifest neurologic or hematologic symptoms. Atypical presentations of hyperthyroidism often pose a great challenge in diagnosis and treatment. We report a case of Basedow's paraplegia and pancytopenia that was precipitated by hyperthyroidism. The unusual manifestations led to unnecessary examinations and delayed the treatment of hyperthyroidism. The classical symptoms of Basedow's paraplegia are subacute symmetric weakness of the lower extremities with areflexia and sparing sensation or sphincter involvement. Control of the hyperthyroidism mitigated the neurologic and hematologic complications and prevented unnecessary studies.

Topics: Adrenergic beta-Antagonists; Adult; Antithyroid Agents; Female; Humans; Hyperthyroidism; Methimazole; Pancytopenia; Paraplegia; Propranolol

Topics: Adult; Antithyroid Agents; Chemical and Drug Induced Liver Injury; Female; Humans; Hyperthyroidism; Incidence; Liver Diseases; Liver Transplantation; Male; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; United States

Hyperthyroidism is characterized by hyperphagia and increased basal metabolic rate. Ghrelin peptide is implicated in food intake through activation of the orexigenic neuropeptide Y/agouti related protein in the arcuate nucleus of hypothalamus. Also different studies suggested that ghrelin might play a role in states of energy insufficiency, controlling body weight. We therefore evaluate ghrelin levels in severe hyperthyroidism before and after medical treatment when euthyroidism was achieved, in order to evaluate its possible role in the increase of appetite and in the metabolic changes observed in hyperthyroidism. Serum ghrelin and insulin levels were measured after an oral glucose tolerance test (OGTT), in 7 severe hyperthyroid female patients, before and after medical treatment when euthyroidism was achieved. Body mass index (BMI), percentage of body fat and lean mass was also estimated in hyperthyroidism as well as in euthyroidism. Basal insulin levels were statistically higher in hyperthyroid patients with respect to euthyroid state after treatment (p=0.02, t=3.379), while homeostasis model assessment (HOMA) index for insulin sensitivity was statistically higher in hyperthyroidism (group 1) compared to euthyroidism (group 2) (1.64+/-0.69 vs 0.78+/-0.44, p=0.019, t=3.389). Fasting ghrelin concentrations were significantly reduced in group 1 compared to group 2 (938+/-578 pg/ml vs 1402+/-566 pg/ml, p<0.05, t=-2.489). Oral glucose loading induced suppression of ghrelin level in both groups, but the area under the curve for ghrelin during the OGTT in euthyroidism was greater compared to hyperthyroidism (p=0.05, t=-2.485). After medical treatment, a statistically significant increase in BMI (23.1+/-4.3 vs 25.9+/-5.1) (p=0.007, t=-4.399) was also observed. In hyperthyroidism, basal ghrelin levels showed a negative correlation with BMI (p=0.042, r=-0.829), insulin (p<0.001, r=-1.000), and HOMA index (p=0.019, r=-0.886). No correlation was found between ghrelin levels and thyroid hormone values. Ghrelin levels are decreased in hyperthyroidism and increase when euthyroidism is achieved. BMI and insulin are the main factors that influence ghrelin concentration in hyperthyroidism. T3 and T4 levels do not influence ghrelin levels. There is no evidence that ghrelin is responsible for the increase appetite seen in hyperthyroidism.

Topics: Adult; Antithyroid Agents; C-Peptide; Female; Ghrelin; Glucose Tolerance Test; Humans; Hyperthyroidism; Insulin; Methimazole; Middle Aged; Thyrotropin; Thyroxine; Triiodothyronine

We report a case of hepatotoxicity induced by methimazole treatment in a patient affected by hyperthyroidism. A 54-year-old man, presented to our observation for palpitations, excessive sweating, weakness, heat intolerance and weight loss. On physical examination, his blood pressure was 140/90 mmHg and heart beat was 100/min regular. He had mild tremors and left exophthalmos. Laboratory test revealed a significant increase in serum thyroid hormone levels with a decrease in thyroid stimulating hormone levels. A diagnosis of hyperthyroidism was made and he began treatment with methimazole (30 mg/day). Fourteen days later, he returned for the development of scleral icterus, followed by dark urine, and abdominal pain in the right upper quadrant. Laboratory examinations and liver biopsy performed a diagnosis of cholestatic hepatitis, secondary to methimazole usage. Methimazole was promptly withdrawn and cholestyramine, ursodeoxycholic acid, and chlorpheniramine were given. After five days, abdominal pain resolved and laboratory parameters returned to normal. Naranjo probability scale indicated a probable relationship between hepatotoxicity and methimazole therapy. In conclusion physicians should be aware the risk of hepatotoxicity related with methimazole.

Topics: Abdominal Pain; Antithyroid Agents; Biopsy; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Scleral Diseases

Topics: Antithyroid Agents; Female; Humans; Hyperthyroidism; Methimazole; Pregnancy; Propylthiouracil; Thyroid Crisis

A 55-years-old woman, with a history of hypertension and ischemic stroke with residual left hemiparesis, was admitted to our hospital because of dyspnoea with clinical evidence of acute pulmonary edema. She was found to have a sinus tachycardia with ST-elevation in leads D1, aVL and V1-V4 in the electrocardiogram, and akinesis of the left ventricular apex with overall left ventricular systolic function being severely impaired and an ejection fraction of 28% on echocardiography. Orotracheal intubation was performed and mechanical ventilation was immediately started. Emergency cardiac catheterization was performed 2 h after the symptom onset. Coronary angiography showed no significant coronary artery disease. Blood analysis revealed an increase in the creatine kinase MB fraction, a significant positive detection in troponin T, a white blood cell count of 35000 per microliter, C-reactive protein of 59,9 mg/dl, and transient elevation in the concentration of free triiodothyronine, free thyroxine, thyroid globulin antibody, and thyroid peroxidase antibody. The symptoms improved during the next days, and follow-up echocardiography 18 days later showed complete resolution of the left ventricular dysfunction. These data suggest that tako-tsubo cardiomyopathy may be induced in patients with sepsis and transient hyperthyroidism.

Topics: Amlodipine; Anti-Bacterial Agents; Antihypertensive Agents; Antithyroid Agents; Aspirin; Echocardiography; Electrocardiography; Female; Glucocorticoids; Humans; Hyperthyroidism; Methimazole; Middle Aged; Ofloxacin; Platelet Aggregation Inhibitors; Prednisone; Propranolol; Ramipril; Sepsis; Takotsubo Cardiomyopathy

I have a patient who has hyperthyroidism due to Graves disease. She was taking methimazole but discontinued when she found out she was pregnant. She is currently close to delivery and might require antithyroid therapy in the postpartum period. Can methimazole cross into human milk, and is breastfeeding safe for her infant?. The exposure of infants to methimazole or propylthiouracil through breast milk is minimal and not clinically significant. Women with hyperthyroidism using methimazole or propylthiouracil should not be discouraged from breastfeeding, as the benefits of breastfeeding largely outweigh the theoretical minimal risks.

Topics: Antithyroid Agents; Breast Feeding; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Humans; Hyperthyroidism; Infant; Infant, Newborn; Lactation; Maternal Exposure; Methimazole; Milk, Human; Pregnancy; Propylthiouracil; Thyroid Gland; Treatment Outcome

Topics: Animals; Antithyroid Agents; Cat Diseases; Cats; Hyperthyroidism; Lymphatic Diseases; Methimazole

We describe a case of severe congestive heart failure and right ventricular overload associated with overt hyperthyroidism, completely reversed with antithyroid therapy in a few week. It represents a very unusual presentation of overt hyperthyroidism because of the severity of right heart failure. The impressive right ventricular volume overload made mandatory to perform transesophageal echo and angio-TC examination to exclude the coexistence of ASD or anomalous pulmonary venous return. Only a few cases of reversible right heart failure, with or without pulmonary hypertension, have been reported worldwide. In our case the most striking feature has been the normalization of the cardiovascular findings after six weeks of tiamazole therapy.

Topics: Adrenergic beta-Antagonists; Drug Therapy, Combination; Dyspnea; Echocardiography, Transesophageal; Electrocardiography; Female; Follow-Up Studies; Furosemide; Heart Failure; Heparin, Low-Molecular-Weight; Humans; Hyperthyroidism; Methimazole; Middle Aged; Recovery of Function; Risk Assessment; Severity of Illness Index; Thyroid Function Tests; Treatment Outcome; Ventricular Dysfunction, Right

Thyroid hormone resistance occurs when a genetic mutation in the thyroid hormone receptor leads to reduced hormone binding affinity; the concentration of free thyroid hormone in the circulation is inversely correlated with the hormone binding affinity of the mutant receptor. Thyroid hormone resistance mutations are associated with a wide variety of phenotypes and subsequent treatment challenges. Among the more common symptoms are hyperactivity, emotional lability, a below average intelligence quotient, and short stature. We report here a patient who presented with thyroid hormone resistance at an early age, providing an opportunity to optimize her overall growth and development. We review the limited information currently available in the literature addressing the treatment of thyroid hormone resistance in children and describe the approach used to determine the treatment plan in this young child.

Topics: Antithyroid Agents; Diagnosis, Differential; DNA Mutational Analysis; Female; Humans; Hyperthyroidism; Infant; Methimazole; Mutation; Receptors, Thyroid Hormone; Thyroid Function Tests; Thyroid Hormone Resistance Syndrome; Thyroxine

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

A 25-yr-old female tetraplegic patient experienced autonomic dysreflexia episodes involving hypertension, headache, facial flushing, and tachycardia. The symptoms were not related to the bladder or bowel. The episodes did not seem to be linked to any mechanical cause. The patient was incidentally diagnosed with hyperthyroidism. Treatment with antithyroid medication resulted in resolution of the autonomic dysreflexia. This case suggests that hyperthyroidism may trigger autonomic dysreflexia in tetraplegic patients.

Topics: Adult; Antihypertensive Agents; Antithyroid Agents; Autonomic Dysreflexia; Female; Humans; Hyperthyroidism; Methimazole; Propranolol; Quadriplegia

Topics: Animals; Antithyroid Agents; Carbimazole; Cat Diseases; Cats; Diagnosis, Differential; Hyperthyroidism; Lymphatic Diseases; Methimazole

Topics: Animals; Antithyroid Agents; Chinchilla; Diabetes Complications; Diabetes Mellitus; Diagnosis, Differential; Female; Glipizide; Hyperthyroidism; Hypoglycemic Agents; Methimazole; Rodent Diseases; Switzerland

The extent of reversibility of loss of bone mass density (BMD) in hyperthyroid patients after treatment is not clear.. The bone density measured by dual X-ray absorptiometry (DXA), the parameters of quantitative ultrasound (QUS) and biochemical markers of bone turnover of 22 patients were measured before and after one year of treatment with thiamazole and levothyroxine.. The mean BMD of lumbar spine, femoral neck, Ward triangle and total hip bone density increased by 5.9, 3.8, 3.0 and 6.7%, respectively, after one year of treatment, all significant increases except the increase in Ward triangle bone mass density. There was no significant change in QUS parameters, although the increase in broadband ultrasound attenuation (BUA) of the left and right calcaneus of 5.2 and 4.2%, respectively, suggests reversibility in the long term. Urinary pyridinoline cross-links declined significantly and normalised after treatment. Bone-specific alkaline phosphatase declined after an initial rise, not (yet) reaching normal values after one year of treatment.. The decline in BMD in hyperthyroid patients measured by DXA seems to be reversible after treatment of hyperthyroidism, whereas a change in the QUS parameters, probably also an indicator of bone elasticity and architecture, could not be found.

Topics: Adult; Biomarkers; Bone and Bones; Bone Density; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Thyroxine; Ultrasonography; Young Adult

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

Propylthiouracil (PTU), independent of its antithyroid effect, is recently found to have a potent antiatherosclerotic effect. The aim of this study is to investigate whether PTU has a beneficial effect on endothelial function.. Ninety patients with a history of hyperthyroidism receiving either PTU (n=45) or methimazole (MMI) (n=45) during the euthyroid status were enrolled in this study. Brachial artery endothelium-dependent (flow-mediated dilatation [FMD]) and endothelium-independent (nitroglycerin-mediated dilatation) responses were assessed by high-resolution ultrasound image. Data for these two groups were compared with those of 41 healthy control subjects. The FMD values were significantly increased in patients maintained on PTU versus those in the MMI and control groups (9.3+/-4.4%, 3.4+/-2.5%, and 3.6+/-3.4%, respectively; P<0.01). Nitroglycerin-mediated dilatation had no significant difference between the PTU, MMI, and control groups (17.4+/-7.5%, 15.9+/-6.1%, and 17.5+/-6.8%, respectively; P=0.455). On multivariate analysis, no significant relationship was found between the FMD and thyroid hormone index levels. To further elucidate whether PTU has a direct effect on endothelial function, the effect of PTU on isolated segments of Sprague-Dawley rat aorta was studied. Vasodilatation induced by PTU was endothelium-dependent and could be blocked by pretreatment with nitric oxide (NO) inhibitors. PTU also increased NO formation in aortic segments.. This study demonstrated that PTU produced endothelium-dependent vasodilatation through thyroid-independent and NO-mediated mechanisms that may contribute to its beneficial effect on atherosclerosis.

Topics: Adult; Animals; Antithyroid Agents; Aorta, Thoracic; Brachial Artery; Case-Control Studies; Cohort Studies; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Nitric Oxide; Propylthiouracil; Rats; Rats, Sprague-Dawley; Ultrasonography; Vasodilation

A nine-year-old, domestic shorthair cat was diagnosed with hyperthyroidism and treated with methimazole, which resulted in lethargy, inappetence and marked generalised lymphadenomegaly within two weeks of initiation of therapy. Cytology, histopathology and immunohistochemistry were suggestive of atypical lymphoid hyperplasia. Cessation of treatment resulted in resolution of all clinical signs and physical abnormalities within two days. Subsequent treatment with radioactive iodine cured this cat of its hyperthyroidism. The lymphadenomegaly did not return at any stage and the cat is currently asymptomatic. Although methimazole administration for feline hyperthyroidism has been associated with many side effects, lymphadenomegaly has, to the authors' knowledge, not been previously reported.

Topics: Animals; Antithyroid Agents; Cat Diseases; Cats; Diagnosis, Differential; Hyperthyroidism; Lymphatic Diseases; Male; Methimazole

Patients with thyroid diseases have abnormalities of blood coagulation including an alteration of von Willebrand factor (vWF) levels. Because vWF plays an important role in primary hemostasis, we hypothesized that heightened and decreased vWF levels in hyper- and hypothyroidism enhance and decrease platelet plug formation, respectively.. We followed a cohort of 120 patients with overt hyperthyroidism, patients with subclinical and overt hypothyroidism, and euthyroid controls. vWF and in vitro platelet plug formation as collagen-epinephrine-induced closure time (CEPI-CT) were measured at baseline and during therapy with thiamazole or T(4).. Baseline vWF levels were higher in patients with hyperthyroidism and lower in patients with overt hypothyroidism than in controls (P < 0.01). High vWF antigen levels were associated with increased baseline platelet plug formation in patients with hyperthyroidism as compared with controls [114 sec (95% confidence interval, 105-122 sec) vs. 130 sec (120-140 sec), P = 0.01]. After 8 wk of therapy with thiamazole, serum concentrations of T(4) and vWF levels decreased to normal values (P < 0.01 vs. baseline), and CEPI-CT was prolonged as compared with baseline (P < 0.01). During therapy with T(4), vWF levels increased (P < 0.05 vs. baseline) and CEPI-CT was shortened as compared with baseline (P < 0.01).. Hyperthyroidism-induced vWF elevation is associated with enhanced platelet function and therefore shortened CEPI-CT values. These changes may contribute to the higher risk for cardiovascular disease in patients with hyperthyroidism. Platelet plug formation decreases during therapy with thiamazole. Furthermore, CEPI-CT appears to be sensitive to detect acquired von Willebrand disease associated with overt hypothyroidism.

Topics: Adult; Antithyroid Agents; Cohort Studies; Collagen; Epinephrine; Factor VIII; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Middle Aged; Multivariate Analysis; Platelet Aggregation; Platelet Function Tests; Ristocetin; Thyroxine; Vasoconstrictor Agents; von Willebrand Factor

Topics: Contrast Media; Female; Humans; Hyperthyroidism; Iodine; Methimazole; Middle Aged; Propranolol; Tachycardia, Sinus

A 81-year-old woman with a thyroid tumor and subclinical hyperthyroidism since ten years ago was admitted to our hospital for palpitations and hyperthyroidism (FT(4) 1.75 ng/dl, FT(3) 5.37 pg/ml, TSH<0.03 microIU/ml). Although thyroid stimulating antibody (TSAb) was transiently and mildly positive, anti-TSH receptor antibody (TRAb), microsome test, and thyroid test were negative. Thyroid echogram showed an isoechoic nodule in the left lobe (33 x 42 x 22 mm) and a small nodule (10 x 15 x 9 mm) in right lobe. Thyroid scintiscan showed a hyperfunctional (hot) nodule in left thyroid lobe with suppressed uptake in the remainder of the gland. The uptake rate of thyroidal radioiodine ((123)I) in 24 hours was within the normal range (7.3%). Based on the above findings, a diagnosis of Plummer disease was made. Since she refused invasive surgical or radioiodine treatment, she was treated with 10 mg thiamazole daily. After treatment with propranolol and thiamazole, the thyrotoxic symptoms disappeared and thyroid function returned to normal level. She had osteoporosis but she had neither atrial fibrillation nor cardiac symptoms. This was a rare case of Plummer disease that appeared in extremely old age after a long course of subclinical hyperthyroidism.

Topics: Adenoma; Aged, 80 and over; Antithyroid Agents; Autoantibodies; Female; Humans; Hyperthyroidism; Methimazole; Osteoporosis, Postmenopausal; Thyroid Nodule; Thyrotropin

Vascular responsiveness changes in hyperthyroid patients remains controversial. This study attempts to determine whether the vasomotor activity can be influenced by hyperthyroid conditions, and, if so, whether changes induced by hyperthyroidism may be restored to normal during the euthyroid state after treatment.. A case-control clinical study.. Forty-five pretreated hyperthyroid patients (mean age 36.62 +/- 10.12 years, 36 female) were compared with 45 gender- and age-matched control subjects (mean age 38.98 +/- 11.17 years, 40 female). Brachial artery endothelium-dependent flow-mediated vasodilation (FMD) and endothelium-independent nitroglycerin-mediated vasodilation (NMD) responses were assessed noninvasively by high-resolution ultrasound imaging. Among the 45 hyperthyroid patients, 27 patients underwent the same procedures prospectively in the post-treatment euthyroid state.. The FMD values were significantly increased in hyperthyroid patients vs. those of controls (8.94 +/- 5.65%vs. 3.77 +/- 3.42%, P < 0.001), whereas NMD levels were not significantly different (18.17 +/- 7.76%vs. 17.28 +/- 6.63%, P = 0.560). Multiple regression analysis revealed that the presence of hyperthyroidism was the only significant factor associated with FMD. In the follow-up study of 27 hyperthyroid patients, the FMD values were significantly decreased in the post-treatment euthyroid state compared with those in the pretreated hyperthyroid state (6.40 +/- 4.27%vs. 8.83 +/- 4.61%, P = 0.021), although these values were still higher than those of controls.. This study demonstrated that endothelium-dependent FMD was increased in the hyperthyroid patients, and could be partially restored by treatment with antithyroid agents.

Topics: Adult; Antithyroid Agents; Brachial Artery; Case-Control Studies; Endothelium, Vascular; Female; Follow-Up Studies; Humans; Hyperthyroidism; Methimazole; Middle Aged; Nitroglycerin; Propylthiouracil; Prospective Studies; Regional Blood Flow; Regression Analysis; Ultrasonography; Vasodilation; Vasodilator Agents

Drug-induced liver injury might be responsible for 1 of 600 to 3500 of all hospital admissions. About 2-3% of all drug adverse effects may be connected with the liver. There could be pure injury of heaptic cells or impairment of hepatocellular bile secretion. In our case there was cholestatic liver injury after the use of thiamazole with the complete regression after the discontinuation of the drug. For two years' the patient was treated with methyltiouracyl without any side effects. After 19 years, because of thyreotoxicosis, the methimazole was used. The acute cholestatic liver injury with the high serum bilirubin level (41.4 mg/dl) was observed. Despite the discontinuation of the drug the patient was deceased.. There are possible cross reactions among imidazolines in patients who are predispose to develop drug-induced liver failure. The doctors should pay much more attention to possible drug side effects.

Topics: Aged; Bilirubin; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Female; Humans; Hyperthyroidism; Liver Failure, Acute; Liver Function Tests; Methimazole; Treatment Outcome

Many possible causes of resistance to human recombinant erythropoietin (rh-EPO) have been reported in patients with renal failure. This case presents an unusual cause of erythropoietin-resistant anemia in a patient with chronic renal failure. A 61-year-old male patient who was on chronic hemodialysis program due to diabetic nephropathy for seven months developed erythropoietin resistant anemia. No iron deficiency was revealed by laboratory data, no megaloblastic anemia were found by biochemical investigation, and no inflammatory states including infection or neoplastic diseases were disclosed by abdominal ultrasonography, chest X-ray, bone marrow aspiration and biopsy, or other methods (normal C-reactive protein levels). This hemodialysis patient had epoetin-resistant anemia with primary autoimmune hyperthyroidism. The anti-thyroid therapy was effective not only against the hyperthyroidism but also against his epoetin resistant anemia.

Topics: Anemia; Antithyroid Agents; Autoimmune Diseases; Drug Resistance; Erythropoietin; Humans; Hyperthyroidism; Kidney Failure, Chronic; Male; Methimazole; Middle Aged; Recombinant Proteins; Renal Dialysis

Aplasia cutis congenita (ACC) is a condition in which localized or widespread areas of skin are absent at birth. Defective lesions show complete absence of all layers of skin, occasionally extending to skull or dura. ACC is etiologically heterogeneous; many different etiologies including teratogens have been documented.. We describe the first reported case of a monozygotic twin with ACC after exposure to methimazole in utero. The female patient was born at 36 weeks gestation as the first child of monozygotic twins. The mother received methimazole between the 11th and 17th weeks of pregnancy because of transient hyperthyroidism. The second child did not have ACC. The patient had defects of the scalp, skull, and dura (7 x 5 cm) on the sagittal line of the parieto-occipital region. No other malformations were noted. The scalp defect has been treated daily with sterile physiological saline and petrolatum dressing in addition to intravenous antibiotics. Trafermin, a recombinant human fibroblast growth factor, was sprayed from day 6 to promote epithelialization of the scalp defect. On day 21, she had high fever due to infection of the defect lesion, which was controlled by povidone iodine dressing and intravenous antibiotics. The defect of the scalp was well healed after 6 weeks, but the skull defect remained unclosed.. We describe a rare case of a monozygotic twin with ACC and skull defect after methimazole exposure in utero. The findings of our case suggest that methimazole is a potential teratogen of ACC.

Topics: Anti-Bacterial Agents; Antithyroid Agents; Ectodermal Dysplasia; Female; Fibroblast Growth Factors; Humans; Hyperthyroidism; Infant, Newborn; Infections; Male; Methimazole; Peptide Fragments; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Skull; Twins, Monozygotic

Thyrotrophin induces proliferation and function in thyroid cells acting through a seven transmembrane G protein-coupled receptor. The proliferative pathways induced by thyrotropin (TSH) in thyrocytes in vivo are not completely understood yet. The aim of this work is to evaluate if Ras can be induced by TSH in rat thyroids, and whether extracellular regulated kinase (ERK) may be involved in the subsequent intracellular signalling cascade. We induced hypothyroidism in Wistar rats by methimazole (MMI) treatment (0.03% in the drinking water for 21 days). A subset of the hypothyroid rats received T4 (1 microg/100 g bw) during the last 10 days of MMI treatment. Hyperthyroidism was induced by subcutaneous injections of T4 (10 microg/100 g bw) during 10 days in another group of rats. Our data show that in the hypothyroid rats there is a clear positive Ras modulation, but a decrease in pERK. In contrast, thyroidal pERK increases in T4-induced hyperthyroidism, but without any change in RAS, although these changes did not reach statistical significance. Thus, while the rat thyroid proliferation induced by TSH may involve an increase in RAS signalling, the subsequent cascade does not involve ERK phosphorilation, which in fact, increases during T4-induced hyperthyroidism.

Topics: Animals; Cell Proliferation; Hyperthyroidism; Hypothyroidism; Male; MAP Kinase Signaling System; Methimazole; Organ Size; Phosphorylation; ras Proteins; Rats; Rats, Wistar; Thyroid Gland; Thyrotropin; Thyroxine

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

Recurrent deep venous thrombosis despite well conducted anticoagulant treatment is an uncommon, but possible, event. It has been hypothesized that overt hyperthyroidism may increase thromboembolic risk. We present the case of an elderly man with a recurrent episode of deep venous thrombosis during optimal oral vitamin K antagonist treatment, associated with a new diagnosis of overt hyperthyroidism, with no evidence of occult cancer and normal levels of antiphosholipid antibodies.

Topics: Aged; Anticoagulants; Antithyroid Agents; Humans; Hyperthyroidism; Male; Methimazole; Recurrence; Venous Thrombosis; Warfarin

Hyperthyroidism is a common disease in the elderly. Antithyroid medications such as methimazole are one of the few treatment options.. A 76-year-old white woman presented to the clinic with a 1-week history of fatigue, sleepiness, 7-pound weight loss, and tachycardia. Her blood work showed low levels of thyroid-stimulating hormone and high levels of free thyroxine. Due to persistence of her symptoms, she was hospitalized and started on methimazole 10 mg TID. Six weeks after receiving methimazole for the treatment of hyperthyroidism, she had severe jaundice and itching. Results of her liver function tests showed elevation of her alkaline phosphatase and liver transaminase levels, as well as hyperbilirubinemia, formed mainly of the conjugated fraction. Methimazole-induced cholestatic jaundice was diagnosed. Her symptoms gradually improved after discontinuation of the medication, and plasma bilirubin levels were near normal after 8 weeks without methimazole.. We report here a probable association between methimazole use and severe cholestatic jaundice in an elderly hyperthyroid patient. The patient's jaundice was reversed after drug discontinuation.

Topics: Aged; Alanine Transaminase; Alkaline Phosphatase; Antithyroid Agents; Bilirubin; Female; Humans; Hyperthyroidism; Jaundice, Obstructive; Liver Function Tests; Methimazole

Topics: Adult; Antithyroid Agents; Female; Humans; Hyperthyroidism; Methimazole; Rhabdomyolysis

To compare survival times for cats with hyperthyroidism treated with iodine 131, methimazole, or both and identify factors associated with survival time.. Retrospective case series.. 167 cats.. Medical records of cats in which hyperthyroidism had been confirmed on the basis of high serum thyroxine concentration, results of thyroid scintigraphy, or both were reviewed.. 55 (33%) cats were treated with 131I alone, 65 (39%) were treated with methimazole followed by 131I, and 47 (28%) were treated with methimazole alone. Twenty-four of 166 (14%) cats had preexisting renal disease, and 115 (69%) had preexisting hepatic disease. Age was positively correlated (r = 0.4) with survival time, with older cats more likely to live longer. Cats with preexisting renal disease had significantly shorter survival times than did cats without preexisting renal disease. When cats with preexisting renal disease were excluded, median survival time for cats treated with methimazole alone (2.0 years; interquartile range [IQR], 1 to 3.9 years) was significantly shorter than median survival time for cats treated with 131I alone (4.0 years; IQR, 3.0 to 4.8 years) or methimazole followed by 131I (5.3 years; IQR, 2.2 to 6.5 years).. Results suggest that age, preexisting renal disease, and treatment type were associated with survival time in cats undergoing medical treatment of hyperthyroidism.

Topics: Age Factors; Animals; Antithyroid Agents; Cat Diseases; Cats; Drug Therapy, Combination; Female; Hyperthyroidism; Iodine Radioisotopes; Kidney Diseases; Male; Methimazole; Retrospective Studies; Survival Rate; Treatment Outcome

The best-known adverse hematologic reaction of methimazole is agranulocytosis. Aplastic anemia is extremely rare. The prognosis within the entity of aplastic anemias is surprisingly good, despite the severe and prolonged course of the disease. The present article reports the case of a 74-yr-old female patient who exhibited aplastic anemia with severe clinical symptoms 8 weeks after the initiation of methimazole administration. The hemorrhagic symptoms were aggravated by a coumarin overdose. Supportive hemotherapy and antibiotic treatment were supplemented with recombinant human granulocyte colony-stimulating factor and high-dosage corticosteroids. The granulocyte count normalized on day 5 of treatment, the platelet count exceeded the critical value on day 11, and on day 25 the patient was discharged in remission.

Topics: Aged; Anemia, Aplastic; Coumarins; Drug Overdose; Female; Granulocyte Colony-Stimulating Factor; Humans; Hypertension; Hyperthyroidism; Methimazole; Methylprednisolone; Platelet Transfusion; Recombinant Proteins

Thirteen cats, newly diagnosed with hyperthyroidism, were treated with a transdermal formulation of methimazole at a dose of 5 mg (0.1 mL) (concentration of 50 mg/mL) applied to the internal ear pinna every 12 h for 28 d. Baseline hematologic and biochemical values, along with serum thyroxine (T4) levels, were obtained on presentation (day 0). Cats were evaluated at 14 d (D14) and 28 d (D28) following transdermal therapy. At each visit, a physical examination, a complete blood cell count, a serum biochemical analysis, and a serum T4 evaluation were performed. Ten cats completed the study. Clinical improvement, as well as a significant decrease in T4, was noted in all cats. Serum T4 measured at D14 and D28 were significantly lower at 27.44 nmol/L, s = 37.51 and 14.63 nmol/L, s = 10.65, respectively (P < 0.0001), as compared with values at D0 (97.31 nmol/L, s = 37.55). Only 1 cat showed a cutaneous adverse reaction along with a marked thrombocytopenia. The results of this prospective clinical study suggest that transdermal methimazole is an effective and safe alternative to conventional oral formulations.

Topics: Administration, Cutaneous; Animals; Antithyroid Agents; Blood Cell Count; Blood Chemical Analysis; Cat Diseases; Cats; Female; Hyperthyroidism; Male; Methimazole; Prospective Studies; Safety; Thyroxine; Treatment Outcome

Topics: Adrenergic beta-Antagonists; Aged; Agranulocytosis; Amiodarone; Anti-Arrhythmia Agents; Antithyroid Agents; Atrial Fibrillation; Chest Pain; Cholangitis; Glucocorticoids; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Plasmapheresis

Topics: Acidosis; Adult; Antithyroid Agents; Atrial Fibrillation; Biotransformation; Carbimazole; Diffusion; Drug Administration Schedule; Humans; Hyperthyroidism; Kidney Failure, Chronic; Male; Methimazole; Prodrugs; Renal Dialysis

A 28-year-old man presented with weight loss, jaundice, and pruritus. This was diagnosed to be secondary to Graves disease and the patient was prescribed methimazole. He returned 2 weeks later with worsening of his jaundice. Further investigation, including liver biopsy, indicated that there was superimposed methimazole-induced cholestasis. Discontinuation of methimazole and treatment of hyperthyroidism with lithium followed by radioactive iodine therapy resulted in resolution of his symptoms. This case highlights the fact that worsening cholestasis after therapy for Graves disease should raise the possibility of thionamide-induced exaggeration of liver cholestasis.

Topics: Adult; Antithyroid Agents; Cholestasis, Intrahepatic; Humans; Hyperthyroidism; Male; Methimazole

Management of a hyperthyroid patient unable to take oral or rectal medication is a difficult clinical problem. The need for an alternative parenteral route of antithyroid medication administration in thyrotoxic patients occurs in certain rare cases, such as emergent gastrointestinal surgery, bowel ileus or obstruction, or severe vomiting and diarrhea. We report a simple and successful protocol for the preparation and use of intravenous methimazole (MMI) for treatment of hyperthyroidism in patients intolerant of orally and rectally administered thionamides.. Five hundred milligrams of methimazole USP powder was reconstituted with pH-neutral 0.9% sodium chloride solution to a final volume of 50 mL using aseptic technique, then filtered through a 0.22-microm filter. MMI injection was administered as a slow intravenous push over 2 minutes and followed by a saline flush.. A 76-year-old man, intolerant of oral and rectal medications because of an ileus and intractable diarrhea, who developed worsening thyrotoxicosis after an emergent spinal cord decompression, and a 42-year-old man with chronic liver disease and hyperthyroidism, requiring emergent exploratory laparotomy and maintenance of complete bowel rest because of persistent gastrointestinal bleeding were rendered euthyroid using intravenous MMI.. Two cases of hyperthyroidism successfully treated with a preparation of intravenous MMI are described.

Topics: Adult; Aged; Antithyroid Agents; Drug Administration Routes; Humans; Hyperthyroidism; Infusions, Intravenous; Male; Methimazole; Thyroid Gland; Time Factors

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

Thionamides are the main therapeutic arsenal for treating hyperthyroidism. Perhaps the first case of a patient who developed a transient pituitary hyperthyroidism after discontinuation of a lengthy intake of a thionamide is reported.. A 48-year-old woman presented with menstrual irregularities when hypothyroidism with pituitary enlargement was detected. She had been undergoing treatment with methimazole for Graves's hyperthyroidism since the age of 34. Three months after discontinuation of methimazole she presented with clinical and laboratory evidence of thyrotoxicosis, with elevated thyroid-stimulating hormone (TSH) levels and blunted response to thyrotropin releasing hormone (TRH). This secondary hyperthyroidism was self-limited and resolved a few months later.. Chronic primary hypothyroidism caused by lengthy use of thionamides can result in pituitary hyperplasia and transient thyrotrope dysfunction.

Topics: Anti-Anxiety Agents; Chronic Disease; Female; Follow-Up Studies; Humans; Hyperthyroidism; Hypothyroidism; Methimazole; Middle Aged; Propranolol; Thyroid Gland; Thyrotoxicosis; Thyrotropin; Thyroxine; Time Factors; Treatment Outcome; Triiodothyronine; Ultrasonography

Skeletal muscle constitutes the major target organ for the thermogenic action of thyroid hormone. We examined the possible relation between energy expenditure (EE), thyroid status, and the contents of Ca2+-ATPase and Na+-K+-ATPasein human skeletal muscle. Eleven hyperthyroid patients with Graves' disease were studied before and after medical treatment with methimazole and compared with eight healthy subjects. Muscle biopsies were taken from the vastus lateralis muscle, and EE was determined by indirect calorimetry. Before treatment, the patients had two- to fivefold elevated total plasma T3 and 41% elevated EE compared with when euthyroidism had been achieved. In hyperthyroidism, the content of Ca2+-ATPase was increased: (mean +/- SD) 6,555 +/- 604 vs. 5,212 +/- 1,580 pmol/g in euthyroidism (P = 0.04) and 4,523 +/- 1,311 pmol/g in healthy controls (P = 0.0005). The content of Na+-K+-ATPase showed 89% increase in hyperthyroidism: 558 +/- 101 vs. 296 +/- 34 pmol/g (P = 0.0001) in euthyroidism and 278 +/- 52 pmol/g in healthy controls (P < 0.0001). In euthyroidism, the contents of both cation pumps did not differ from those of healthy controls. The Ca2+-ATPase content was significantly correlated to plasma T3 and resting EE. This provides the first evidence that, in human skeletal muscle, the capacity for Ca2+ recycling and active Na+-K+ transport are correlated to EE and thyroid status.

Topics: Adult; Antithyroid Agents; Biopsy; Calcium-Transporting ATPases; Calorimetry, Indirect; Energy Metabolism; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Muscle, Skeletal; Sodium-Potassium-Exchanging ATPase

Thyroid hormones have significant metabolic effects, and muscle wasting and weakness are prominent clinical features of chronic hyperthyroidism. To assess the underlying mechanisms, we examined seven hyperthyroid women with Graves' disease before (Ht) and after (Eut) medical treatment and seven control subjects (Ctr). All subjects underwent a 3-h study in the postabsorptive state. After regional catheterization, protein dynamics of the whole body and of the forearm muscles were measured by amino acid tracer dilution technique using [15N]phenylalanine and [2H4]tyrosine. Before treatment, triiodothyronine was elevated (6.6 nmol/l) and whole body protein breakdown was increased 40%. The net forearm release of phenylalanine was increased in hyperthyroidism (microg.100 ml(-1).min(-1)): -7.0 +/- 1.2 Ht vs. -3.8 +/- 0.8 Eut (P = 0.04), -4.2 +/- 0.3 Ctr (P = 0.048). Muscle protein breakdown, assessed by phenylalanine rate of appearance, was increased (microg.100 ml(-1).min(-1)): 15.5 +/- 2.0 Ht vs. 9.6 +/- 1.4 Eut (P = 0.03), 9.9 +/- 0.6 Ctr (P = 0.02). Muscle protein synthesis rate did not differ significantly. Muscle mass and muscle function were decreased 10-20% before treatment. All abnormalities were normalized after therapy. In conclusion, our results show that hyperthyroidism is associated with increased muscle amino acid release resulting from increased muscle protein breakdown. These abnormalities can explain the clinical manifestations of sarcopenia and myopathy.

Topics: Adult; Antithyroid Agents; Body Composition; Female; Forearm; Humans; Hyperthyroidism; Kinetics; Methimazole; Middle Aged; Muscle Proteins; Muscle, Skeletal; Nitrogen Isotopes; Phenylalanine; Thyroid Hormones

To investigate the risk of hypothyroidism after radioiodine (131I) treatment for hyperfunctioning thyroid nodules.. Retrospective analysis of patients treated with 131I for hyperfunctioning thyroid nodules and followed up for a maximum of 20 years.. A total of 346 patients treated with 131I in the years 1975-95, for a single hyperfunctioning nodule.. Hypothyroidism was defined as TSH levels > 3.7 mU/l. Kaplan-Meier survival analysis was used to analyse permanence of euthyroidism after 131I. A stepwise Cox proportional hazard model was used to identify factors influencing the progression to hypothyroidism.. The cumulative incidence of hypothyroidism was 7.6% at 1 year, 28% at 5 years, 46% at 10 years and 60% at 20 years. Age (P < 0.01), 24-th 131I uptake (P < 0.05) and previous treatment with methimazole (MMI, P < 0.1) were associated with a faster progression towards hypothyroidism, while thyroid and nodule size, thyroid status at diagnosis and degree of extranodular thyroid parenchymal suppression had no influence. In hyperthyroid patients with partial parenchymal suppression, however, previous MMI treatment was the most important prognostic factor (P < 0.01).. After 20 years of follow-up, 60% of patients treated with 131I for a single hyperfunctioning nodule are hypothyroid. Factors increasing the risk of hypothyroidism are age, 131I uptake and MMI pretreatment. The prognostic value of this last factor, however, depends on the degree of suppression of the extranodular thyroid parenchyma at the scan.

Topics: Adult; Age Factors; Aged; Antithyroid Agents; Disease Progression; Epidemiologic Methods; Female; Humans; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Radiation Injuries; Thyroid Gland; Thyroid Nodule; Thyrotropin; Treatment Outcome

Hyperthyroidism is associated with an increase in myocardial oxygen consumption that, due to an imbalance of oxygen demand and supply, can cause angina. However, subclinical hyperthyroidism rarely presents as chest pain in the resting state. Herein, we present a case of subclinical hyperthyroidism involving a 58-year-old male who complained of frequent chest tightness and typical electrocardiographic changes while in a resting state. Coronary angiography showed no significant lesion. Laboratory data showed that the patient suffered from hyperthyroidism, for which he was successfully treated with anti-thyroid agents. We are reminded that typical chest pain might be the first symptom of hyperthyroidism.

Topics: Angina, Unstable; Antithyroid Agents; Chest Pain; Coronary Angiography; Electrocardiography; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Treatment Outcome

Hyperthyroidism is associated with increased psychiatric morbidity. It may alter the clinical course of alcohol withdrawal syndrome. We report a 69 year old man who presented prolonged alcohol withdrawal syndrome associated with hyperthyroidism. Initially, he developed typical alcohol withdrawal syndrome including tremor, disorientation, delirium and visual hallucination of small animals. Thyroid function tests revealed a free triiodothyronine (T3) of 6.1 pg/dl (range, 3.0 to 5.8), a free thyroxine (T4) of 2.3 ng/dl (range, 0.85 to 2.15) and a thyroid stimulating hormone (TSH) of 0.003 microU/ml (range, 0.3 to 4.0), and thiamazole was administered. Even after a month, he continuously presented persecutory delusion, auditory hallucination and cognitive dysfunction. Although these symptoms did not respond to the medication including antipsychotics, they totally passed away after the thyroid function reached down to the normal level (free T3 3.0 pg/ml, free T4 1.1 ng/dl, TSH 0.004 microU/ml). In addition, cognitive function was recovered to the normal level as he scored 28/30 on the Mini Mental State Examination. We propose that hyperthyroidism contributed to the occurrence of psychotic symptoms and cognitive dysfunction.

Topics: Aged; Alcohol Withdrawal Delirium; Ethanol; Humans; Hyperthyroidism; Male; Methimazole; Substance Withdrawal Syndrome; Thyroid Function Tests; Treatment Outcome

The presence of severe neurological symptoms in thyroid diseases has highlighted the importance of thyroid hormones in the normal functioning of the mature brain. Since, ATP is an important excitatory neurotransmitter and adenosine acts as a neuromodulatory structure inhibiting neurotransmitters release in the central nervous system (CNS), the ectonucleotidase cascade that hydrolyzes ATP to adenosine, is also involved in the control of brain functions. Thus, we investigated the influence of hyper-and hypothyroidism on the ATP, ADP and AMP hydrolysis in hippocampal and cortical slices from adult rats. Hyperthyroidism was induced by daily injections of l-thyroxine (T4) 25 microg/100 g body weight, for 14 days. Hypothyroidism was induced by thyroidectomy and methimazole (0.05%) added to their drinking water for 14 days. Hypothyroid rats were hormonally replaced by daily injections of T4 (5 microg/100 g body weight, i.p.) for 5 days. Hyperthyroidism significantly inhibited the ATP, ADP and AMP hydrolysis in hippocampal slices. In brain cortical slices, hyperthyroidism inhibited the AMP hydrolysis. In contrast, hypothyroidism increased the ATP, ADP and AMP hydrolysis in both hippocampal and cortical slices and these effects were reverted by T4 replacement. Furthermore, hypothyroidism increased the expression of NTPDase1 and 5'-nucleotidase, whereas hyperthyroidism decreased the expression of 5'-nucleotidase in hippocampus of adult rats. These findings demonstrate that thyroid disorders may influence the enzymes involved in the complete degradation of ATP to adenosine and possibly affects the responses mediated by adenine nucleotides in the CNS of adult rats.

Topics: 5'-Nucleotidase; Adenine Nucleotides; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphatases; Adenosine Triphosphate; Animals; Antigens, CD; Antithyroid Agents; Apyrase; Cerebral Cortex; Hippocampus; Hydrolysis; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Organ Culture Techniques; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Thyroidectomy; Thyroxine

We studied the intervention of nitric oxide (NO), prostacyclin and endothelium-derived hyperpolarizing factor (EDHF) in mediating responses to acetylcholine in thyroid arteries from euthyroid and methimazole-treated (MT) patients.. Branches of the superior thyroid artery were obtained from 19 euthyroid patients and 17 MT patients (euthyroid at the time of surgery) undergoing total thyroidectomy or hemithyroidectomy. Artery rings were suspended in organ baths for isometric recording of tension.. Acetylcholine caused endothelium-dependent relaxation of greater magnitude in arteries from MT patients (pD(2) (-log EC(50)) values were 7.68 +/- 0.19 in euthyroid and 8.17 +/- 0.26 in MT patients, P < 0.05). The relaxation was unaffected by indomethacin and was partially reduced by the NO-synthase inhibitor NG-monomethyl-L-arginine (L-NMMA). This reduction was higher in arteries from MT patients (50 +/- 6%) as compared with euthyroid patients (36 +/- 6%) (P < 0.05). Inhibition of K(+) channels using apamin combined with charybdotoxin or high K(+) solution abolished the relaxation resistance to L-NMMA and indomethacin. The maximal contraction response to noradrenaline (as a percentage of the response to 100 mM KCl) was lower in MT than in euthyroid patients (57 +/- 10 and 96 +/- 8 respectively, P < 0.05). The hyporesponsiveness to noradrenaline in arteries from MT patients was corrected by L-NMMA. The results indicate that: (i) thyroid arteries from MT patients show an increased relaxation response to acethylcholine and a decreased contraction response to noradrenaline due to overproduction of NO; (ii) EDHF plays a prominent role in acetylcholine-induced relaxation through activation of Ca(2+)-activated K(+) channels; (iii) the abnormal endothelium-dependent responses in arteries from MT patients are not corrected by medical treatment.

Topics: Acetylcholine; Adult; Antithyroid Agents; Apamin; Arteries; Biological Factors; Calcium; Charybdotoxin; Endothelium, Vascular; Enzyme Inhibitors; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Muscle Relaxation; Muscle, Smooth, Vascular; Nitric Oxide; Nitric Oxide Synthase; Norepinephrine; omega-N-Methylarginine; Potassium; Potassium Channel Blockers; Potassium Channels; Thyroid Gland

Topics: Antithyroid Agents; Drug Therapy, Combination; Graves Disease; Humans; Hyperthyroidism; Methimazole; Thyroxine

Thyroid hormones have pronounced effects on the cardiovascular system. Thyrotoxicosis affects blood pressure (BP), modifying both diastolic (DBP) and systolic (SBP) pressures. There are no studies examining BP with ambulatory blood pressure monitoring (ABPM) in hyperthyroidism before and after control of thyroid function. Our aims were (1) to analyse ABPM in a group of normotensive hyperthyroid patients before and after normalizing circulating thyroid hormones and (2) to compare these results with those obtained in a group of euthyroid subjects.. We studied 20 normotensive hyperthyroid subjects [18 women; age (mean +/- SEM) 49.0 +/- 3.0 years] and 15 healthy subjects. Patients were evaluated by ABPM over 24 h, at diagnosis and after therapy (n = 18).. The average 24-h, daytime and night-time SBP was significantly greater in hyperthyroid patients than in controls with no significant differences in DBP. Circadian BP rhythm, estimated by the difference between mean values of SBP, DBP and mean BP during daytime and night-time, was unchanged. The average 24-h and daytime SBP significantly decreased after normalizing thyroid function in the 18 hyperthyroid evaluated patients. Daytime SBP and DBP were higher than night-time values both before and after control of thyroid function. However, no differences in circadian BP rhythm were observed.. Normotensive hyperthyroid patients exhibit higher ambulatory SBP throughout 24 h than normotensive euthyroid subjects. Control of hyperthyroidism decreases ambulatory SBP values. Mean nocturnal fall in BP is comparable in normotensive hyperthyroid patients and control subjects.

Topics: Antithyroid Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Circadian Rhythm; Female; Heart Rate; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Propylthiouracil; Regression Analysis; Thyroid Gland; Thyroid Hormones

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

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

Neuromuscular presentations are common in thyroid disease, although the mechanism is unclear. In the present study, we investigated the pathogenesis in a boy with autosomal-dominant hyperthyroidism presenting with neuromuscular symptoms.. The TSHr gene was investigated by direct sequencing. Functional properties of the mutant TSHr were investigated during transient expression in COS-7 cells. Family members were investigated by clinical and biochemical examinations.. Sequence analysis revealed a previously reported heterozygous missense mutation Glycine 431 for Serine in the first transmembrane segment, leading to an increased specific constitutive activity. Three additional affected family members carried the same mutation. There was no indication of autoimmune disorder. All symptoms disappeared upon treatment with thacapzol and L-thyroxine and subsequent subtotal thyroidectomy.. The data imply that neuromuscular symptoms can be caused by excessive thyroid hormone levels rather than by autoimmunity.

Topics: Child; Diagnosis, Differential; Genes, Dominant; Germ-Line Mutation; Humans; Hyperthyroidism; Male; Methimazole; Neuromuscular Diseases; Receptors, Thyrotropin; Risk Assessment; Severity of Illness Index; Thyroid Function Tests

To evaluate the relationship between the incidence of congenital malformations of newborns and maternal hyperthyroidism with antithyroid drug (ATD) therapy during pregnancy.. The clinical data of 100 cases of pregnant women with hyperthyroidism and their 101 offsprings born in Peking Union Medical College Hospital during 1983-2003 were analyzed retrospectively. According to the maternal thyroid function, and antithyroid drugs taken during the first trimester of pregnancy, subjects were divided into different groups. The incidence of congenital malformations of newborns and risk factors, especially the effects of maternal hyperthyroidism with antithyroid drug therapy were analysed.. The prevalence of congenital malformation in infants born to mothers who had hyperthyroidism during pregnancy (6.9%, 7/101) was significantly higher than that of all the infants born in the same hospital during the same period (0.9%, 212/22 765, P < 0.01). The difference of the incidence of malformed infants born to mothers with hyperthyroidism (9.6%, 5/52) or euthyroidism (4.1%, 2/49) during the first trimester was not significant (P > 0.05). The incidence of malformed infants whose mothers received methimazole (MMI; 41.7%, 5/12) was significantly higher than that of mothers treated with propylthiouracil (PTU) (3.6%, 1/28) and without ATDs (1.6%, 1/61), respectively (P < 0.01). The Loglinear model analyses showed that mothers receiving MMI during the first trimester of pregnancy was independent risk factor for the increased incidence of malformation of their infants (L.R. square = 15.668, P = 0.0003).. The risk of congenital malformation in infants whose mothers take MMI during the first trimester may be increased. Therefore, we suggest that MMI should not be used as a choice of drug in treatment of pregnant women with hyperthyroidism.

Topics: Antithyroid Agents; Female; Humans; Hyperthyroidism; Incidence; Infant, Newborn; Methimazole; Mothers; Pregnancy; Pregnancy Complications; Prevalence; Propylthiouracil; Thyroid Function Tests; Thyrotropin; Thyroxine

Thyroid hormones have a dramatic effect on human behavior. However, their role on sexual behavior and performance has seldom been investigated in men.. The objective of this study was to evaluate the prevalence of sexual dysfunctions in patients with hyper- and hypothyroidism and their resolution after normalization of thyroid hormone levels.. We conducted a multicenter prospective study at endocrinology and andrology clinics in university hospitals.. The study included 48 adult men, 34 with hyperthyroidism and 14 with hypothyroidism.. Subjects were screened for hypoactive sexual desire (HSD), erectile dysfunction (ED), premature ejaculation (PE), and delayed ejaculation (DE) on presentation and 8-16 wk after recovery from the thyroid hormone disorder.. In hyperthyroid men, HSD, DE, PE, and ED prevalence was 17.6, 2.9, 50, and 14.7%, whereas in hypothyroid men, the prevalence of HSD, DE, and ED was 64.3% and of PE was 7.1%. After thyroid hormone normalization in hyperthyroid subjects, PE prevalence fell from 50 to 15%, whereas DE was improved in half of the treated hypothyroid men. Significant changes were found in the subdomains of the International Index of Erectile Function; ejaculation latency time doubled after treatment of hyperthyroidism (from 2.4 +/- 2.1 to 4.0 +/- 2.0 min), whereas for hypothyroid men it declined significantly, from 21.8 +/- 10.9 to 7.4 +/- 7.2 (P < 0.01 for both). TSH and thyroid hormone levels normalized rapidly after treatment, and changes in circulating sex steroids partially reflected the changes in SHBG levels.. In summary, most patients with thyroid hormone disorders experience some sexual dysfunctions, which can be reversed by normalizing thyroid hormone levels. Despite the associated changes in sex hormone levels, the high prevalence of ejaculatory disorders and their prompt reversibility suggest a direct involvement of thyroid hormones in the physiology of ejaculation.

Topics: Adrenergic beta-Antagonists; Antithyroid Agents; Benzodiazepines; Drug Therapy, Combination; Ejaculation; Erectile Dysfunction; Follow-Up Studies; Humans; Hyperthyroidism; Hypothyroidism; Libido; Male; Methimazole; Prevalence; Propranolol; Prospective Studies; Sexual Dysfunction, Physiological; Thyroid Hormones; Thyroxine; Treatment Outcome

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

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

Topics: Adult; Aged; Antithyroid Agents; Female; Goiter; Humans; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Randomized Controlled Trials as Topic; Recurrence; Thyroid Function Tests; Thyroid Hormones; Treatment Outcome

Thyroid hormones exert significant changes in the metabolism of bile acids. However, in humans, the effect of thyroid hormone on cholesterol 7alpha-hydroxylase (cyp7a), the rate- controlling enzyme in the classical bile acid biosynthetic pathway, remains poorly understood and has been difficult to study directly in vivo. Previous studies from our laboratory have shown that the activity of the human cholesterol 7alpha-hydroxylase gene promoter is repressed by T(3) in cultured cells. Accordingly, we hypothesized that T(3) would negatively regulate human CYP7A1 gene expression in vivo. We tested this hypothesis by inducing hypo- and hyperthyroidism in transgenic mice expressing the human CYP7A1 gene. Hypothyroidism did not affect the abundance of human cyp7a mRNA in transgenic mice. In hyperthyroid male mice, human cyp7a mRNA abundance was decreased. No significant change in cyp7a mRNA abundance was observed in hyperthyroid female mice. Gender differences in the amount of cholesterol and bile acids in gallbladder bile were also observed. The data indicate that thyroid hormone can repress the human CYP7A1 gene in transgenic mice, but this effect is dependent on gender in this in vivo model.

Topics: Animals; Bile; Bile Acids and Salts; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Cholesterol, HDL; Diet; Female; Gallbladder; Gene Expression Regulation; Humans; Hyperthyroidism; Hypothyroidism; Iodine; Male; Methimazole; Mice; Mice, Transgenic; RNA, Messenger; Sex Characteristics; Transfection; Triiodothyronine

Antioxidant effects of paraoxonase, a high density lipoprotein (HDL)-associated enzyme that inhibits low density lipoprotein cholesterol (LDL-C) oxidation in human serum, have been reported. Patients with thyroid dysfunction are more susceptible to oxidative stress, and may show enhanced LDL-C oxidation. The purpose of this study was to evaluate serum paraoxonase activity in patients with hyperthyroidism before and after treatment with methimazole (MMI).. Twenty-four hyperthyroid patients (15 women and nine men, aged 43.0 +/- 12.9 years) and 23 age- and sex-matched healthy controls were studied. Serum paraoxonase activity, lipid, lipoprotein and apolipoprotein levels were measured in fasting samples. Patients were treated with MMI 20-30 mg daily for the first month, and 5-10 mg daily thereafter, and re-evaluated after 6-9 months of treatment.. Significantly lower serum paraoxonase activity was present in hyperthyroid patients before treatment compared with the controls (43.4 +/- 21.9 vs. 72.6 +/- 41.2 U/ml, P < 0.005). After a mean follow-up of 7.3 months, 15 patients became euthyroid (treated) and nine were still hyperthyroid. After follow-up, serum paraoxonase activity had increased to 62.2 +/- 37.4 U/ml in those who became euthyroid (P < 0.05 compared with baseline). In patients who were still hyperthyroid serum paraoxonase was unchanged from baseline, at 43.2 +/- 23.2 U/ml.. Serum paraoxonase is reduced in patients with hyperthyroidism and reverts to normal after euthyroidism is attained. Reduced serum paraoxonase activity in thyrotoxicosis might predispose lipids to oxidation.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Aryldialkylphosphatase; Case-Control Studies; Female; Follow-Up Studies; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged

Hyperhomocysteinemia is a risk factor for premature atherosclerotic vascular diseases. It is known that plasma homocysteine levels are higher in hypothyroid patients compared to healthy subjects. The aim of our study was to assess plasma total homocysteine concentrations in hyperthyroid patients before and after treatment when euthyroid status was reached and compare them with control group. Thirteen hyperthyroid patients (age, 42.9 +/- 15.6 year) and eleven healthy subjects (age, 39.9 +/- 12.5 year) were involved in the study. Plasma levels of homocysteine and serum cholesterol, triglyceride, HDL cholesterol, urea, creatinine, vitamin B12, folate were measured before and after treatment. LDL cholesterol and creatinine clearances were calculated. Pretreatment homocycteine levels of the hyperthyroid patients were significantly lower than healthy controls (11.5 +/- 3.6 micromol/L vs. 15.1 +/- 4.5 micromol/L, respectively, p<0.05). Posttreatment homocysteine levels were significantly higher than pretreatment levels (13.9 +/- 6.3 micromol/L vs. 11.5 +/- 3.6 micromol/L, respectively, p<0.05) and posttreatment creatinine clearance were lower than pretreatment level (103.5 +/- 12.7 ml/min vs. 114.2 +/- 9.3 ml/min, respectively, p<0.01). Lower homocysteine levels in hyperthyroidism can be partially explained with the changes in creatinine clearance.

Topics: Adult; Antithyroid Agents; Case-Control Studies; Creatinine; Female; Homocysteine; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Osmolar Concentration; Propylthiouracil

Thyrotoxicosis may present with a variety of cardiovascular symptoms. Sinus tachycardia is the most frequently encountered electrocardiographic abnormality and conduction disturbances are extremely uncommon. We present a case of first degree atrio-ventricular block in a patient with newly diagnosed hyperthyroidism and discuss the underlying pathophysiological mechanisms and the clinical implications from the internist's standpoint.

Topics: Acute Disease; Adult; Anti-Arrhythmia Agents; Antithyroid Agents; Female; Heart Block; Humans; Hyperthyroidism; Methimazole; Propranolol; Thyrotoxicosis

Topics: Adrenal Insufficiency; Adult; Anesthetics, Intravenous; Anti-Inflammatory Agents; Antithyroid Agents; Cholecystectomy; Estradiol; Etomidate; Female; Fentanyl; Humans; Hydrocortisone; Hyperthyroidism; Methimazole; Polyendocrinopathies, Autoimmune; Postoperative Complications; Thyroiditis

The activity of liver mitochondrial flavoprotein-dependent glycerol-3-phosphate dehydrogenase (GPDH) is considered a reliable marker of thyroid status in acute and short-lasting experiments. The aim of this study was to ascertain whether GPDH activity could also be used as an index of thyroid status during chronic experiments over several months. We therefore analyzed GPDH activity in liver mitochondria of female inbred Lewis rats with thyroid status altered for 2 to 12 months. Hyperthyroid state was maintained by triiodothyronine (T (3)) or thyroxine (T (4)) administration, while methimazole was employed for inducing hypothyroidism. We found a seven- and three-fold increase of GPDH activity in female rats after T (3) or T (4) administration, respectively, compared to euthyroid females (8.9 +/- 2.3 nmol/min/mg protein), whereas administration of methimazole reduced the enzyme activity almost to one-third of the euthyroid values. These changes were not significantly influenced by the duration of hyperthyroid or hypothyroid treatment. We conclude that the level of the rat liver GPDH activity could serve as a useful marker for evaluation of hyperthyroid and hypothyroid status in chronic long-lasting experiments on female inbred Lewis rats.

Topics: Animals; Female; Glycerolphosphate Dehydrogenase; Hyperthyroidism; Hypothyroidism; Methimazole; Mitochondria, Liver; Rats; Rats, Inbred Lew; Thyroid Gland; Thyroxine; Triiodothyronine

A 35-year-old Asian male, treated for hyperthyroidism, systemic lupus erythematosis, and uremia presented with low serum total thyroxine (T4) and normal serum thyrotropin (TSH) levels. He had been receiving prednisone and methimazole for 15 weeks. Free T4 measured by direct equilibrium dialysis was in the hypothyroid range (0.3 ng/dL; normal, 0.8-2.7). Two possibilities were considered: (1) a weakly bound dialyzable inhibitor in uremic serum that interfered with this serum free T4 determination or (2) hypothyroidism with persistent TSH suppression because of prior hyperthyroidism. To determine whether a weakly bound inhibitor was involved, the patient's serum was serially diluted using two diluents: (1) an ultrafiltrate of the patient's serum, which would contain any unbound inhibitor, as well as free T4 and (2) an inert diluent. Free T4 measurements were similar with both, providing evidence against the presence of a dialyzable and ultrafilterable inhibitor. In conclusion, this patient was hypothyroid because of antithyroid drug administration, associated with prolonged central TSH suppression from preexisting hyperthyroidism. Discontinuation of methimazole resulted in normalization of serum total T4 and TSH values. Thus, paired, serial serum dilutions, using two different diluents, provided evidence for differentiation of appropriately low free T4 measurements (because of hypothyroidism), from spuriously low free T4 measurements (because of an interfering inhibitor).

Topics: Adult; Antithyroid Agents; Humans; Hyperthyroidism; Male; Methimazole; Renal Insufficiency; Thyrotropin; Thyroxine; Treatment Outcome

Hyperthyroidism and chronic renal disease occur commonly in geriatric cats, often in association with potentially life-threatening primary or secondary hypertension. Early treatment of hypertension minimizes damage to vital organs. This case illustrates the complexity of managing hypertension in a geriatric cat with both hyperthyroidism and renal disease.

Topics: Animals; Antihypertensive Agents; Antithyroid Agents; Cat Diseases; Cats; Diagnosis, Differential; Enalapril; Female; Hypertension; Hyperthyroidism; Kidney Diseases; Methimazole; Treatment Outcome

This study was aimed at evaluating serum osteoprotegerin (OPG) concentrations in a cohort of patients with hyperthyroidism before and after methimazole (MMI) treatment. One hundred fourteen hyperthyroid patients [93 with Graves disease (GD) and 21 with toxic nodular goitre (TNG)] and 68 matched for sex and age healthy subjects were evaluated for serum free-thyroxine (FT4), free-triiodiothyronine (FT3), thyrotropin (TSH), TSH receptor antibodies (TRAb), bone alkaline phosphatase (BALP), C-telopeptides of type-1 collagen (CrossLaps), OPG levels, and bone mineral density (BMD). In hyperthyroid patients, the biochemical evaluations were performed before and after 6 and 12 months of MMI treatment, whereas BMD was measured at baseline and after 12 months of treatment. Hyperthyroidism was more severe in GD than TNG patients. Serum OPG levels were found to be significantly higher in hyperthyroid patients than in the healthy subjects (4.3 pmol/l, range: 1.6-12.0, vs. 2.2 pmol/l, range: 1.4-6.0; P < 0.001), the values being higher in GD patients than TNG. A significant correlation between serum OPG levels and age was found in the healthy subjects (r: 0.48; P < 0.001) but not in hyperthyroid patients (r: -0.03; P = 0.8). In the healthy subjects, serum OPG levels were also positively correlated with both serum FT4 (r: 0.23; P = 0.03) and FT3 (r: 0.24; P = 0.04) levels. In hyperthyroid patients, however, serum OPG was still correlated with FT3 levels (r: 0.38; P < 0.001), whereas the correlation with serum FT4 was lost (r: 0.19; P = 0.06). In hyperthyroid patients, but not in the healthy subjects, serum OPG levels were correlated positively with CrossLaps (r: 0.20; P = 0.03) and negatively with BALP (r: -0.24; P = 0.01) and BMD (r: -0.33; P = 0.01). After 6 months of MMI treatment, serum OPG concentrations decreased significantly in TNG patients (from 3.5 pmol/l, range: 1.6-8.0, to 2.3 pmol/l, range: 1.0-4.3; P < 0.001), whereas a not significant change in OPG levels occurred in GD patients (from 4.8 pmol/l, range: 1.8-12.0, to 4.2 pmol/l, range: 1.0-14.0; P = 0.7). At Month 12 of treatment, serum OPG concentrations were significantly lower than those measured at baseline in both TNG (2.5 pmol/l, range: 1.0-3.1, vs. 3.5 pmol/l, range: 1.6-8.0; P < 0.001) and GD (2.1 pmol/l, range: 1.0-8.6, vs. 4.8 pmol/l, range: 1.8-12.0; P < 0.001). At this time, no significant differences in serum OPG, CrossLaps, and BALP values were found between patients and control subjects. At t

Topics: Adult; Aged; Chi-Square Distribution; Cohort Studies; Female; Follow-Up Studies; Glycoproteins; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Osteoprotegerin; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Statistics, Nonparametric; Thyroid Hormones

Antithyroid drugs such as propylthiouracil (PTU) and methimazole (MMI) are common medications in Chinese patients with hyperthyroidism and PTU-induced antineutrophil cytoplasmic antibody (ANCA) positive vasculitis has been reported. The current cross-sectional study aimed to investigate the prevalence and the target antigens of ANCA in Chinese patients with hyperthyroidism pre- and post-antithyroid medication therapy.. Sera from 216 patients with hyperthyroidism in our hospital were collected from January to July in 2002. Patients were divided into four groups: untreated (n = 34); treated with PTU (n = 62); treated with MMI (n = 77); and treated with both PTU and MMI (n = 43). Indirect immunofluorescence (IIF) assay was used to detect ANCA and ANA. Antigen-specific ELISAs were used to detect antigen specificities. The known antigens included myeloperoxidase (MPO), proteinase 3 (PR3), human leukocyte elastase (HLE), lactoferrin, bactericidal/permeability-increasing protein (BPI), cathepsin G and azurocidin.. 33/216 sera were IIF positive, 20 of the 33 samples were ANCA positive, 11 samples were ANA positive, and two samples were both P-ANCA and ANA positive. The prevalence of positive ANCA in patients receiving PTU (14/62, 22.6%) was significantly higher than that of untreated patients (1/34, 2.9%) and patients treated with MMI (0/77, 0), P < 0.017. Of the 22 IIF-ANCA positive samples, 12 (54.5%) sera recognized lactoferrin, seven (31.8%) sera recognized HLE, four sera recognized MPO and azurocidin respectively, three sera recognized PR3 and cathepsin G respectively, and one serum recognized BPI. Six of the 22 (27.3%) patients with ANCA positive had clinical evidence of vasculitis. All patients with MPO-ANCA and two of the three patients with PR3-ANCA had clinical vasculitis.. PTU is associated with the production of ANCA in patients with hyperthyroidism. PTU-induced ANCA are due to polyclonal activation of B cells. Anti-MPO and anti-PR3 antibodies may associate the occurrence of clinical vasculitis.

Topics: Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Asian People; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Epitopes; Female; Fluorescent Antibody Technique, Indirect; Humans; Hyperthyroidism; Methimazole; Middle Aged; Propylthiouracil

During 1 year of amiodarone intake development of amiodarone-associated thyroid dysfunction was observed in 25% of patients (hypothyroidism and thyrotoxicosis in 19.2 and 5.8%, respectively). Development of hypothyroidism was not accompanied with loss of antiarrhythmic efficacy of amiodarone and therapy with L-thyroxin was conducted at the background of continued amiodarone intake. In all patients with clinical and in less than one half (47.6%) of patients with subclinical forms of hypothyroidism replacement therapy with L-thyroxin was carried out. Development of amiodarone-associated thyrotoxicosis was accompanied with loss of antiarrhythmic efficacy of amiodarone in all cases. In all patients with thyrotoxicosis which developed during amiodarone intake thyrostatic therapy with mercasolil was carried out and in case of its inefficacy prednisolone was added. In 87.5% of patients with thyrotoxicosis correction of the thyroid status was conducted under conditions of continued amiodarone intake as this drug had been prescribed because of life saving indications. Achievement of euthyroid state was followed by restoration of antiarrhythmic efficacy of amiodarone. Amiodarone was discontinued just in 1 patient with ventricular extrasystole as correction of thyroid status and restoration of euthyroidosis enabled effective use of other antiarrhythmic drugs.

Topics: Amiodarone; Anti-Arrhythmia Agents; Anti-Inflammatory Agents; Antithyroid Agents; Data Interpretation, Statistical; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Middle Aged; Prednisolone; Prevalence; Thyroid Diseases; Thyroxine; Time Factors

Topics: Adenoma; Adult; Antithyroid Agents; Diagnosis, Differential; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Medicine, Chinese Traditional; Methimazole; Phytotherapy; Thyroid Neoplasms

We report two infants with gastrointestinal anomalies: one with esophageal atresia and tracheo-esophageal fistula and the other with biliary tree atresia, born to hyperthyroid women diagnosed and treated with methimazole after 14 weeks' gestation. Euthyroidism was documented in both infants. These cases raise the issue of whether untreated hyperthyroidism and not methimazole intake is the teratogen.

Topics: Abnormalities, Multiple; Adolescent; Adult; Antithyroid Agents; Biliary Atresia; Digestive System; Digestive System Abnormalities; Esophageal Atresia; Female; Humans; Hyperthyroidism; Infant, Newborn; Methimazole; Pregnancy; Pregnancy Complications; Time Factors; Tracheoesophageal Fistula; Treatment Outcome

The objectives of this study were to assess serum thyroxine concentrations and clinical response in hyperthyroid cats to treatment with transdermal methimazole, and to determine if further investigation is indicated. Clinical and laboratory data from 13 cats with hyperthyroidism were retrospectively evaluated. Methimazole (Tapazole, Eli Lilly) was formulated in a pleuronic lecithin organogel (PLO)-based vehicle and was applied to the inner pinna of the ear at a dosage ranging from 2.5mg/cat q 24h to 10.0mg/cat q 12h. During the treatment period, cats were re-evaluated at a mean of 4.3 weeks (recheck-1), and again at a mean of 5.4 months (recheck-2). Clinical improvement was observed, and significant decreases in thyroxine concentrations were measured at recheck-1 (mean: 39.57nmol/L, SEM: 14.4, SD: 41.2) and recheck-2 (mean: 36.71nmol/L, SEM: 13.9, SD: 45.56) compared to pretreatment concentrations (mean: 97.5nmol/L, SEM: 11.42, SD: 39.5). No adverse effects were reported.

Topics: Administration, Cutaneous; Animals; Antithyroid Agents; Cat Diseases; Cats; Ear, External; Female; Hyperthyroidism; Male; Methimazole; Records; Retrospective Studies; Thyroxine; Treatment Outcome

Subclinical hyperthyroidism has been associated with harmful cardiac effects, but its treatment remains controversial. This study was designed to assess the cardiac effects of the normalization of serum TSH concentration in patients with endogenous subclinical hyperthyroidism. Ten patients (median age, 59 yr; range, 16-72 yr) with normal serum free T(4) and free T(3) concentration and a stable suppression of serum TSH levels were evaluated by Doppler-echocardiography, by standard and 24-h electrocardiography monitoring (Holter), and by the clinical Wayne index. Ten subjects, matched for age and sex, were used as controls. Patients were reevaluated 6 months after achieving stabilized euthyroidism by using methimazole with a median initial dose of 20 mg daily (10-30 mg daily). After reaching euthyroidism, we found a significant decrease in the heart rate (P = 0.008), the total number of beats during 24 h (P = 0.004), and the number of atrial (P = 0.002) and ventricular (P = 0.003) premature beats. Echocardiographical data resulted in a reduction of the left ventricular mass index (P = 0.009), interventricular septum thickness (P = 0.008), and left ventricular posterior wall thickness (P = 0.004) at diastole. Furthermore, the early diastolic peak flow velocity deceleration rate was significantly higher (P = 0.02) in the untreated patients compared with controls. The Wayne clinical index was higher in patients than in controls (P = 0.001) and decreased after treatment (P = 0.004). Serum TSH concentration returned to normal values after 2.5 months (range, 1.0-7.0 months) on methimazole therapy (0.05 vs. 1.42 mU/liter; P = 0.002). Serum free T(4) values were normal in patients before treatment but significantly decreased after reaching the euthyroidism (16.9 vs. 11.5 pmol/liter; P = 0.002). In contrast, serum free T(3) concentration did not differ among the groups. In conclusion, our findings support that early antithyroid therapy should be considered in patients with endogenous subclinical hyperthyroidism, where it is needed to prevent potential progression to a more advanced heart disease.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Arrhythmias, Cardiac; Diastole; Echocardiography; Electrocardiography; Female; Heart Diseases; Heart Rate; Heart Ventricles; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Systole; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

Topics: Antithyroid Agents; Carbimazole; Choanal Atresia; Female; Humans; Hyperthyroidism; Infant, Newborn; Methimazole; Pregnancy; Pregnancy Complications; Teratogens

The effects of the thyroid state on oxidative damage, antioxidant capacity, susceptibility to in vitro oxidative stress and Ca(2+)-induced permeabilization of mitochondria from rat tissues (liver, heart, and gastrocnemious muscle) were examined. Hypothyroidism was induced by administering methimazole in drinking water for 15 d. Hyperthyroidism was elicited by a 10 d treatment of hypothyroid rats with triiodothyronine (10 micro g/100 g body weight). Mitochondrial levels of hydroperoxides and protein-bound carbonyls significantly decreased in hypothyroid tissues and were reported above euthroid values in hypothyroid rats after T(3) treatment. Mitochondrial vitamin E levels were not affected by changes of animal thyroid state. Mitochondrial Coenzyme Q9 levels decreased in liver and heart from hypothyroid rats and increased in all hyperthyroid tissues, while Coenzyme Q10 levels decreased in hypothyroid liver and increased in all hyperthyroid tissues. The antioxidant capacity of mitochondria was not significantly different in hypothyroid and euthyroid tissues, whereas it decreased in the hyperthyroid ones. Susceptibility to in vitro oxidative challenge decreased in mitochondria from hypothyroid tissues and increased in mitochondria from hyperthyroid tissues, while susceptibility to Ca(2+)-induced swelling decreased only in hypothyroid liver mitochondria and increased in mitochondria from all hyperthyroid tissues. The tissue-dependence of the mitochondrial susceptibility to stressful conditions in altered thyroid states can be explained by different thyroid hormone-induced changes in mitochondrial ROS production and relative amounts of mitochondrial hemoproteins and antioxidants. We suggest that susceptibilities to oxidants and Ca(2+)-induced swelling may have important implications for the thyroid hormone regulation of the turnover of proteins and whole mitochondria, respectively.

Topics: Animals; Antioxidants; Calcium; Hyperthyroidism; Hypothyroidism; In Vitro Techniques; Lipid Peroxidation; Male; Methimazole; Mitochondria, Heart; Mitochondria, Liver; Mitochondria, Muscle; Mitochondrial Swelling; Oxidative Stress; Rats; Rats, Wistar; Triiodothyronine; Ubiquinone; Vitamin E

Topics: Adrenergic beta-Antagonists; Anorexia Nervosa; Antithyroid Agents; Body Image; Female; Humans; Hyperthyroidism; Methimazole; Sweating; Tachycardia; Weight Loss

We report the case of a 63-year-old patient with sudden onset of an acute syndrome of auditory hallucinations and delusions. Considering the anamnesis, course of the illness, and organopathologic results, we assumed an organic schizophreniform disorder within the scope of pre-existing autoimmune thyroiditis. Under treatment with high-potency neuroleptics, we observed partial regression and, after strumectomy, complete regression of the psychotic symptoms. Apparently, the acute organic schizophreniform disorder was caused by a changed metabolic situation with a transition to hyperthyroidism coinciding with beginning a small dose of antithyroid drugs.

Topics: Antipsychotic Agents; Delusions; Female; Hallucinations; Humans; Hyperthyroidism; Methimazole; Middle Aged; Psychotic Disorders; Thyroidectomy; Thyroiditis, Autoimmune

Neutropenic colitis, characterized by neutropenia plus cecal and ascending colon inflammation, is a rare complication of chemotherapy in hematological malignancies and, less commonly, of medication used to treat other diseases (e.g., hyperthyroidism). We report a case of neutropenic colitis with cecal perforation in a 44-year-old woman treated with methimazole for hyperthyroidism. The patient had received subtotal thyroidectomy for hyperthyroidism in 1984 and recurrent hyperthyroidism was found in 1993. She was then treated with methimazole for almost 3 months, when sustained fever, diarrhea, weakness, and progressive abdominal pain developed. Due to the findings of peritonitis and neutropenia, she underwent emergent laparotomy. During the operation, chronic ulceration of the cecum with perforation was found and resection of the ileocecal segment and ileostomy were performed. Three months later, closure of the ileostomy with anastomosis of the ileocolostomy was performed. Her condition was stable during 9 years' follow-up. In conclusion, neutropenic enterocolitis has a broad spectrum of clinical presentations that require alertness in patients with neutropenia. When detected late, it may lead to bowel perforation and even mortality.

Topics: Adult; Antithyroid Agents; Cecal Diseases; Colitis; Female; Humans; Hyperthyroidism; Intestinal Perforation; Methimazole; Neutropenia

In hyperthyroidism-complicated pregnancies, medical therapy is necessary to reach an euthyroid condition, and propylthiouracil (PTU) or methimazole (MMI) are used. These drugs are equally effective, but may cause fetal and neonatal hypothyroidism because they freely cross the placenta. Although PTU has not been significantly associated with embryo-fetal anomalies, it has been suggested that MMI might be responsible for a specific embryopathy.. Two cases of major congenital anomalies after MMI exposure during pregnancy are reported.. PTU should be the drug of choice, and the use of MMI should be restricted to cases with allergic reactions, intolerance, or poor response to PTU.

Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Ectodermal Dysplasia; Female; Humans; Hyperthyroidism; Infant, Newborn; Male; Maternal Age; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy, High-Risk; Scalp; Twins

Recently, a few studies have shown the safety of methimazole (MMI) therapy of thyrotoxic lactating mothers on thyroid function of their infants. However, it is not known whether the effect of moderately high doses of MMI therapy on lactating mothers can be dangerous for breast-fed infants. Eighty-eight thyrotoxic lactating mothers and their infants were studied. 46 received 20 mg MMI and 42 were given 30 mg MMI during the first month, 10 mg for the second and 5-10 mg for additional 10 months of therapy. Serum T4, T3 and TSH concentrations and in hyperthyroid MMI treated mothers and their RT3U were measured in hyperthyroid MMI treated mothers and their infants, before and at 1, 2, 6, and 12 months after initiation of therapy. Serum MMI was measured in the infants of thyrotoxic mothers taking 20-30 mg MMI. Mean+/-SD of free T4 index (FT4I) in thyrotoxic mothers treated with 20 and 30 mg MMI for one month decreased from 20.1+/-4.2 to 9.7+/-1.5 (p<0.001) and from 20.6+/-4.8 to 8.6+/-3.0 (p<0.001), respectively. Values for free T3 index (FT3I) decreased from 587+/-53 to 180+/-39 (p<0.001) and from 610+/-49 to 151+/-31 (p<0.001) in those treated with 20 and 30 mg MMI, respectively. By the end of one month 5 had elevated FT4I or FT3I or both and 12 had elevated TSH. The dose of MMI was adjusted and thyroid function remained normal up to 12 months of MMI therapy in thyrotoxic lactating mothers. Serum T4, T3 and TSH concentrations of breast-fed infants were normal before and up to 12 months of MMI therapy of their breast-feeding mothers. The lowest T4 and T3 and the highest TSH values were 101 nmol/l, 1.8 nmol/l and 4.1 mU/l, respectively. Serum MMI levels were <0.03 in 7 and 0.03, 0.034 and 0.035 microg/ml in the other 3 infants. We conclude that the treatment of hyperthyroid lactating mothers with doses of 20-30 mg MMI day does not cause deleterious effects on thyroid function of their breast-fed infants.

Topics: Antithyroid Agents; Breast Feeding; Female; Humans; Hyperthyroidism; Infant; Lactation; Methimazole; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

Hyperthyroidism affects the circulatory system, producing an increase in cardiac output and an enhanced vascular bed volume. These phenomena are important in the regulation of blood pressure. The present study was designed to evaluate the effects of short- and long-term treatment of hyperthyroidism on arterial pressure, taking into account the indices of cardiac function and peripheral vessel resistance.. Fifty-one patients with hyperthyroidism and 30 healthy controls were investigated. The patients were examined before treatment, two weeks after initiation of therapy, and after attainment of a euthyroid state. Thiamazole was used as the antithyroid agent. Blood pressure and serum thyroid hormones were determined and ultrasonographic examination was performed on all the subjects, after the application of a diet containing 120 mmol of sodium and 70 mmol of potassium for three days.. Patients with hyperthyroidism had higher systolic blood pressure and lower diastolic blood pressure than the healthy controls. After short-term treatment, systolic blood pressure returned to normal, while diastolic blood pressure was normalized only after long-term treatment.. Regulation of blood pressure in patients with hyperthyroidism is a complex process. Systolic blood pressure is mainly related to cardiac output and returns to normal range shortly after the initiation of therapy, while diastolic blood pressure is related to peripheral vascular resistance and is normalized after long-term treatment.

Topics: Adolescent; Adult; Antithyroid Agents; Blood Pressure; Female; Heart Rate; Hemodynamics; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Statistics as Topic; Thyroid Gland; Thyroid Hormones

To relate thyroid, steroid and pituitary hormones to ovarian ultrasonographic findings in hyperthyroid patients before and during treatment.. Ultrasonography of the ovaries and serum hormone determination by immunoassay were performed before and during thiamazole therapy in 18 women of fertile age treated for hyperthyroidism at the Danderyd Hospital from 1996 to 1998.. When hyperthyreotic, the patients had elevated serum levels of sex hormone-binding globulin (SHBG) and subnormal values of cortisol, free testosterone (fT) and dehydroepiandrosterone (DHEA). In the euthyreotic state following treatment, endocrine variables were normalized. Patients with a short duration of the disease had higher pretreatment levels of free thyroxine (fT4), SHBG and testosterone and lower corticosteroid binding globulin (CBG) and cortisol levels compared to patients with a long duration of the disease. The pretreatment ultrasonographic picture was abnormal in 16 of 18 patients. Of the 8 patients who were examined by ultrasonography after 3 months of treatment, all but 1 showed a normal picture. Samples from patients showing an abnormal ultrasonographic picture had significantly higher fT4 and lower free testosterone (fT) values than samples from patients with a normal ultrasonographic picture.. Ultrasonographic findings showing a multicystic/multifollicular picture, resembling polycystic ovaries (PCO), in hyperthyroidism may be related to direct effects of thyroid hormones on the ovaries and/or altered intraovarian androgen environment due to elevated SHBG levels. It is highly recommended to assess the thyroid status in patients with multicystic/multifollicular ovaries/PCO.

Topics: Adrenal Cortex Hormones; Adult; Antithyroid Agents; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Humans; Hydrocortisone; Hyperthyroidism; Methimazole; Middle Aged; Ovary; Sex Hormone-Binding Globulin; Testosterone; Thyroxine; Transcortin; Ultrasonography

Hyperthyroidism is characterized by increased levels of circulating free fatty acids (FFA) and increased lipid oxidation, but it is uncertain which regional fat depots contribute. The present study was designed to define the participation of femoral and abdominal fat stores in the overall stimulation of lipolysis in hyperthyroidism in the basal state and during insulin stimulation. We studied nine women with newly diagnosed hyperthyroidism (HT) and after (euthyroidism, ET) medical treatment with methimazol and compared with eight control subjects (CTR). All subjects were studied in the postabsorptive state and during a 3-h hyperinsulinemic euglycemic clamp with microdialysis catheters sc in the abdominal and femoral adipose tissue. Before treatment, patients had elevated circulating concentrations of triiodthyronine, FFA, and glycerol. Levels of interstitial glycerol ( micro mol/liter) in abdominal adipose tissue [485 +/- 24 (HT), 226 +/- 20 (ET) (P < 0.001), 265 +/- 34 (CTR) (P < 0.001)] and in femoral adipose tissue [468 +/- 41(HT), 245 +/- 29 (ET) (P < 0.01), 278 +/- 31(CTR) (P < 0.005)] were elevated in the basal hyperthyroid state, and these differences prevailed during the glucose clamp [230 +/- 23 (HT), 113 +/- 13 (ET) (P < 0.01), 132 +/- 22(CTR) (P < 0.01) and 303 +/- 39 (HT), 122 +/- 15 (ET) (P < 0.01), 166 +/- 21(CTR) (P < 0.01)]. These results suggest that femoral and abdominal adipose tissue contribute equally to the excessive rate of lipolysis in hyperthyroidism and that both tissues are resistant to the actions of insulin.

Topics: Abdomen; Adipose Tissue; Adult; Antithyroid Agents; Blood Flow Velocity; Energy Metabolism; Fatty Acids, Nonesterified; Female; Femur; Food; Glucose Clamp Technique; Glycerol; Humans; Hyperinsulinism; Hyperthyroidism; Lipolysis; Methimazole; Microdialysis; Middle Aged; Triiodothyronine

Topics: Adrenergic beta-Antagonists; Antithyroid Agents; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Propylthiouracil; Treatment Failure

Topics: Antithyroid Agents; Autoimmune Diseases; Baclofen; Cyclophosphamide; Heart; Humans; Hyperthyroidism; Immunosuppressive Agents; Male; Methimazole; Middle Aged; Multiple Sclerosis, Chronic Progressive; Stroke Volume; Tachycardia, Sinus

The treatment for hyperthyreoidism is usually conservative and consists of medications that limit the production of thyroid hormones. The diagnose of hyperthyreoidism was set up according to clinical finding, to determine the level of FT3, FT4, TSH with thyroid scintigraphy, and ultrasonography. In this study we showed the result in the therapy of the hyperthyreoidism with Favistan-Tiamazol tbl. during the period 2000-2001.

Topics: Adult; Antithyroid Agents; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged

Topics: Adult; Antithyroid Agents; Humans; Hyperthyroidism; Male; Methimazole; Seaweed; Tablets; Time Factors

The presence of TSH receptor antibody (TRAb) is rarely responsible for hyperthyroidism due to metastatic lesions of thyroid carcinoma. A 70-year-old woman was incidentally found to be thyrotoxic around the time that external irradiation was performed for multiple bone metastases 9 years after subtotal thyroidectomy for follicular carcinoma. Hyperthyroidism persisted after oral administration of thiamazole. Relevant laboratory data were as follows: FT4 9.6 ng/L, FT3 7.3 ng/L, TSH <0.19 mU/L, TBII 70, TSAb 735, and Tg 32,000 microg/L. 131I-total body scan showed 131I accumulation in the occipital bone, cervical vertebra, thoracic vertebra, ilium, and residual thyroid gland. Since the ilium uptake (11.6) was markedly higher compared to the residual thyroid gland uptake (0.14), four subsequent 131I therapies were performed. The patient became hypothyroid, and TBII became negative. TSAb became negative after the first 131I-therapy but has increased again to 204 at present. Tg was 1,962 microg/L despite high TSH levels. 131I accumulation in the residual thyroid, cervical vertebra, and thoracic vertebra disappeared. Also 131I accumulation in the ilium has gradually decreased, but the image in the occipital bone has become markedly distinctive. This is a rare case characterized by TRAb-positive hyperthyroidism, by T3-predominant thyrotoxicosis, and by stronger accumulation of 131I in the metastatic tumor than in the residual thyroid gland. Thus, the response to TRAb and 131I-therapy is different among metastatic thyroid tissues.

Topics: Adenocarcinoma, Follicular; Aged; Antithyroid Agents; Autoantibodies; Bone Neoplasms; Female; Humans; Hyperthyroidism; Immunoglobulins, Thyroid-Stimulating; Iodine Radioisotopes; Methimazole; Receptors, Thyrotropin; Thyroglobulin; Thyroid Neoplasms; Thyrotropin; Thyroxine; Triiodothyronine

The objective of this study was to determine side-effects associated with iodized oil injection in patients with simple goiter. In an iodine-deficient population, 3420 patients with simple goiter, who were not taking supplemental iodine, were chosen for this study. They received a single intramuscular injection of 1 ml iodized oil, containing 480 mg iodide. Clinical and laboratory evaluations were performed every 3 months for one year and every 6 months for the next 4 years. The incidence of hypo- and hyperthyroidism was 0.6% each, with equal prevalence in both sexes. Most cases of hypo- and hyperthyroidism were observed during the first 5 months after the injection. Eight cases of hyperthyroidism were asymptomatic. A further 8 patients had overt thyrotoxicosis and required treatment with methimazole for 18 months. Recurrence of hyperthyroidism was observed in one patient. Five hypothyroid patients were diagnosed only by abnormal thyroid function tests, and 4 cases needed no treatment. Others received T4 treatment for a mean of 14.5 months. Among 14 T4-treated patients, recurrence of hypothyroidism occurred in 7 patients after treatment was discontinued. Twenty-nine patients (0.8%) were afflicted with dermatologic complications. The most common dermatologic side-effect was urticarial reaction. In 15 subjects, skin lesions appeared 8 to 14 days after injection. It is concluded that side-effects of iodized oil injection are rare, and in most cases the complications are transient and self-limited. The occurrence of iodine induced hyperthyroidism following iodized oil administration is close to the ratio observed in spontaneous thyrotoxicosis.

Topics: Adolescent; Adult; Child; Child, Preschool; Female; Goiter; Humans; Hyperthyroidism; Hypothyroidism; Injections, Intramuscular; Iodized Oil; Male; Methimazole; Prospective Studies; Recurrence; Skin Diseases; Thyrotropin; Thyroxine; Triiodothyronine

Hyperthyroidism is associated with a higher incidence of arterial thromboembolism; increasing age, atrial fibrillation, and mitral valve abnormalities are risk factors. However, the contribution of endogenous coagulation parameters is unclear. Because thyroid hormone influences receptor and transcription factors, it can be expected that it will influence proteins involved in coagulation processes synthetised in many cells. Fourteen hyperthyroid patients were studied untreated, after 1 week of treatment with propranolol, and after therapeutic treatment with thiamazol. Fourteen matched controls were used for comparison. On each occasion, endothelial marker proteins, coagulation/fibrinolysis factors, and inflammatory (liver) markers were measured. Excess thyroid hormone was associated with elevated levels of most endothelium-associated proteins. In addition, plasma fibronectin and fibrinogen were increased, while plasminogen was decreased. No evidence was found that hyperthyroidism was associated with coagulation/fibrinolysis activation, or with increased levels of the inflammation markers interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) or C-reactive protein (CRP). Propranolol treatment only lowered the von Willebrand factor propeptide, and slightly increased plasminogen. Treatment with thiamazol returned all parameters to normal. Hyperthyroidism increased the plasma levels of most endothelial marker proteins, and of some liver-synthetized proteins. No evidence for coagulation/fibrinolysis activation was found. However, it appears that endothelial activation, which is indicative of a procoagulant state, is present in hyperthyroidism. This may explain the association between hyperthyroidism and thromboembolism especially if other risk factors are present. von Willebrand factor II (vWF:Ag-II) levels may be suitable markers to evaluate acute changes in endothelial function because this parameter responds more rapidly to changes in endothelial function than other factors.

Topics: Adrenergic beta-Antagonists; Adult; Antithyroid Agents; Biomarkers; Blood Coagulation; Endothelium, Vascular; Female; Fibrinolysis; Humans; Hyperthyroidism; Inflammation; Liver; Male; Methimazole; Middle Aged; Propranolol; Protein Biosynthesis; Proteins; Reference Values

Myopathy frequently develops in patients with hyperthyroidism, but its precise mechanism is not clearly understood. In this study we focused on the purine nucleotide cycle, which contributes to ATP balance in skeletal muscles. To investigate purine metabolism in muscles, we measured metabolites related to the purine nucleotide cycle using the semiischemic forearm test. We examined the following four groups: patients with untreated thyrotoxic Graves' disease (untreated group), patients with Graves' disease treated with methimazole (treated group), patients in remission (remission group), and healthy volunteers (control group). To trace the glycolytic process, we measured glycolytic metabolites (lactate and pyruvate) as well as purine metabolites (ammonia and hypoxanthine). In the untreated group, the levels of lactate, pyruvate, and ammonia released were remarkably higher than those in the control group. Hypoxanthine release also increased in the untreated group, but the difference among the patient groups was not statistically significant. The accelerated purine catabolism did not improve after 3 months of treatment with methimazole, but it was completely normalized in the remission group. This indicated that long-term maintenance of thyroid function was necessary for purine catabolism to recover. We presume that an unbalanced ATP supply or conversion of muscle fiber type may account for the acceleration of the purine nucleotide cycle under thyrotoxicosis. Such acceleration of the purine nucleotide cycle is thought to be in part a protective mechanism against a rapid collapse of the ATP energy balance in exercising muscles of patients with hyperthyroidism.

Topics: Adenosine Monophosphate; Adenosine Triphosphate; Adult; Ammonia; Exercise; Female; Glycolysis; Humans; Hyperthyroidism; Inosine Monophosphate; Lactic Acid; Male; Methimazole; Muscle, Skeletal; Purine Nucleotides; Thyroid Gland

Experimental evidence suggests an involvement of thyroid hormones in myocardial nonmyocyte component growth. We evaluated the possible role of thyroid hormones in myocardial remodeling by ultrasonic tissue characterization (videodensitometry) in 8 hyperthyroid patients, in 10 hypothyroid patients, and in 2 patients with thyroid hormone resistance syndrome (RTH), before, 60, and 120 days after treatment (T0, T60, T120), and in 10 age-matched euthyroids. According to a previously described procedure, the derived collagen volume fraction (dCVF%, an echocardiographic index estimating the collagen content) was predicted from the pixel-level frequency distribution width (broadband, Bb) of the selected echocardiographic images. Thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were assessed by immunometric method. QT interval dispersion (QTd) on basal electrocardiogram was measured as a marker of dyshomogeneous ventricular repolarization. At T0, Bb and dCVF% were normal in hyperthyroid and euthyroid patients, and slightly increased in RTH patients, whereas significantly higher values were found in hypothyroids. At T60, a significant reduction in Bb was observed in hypothyroids, with nearly normal dCVF% values. This trend was confirmed at T120 with complete normalization of echoreflectivity. No echoreflectivity changes were observed in hyperthyroid and RTH patients during treatment. QTd was significantly increased in hypothyroids at T0, while no significant differences were found among groups at T60 and T120. Because the different videodeonsitometric myocardial properties observed in hypothyroid versus hyperthyroid patients correspond to an increase of dCVF%, this study suggests that thyroid hormones exert an inhibitory effect on myocardial collagen synthesis in humans.

Topics: Adult; Antithyroid Agents; Collagen; Echocardiography; Electrocardiography; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Middle Aged; Thyroid Diseases; Thyroid Hormone Resistance Syndrome; Thyroid Hormones; Thyroxine; Triiodothyronine; Ventricular Remodeling

Hyperthyroidism is associated with enhanced systolic function. The present study was designed to evaluate systolic cardiac function in patients with hyperthyroidism during a short-term and a long-term pharmacotherapy. The diagnostic value of various indices of the left ventricle function was analysed. Fifty-one hyperthyroid patients were investigated before initiation of the treatment, after 14 days of therapy with thiamazol (mean dose 54 mg/24 hr), a short-term treatment and after attainment of normal thyroid function, a long-term treatment (mean period 9 months). Control values were obtained from 30 healthy individuals. All investigated subjects were aged 18-50 yr. The following indices were determined with ultrasonocardiographic method: preejection period (PEP), left ventricle ejection time (LVET), preejection period index (PEPI) and left ventricle ejection time index (LVETI), index PEP/LVET, left ventricle shortening fraction (LVSF), left ventricle ejection fraction (LVEF), mean velocity of the circumferential fiber shortening (mVcf), contractility index (CIx), stroke volume (SV), cardiac index (CI), output-pressure index (OPI) and end-systolic wall stress (ESWS). Additionally, total peripheral resistance index (TPRI) and double product (DP) were calculated. In patients with untreated hyperthyroidism, a significant shortening of PEP, PEPI, LVET and low PEP/LVET index and TPRI as well as increased LVSF, LVEF, mVcf, CIx, CI, OPI and DP were shown. There was no changes in LVETI, SV and ESWS. A short-term treatment resulted in changes in PEP, PEPI, LVET, mVcf, CI and OPI in direction of normal values. After a long-term treatment all altered indices were normal with an exception of OPI, CI and DP. It is concluded that enhanced systolic function of the heart in patients with hyperthyroidism becomes normal after pharmacological control of the thyroid gland. Some changes are seen after a short-term treatment with thiamazol. The indices which reverse early are PEP, PEPI, LVET, mVcf and CI. Changes in ejection function of the left ventricle in patients with hyperthyroidism are resulted from increased heart rate and were found to be related to total peripheral vascular resistance.

Topics: Adult; Antithyroid Agents; Female; Humans; Hyperthyroidism; Male; Methimazole; Severity of Illness Index; Ventricular Dysfunction, Left

We present a case of severe hyperemesis gravidarum (HG) associated with thyrotoxicosis in a woman with a past history of an eating disorder. She had developed persistent HG from early pregnancy until about at the end of the second trimester with a body loss of 14 kg. Total parenteral nutrition was effective in alleviateing HG. It is suggested that even a past history of an eating disorder could be at risk of developing HG.

Topics: Adult; Anorexia Nervosa; Antithyroid Agents; Female; Fetal Growth Retardation; Gestational Age; Humans; Hyperemesis Gravidarum; Hyperthyroidism; Methimazole; Parenteral Nutrition, Total; Pregnancy; Pregnancy Complications; Thyrotropin; Thyroxine; Triiodothyronine

Dehydroepiandrosterone (DHEA) and DHEA-sulphate (S) have been suggested to play protective roles in many pathological states, some of which are observed in hyperthyroidism. If DHEA and DHEA-S levels change in hyperthyroidism, they might participate as a possible causative link with such pathophysiological changes in hyperthyroidism. However, the CRH-ACTH-DHEA system in hyperthyroidism has not been clearly defined. We examined plasma levels of DHEA and DHEA-S together with ACTH and cortisol in both hyperthyroid (Hyper) and euthyroid states (Eu).. Eighteen patients (5 men and 13 women, aged 46.9 +/- 2.8 years) with Graves' disease were studied before treatment and again in the euthyroid state following treatment with methimazole. A 100 microg hCRH stimulation test and a low-dose (0.5 microg) 1-24 ACTH stimulation test were performed on separate days. Basal levels and A area under the response curve (AUC) were compared between Hyper and Eu.. DHEA-S was higher in Hyper than in Eu. However, basal DHEA did not differ between Hyper and Eu. The ratio of DHEA to DHEA-S was lower in Hyper than in Eu. AAUC of DHEA during a CRH test was lower in Hyper than in Eu. However, AAUC of DHEA during an ACTH test was similar in both Hyper and Eu. Basal ACTH was higher in Hyper than in Eu. In both CRH and ACTH tests, AAUC of cortisol response was lower in Hyper than in Eu, although the basal cortisol level was not different.. The balance of the conversion between DHEA-S and DHEA in the hyperthyroid state favoured DHEA-S. Similar to cortisol, the DHEA response in the CRH test in hyperthyroidism seemed to be insufficiently compensated for by increased ACTH, although the DHEA response to low-dose ACTH was similar in the hyperthyroid and euthyroid states. Increased DHEA-S might play some role in the pathological states in many organs in hyperthyroidism.

Topics: Adrenocorticotropic Hormone; Adult; Antithyroid Agents; Area Under Curve; Corticotropin-Releasing Hormone; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Humans; Hydrocortisone; Hyperthyroidism; Male; Methimazole; Middle Aged; Thyrotropin; Thyroxine; Triiodothyronine

Free radicals, hydroxyperoxides and H(2)O(2) are all known to damage cell components. This study was designed to compare the concentrations of hydroxyperoxide and free radical scavengers in the cardiac muscles of old rats in the hyper- or hypothyroid condition, to determine whether rates of peroxidation would differ with age, thyroid status, or both. Rats were rendered hyper- or hypothyroid by administration of l-thyroxine or methimazole for 4 weeks. Among the old rats, the lipid peroxide (LPO) concentrations, measured as thiobarbituric acid (TBA) reactants, were significantly greater in the hyperthyroid than in the euthyroid state and the LPO concentrations measured as TBA+Fe(3+) reactants, which may be precursors of LPO, were significantly greater in the hyperthyroid state, whereas in young rats, the LPO concentrations measured by TBA or TBA+Fe(3+) methods did not differ significantly in the hyperthyroid state. In the euthyroid state, the concentration of LPO measured as TBA+Fe(3+) reactants was significantly reduced with age. Xanthine oxidase (XOD) activity also was markedly increased with age, being more pronounced in the hyperthyroid than in the euthyroid state. The Mn and Cu/Zn superoxide dismutase activities were greater in the hyperthyroid than in the euthyroid state. Glutathione peroxidase activity decreased with age in the euthyroid and, particularly, in the hyperthyroid state. Catalase activity was not affected in the old rats. Concentrations of alpha-tocopherol in the old rats were high in the hyperthyroid state and low in the hypothyroid state, whereas the levels of beta- and gamma-tocopherols in these rats were unchanged in both conditions as compared with the euthyroid state findings. Data suggest that the site of free radical generation differs in older rats, with additional shifts in the location of intracellular lipid peroxidation being noted during hyperthyroidism. Thus, as rats age, the reduction of the free radical scavenger system and the increase in LPO and XOD activities might induce myocardial dysfunction.

Topics: Aging; Analysis of Variance; Animals; Antithyroid Agents; Glutathione Peroxidase; Hyperthyroidism; Hypothyroidism; Lipid Peroxidation; Male; Malondialdehyde; Methimazole; Myocardium; Rats; Rats, Wistar; Superoxide Dismutase; Thyroid Diseases; Thyroid Gland; Thyroxine; Vitamin E; Xanthine Oxidase

Lead is a widespread toxic metal that accumulates predominantly in human bone. Altered bone metabolism in hyperthyroidism is characterized mainly by bone resorption. Thus, we speculated that lead excretion could be increased in hyperthyroid patients. In 12 hyperthyroid patients (43.3 +/- 16.1 years) who were not previously occupationally exposed to lead, lead concentrations in blood (PbB), spot urine samples corrected by urine creatinine (PbUs), and in 24-hour urine samples (PbU24) were determined in the hyperthyroid state and after euthyroidism had been induced by therapy. Serum osteocalcin (OC) and desoxypyridinoline crosslinks (Pyr) served as specific markers for bone metabolism. After induction of euthyroidism (duration of antithyroid therapy: mean 17.3 +/- 6.9 weeks) PbB was reduced (3.7 +/- 2.6 vs. 5.7 +/- 4.7 microg/dL, p = 0.041) as was PbUs (0.39 +/-0.27 vs. 0.61 +/- 0.32 microg/mg Cr, p = 0.005). A fourfold decrease of PbU24 was associated with a 3.3-fold decrease of Pyr, and moreover there was a significant correlation between Pyr and PbUs (r = 0.58, p = 0.047). Concentration of total triiodothyronine correlated with Pyr (r = 0.66, p = 0.018), but not with PbB or PbUs. OC showed only a tendency to be increased before antithyroid medication, and did not correlate with either thyroid hormone or Pyr. Our results indicate that in hyperthyroid patients, even when not previously exposed to lead, lead excretion is increased due to bone resorption.

Topics: Adult; Antithyroid Agents; Circadian Rhythm; Creatinine; Female; Humans; Hyperthyroidism; Lead; Male; Methimazole; Middle Aged; Osteocalcin; Pyridines; Reference Values

Calcium-dependent uncoupling of liver mitochondrial oxidative phosphorylation by a non-metabolizable long chain fatty acyl analogue was compared with uncoupling induced by in vivo thyroid hormone treatment. beta,beta'-Methyl-substituted hexadecane alpha, omega-dioic acid (Medica 16) is reported here to induce a saturable 20-30% decrease in liver mitochondrial DeltaPsi, DeltapH and protonmotive force which proceeds in the presence of added Ca(2+) to cyclosporin A-sensitive mitochondrial permeabilization. Ca(2+)-dependent uncoupling by Medica 16 was accompanied by atractylate-enhanced, bongkrekic-inhibited activation of mitochondrial Ca(2+) efflux. The direct mitochondrial effect exerted in vitro by Medica 16 is similar to that induced by in vivo thyroid hormone treatment. Hence, the thyromimetic protonophoric activity of Medica 16 and the uncoupling activity of TH converge onto components of the mitochondrial permeabilization transition pore.

Topics: Animals; Hyperthyroidism; Hypolipidemic Agents; Hypothyroidism; Ion Channels; Male; Membrane Proteins; Methimazole; Mitochondria, Liver; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Palmitic Acids; Proton-Motive Force; Rats; Triiodothyronine; Uncoupling Agents

To study fracture risk and risk factors for fractures in patients with hyperthyroidism.. Historical follow-up.. A total of 864 patients with diffuse toxic goiter (ICD 10: E05.0) or toxic nodular goiter (E05.2) were contacted through a self-administered questionnaire. Each respondent was compared to an age: (+/- 5 years) and gender-matched control from a random sample of the background population who responded to the same questionnaire.. Among the patients 621 (72%) responded and of these 617 could be analyzed. Within the first 5 years before the diagnosis, the patients had the same fracture risk as the controls (RR = 1.2, 95% CI; 0.7-2.0). After the diagnosis, fracture risk was elevated among the patients (RR = 1.7, 95% CI: 1.2-2.3), especially in the age group 50 years or older (RR = 2.2, 95% CI: 1.5-3.3). Fracture risk was elevated for fractures of the spine (RR = 8.9, 95% CI: 1.6-48.4), and the forearms (RR = 3.1, 95% CI: 1.6-6.2), but not at other skeletal sites. Treatment with radioactive iodine alone was associated with an increased fracture risk (OR = 2.7, 95% CI: 1.2-6.0), a risk that was not present in patients who, in addition to radioactive iodine, also had received methimazole (RR = 1.5, 95% CI: 0.7-3.2).. Our study demonstrated an increased fracture risk in hyperthyroidism, a fracture risk that was present with radioactive iodine treatment alone, but not in subjects that had received both radioactive iodine and methimazole or other types of antithyroid therapy.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Antithyroid Agents; Case-Control Studies; Female; Follow-Up Studies; Fractures, Bone; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Risk Factors; Surveys and Questionnaires

Topics: Animals; Antithyroid Agents; Cat Diseases; Cats; Diagnosis, Differential; Fatal Outcome; Hydrothorax; Hyperthyroidism; Lung Diseases; Male; Methimazole; Pleural Diseases; Radiography, Thoracic; Torsion Abnormality

The mechanism by which thyroid hormones promote bone growth has not yet been elucidated. In vitro, thyroid hormones stimulate insulin-like growth factor-I (IGF-I) production by osteoblasts, which is important for the anabolic effects of the hormone on bone. To determine whether the IGF-I/IGF binding protein (IGFBP) profile is affected when thyroid hormone production is altered in vivo, we studied 36 women who had recently been diagnosed with hyperthyroidism (age: 29-67 years; 19 with Graves' disease, 17 with toxic nodular goiter) and 36 age-matched healthy women as controls. Serum IGF-I, and its binding proteins (IGFBP-3, IGFBP-4, and IGFBP-5), as well as bone mineral density (BMD) at the lumbar spine, femoral neck, and radius midshaft were measured before and 1 year after antithyroid (methimazole) treatment. Serum IGF-I levels were significantly increased in the hyperthyroid patients before treatment (214 +/- 18.2 ng/mL vs. 145 +/- 21.3 ng/mL; p < 0.05). There was no difference in IGF-I levels of patients with Graves' disease and toxic nodular goiter. Serum IGF-I concentrations returned to normal after treatment with methimazole. Serum IGFBP-3 and IGFBP-4 values were significantly elevated in the hyperthyroid group before treatment (3960 +/- 220 ng/mL and 749.7 +/- 53.1 ng/mL vs. 2701 +/- 180 ng/mL and 489.9 +/- 32.4 ng/mL; p < 0.05 and p < 0.01, respectively) and were reduced to those of controls after treatment. Serum IGFBP-5 of hyperthyroid subjects was not different from that of controls either before or after therapy. Serum free thyroxine showed a positive correlation with serum levels of IGF-I (r = 0.73, p < 0.05), IGFBP-3 (r = 0.59, p < 0.05), and IGFBP-4 (r = 0.67, p < 0.05) but not IGFBP-5. BMD at the radius midshaft was significantly lower in hyperthyroid patients at the start of the study and showed a positive correlation with serum IGF-I (r = 0.58; p < 0.001) and a negative correlation with IGFBP-4 (r = -0.61; p < 0.05). Radius BMD showed a 7.2% increase in the hyperthyroid group after 1 year of methimazole treatment, and the correlation between BMD and serum IGF-I disappeared. Our data indicate that thyroid hormones may influence the IGF-I/IGFBP system in vivo in hyperthyroidism. The anabolic effects of increased levels of IGF-I may be limited in hyperthyroidism due to the increases of inhibitory IGFBPs that can counteract the anabolic effects and contribute to the observed net bone loss.

Topics: Adult; Aged; Antithyroid Agents; Bone Density; Female; Humans; Hyperthyroidism; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Methimazole; Middle Aged; Radius; Reference Values

A 45-year-old woman was referred to our hospital because of hyperthyroidism complicated by atrial fibrillation and heart failure. Laboratory data revealed pancytopenia, with a white blood cell count of 2,600/microliter, red blood cell count of 330 x 10(4)/microliter, and platelet count of 6.2 x 10(4)/microliter. The patient had normal transaminase levels, but tests for hepaplastin and cholinesterase showed values of 34% and 1.4 U/ml, respectively, indicating liver dysfunction. There was also decreased excretion of indocyanine green. After initiation of treatment with 30 mg thiamazole and 20 mg propranolol daily, the patient's thyroid function normalized and the other abnormal laboratory findings such as pancytopenia and liver dysfunction also disappeared. Pancytopenia is a rare complication of hyperthyroidism. In this case, various laboratory abnormalities were normalized by antithyroid therapy alone, indicating that the hyperthyroidism itself was closely related to the pathogenesis of pancytopenia and liver dysfunction.

Topics: Antithyroid Agents; Female; Humans; Hyperthyroidism; Liver Diseases; Methimazole; Middle Aged; Pancytopenia

Hyperthyroidism is associated with enhanced osteoblastic and osteoclastic activity, and patients frequently have low bone mineral density and high bone turnover. The aim of this study was to examine the bone formation and resorption markers trend in 12 female patients, before and after normalization of thyroid activity. The following measurements were made at baseline and 1 and 6 months after hormone normalization induced by methimazole treatment: total alkaline phosphatase (ALP), bone alkaline phosphatase (BALP), collagen type C-terminal propeptide (PICP), osteocalcin (BGP), telopeptide (ICTP), urinary-hydroxyproline/urinary creatinine (uOHP/uCreat), urinary calcium/urinary creatinine (uCa/uCreat) and deoxypyridinoline crosslinks (D-Pyr). Compared with controls, all of these parameters were significantly increased (ALP p = 0.014; BALP p = 0.0001; PICP p = 0.013; BGP p = 0.009; ICTP p = 0.0001; uOHP/uCreat p = 0.002; uCa/uCreat p = 0.044; crosslinks p = 0.0001). After treatment the values of ALP, BALP and PICP in hyperthyroid patients showed an initial slight increase and then a significant downwards trend (ALP p = 0.008, BAP p = 0.001, PICP p = 0.026). Furthermore, resorption markers showed a significant decrease (uOHP/ uCreat p < 0.005 and D-Pyr p < 0.008). As regards lumbar BMD patients, measurements were significantly reduced in comparison with the control group (p = 0.005). Six months after serum thyroid hormones level normalization, we observed a significant increase (p=0.014 vs baseline). Both neoformation and resorption markers are useful to assess pathological bone turnover and bone involvement in hyperthyroidism. They could also be employed to monitor the effect of antithyroid treatment on bone and to indicate if bone antiresorption therapy should be considered.

Topics: Adult; Aged; Alkaline Phosphatase; Amino Acids; Antithyroid Agents; Bone and Bones; Bone Density; Bone Remodeling; Collagen; Collagen Type I; Creatinine; Female; Humans; Hydroxyproline; Hyperthyroidism; Isoenzymes; Methimazole; Middle Aged; Osteocalcin; Peptide Fragments; Peptides; Procollagen

Two cases of hyperthyroidism with hyperpigmentation are presented. In both cases, hyperpigmentation was seen on the lower extremities, most strikingly on the shins, backs of the feet and the nail bed. Histology of the pigmented skin showed basal melanosis and heavy deposition of haemosiderin around dermal capillaries and sweat glands. Treatment with mercazol in both cases resulted in no significant waning of pigmentation. Distribution of hyperpigmentation, haemosiderin deposition and poor response to the treatment may be characteristic features of the pigmentation caused by hyperthyroidism, and may represent differences from the pigmentation seen in Addison's disease.

Topics: Addison Disease; Adult; Antithyroid Agents; Hemosiderosis; Humans; Hyperpigmentation; Hyperthyroidism; Male; Melanosis; Methimazole; Middle Aged; Sweat Gland Diseases

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

Four patients with clinical diagnosis of amyotrophic lateral sclerosis syndrome and laboratory results of hyperthyroidism were reported. There were 3 women aged 27, 59, 59 years and 1 man aged 50 years. All of them had symptoms and signs of dysarthria and dysphagia, fasciculations of the tongue, muscle weakness with generalized hyperreflexia. After treatment with antithyroid drugs, motor weakness and dysphagia improved.

Topics: Adult; Amyotrophic Lateral Sclerosis; Antithyroid Agents; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Treatment Outcome

Ms. K., a white, 47-year-old female with a history of hyperthyroidism had been treated with methimazole daily for a period of 9 years. She presented with a 2-day history of fever higher than 103 degrees F and cellulitis of the right arm after a scratch injury. White blood cell count (WBC) was noted at 0.4 x 10(3)/microL and neutrophils at 5.6%, indicating agranulocytosis. Methimazole was discontinued by the patient with the onset of symptoms. Appropriate intravenous antibiotic therapy and reverse isolation were provided in the acute-care setting, as well as administration of the granulocyte colony-stimulating factor (G-CSF) filgrastim. No recovery of the granulocyte count or improvement of clinical condition was noted until her sixth day of admission, at which time her WBC increased to 2.6 x 10(3)/microL. The administration of intravenous antifungals and antibiotics prevented overwhelming sepsis, while giving the G-CSF the opportunity to stimulate growth of granulocytes to finally fight the offending organisms and save this patient.

Topics: Antithyroid Agents; Female; Humans; Hyperthyroidism; Infection Control; Leukocyte Count; Methimazole; Middle Aged; Neutropenia; Nurse Practitioners

In this study, plasma leptin concentrations were measured in rats artificially rendered hyper- or hypothyroid by administration of thyroxine or TRH, by administration of methimazole, or by thyroidectomy. Compared with those in untreated controls, leptin immunoreactivity was not affected in the hyperthyroid state, but was significantly increased in hypothyroid animals. Methimazole administration for longer time periods caused a stepwise increase in plasma leptin immunoreactivity. Greatest leptin concentrations were seen after 28 days of methimazole. Seven days after withdrawal of the methimazole, leptin concentrations no longer differed from those observed in control animals. In hypothyroid animals, expression of leptin mRNA was increased in both retroperitoneal and epididymal adipose tissue, whereas no difference was seen for subcutaneous or mesenteric fat. Incubation of rat leptin with plasma of eu- or hypothyroid rats and subsequent HPLC analysis of leptin plasma peaks gave no indication of an altered hormone stability. We conclude that, in hypothyroid rats, leptin concentrations may be increased as a result of stimulated leptin synthesis in retroperitoneal and epididymal adipose tissue.

Topics: Adipose Tissue; Analysis of Variance; Animals; Antithyroid Agents; Chromatography, Gel; Chromatography, High Pressure Liquid; Hyperthyroidism; Hypothyroidism; Leptin; Male; Methimazole; Radioimmunoassay; Rats; Rats, Wistar; RNA, Messenger; Thyroidectomy; Thyrotropin-Releasing Hormone; Thyroxine

To determine the age-related changes in thyroid hormone (TH) effects on cardiac glucose transporter one (GLUT-1) and four (GLUT-4) isoforms, male Fischer 344 rats at 4, 12, and 25 months of age were studied at euthyroid, hyperthyroid and hypothyroid conditions. Hyperthyroidism was induced with daily intraperitoneal injections of triiodothyronine (15 microg/100 gm) for 10 days. Hypothyroidism was achieved with 0.025% methimazole in the drinking water for 4 weeks. Immunoblot analysis indicated that at euthyroid basal conditions GLUT-1 protein was not significantly altered with age while GLUT-4 protein was significantly reduced in 25 month old rats (82.0 +/- 28.8% of a 4 month old rat p <0.01). In 4 months old rats, GLUT-1 was increased in both hypothyroidism (432.5 +/- 208.7% of age-matched euthyroid control) and to a lesser extent in hyperthyroidism (242.0 +/- 93.3% of control) p<0.01. In 25 month old rats, hyperthyroidism was also associated with increased GLUT-1 mass (190.8 +/- 117.6% of age-matched euthyroid control) p<0.01. Hypothyroidism in this age group was not associated with significant change in GLUT-1 protein. The cardiac GLUT-4 protein was increased during both hypothyroidism and hyperthyroidism. The changes of GLUT-4 in aged rats were similar to those found in young rats. It is concluded that TH effect on GLUT-1 expression in the heart is altered with age while TH effects on GLUT-4 are age independent.

Topics: Aging; Animals; Blotting, Western; Creatinine; Glucose Transporter Type 1; Glucose Transporter Type 4; Heart; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Monosaccharide Transport Proteins; Muscle Proteins; Myocardium; Organ Size; Rats; Rats, Inbred F344; Thyroxine; Triiodothyronine

The aplastic anemia methimazole induced is a rare event. We describe a case of a woman, affected by hyperthyroidism, who suffers from bone marrow aplasia during Tapazole treatment, and literature has been reviewed. Stopping methimazole and beginning a therapy with methylprednisolone in high dosage, intravenous IgG in high dosage, filgastrin and danatrol, medullary recover after 11 days of treatment is obtained. By analyzing our case and the 12 further cases described, we find that the prognosis of aplastic anemia during the treatment of antithyroid therapy, is rather good. Even if the pathogenetic mechanism of Tapazole induced bone marrow aplasia, it seems to be immuno-mediated in most cases, a direct toxicity in bone marrow cannot be excluded. In examined cases the antithyroid dosage was medium high (mean 40 mg/die). Therefore the use of Tapazole in low doses (15 mg/die) effective in almost all hyperthyroid patient must be considered, when possible, the best therapeutic choice, since it is safer in the incidence of important side effects such as bone marrow aplasia, especially in elderly patients or in patients with chronic renal failure.

Topics: Adult; Aged; Anemia, Aplastic; Anti-Inflammatory Agents; Antithyroid Agents; Danazol; Estrogen Antagonists; Female; Follow-Up Studies; Humans; Hyperthyroidism; Immunoglobulins, Intravenous; Male; Methimazole; Methylprednisolone; Middle Aged; Time Factors

Topics: Antithyroid Agents; Female; Graves Disease; Humans; Hyperthyroidism; Infant, Newborn; Male; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Skin Abnormalities

Bilateral kidney agenesias (Potter syndrome) in a newborn of a hyperthyroid woman receiving methimazole during early pregnancy. This is a clinical case of a hyperthyroid woman that received methimazole during early pregnancy who gave birth to a girl with bilateral kidney agenesis. The initial clinical data was the presence of oligohydramnios detected by an ultrasound (US) at 19 gestational weeks. Another US at the term of the gestation showed anhydramnios, absence of renal silhouettes and bladder, which was corroborated when the girl was born. She died two days after she was born. Sufficient evidence exists that the methimazole administered during the early pregnancy can cause diverse congenital malformations including Potter's syndrome.

Topics: Abnormalities, Multiple; Antithyroid Agents; Face; Female; Humans; Hyperthyroidism; Infant, Newborn; Kidney; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Prenatal Exposure Delayed Effects; Syndrome

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

Ninety-three hyperthyroid patients were treated with 1 dose of iodine-131 (131I) during the past 10 years. Thirty-three were pretreated with propylthiouracil (PTU), 22 with methimazole (MMI), and 38 received no antithyroid drugs (ATD). ATD were discontinued 5-55 days before 131I therapy in three fourths of the cases and more than 4 months before therapy in one fourth of the cases. The frequency of cures in the 3 groups, 6-8 months after radioiodine therapy, was retrospectively studied. The cure rate among those who discontinued PTU for 5-55 days before 131I was significantly reduced (24%), compared with those who discontinued MMI for the same duration (61%) or those who received no ATD (66%). When PTU was discontinued for more than 4 months, the cure rate was similar to those who received no ATD. It is concluded that if ATD are used as initial therapy for hyperthyroidism, then PTU (but not MMI) may reduce the therapeutic efficacy of subsequent 131I. The reduction in cure rate was observed even when PTU was discontinued for as long as 55 days before 131I therapy. To our knowledge, this is the first report to compare, in one study, the effects of pretreatment with PTU and MMI on 131I therapy.

Topics: Adult; Antithyroid Agents; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Premedication; Propylthiouracil; Retrospective Studies; Treatment Outcome

Topics: Aged; Agranulocytosis; Antithyroid Agents; Female; Focal Infection; Gallium Radioisotopes; Humans; Hyperthyroidism; Methimazole; Pneumonia, Bacterial; Pseudomonas Infections; Radionuclide Imaging

Hyperthyroidism is the most common disorder of the thyroid. Patients typically present with complaints consistent with a hypermetabolic state, including nervousness, weight loss, heat intolerance, palpitations, irritability, and tremor. This case report reviews a 34-year-old woman who presented with unilateral upper extremity weakness, weight gain, and an episode of atrial fibrillation, the latter coinciding with a 36-hour lack of sleep and excess alcohol and caffeine intake. Although an extensive neurologic evaluation failed to identify any abnormality, the patient's laboratory analysis revealed elevations in thyroxine (T4) and triiodothyronine (T3) levels with unsuppressed thyroid-stimulating hormone levels. Subsequent treatment with the antithyroid drug methimazole (Tapazole) provided complete relief of symptoms. This case report illustrates how health care providers can be diverted to pursue a neurologic etiology when muscle weakness presents as a unilateral symptom. Plausible alternative causes for muscle weakness and other symptoms are presented.

Topics: Adult; Antithyroid Agents; Diagnosis, Differential; Female; Humans; Hyperthyroidism; Methimazole; Muscle Weakness; Nursing Assessment

Topics: Antithyroid Agents; Exophthalmos; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Prednisone

The present study was designed to evaluate the changes in the plasma lipid peroxidation and antioxidant system in 15 adult volunteer patients in hyperthyroid and euthyroid states. In these patients, plasma concentrations of lipid peroxides were decreased and, ascorbic acid and vitamin E levels were significantly increased in euthyroid status in comparison to hyperthyroid status. A significant increase in the plasma GPx activity (P < 0.01) and a decrease in GST (P < 0.001) was observed after euthyroidism was sustained with methimazole therapy. In conclusion, hyperthyroidism tends to enhance lipid peroxide content and an increase in GST and decreases in GPx, vitamin E and ascorbic acid levels accompany to this change in the plasma. The achievement of euthyroidism led an improvement in these parameters.

Topics: Adult; Antioxidants; Antithyroid Agents; Ascorbic Acid; Female; Glutathione Transferase; Humans; Hyperthyroidism; Lipid Peroxides; Male; Methimazole; Middle Aged; Vitamin E

The effects of hyperthyroidism and hypothyroidism on brown adipose tissue (BAT) thermogenesis and phospholipid fatty acid composition were investigated in rats. Chronic triiodothyronine (T3) treatment (hyperthyroidism) increased the interscapular BAT pad weight, its triacylglycerol content, and its DNA content. It did not affect basal and noradrenaline-stimulated in vitro oxygen consumption of BAT expressed per microg DNA, although it significantly increased the oxygen consumption of the whole BAT pad. T3 treatment had little effect on phospholipid content and phospholipid fatty acid composition. In contrast, chronic methimazole treatment (hypothyroidism) decreased the BAT pad weight and the triacylglycerol content, but did not significantly change the DNA content in comparison with the control. It significantly decreased the noradrenaline-stimulated BAT oxygen consumption expressed per microg DNA and per BAT pad, but did not change the basal oxygen consumption. Methimazole treatment significantly affected phospholipid content and phospholipid fatty acid composition. Among the major fatty acids of BAT, it decreased docosahexaenoic acid (DHA), arachidonic acid, palmitic acid, palmitoleic acid, and oleic acid, and it increased linoleic acid, stearic acid, and eicosapentaenoic acid. A regression analysis revealed a positive relationship between in vitro respiration and DHA levels in phospholipids (r = 0.404, p<0.05). These results suggest that thyroid hormones have trophic action on BAT and are necessary for BAT thermogenic activity. This study also suggests that DHA is involved in the regulation of BAT thermogenic activity, as we previously indicated.

Topics: Adipose Tissue, Brown; Animals; Antithyroid Agents; Body Temperature Regulation; Docosahexaenoic Acids; Fatty Acids; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Organ Size; Oxygen Consumption; Phospholipids; Rats; Rats, Wistar; Thyroid Hormones; Triiodothyronine

We present a case of 52 years old woman with cutaneous lupus erythematosus and methimazole induced bone marrow aplasia with agranulocytosis and liver damage.

Topics: Anemia, Aplastic; Antithyroid Agents; Bone Marrow; Chemical and Drug Induced Liver Injury; Female; Humans; Hyperthyroidism; Leukocytosis; Lupus Erythematosus, Cutaneous; Methimazole; Middle Aged

A 31-year-old male and a 31-year-old female rhesus monkey developed clinical signs consistent with hyperthryoidism. These included a ravenous appetite, hyperactivity, and accentuated ratchet movement and hand tremors while performing fine motor tasks. Bilaterally enlarged thyroid glands were palpated in both monkeys. A unique clinical finding of the female as the hypertrophic cardiomyopathy. The T3 and T4 levels in the male rhesus were 3.79 ng/ml and 28.20 microg/dl, respectively. T3 and T4 levels in the female were 4.33 ng/ml and 22.2 microg/dl, respectively. A biopsy of the enlarged thyroids demonstrated a typical multinodular goiter with cystic hyperplasia. The female rhesus was successfully treated with methimazole, but the hypertrophic cardiomyopathy did not resolve. The relationship between erythrocytosis and T4 levels common to humans and cats is also evident in the rhesus monkey.

Topics: Aging; Animals; Female; Hunger; Hyperthyroidism; Macaca mulatta; Male; Methimazole; Monkey Diseases; Movement; Polycythemia; Thyroid Gland; Thyroxine; Time Factors; Triiodothyronine

A three-part study explored the basis for an interaction between changes in thyroid status and bulbospinal serotonin (5HT) metabolism. In experiment 1, three well-characterized models of primary hypothyroidism were all accompanied by significant increases in 5HT metabolism. In experiment 2, circulating thyroid hormone levels were experimentally varied from very low methimazole (Meth) treatment to very high (T3 implants: 2.5, 5.0, or 7.5 mg triiodothyronine). As in experiment 1, Meth led to elevated 5HT. Hyperthyroidism was accompanied by significant reductions in 5HT, while urinary norepinephrine excretion paralleled 5HT. In experiment 3, rats were subjected to Meth either 2 weeks before or after induction of diabetes with streptozotocin (Stz). Meth prevented Stz-associated reductions in 5HT and attenuated development of hyperphagia. Meth could not reverse established Stz-associated reduction in 5HT or hyperphagia, although both were slightly attenuated. Thus, although the first two experiments argue for a simple inverse relationship between circulating thyroid hormone levels and 5HT in the brain, experiment 3 demonstrated that Stz-associated decrements in 5HT could not be reversed by subsequent lowering of circulating thyroid hormone. Nor did accompanying measurements indicate that glycemic status or circulating levels of leptin were important predictors of 5HT. Thus the interaction between thyroid hormones and 5HT is both more subtle and more complex than previously thought.

Topics: Animals; Blood Glucose; Body Weight; Brain Stem; Diabetes Mellitus, Experimental; Hydroxyindoleacetic Acid; Hyperphagia; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Norepinephrine; Rats; Rats, Sprague-Dawley; Serotonin; Spinal Cord; Thyroid Hormones; Tryptophan

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

Experimental models of hypothyroidism and hyperthyroidism in Sprague-Dawley rats were established in this study. Diazepam was given to rats at a single oral dose of 30-40 mg.kg-1 and the plasma concentration of diazepam was detected by HPLC. The results showed that the plasma concentration of diazepam was significantly higher in hypothyroid rats than that in controls (P < 0.05). The Cmax, AUC and T1/2 (Ka) were increased. The Vd was decreased and the elimination was slowed. Mild hyperthyroidism showed nearly no effect on the plasma concentration, Cmax and AUC of diazepam in the rats. But when the rats became more heavily hyperthyroid, the plasma concentration, Cmax and AUC of diazepam were increased gradually. The absorption of diazepam was changed slightly in mild and moderate hyperthyroid rats, the Vd was decreased and the elimination was accelerated. In heavily hyperthyroid rats, however, the absorption of diazepam was obviously accelerated. The Vd was decreased and the elimination was slowed. Therefore, we conclude that different thyroid status may have different effects on the pharmacokinetics of diazepam.

Topics: Animals; Anti-Anxiety Agents; Area Under Curve; Diazepam; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Random Allocation; Rats; Rats, Sprague-Dawley

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 58-year-old woman was admitted because of jaundice, ascites and marked oedema. For three years she had suffered from nervousness, decreasing fitness and weight loss, which had been assumed as due to chronic alcoholism. Liver biopsy revealed extensive fibrosis, in part with early cirrhotic transformation. This was followed by cardiac failure with atrial fibrillation (ventricular rate 140/min) and marked pleural effusions. The thyroid was diffusely enlarged and there were signs of exophthalmos.. Bilirubin concentration was 3 mg/dl, lactate dehydrogenase activity was 310 U/l, cholesterase 1.3 kU/l and the prothrombin test was 21%. The TSH level was 0.01 microU/ml while the free thyroxine level was 4.7 ng/dl and that of free triiodothyronine 13.5 pg/ml. Chest radiograph revealed cardiomegaly, bilateral peripheral pulmonary congestion and pleural effusions to midfield. Right heart catheterization excluded pulmonary hypertension; cardiac output was 10l/min. The thyroid was enlarged on ultrasound and diffusely echopoor, as in immune thyroid disease.. Cardiac failure regressed and thyroid function normalized within ten days on propranolol, 4 x 40 mg and thiamazole 3 x 40 mg daily intravenously. Subtotal thyroidectomy was performed three weeks later with subsequent thyroid hormone substitution. Liver functions were normal six months later and ultrasound showed no signs of cirrhotic change and the ascites had resolved.. Hyperthyroidism is frequently associated with changes in liver functions. In extreme cases, high-output cardiac failure may occur, with liver congestion and clinical as well as histological changes like those in liver cirrhosis.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Antithyroid Agents; Arrhythmias, Cardiac; Autoimmune Diseases; Female; Heart Failure; Humans; Hyperthyroidism; Liver Cirrhosis; Methimazole; Middle Aged; Propranolol; Thyroid Hormones; Thyroidectomy; Ultrasonography

A 65-years-old woman admitted to the hospital in order to treat of the mediastinal tumor, but she suffered from palpitation, slight fever, sweating, uneasiness, sleeplessness and weightloss. On the physical examination, she was experiencing tachycardia, fevering (37.2 approximately 37.6 degrees C). Skin was moist but had no exophtalmos or neck tumor. Chest X-ray showed an abnormal shadow in the upper mediastinum. On chest CT, a tumor mass (9 x 5 x 4 cm) with cystic regions and scattered calcifications occupied from anterior to posterior mediastinum. The tumor compressed trachea to the left and right brachiocephalic vein and SVC to the right. Lower portion of the tumor intruded into behind of the trachea. Lymph node swelling of mediastinum was also detected. Results of general laboratory examination were within normal limits. Thyroid function test revealed hyperthyroidism; T3U 58%, free T3 24.4 pg/ml, free T4 6.0 ng/dl and thyroglobulin 967 mg/dl, but TSH was < 0.01 microIU/ml. After daily administration of methimazole (300 mg/day) for 4 weeks, thyroid function became to normal level and symptoms of hyperthyroidism was disappeared. The tumor was completely extirpated with right hemithyroidectomy and lymph node dissection under neck colla incision and median sternotomy. Pathological finding of the tumor showed follicular-fetal adenoma of thyroid with hyaloid degeneration and cystic change. There was no finding suspected of Graves' disease. She is well without any complications for 8 months after operation. Some discussion of the literature was mentioned.

Topics: Adenoma; Aged; Antithyroid Agents; Female; Goiter, Substernal; Humans; Hyperthyroidism; Methimazole; Thyroid Neoplasms

Leptin, the product of the ob gene, is a recently discovered hormone secreted by adipocytes. Serum leptin concentrations increase in correlation with the percentage of body fat, but besides that, little is known about the physiological actions of leptin in humans. The aim of this study was to assess the influence of hypo- and hyperthyroidism on serum leptin levels. Thirty-two patients (16 with hypothyroidism and 16 with hyperthyroidism) were studied before and after treatment with replacement doses of T4 (hypothyroid patients) or methimazole (hyperthyroid), when thyroid function was normal. Control serum for each group was obtained from healthy age-, sex-, and body mass index-matched subjects. Plasma leptin levels were measured by specific RIA. The mean leptin level in the hypothyroid patients was lower before treatment (4.7 +/- 0.7 microg/L) than that in the controls (8.6 +/- 1.4 microg/L; P < 0.02) and was lower than that during treatment with T4 and normalization of thyroid function in the same group of patients (6.3 +/- 0.8 microg/L; P < 0.05). Leptin levels in the hyperthyroid patients were similar before (7.2 +.0 1.1 microg/L) and after normalization of thyroid function following treatment with methimazole (6.2 +/- 1.1 microg/L) and were similar to the control value (8.8 +/- 1.4 microg/L). In conclusion, leptin levels are decreased in the hypothyroid patients and unchanged in hyperthyroidism. Whether decreased leptin levels may contribute to the decreased energy expenditure in patients with hypothyroidism merits further investigation.

Topics: Female; Humans; Hyperthyroidism; Hypothyroidism; Leptin; Male; Methimazole; Proteins; Thyroxine

131I treatment is an effective alternative to surgery in patients with a large, (non-)toxic, compressive goiter. Late development of hyperthyroidism after 131I therapy for nontoxic nodular goiter is considered rare. We have seen this complication in 3 of approximately 80 patients treated with radioiodine for volume reduction of a large, multinodular goiter. Three women, aged 60 to 71 years, had large, multinodular goiters causing tracheal compression. They were clinically euthyroid before 131I therapy and had normal free thyroxine (FT4) levels. Serum thyroid-stimulating hormone (TSH) levels were normal in 2 patients and undetectable in 1 patient. Patients 1 and 2 received a single dose of 86 and 48 mCi 131I, respectively. Patient 3 received 20 mCi 131I twice (interval 1 month). Clinical and biochemical thyrotoxicosis with high thyroid radioactive iodide uptake (RAIU) developed 10, 6, and 3 months after 131I therapy, respectively, although at control visits 1 to 3 months earlier, serum TSH and FT4 levels were normal. Thyrotoxicosis responded well to methimazole in all three patients. The late occurrence of thyrotoxicosis, high RAIU, and good response to methimazole argue against thyroiditis as the cause of thyrotoxicosis. Serum levels of TSH receptor antibodies, which were undetectable before therapy (patients 1 and 2), were clearly elevated in all three patients during thyrotoxicosis. This is in favor of autoimmune hyperthyroidism as the cause of thyrotoxicosis. These cases illustrate that severe autoimmune hyperthyroidism may occur several months after radioiodine treatment for nontoxic, multinodular goiter. Information about symptoms of hyperthyroidism and regular control visits in the first year after therapy are important in these patients.

Topics: Aged; Autoantibodies; Autoimmune Diseases; Female; Goiter, Nodular; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Middle Aged; Receptors, Thyrotropin; Thyrotropin; Thyroxine

The effects of thyroid and glucocorticoid hormones on the expression of the Kv1.5 potassium channel gene were studied in the rat left ventricle. Rats were rendered hypothyroid by oral administration of methimazole (MMI). Hyperthyroidism was induced in the MMI-treated rats by administration of L-thyroxine (T4). Kv1.5 mRNA levels decreased markedly in the hypothyroid rats, whereas they increased in the hyperthyroid rats. Propranolol, a beta-adrenergic blocker, did not inhibit the T4-dependent increase in Kv1.5 mRNA, indicating that the increase is not due to the increased beta-adrenergic stimuli under hyperthyroidism. Accordingly, treatment of the MMI-treated hypothyroid rats with isoproterenol, a beta-adrenergic receptor agonist, did not increase the mRNA. The Kv1.5 mRNA levels positively correlated with the thyroid hormone levels in sera. When rats were adrenalectomized and rendered hypothyroid, Kv1.5 mRNA become undetectable. Administration of 3,3',5-triiodothyronine (T3) at a dose to induce hyperthyroidism did not restore the mRNA level. However, T3 significantly increased the mRNA level when dexamethasone was co-administered at a physiological dose. These results for the first time demonstrate that thyroid hormone up-regulates Kv1.5 mRNA levels in the rat left ventricle and they demonstrate that glucocorticoid is required for this induction.

Topics: Animals; Dexamethasone; Heart Ventricles; Hyperthyroidism; Hypothyroidism; Kv1.5 Potassium Channel; Male; Methimazole; Myocardium; Potassium Channels; Potassium Channels, Voltage-Gated; Propranolol; Rats; Rats, Wistar; RNA, Messenger; Thyroid Gland; Thyroxine; Transcription, Genetic; Triiodothyronine

Topics: Abnormalities, Drug-Induced; Adult; Antithyroid Agents; Esophageal Atresia; Female; Humans; Hyperthyroidism; Infant, Newborn; Male; Methimazole; Pregnancy; Pregnancy Complications; Tracheoesophageal Fistula

The effects of altered thyroid states on lipid peroxidation, antioxidant capacity, and susceptibility to oxidative stress of rat tissues were examined. Hypothyroidism was induced by administering methimazole in drinking water for 15 days. Hyperthyroidism was elicited by a 10-day treatment of hypothyroid rats with tri-iodothyronine (10 micrograms/100 g body weight). In tissues of hypothyroid rats the lipid peroxidation was not modified, whereas in hyperthyroid rats lipid peroxidation increased in liver and heart but not in skeletal muscle. The glutathione peroxidase activity increased significantly in heart and muscle of hypothyroid rats and in muscle of hyperthyroid rats. The glutathione reductase activity was not modified in tissues of hypothyroid and hyperthyroid rats. In both rat groups the whole antioxidant capacity of tissues decreased, but significantly only in liver and heart. The results obtained studying the response to oxidative stress in vitro indicated that the susceptibility to oxidative challenge was increased in all tissues of hyperthyroid rats and in heart and muscle of hypothyroid animals. These results are explainable in terms of tissue variations in haemoprotein content and/or of antioxidant capacity. Since it has been reported that hypothyroidism offers in vivo protection against free radical damage, we suggest that such an effect could be due to greater effectiveness of cellular defence systems different from antioxidant ones.

Topics: Analysis of Variance; Animals; Antioxidants; Antithyroid Agents; Glutathione Peroxidase; Glutathione Reductase; Hyperthyroidism; Hypothyroidism; Lipid Peroxidation; Liver; Male; Methimazole; Muscle, Skeletal; Myocardium; Oxidative Stress; Rats; Rats, Wistar; Thyroid Diseases; Thyroid Gland; Triiodothyronine

Congenital hyperthyroidism is a rare, transient disease usually caused by transmission of thyrotropin receptor autoantibodies from the mother with Graves' disease to her child. We report a German women and her two sons who had congenital, but persistent hyperthyroidism without any signs of autoimmunity. Direct sequencing of the polymerase chain reaction-amplified exon 10 of the thyrotropin receptor genomic DNA revealed in the mother and both sons a transition of GCC to GTC, resulting in an exchange of alanine 623 to valine. This germline mutation in a highly conserved region of the thyrotropin receptor resulted in a constitutive activation of the cyclic adenosine monophosphate-generating cascade with resulting hyperthyroidism. Analysis of the family for a corresponding BstXI restriction-site polymorphism revealed heterozygosity for this mutation in the affected family members, but not in the father or other relatives. We conclude that whenever congenital hyperthyroidism is persistent and parameters of autoimmunity are absent, a constitutively active thyrotropin receptor mutation should be considered. Treatment appears to require aggressive means such as total thyroidectomy or ablation by 131iodine because two subtotal thyroidectomies in the mother were insufficient to control the disease.

Topics: Adult; Antithyroid Agents; Child, Preschool; DNA; Female; Germ-Line Mutation; Humans; Hyperthyroidism; Infant; Male; Methimazole; Pedigree; Point Mutation; Receptors, Thyrotropin

Hypo- or hyperthyroid states were induced in adult male mallards (Anas platyrhynchos) by subchronic exposure to daily injections of methimazole or a 9:1 ratio of thyroxine (T4): triiodothyronine (T3). The levels of T4 given were 0, 125, 250, or 500 micrograms/kg/day and for methimazole; 10 mg/kg/day for 22 or 21 days. Plasma T3 showed a lasting decrease with T4:T3 treatment, despite the attempt to maintain the normal T4:T3 ratio. Antibody formation to sheep red blood cells was decreased only at the 125 micrograms/kg/day dose of T4, and was unaffected by methimazole treatment. Natural killer cell activity to RP-9 tumor cells and macrophage phagocytosis of killed, opsonized Saccaromyces cereviseae were unaffected by treatment throughout the study. However, lectin-dependent cellular cytotoxic activity to RP-9 tumor cells was significantly decreased after 21 days of methimazole treatment, indicating that hypothyroidism may have an influence on cell-mediated immunity. Hypo- and hyperthyroid conditions had opposing effects on plasma cholesterol levels.

Topics: Animals; Antithyroid Agents; Biomarkers; Blood Chemical Analysis; Cholesterol; Cytotoxicity Tests, Immunologic; Dose-Response Relationship, Drug; Ducks; Hyperthyroidism; Hypothyroidism; Killer Cells, Natural; Lectins; Leukocyte Count; Male; Methimazole; Phagocytosis; Thyroid Hormones; Tumor Cells, Cultured

We describe a 26-year-old male hemodialysis patient with erythropoietin (EPO) resistant anemia associated with primary hyperthyroidism. Use of the anti-hyperthyroid drug, methimazole, led to improvement of his hyperthyroidism and anemia. Before the anti-hyperthyroid therapy, he had received transfusions to maintain an adequate hematocrit during recombinant human EPO therapy. After the therapy, his hyperthyroidism improved and his hematocrit gradually increased without any transfusion. These findings suggest that the patient's EPO resistant anemia was the result of primary hyperthyroidism, and that this complication is reversible if accurate treatment is given.

Topics: Adult; Anemia; Antithyroid Agents; Erythropoietin; Hematocrit; Humans; Hyperthyroidism; Kidney Failure, Chronic; Male; Methimazole; Recombinant Proteins; Renal Dialysis

Thyroid hormone (T3) responsiveness of the PEPCK promoter in vivo was examined in both PEPCK/bGH(460) and PEPCK/bGH(335) mouse lines. Transgenic and non-transgenic littermates were treated with methimazole or PTU for 6 or 4 weeks, respectively, then treated +/- T3 for 10 days. In PEPCK/bGH(460) and PEPCK/bGH(355) transgenic mice, the bGH mRNA was decreased by 65% and 46%, respectively, in hyperthyroid mice when compared to euthyroid controls. Endogenous PEPCK mRNA was decreased by 33% in hyperthyroid non-transgenic mice. The conclusion of this study is that chronic hyperthyroidism in mice inhibits PEPCK-directed expression of the transgene when either the -460/+73 or the -355/+73 promoter/regulatory elements are used.

Topics: Animals; Antithyroid Agents; Cattle; Gene Expression Regulation, Enzymologic; Growth Hormone; Hyperthyroidism; Liver; Methimazole; Mice; Mice, Transgenic; Phosphoenolpyruvate Carboxykinase (GTP); Promoter Regions, Genetic; Regulatory Sequences, Nucleic Acid; RNA, Messenger; Triiodothyronine

Two recent studies have claimed that thyroid hormone administration accelerates malic enzyme gene expression in the neonatal brain in contrast to the well-documented lack of effect of triiodothyronine on malic enzyme gene expression in the adult brain. Since these observations conflict with earlier observations in our laboratory, we reinvestigated the effect of thyroid hormone status on the ontogeny of malic enzyme gene expression in the neonatal rat. Neither hypothyroidism nor hyperthyroidism influenced the ontogenesis of malic enzyme activity in neonatal brain whereas the patterns of gene expression and enzyme activity in liver were markedly affected. Our results suggest that tissue-specific factors in brain block thyroid hormone-induced gene expression by thyroid hormone.

Topics: Aging; Animals; Animals, Newborn; Brain; Female; Gene Expression Regulation, Enzymologic; Hyperthyroidism; Hypothyroidism; Liver; Malate Dehydrogenase; Methimazole; Organ Specificity; Pregnancy; Rats; Rats, Sprague-Dawley; RNA, Messenger; Thyroid Gland; Transcription, Genetic; Triiodothyronine

The aim of the present study was to evaluate the impact of hyperthyroidism on the cardiovascular system by separately analyzing the sympathetic and parasympathetic influences on heart rate. Heart rate variability was evaluated by autoregressive power spectral analysis. This method allows a reliable quantification of the low frequency (LF) and high frequency (HF) components of the heart rate power spectral density; these are considered to be under mainly sympathetic and pure parasympathetic control, respectively. In 10 newly diagnosed untreated hyperthyroid patients with Graves' disease, we analyzed power spectral density of heart rate cyclic variations at rest, while lying, and while standing. In addition, heart rate variations during deep breathing, lying and standing, and Valsalva's maneuver were analyzed. The results were compared to those obtained from 10 age-, sex-, and body mass index-matched control subjects. In 8 hyperthyroid patients, the same evaluation was repeated after the induction of stable euthyroidism by methimazole. Heart rate power spectral analysis showed a sharp reduction of HF components in hyperthyroid subjects compared to controls [lying, 13.3 +/- 4.1 vs. 32.0 +/- 5.6 normalized units (NU; P < 0.01); standing, 6.0 +/- 2.7 vs. 15.0 +/- 4.0 NU (P < 0.01); mean +/- SEM]. On the other hand components were comparable in the 2 groups (lying, 64.0 +/- 6.9 vs. 62.0 +/- 6.5 NU; standing, 77.0 +/- 6.5 vs. 78.0 +/- 5.4 NU). Hence, the LF/HF ratio, which is considered an index of sympathovagal balance, was increased in hyperthyroid subjects while both lying (11.3 +/- 4.5 vs. 3.5 +/- 1.1; P < 0.05) and standing (54.0 +/- 12.6 vs. 9.8 +/- 2.6; P < 0.02). This parameter was positively correlated with both T3 (r = 0.61; P < 0.05) and free T4 (r = 0.63; P < 0.05) serum levels. Among traditional cardiovascular autonomic tests, the reflex response of heart rate during lying to standing was significantly lower in hyperthyroid patients than in controls (1.12 +/- 0.03 vs. 1.31 +/- 0.04; P < 0.002). No statistically significant difference in reflex responses between the two groups was found in deep breathing or Valsalva's maneuver. In the 8 patients reexamined after methimazole treatment, we observed complete normalization of altered cardiovascular parameters, with slight predominance of the vagal component compared with controls. These results suggest that thyroid hormone excess may determine reduced parasympathetic activity and, thus, a relative hypers

Topics: Adolescent; Adult; Antithyroid Agents; Autonomic Nervous System; Electrocardiography; Female; Heart Conduction System; Heart Rate; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Reference Values

Cholestatic jaundice caused by imidazole derivates is a rare complication of antithyroid therapy. Only 20 such cases have been reported in the literature since the introduction of methimazole in 1949 and of carbimazole in 1953. We present a further case of methimazole-induced cholestatic liver injury, mimicking sclerosing cholangitis, where the etiology has been proven by a clear chronological relationship and the lack of other causative factors.

Topics: Adenoma; Aged; Antithyroid Agents; Bile Ducts, Intrahepatic; Chemical and Drug Induced Liver Injury; Cholangiopancreatography, Endoscopic Retrograde; Cholangitis, Sclerosing; Cholestasis, Intrahepatic; Diagnosis, Differential; Humans; Hyperthyroidism; Liver Function Tests; Male; Methimazole; Thyroid Neoplasms

To determine whether the low density lipoprotein (LDL) receptor pathway is involved in the catabolism of plasma lipoprotein (a) [Lp(a)], serum lipids, Lp(a), and LDL receptor activity were measured in seven patients with hyperthyroidism before and after methimazole treatment given hyperthyroidism is associated with enhanced LDL receptor activity. LDL receptor activity in patients was estimated by the equation using the serum concentrations of apolipoprotein (apo) B and C-II. When euthyroidism was achieved after treatment, not only did serum total cholesterol, high density lipoprotein-cholesterol, apo B, and LDL-cholesterol (LDL-Ch) levels rise, but Lp(a) significantly increased and calculated LDL receptor activity significantly decreased. The changes in LDL receptor activity were significantly correlated with the changes in LDL-Ch as expected, but not with changes in Lp(a). These results suggest that the serum concentration of Lp(a) is lowered in hyperthyroidism, probably by a mechanism other than the enhanced activity of the LDL receptor, and that the LDL receptor pathway is involved in the catabolism of Lp(a) to a limited extent.

Topics: Apolipoproteins; Female; Humans; Hyperthyroidism; Lipoprotein(a); Lipoproteins, LDL; Male; Methimazole; Receptors, LDL; Thyroid Function Tests

The mechanism of exercise intolerance in hyperthyroidism has not been fully elucidated. This study was undertaken to determine if hyperthyroidism reduced the efficiency of sub-maximal exercise.. We measured cardiorespiratory variables up to the anaerobic threshold (AT) during ramp-loading cycle ergometry in 12 patients (New York Heart Association functional class II or III). Studies were performed in the hyperthyroid state and repeated in the euthyroid state after 10 months of medical treatment. In 10-W steps from rest to the AT, we measured oxygen uptake (VO2) as a measure of total body work rate, and pressure rate product (PRP) as a measure of cardiac work rate. Loading watts at AT divided by the increment of Vo2 from rest to the AT (delta Watt/delta VO2) was calculated as an index of work efficiency (where delta means the increment of each value from rest to the AT).. VO2 and PRP at the AT were not significantly different between hyperthyroid and euthyroid states (VO2, 16.6 +/- 3.0 vs 17.5 +/- 2.3 mL/min/kg; PRP, 229 +/- 41 vs 218 +/- 28 x 10(2) mm Hg/min). However, loading watts at the AT were significantly lower in the hyperthyroid than the euthyroid state (28 +/- 22 vs 60 +/- 14 W: p < 0.01). VO2 and PRP while hyperthyroid were significantly higher than when euthyroid at every 10-W step during ramp-loading exercise. Furthermore, delta Watt/delta VO2 was significantly lower in hyperthyroid than euthyroid states (p < 0.001). There was a significant inverse correlation-ship between triiodothyronine and delta Watt/delta Vo2 (r = -0.654, p < 0.001).. Hyperthyroidism causes low work efficiency, which may limit exercise tolerance.

Topics: Adult; Anaerobic Threshold; Antithyroid Agents; Blood Pressure; Exercise Test; Exercise Tolerance; Female; Follow-Up Studies; Heart; Heart Rate; Humans; Hyperthyroidism; Lung; Male; Methimazole; Middle Aged; Oxygen Consumption; Physical Exertion; Rest; Thyrotropin; Thyroxine; Triiodothyronine

High levels of thyroid hormones accelerate bone turnover. The aim of the present study was to evaluate the effects of treatment with alendronate in patients affected by hyperthyroidism and osteoporosis. We studied 40 hyperthyroid patients with bone loss, divided into two groups according to menopausal state. Before treatment and after 6 and 12 months, serum thyroid hormones levels, serum osteocalcin level and bone mineral density were evaluated. In all patients we observed an increase in bone mineral density after treatment with alendronate, and a corresponding decrease in serum osteocalcin level.

Topics: Adult; Alendronate; Bone Density; Female; Humans; Hyperthyroidism; Methimazole; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Thyrotropin; Thyroxine; Triiodothyronine

Changes in magnesium metabolism, along with those in sodium, were investigated in 17 patients with Graves' disease (14 females and 3 males, mean +/- SD, 44.8 +/- 12.2 years) and their relationship to plasma levels of thyroid hormones were assessed before and after treatment. Each patient was studied in hyperthyroid state and euthyroid state after treatment. Each patient was studied in hyperthyroid state and euthyroid state after treatment with methimazole. Treatment with methimazole increased the magnesium concentration both in erythrocytes (2.00 +/- 0.18 vs. 2.08 +/- 0.24 mmol/l cells, P < 0.05) and in serum (0.72 +/- 0.12 vs. 0.84 +/- 0.11 mmol/l, P < 0.001) but both urinary output and fractional excretion of magnesium decreased significantly (P < 0.05 and P < 0.001, respectively). The erythrocyte sodium concentration decreased with treatment (10.7 +/- 2.6 vs. 8.1 +/- 1.1 mmol/l cells, P < 0.001) but the serum sodium remained unchanged (140.9 +/- 1.9 vs. 140.9 +/- 2.1 mmol/l, NS). Urinary excretion of sodium also decreased with treatment (P < 0.05), but only changes in indices of magnesium metabolism (decrease in renal fractional excretion, rise in serum level) correlated significantly with those of the thyroid functions with treatment. These observations clearly indicate that in Graves' disease, the magnitude of magnesium metabolism alteration is closely related to the extent of the increase in thyroid hormones in plasma.

Topics: Adult; Aged; Erythrocytes; Female; Humans; Hyperthyroidism; Magnesium; Male; Methimazole; Middle Aged; Sodium; Thyroxine; Triiodothyronine

We present a 15-year-old girl with an unusual clinical course of intractable thyrotoxicosis that was resistant to thiocarbamide therapy and propranolol. Although the latter beta-adrenergic blocking agent has been used as the sole drug in the preparation of thyrotoxicosis patients for thyroidectomy, it was unsatisfactory for control of our case. In contrast, the patient's clinical response to lithium carbonate 900-1500 mg/d for 10 days was very good and no side effects were observed. This demonstrates the importance of lithium as the drug of choice in thyrotoxic emergencies and uncontrolled preoperative patients when rapid and safe inhibition of thyroid hormone secretion is required.

Topics: Adolescent; Antithyroid Agents; Drug Resistance, Multiple; Female; Humans; Hyperthyroidism; Lithium Carbonate; Methimazole; Premedication; Propranolol; Propylthiouracil; Thyroidectomy

Neuromedin B (NB), a bombesin-like peptide, has been recently characterized as a physiological paracrine/autocrine inhibitor of thyrotropin (TSH) secretion. We hypothesized on the basis of our prior experiments that thyroid hormones stimulate pituitary NB secretion which mediates, at least in part, the TSH-suppressive effect of thyroid hormone. Here, we evaluated the time-course of the effect of thyroid hormones administration to eu- and hypothyroid rats on the anterior pituitary content of NB and on serum TSH. As previously reported, the pituitary content of NB increased in hyperthyroidism and decreased in hypothyroidism. Chronic treatment of hypothyroid rats with a physiological dose of thyroxine (0.8 microgram/100 g b.w. s.c, for 3 or 5 days) normalized pituitary NB content, while 5 days of treatment with a pharmacological dose of thriiodothyronine (0.4 microgram/100 g b.w.) induced an increase above that of normal pituitaries. Thyroxine and triiodothyronine injected once, s.c., into hypothyroid rats required 30 min to normalize NB content, which reached higher than normal values in 3-6 h. At these times, the increment in NB preceded or was simultaneous with the suppression of serum TSH. This rapid and marked effect on pituitary neuromedin B content, associated in time with TSH suppression, is in agreement with the hypothesis that neuromedin B may mediate at least in part, the acute suppression of TSH release by thyroid hormone, a hypothesis that still needs further verification.

Topics: Animals; Antithyroid Agents; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Neurokinin B; Pituitary Gland; Rats; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine

Topics: Carbimazole; Consensus Development Conferences as Topic; Humans; Hyperthyroidism; Hypothyroidism; Long-Term Care; Methimazole

Topics: Antithyroid Agents; Carbimazole; Drug Administration Schedule; Humans; Hyperthyroidism; Methimazole; Recurrence

A 19-year-old man had mild diarrhoea at the time that suddenly one night he was unable to turn in his bed and the following morning could not move his arms and legs for 4 hours. Neither he nor any family members had previously had any paralysis. Physical examination was unremarkable except for mild tachycardia and first-degree goitre.. A provocation test with glucose (3 g/kg) and insulin (0.1 IU/kg) caused renewed paralysis for several hours, serum potassium falling from 4.3 to 3.4 mmol/l. The paralysis was reversed on oral potassium (40 mmol) Thyroid function tests revealed hyperthyroidism with an increased concentration of free thyroxine (25.5 pg/ml) and free triiodothyronine (9.7 pg/ml), while thyroid-stimulating hormone was decreased (0.07 mU/I), supporting the diagnosis of autoimmune thyroiditis.. Thyrostatic treatment was started with thiamazole (10 mg every other day). There was no further periodic paralysis and another provocation test was negative.. Fleeting paralysis is often misdiagnosed as being psychogenic. Potassium abnormalities are the most common cause but are only rarely associated with hyperthyroidism. This case of thyrotoxic hypokalaemic paralysis was probably based on a genetic defect of muscle fibre membrane manifesting itself only in the presence of hyperthyroidism.

Topics: Adult; Antithyroid Agents; Diagnosis, Differential; Diarrhea; Electromyography; Glucose; Humans; Hyperthyroidism; Hypokalemia; Insulin; Male; Methimazole; Paralysis; Potassium; Radionuclide Imaging; Thyroid Function Tests; Thyroid Gland; Thyroiditis, Autoimmune; Thyrotropin; Thyroxine; Triiodothyronine; Ultrasonography

To determine the age-related changes in the effect of thyroid hormone on apolipoprotein A1 (ApoA1) gene expression, male Fischer 344 rats at 4 (young) and 26 (aged) mo of age were studied. Hyperthyroidism was induced with daily intraperitoneal injections of 3,5,3'-triiodothyronine (15 micrograms/100 g body wt) for 10 days. Hypothyroidism was induced with 0.025% methimazole in drinking water for 4 wk. Hyperthyroidism was associated with increased serum ApoA1 levels in young rats [7.52 +/- 0.41 vs. 3.67 +/- 0.30 optical density (OD); P < 0.01]. The increase in aged rats (6.5 +/- 0.87 vs. 5.14 +/- 0.09 OD) did not reach statistical significance. Hypothyroidism was not associated with significant changes in serum ApoA1 levels in either young or aged rats. Hyperthyroidism was associated with a 2.5-fold increase in ApoA1 mRNA in young rats and a 1.7-fold increase in aged rats. Hypothyroidism was associated with a 3.6-fold reduction in ApoA1 mRNA in young rats, but there was no significant change in aged hypothyroid rats. Mobility shift assays indicated that the binding of transacting factors to ApoA1 promoter increased in hyperthyroid young rats but not in hyperthyroid aged rats. It is concluded that aging in rats is associated with reduced ApoA1 responsiveness to thyroid hormones. This altered responsiveness could partly be the result of changes in the binding activity of nuclear factors to the ApoA1 promoter.

Topics: Aging; Animals; Antithyroid Agents; Apolipoprotein A-I; Autoradiography; Blotting, Northern; Hyperthyroidism; Hypothyroidism; Liver; Male; Methimazole; Rats; Rats, Inbred F344; Reference Values; RNA, Messenger; Triiodothyronine

To determine how lipid peroxides and free radical scavengers are changed in the brain of hyper- or hypothyroid rats, we examined the behavior of lipid peroxide and free radical scavengers in the cerebral cortex of aged (1.5 years old) rats that had been made hyper- or hypothyroid by the administration of thyroxine or methimazol for 4 weeks. Concentrations of catalase, Mn-superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were increased in hyperthyroid rats compared with euthyroid rats. Concentrations of total SOD, Cu,Zn-SOD and GSH-PX were increased but that of Mn-SOD was decreased in hypothyroid animals. There were no differences among hyperthyroid, hypothyroid and euthyroid rats in the levels of coenzymes 9 or 10. The concentration of lipid peroxides, determined indirectly by the measurement of thiobarbituric acid reactants, was decreased in hyperthyroid rats but not in hypothyroid rats when compared with euthyroid animals. These findings suggest that free radicals and lipid peroxides are scavenged to compensate for the changes induced by hyper- or hypothyroidism.

Topics: Animals; Antithyroid Agents; Brain; Catalase; Free Radical Scavengers; Glutathione Peroxidase; Hyperthyroidism; Hypothyroidism; Lipid Peroxidation; Magnesium; Male; Methimazole; Rats; Rats, Wistar; Superoxide Dismutase; Thyroxine

Topics: Antithyroid Agents; Contrast Media; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Hyperthyroidism; Iodine Compounds; Methimazole; Perchlorates; Risk Factors; Sodium Compounds; Thyroid Function Tests

To study the influence of thyroid hormone on Lp(a) plasma concentration we measured Lp(a), total cholesterol, LDL-C, HDL-C, triglycerides and fT4 levels and determined apo(a) phenotypes in 26 patients with hyperthyroidism in a follow-up study before and after thyreostatic treatment. The pretreatment values of total cholesterol (TC), LDL-C, and Lp(a) were significantly reduced as compared with those of healthy controls. The reduced mean Lp(a) concentrations could not be explained by a difference of apo(a) 'size allele' frequencies between patients and controls. During thyreostatic treatment mean concentrations of TC, LDL-C, and HDL-C increased significantly. The mean Lp(a) value was not changed after 4 weeks of treatment. The individual changes of Lp(a), however, correlated significantly with those of LDL-C levels (R = 0.40, P = 0.04). Eighty-one per cent of the patients showed an increase of Lp(a) or no change of the Lp(a) level and 19% reacted with a decrease upon thyreostatic treatment. The observed lipid and lipoprotein changes were not different in patients with Graves disease or multifocal toxic goiter. The results indicate that Lp(a) plasma levels are decreased in the hyperthyroid state irrespective of the pathogenic mechanism.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Humans; Hyperthyroidism; Lipoprotein(a); Methimazole; Middle Aged; Propranolol; Radionuclide Imaging; Reference Values; Regression Analysis; Thyroid Gland; Thyroxine; Triglycerides; Ultrasonography

Topics: Cholestasis; Humans; Hyperthyroidism; Liver; Male; Methimazole; Middle Aged

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

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

The effects of hyper- and hypothyroidism on the vasorelaxing responses to acetylcholine (ACh), sodium nitroprusside (NP), and CaCl2 were investigated in aortic strips and isolated perfused kidneys. The renal vascular reactivity to ACh and NP was increased in hyperthyroid rats, whereas the concentration-response curve to ACh in hypothyroid rats was flattened. In the renal vasculature from hypothyroid rats, NP produced a dual response: vasoconstriction at low doses and vasodilation at medium to high doses. Aortic strips from hyperthyroid rats showed an increased response to ACh without significant differences between hypothyroid and control groups. Aortic strips from all three experimental groups showed a similar relaxing response to CaCl2. These results indicate that: (1) the raised arterial pressure of hyperthyroid rats is not associated with a reduced endothelium-dependent and calcium-induced vasodilation, and (2) the changes in responsiveness to vasodilators in resistance vessels from hyper- and hypothyroid rats may play a role in the increased and decreased peripheral vascular resistances, respectively, previously reported in such animals.

Topics: Animals; Aorta, Thoracic; Endothelium, Vascular; Hemodynamics; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Muscle, Smooth, Vascular; Rats; Rats, Wistar; Renal Circulation; Thyroxine; Triiodothyronine; Vasodilation; Vasodilator Agents

The authors describe a 62 year-old white male who was diagnosed as autoimmune hyperthyroidism and treated with methimazole and atenolol. Ten days later he showed itching, jaundice and choluria. All drugs were discontinued. The patient was given radioactive iodine. Two months later direct serum bilirubin levels reached 35 mg%. Endoscopic retrograde cholangiogram evidenced normal extrahepatic biliary ducts. The percutaneous liver biopsy showed marked cholestasis specially in the centrolobular zone with a slight infiltrate of mononuclear cells in the portal areas. Together with the liver disease the patient presented an anemic syndrome. Bone marrow aspiration showed rich cellularity, Perls staining showed 70% sideroblasts, with 10% ringed sideroblasts and increased extracorpuscular iron. The patient's evolution was satisfactory. Twenty months after the beginning of the disease clinical and biochemical tests were normal. A new bone marrow aspiration rendered normal. Hepatic cholestasis suffered by our patient was probably due to an adverse reaction of methimazole. Physiopathology of reversible sideroblastic anemia is discussed.

Topics: Anemia, Sideroblastic; Atenolol; Cholestasis, Intrahepatic; Humans; Hyperthyroidism; Liver Function Tests; Male; Methimazole; Middle Aged; Thyroid Function Tests

After coronary angiography a 66-year-old man developed manifest hyperthyroidism (fT3 8.7 pg/ml, fT4 3.7 ng/dl) marked by tremor, restlessness and sweating. The hyperthyroidism was controlled by high dosages of thiamazole (240 mg daily) and lithium (24-36 mmol daily). But the white cell count dropped from 8,000/microliters to 4,900/microliters on the eighth day. Although the thiamazole dose was reduced to 40 mg daily, the granulocytopenia became more severe and, on the 24th day of treatment, agranulocytosis occurred (neutrophilic granulocyte count 200/microliters), although the thiamazole had been discontinued. The patient was then isolated and treated prophylactically with ofloxacin. Simultaneously he received 5 micrograms/kg granulocyte-colony stimulating factor (G-CSF) subcutaneously daily for 7 days. On the sixth day of this treatment the granulocyte count was 520/microliters, next day 3,800/microliters, and after a further 2 days it overshot to 31,000/microliters, then gradually returning to normal values. -It is recommended that the use of G-CSF should be considered also for thyrostatic-induced agranulocytosis, because it may shorten this dangerous phase.

Topics: Aged; Agranulocytosis; Granulocyte Colony-Stimulating Factor; Humans; Hyperthyroidism; Male; Methimazole; Patient Isolation; Thyroid Function Tests

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; Age Factors; Aged; Aged, 80 and over; Drug Monitoring; Humans; Hydrocortisone; Hyperthyroidism; Hypothyroidism; Iodine; Iodine Radioisotopes; Methimazole; Middle Aged; Propylthiouracil; Thyrotropin; Thyroxine

Topics: Adenoma; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Neoplasms

1. The physiological relevance of cardiac and vascular alpha-adrenoceptors may increase in disease states in which beta-adrenoceptors are altered. To test this, positive inotropic and vasoconstrictor responses to phenylephrine were measured in isolated tissues from rats with experimentally-induced hyperthyroidism, hypothyroidism and diabetes as well as in genetically spontaneous hypertensive rats (SHR). 2. In left atria, positive inotropic responses to phenylephrine were increased in hypothyroid and diabetic rats and abolished in hyperthyroid and SHR. 3. In contrast, phenylephrine produced increased positive inotropy in left ventricular papillary muscles from hyperthyroid rats, increased potency in diabetic rats and negative inotropic responses in hypothyroid rats. 4. The potency of phenylephrine as a vasoconstrictor in thoracic aortic rings was increased in hyperthyroid and SHR and decreased in hypothyroid rats. 5. Thus, disease states which alter beta-adrenoceptor responsiveness can independently regulate atrial, ventricular and vascular responses to the alpha 1-adrenoceptor agonist, phenylephrine. Therefore, these disease states may alter the physiological control of the cardiovascular system by noradrenaline and adrenaline as well as the responsiveness in disease states to therapeutic agents acting via alpha-adrenoceptors.

Topics: Animals; Cardiovascular System; Diabetes Mellitus, Experimental; Disease Models, Animal; Hemodynamics; Hypertension; Hyperthyroidism; Hypothyroidism; In Vitro Techniques; Male; Methimazole; Phenylephrine; Rats; Rats, Inbred SHR; Rats, Wistar; Receptors, Adrenergic, alpha-1; Triiodothyronine

Vascular reactivity to vasoconstrictors in relation to altered thyroid function was studied in two preparations: aortic strips and the isolated perfused kidney. To assess whether the possible alterations in vascular reactivity were restricted to a specific agonist or whether they involved the contractile system, receptor-mediated and nonspecific smooth muscle stimulants were used. Male Wistar rats were divided into three groups: control, hyperthyroid and hypothyroid rats. Aortic strips from hypothyroid rats were less sensitive to phenylephrine and KCl when the data were expressed in absolute values or as percentages of the maximum responses. Sensitivity and reactivity in strips from hyperthyroid rats were similar to those observed in control strips. Renal vasculature obtained from hypothyroid rats also showed a markedly reduced sensitivity to phenylephrine, with normal maximal responses. The response to vasopressin at 3-10(-11) mol/l was also decreased, as was the reactivity to barium chloride. In contrast, renal vasculature of hyperthyroid rats showed markedly enhanced reactivity to all agonists: the concentration-response curves were characterized by a similar threshold and a greater maximal response. These results demonstrate that hypothyroidism is accompanied by a marked decrease in sensitivity to vasoconstrictors in large arteries as well as in resistance vessels. This decrease may be secondary to a generalized alteration in the contractile system of vascular smooth muscle cells and may play a role in the decreased blood pressure in these animals. In contrast, isolated perfused kidneys of hyperthyroid rats showed increased vascular reactivity to vasoconstrictors, which may play a role in the maintenance of elevated blood pressure in these animals.

Topics: Animals; Aorta, Thoracic; Barium Compounds; Blood Pressure; Chlorides; Disease Models, Animal; Dose-Response Relationship, Drug; Hyperthyroidism; Hypothyroidism; In Vitro Techniques; Kidney; Male; Methimazole; Muscle Contraction; Muscle, Smooth, Vascular; Perfusion; Phenylephrine; Potassium Chloride; Rats; Rats, Wistar; Thyroxine; Vascular Resistance; Vasoconstrictor Agents; Vasopressins

Changes in serum amino-terminal type III procollagen propeptide (PIIIPN) and hydroxyproline were compared with indices of thyroid function in 33 patients with hyperthyroidism and 16 patients with hypothyroidism before and after treatment. Control values were obtained from 26 healthy individuals. Hyperthyroidism was shown to be associated with an increased level of PIIIPN and hypothyroidism with a decreased PIIIPN level. An increase in PIIIPN was found in 100% of hyperthyroid patients and a decrease in 31% of those with hypothyroidism, while hydroxyproline increased in only 54% of patients with hyperthyroidism and its level was decreased in only 6% of patients with hypothyroidism. Correlation between PIIIPN and thyroxine and triiodothyronine levels was shown. The results obtained suggest that PIIIPN is a valuable index of tissue response to thyroid hormones.

Topics: Adolescent; Adult; Female; Humans; Hydroxyproline; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Middle Aged; Peptide Fragments; Procollagen; Radioimmunoassay; Thyroxine; Triiodothyronine

There is recent evidence that both exogenous and endogenous subclinical thyrotoxicoses are associated with decreased bone mineral density. Scanty information is available on bone metabolism in these conditions when euthyroidism is restored. We evaluated the effect of anti-thyroid drug treatment on bone metabolism in endogenous subclinical hyperthyroidism.. Prospective follow-up study over 2 years during treatment with methimazole, with an untreated control group.. Sixteen post-menopausal women with endogenous subclinical hyperthyroidism associated with multinodular goitre, eight of whom were treated with methimazole.. Serum concentrations of free T4, total T3, TSH, osteocalcin, urinary excretion of hydroxyproline and forearm bone mineral density were measured at regular intervals.. Significant changes in serum osteocalcin concentration or urinary hydroxyproline excretion were not observed in either group. Distal, but not proximal, forearm bone mineral density, expressed as a percentage of the base-line value, was significantly (P < 0.05) higher in the treated than in the untreated subjects in the second year of treatment.. Treatment with methimazole in post-menopausal women with endogenous subclinical hyperthyroidism associated with multinodular goitre can prevent excessive loss of bone, at least in the distal forearm.

Topics: Bone and Bones; Bone Density; Female; Forearm; Goiter; Humans; Hydroxyproline; Hyperthyroidism; Methimazole; Middle Aged; Osteocalcin; Postmenopause; Prospective Studies; Thyrotropin; Thyroxine; Triiodothyronine

Earlier studies have shown that plasma concentrations of endothelin 1 (ET-1) and the receptors for ET are altered during hyperthyroidism, while they are not affected during hypothyroidism. The present study was undertaken to determine the changes in concentration of endogenous ET-1 in various tissues of hyper- and hypothyroid rats. Hyperthyroidism was induced by daily administration of thyroxine (T4, 0.1 mg/kg, i.p.) for 8 weeks, while hypothyroidism was induced by daily administration of methimazole (10 mg/kg, i.p.) for 8 weeks. The concentration of endogenous ET-1 was determined in the brain regions (hypothalamus, corpus striatum, pituitary, hippocampus and spinal cord), heart, adrenals, kidneys and thoracic aorta using a radioimmunoassay procedure. Blood pressure and heart rate were significantly increased in hyperthyroid rats, while they were not affected in hypothyroid rats when compared with control (euthyroid) rats. Serum T4 and T3 levels were significantly increased in hyperthyroid rats, while they were significantly decreased in hypothyroid rats when compared with euthyroid rats. The concentrations of ET-1 in the hypothalamus, corpus striatum, hippocampus and spinal cord were not altered in hyper- or hypothyroid rats when compared with euthyroid rats. However, the pituitary showed a significant (p < 0.001) increase (104%) in ET-1 concentration in hyperthyroid rats when compared with euthyroid ones, while hypothyroid rats did not show any significant change in ET-1 concentration in the pituitary. In peripheral tissues ET-1 concentrations were not altered in the heart and adrenals of hyper- and hypothyroid rats when compared with euthyroid rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenal Glands; Animals; Aorta, Thoracic; Blood Pressure; Brain; Endothelins; Heart Rate; Hyperthyroidism; Hypothyroidism; Injections, Intraperitoneal; Kidney; Male; Methimazole; Myocardium; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Thyroxine

The authors treated a patient with methimazol (Metothyrin)-induced agranulocytosis with human recombinant granulocyte-macrophage colony stimulating factor (GM-CSF). On day seven, after combined antibiotics, corticosteroid and at a dose of 270 ug daily subcutaneous GM-CSF therapy the septic state of the patients rapidly cured and the leucocytes reached the peripheric blood. No side effects were found. The publication of this case history might help to determine the place of human GM-CSF-s therapy in the treatment of agranulocytosis of different origin.

Topics: Administration, Cutaneous; Adult; Aged; Agranulocytosis; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Hyperthyroidism; Leukocyte Count; Methimazole

A case of a 38-year-old male with supraventricular paroxysmal tachycardia existing for more than a decade is reported. He has received amiodarone in a daily dose of 800 mg for three years and the tachycardia returned in 1992. New antiarrhythmic drugs were added but no beneficial effect has been achieved and moreover, a case of ventricular fibrillation occurred. The 12-lead ECG performed during tachycardia and the electrophysiological study showed orthodromic AV reentry tachycardia. Laboratory tests performed proved hyperthyreotic state. Attacks of paroxysmal tachycardia were returned and aggravated by the hyperthyreosis induced by amiodarone. Finally, antiarrhythmic drugs were discontinued and methimazol was introduced. Gradually, the patient become asymptomatic within two months. The most important conclusion of the case reported, that the amiodarone induced hyperthyreosis can be subclinical or obscure. Consequently, a regular control of serum thyreoid hormone levels at least twice a year on patients with long term amiodarone administration should be advised.

Topics: Adult; Amiodarone; Anti-Arrhythmia Agents; Electrocardiography; Humans; Hyperthyroidism; Male; Methimazole; Tachycardia, Atrioventricular Nodal Reentry; Tachycardia, Paroxysmal; Tachycardia, Supraventricular

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

Endothelin (ET) mechanisms were studied in hyper- and hypo-thyroid states in rats. Hyperthyroidism was induced by daily administration of thyroxine (0.1 mg/kg, i.p.) for 8 weeks, while hypothyroidism was induced by daily administration of methimazole (10 mg/kg, i.p.) for 8 weeks. The concentration of endogenous ET-1 was determined in the kidneys using radioimmunoassay. Systemic hemodynamics and renal blood circulation was measured using a radioactive microsphere technique. A significant increase in systolic and diastolic blood pressure, heart rate and cardiac output was observed in hyperthyroid rats as compared to eu- and hypo-thyroid rats. Total peripheral resistance was found to be similar in eu-, hyper- and hypo-thyroid rats. The endogenous concentration of ET-1 in the kidneys was significantly lower in hyper- as compared to eu- and hypo-thyroid rats. The blood flow to the kidneys was significantly increased in hyper- as compared to eu- and hypo-thyroid rats. Infusion of ET-1 (100 ng/kg/min i.v. for 45 min) produced a significant decrease in blood flow to the kidneys of eu-, hyper- and hypo-thyroid rats. The decrease in blood flow was similar in eu-, hyper- and hypo-thyroid rats, indicating that the response of renal blood vessels to exogenous ET-1 is not altered during thyroid dysfunction. Since endogenous ET-1 is involved in the regulation of vascular tone, it may be concluded that in hyper-thyroid rats decrease in concentration of the renal ET-1 could be contributing to an increase in blood flow to the kidney.

Topics: Animals; Endothelins; Hemodynamics; Hyperthyroidism; Hypothyroidism; Kidney; Male; Methimazole; Rats; Rats, Sprague-Dawley; Renal Circulation; Thyroxine

Our purpose was to demonstrate that propylthiouracil and methimazole are equally effective and safe in the treatment of hyperthyroidism during pregnancy.. Between 1974 and 1990 records were available on 185 pregnant patients with a history or diagnosis of hyperthyroidism. Ninety-nine patients were treated with propylthiouracil and 36 with methimazole. The response to therapy was compared with respect to the time to normalization of the free thyroxine index and the incidences of congenital anomalies and hypothyroidism.. The time to normalization of the free thyroxine index was compared in the two groups by means of survival analysis. The median time to normalization of the free thyroxine index on propylthiouracil and methimazole was 7 and 8 weeks, respectively (p = 0.34, log-rank test). The incidence of major congenital malformations in mothers treated with propylthiouracil and methimazole was 3.0% and 2.7%, respectively. No neonatal scalp defects were seen. One infant was overtly hypothyroid at delivery.. Propylthiouracil and methimazole are equally effective and safe in the treatment of hyperthyroidism in pregnancy.

Topics: Chi-Square Distribution; Cohort Studies; Congenital Abnormalities; Female; Follow-Up Studies; Humans; Hyperthyroidism; Incidence; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Propylthiouracil; Prospective Studies; Radioimmunoassay; Retrospective Studies; Thyroxine; Triiodothyronine

The aim of the study was to answer the question whether a rapid decrease in serum triiodothyronine (T3) and thyroxine (T4) levels resulting from the treatment with a full dose (3 x 20 mg daily) of methimazole applied in patients with thyrotoxicosis is associated with the parallel diminution of plasma atrial natriuretic peptide (ANP) and its second messenger-cyclic guanosine monophosphate (cGMP) concentrations. Sixteen patients with thyrotoxicosis of mean age 41.5 +/- 10.5 years participated in the study. Short-term (10 days) methimazole treatment resulted in a significant decrease in serum T3 and T4 concentrations to the values found in 14 healthy subjects serving as control group. Plasma ANP and cGMP levels also decreased significantly during the treatment attaining the normal range. A significant correlation was found between the decrease in serum T3 and T4 concentrations during the treatment and the decrease in plasma ANP level. The decrease in plasma ANP was not closely correlated with the reduction of cGMP levels. These results indicate that: 1) a steep decrease in serum thyroid hormone concentrations induced by a full methimazole treatment during ten days in patients with thyrotoxicosis due to Graves' disease was accompanied by the return of elevated plasma ANP levels to normal range; 2. diminution of serum concentrations of both T3 and T4 during the treatment was correlated with the decrease in plasma ANP; 3) reduction in plasma cGMP concentration associated with short-term methimazole treatment in thyrotoxicosis seems to depend not only on the diminution of plasma ANP level.

Topics: Adult; Atrial Natriuretic Factor; Cyclic GMP; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Thyroxine; Triiodothyronine

The authors used a new protocol, based upon a supersensitive TSH assay, to examine the thyroid status of 1720 patients. Based upon the serum hormone levels, the patients were divided into different clinical groups. The biochemical relationship between the different hormone levels, and the rate of occurrence of various thyroid diseases were studied. 76.1% of the new patients hadn't received any previous treatment. 15.5% of those patients who had received treatment had hyperthyroidism, while 8.4% of those had hypothyroidism. 76% of the new patients, 38.3% of those who had hyperthyroidism, and only 29.7% of those who had hypothyroidism, were euthyroid. Undetectable TSH levels (< 0.03 mU/L) where observed in 51.8% of the new hyperthyroid patients, and in 33.8% of those who had subclinical hyperthyroidism. Similar results were obtained with those who had been previously treated for hyperthyroidism. The new protocol has the following advantages: it's more convenient to the patients, it's quick, it's economical. With this method it is possible to reduce the assays per patient by 31%. The algorithm was supplemented with results of free hormone levels. By doing this the authors were able to measure free-T4 and T3 hormone levels of 150 more patients. According to the authors, the free-T4 test is more informative than the free-T4-index, especially in the border-line cases and in treated hyperthyroidism. Primarily the free-T3 test is most necessary when examining patients treated with methimasol.

Topics: Adrenergic beta-Antagonists; Algorithms; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Mass Screening; Methimazole; Monitoring, Physiologic; Thyroid Function Tests; Thyrotropin; Thyroxine; Triiodothyronine

To further elucidate the mechanism of increased serum ferritin levels in hyperthyroidism, the changes in erythrocytes and serum iron and total iron-binding capacity levels were examined in addition to serum ferritin levels in 13 hyperthyroid patients. The mean values of hemoglobin, red blood cells, and packed cell volume were increased by antithyroid therapy. While the serum levels of iron did not change, those of total iron-binding capacity increased significantly after achieving a euthyroid state. Increased serum ferritin levels returned to normal through antithyroid therapy. Furthermore, the serum ferritin levels of four anemic patients were significantly higher than those of nine nonanemic patients. Thus it is concluded that the increase in serum ferritin levels in patients with hyperthyroidism may be due to the direct action of thyroid hormones on its synthesis, while in some cases complicated with anemia impaired iron utilization by erythropoietic cells may also be involved.

Topics: Adult; Anemia; Erythrocyte Count; Female; Ferritins; Hematocrit; Hemoglobins; Humans; Hyperthyroidism; Iron; Male; Methimazole; Middle Aged; Propylthiouracil

We studied the change of the binding capacity of the sex hormone binding globulin (SHBG-BC) and correlated it with the serum level of thyroid hormone and sex hormone in 17 patients (10 males and 7 female) with hyperthyroidism before and during the 16 weeks of antithyroid treatment. The serum TT4, TT3, FT4I level and SHBG-BC were significantly elevated before treatment compared to normal adults. After the treatment with antithyroid drugs, serum SHBG-BC decreased significantly at 2nd weeks in female (from 312.9 +/- 39.6 to 205 +/- 18.6 nmol/L, P < 0.05) and at 8th weeks in male (from 155.7 +/- 18.6 to 109.7 +/- 7.9 nmol/L, P < 0.05). It continued to decrease to normal range (78.6 +/- 7.3 vs 65.0 +/- 24.1 nmol/L, P > 0.05) at 8th weeks in female, but was still higher than normal range (107.4 +/- 7.2 vs 41.5 +/- 10.2 nmol/L, P < 0.001) even at 16th weeks in male. The change of SHBG-BC was significantly positively correlated to the serum concentration of TT4, TT3 and FT4I(P < 0.001). In male patients the serum testosterone (T) level decreased from a high level of 41.9 +/- 6.2 nmol/L before treatment to 25.4 +/- 3.4 nmol/L at 8th weeks (P < 0.05) and to 19.8 +/- 2.8 nmol/L at 16 weeks which was in normal range. The decrease of serum T level was also positively correlated to the changes of SHBG-BC (P < 0.0001). The serum estradiol (E2) level of female patients was in the upper normal range before the antithyroid treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Estradiol; Female; Humans; Hyperthyroidism; Male; Methimazole; Prospective Studies; Sex Hormone-Binding Globulin; Testosterone; Thyroxine; Triiodothyronine

The effect of thyroid hormones on concentrations of lipoprotein(a) [Lp(a)] was analyzed in 60 patients with active thyroid dysfunction (hyperthyroidism 30 cases, hypothyroidism 32 cases, and 2 cases with opposite changes) and after normalization of the thyroid state. Treatment of hyperthyroidism increased the mean Lp(a) concentrations by 60% (from 73 to 102 mg/L, P < 0.002); at the same time, low-density lipoprotein cholesterol (LDL-C) increased by 53% (from 2.6 to 3.7 mmol/L, P < 0.0001) and apolipoprotein B (apo B) by 35% (from 0.91 to 1.17 g/L, P < 0.0005). In hypothyroidism, the opposite changes were observed: mean Lp(a) decreased from 136 to 114 mg/L (10%, P < 0.02), LDL-C from 4.6 to 3.9 mmol/L (13%, P < 0.01), and apo B from 1.51 to 1.20 g/L (14%, P < 0.01). Although the changes in Lp(a) concentrations did correlate with changes of LDL-C during treatment of hyperthyroidism (r = 0.43, P < 0.05), and with changes in apo B during thyroxine-substitution therapy for hypothyroidism (r = 0.46, P < 0.05), we observed no associations between Lp(a) and LDL-C or apo B in the euthyroid state. These data cannot rule out the possibility that the thyroid hormone-induced increase in LDL-C receptor activity was responsible for the decreased concentrations of Lp(a) in hyperthyroidism. Given that LDL-C is approximately 30% of the Lp(a) molecule but the changes in Lp(a) concentrations are comparable with those in LDL-C (60% vs 53%), and given that Lp(a) is metabolized by an LDL-C-receptor-independent pathway, the present data suggest a direct effect of thyroid hormones on Lp(a) synthesis.

Topics: Adult; Aged; Apolipoproteins B; Cholesterol, LDL; Female; Humans; Hyperthyroidism; Hypothyroidism; Lipoprotein(a); Male; Methimazole; Pregnancy; Propylthiouracil; Thyroxine

Topics: Adolescent; Arousal; Female; Graves Disease; Humans; Hyperthyroidism; Methimazole; Motivation; Neurocognitive Disorders

Male Sprague Dawley rats were rendered hyperthyroid and hypothyroid by the intraperitoneal injections of 1-thyroxine or methimazole and sacrificed 21 days after the start of the treatment. The pituitaries were studied by immunoelectron microscopy by the immunogold labeling technique. In both hyperthyroidism and hypothyroidism, the numbers of growth hormone (GH) cells, GH-secreting granules and immunogolds in the secretory granules all were significantly decreased as compared with those in controls. The results indicate that low or high levels of thyroid hormones may cause decrease of GH production of the pituitary.

Topics: Animals; Growth Hormone; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Microscopy, Immunoelectron; Pituitary Gland; Rats; Rats, Sprague-Dawley; Thyroxine

Hyperthyroidism is associated with altered GH secretion. Whether this is due to changes of somatotroph responsiveness or reflects an alteration in negative feedback signals at the hypothalamic level is unknown. We therefore performed a series of studies to shed some light onto this issue.. Study 1: GHRH (1 microgram/kg b.w.) was injected i.v. in 38 hyperthyroid patients and in 30 normal subjects; in 11 of the patients the GHRH test was repeated following methimazole-induced remission of hyperthyroidism. Study 2: hGH (2 U i.v.) or saline were administered 3 hours prior to GHRH; six hyperthyroid patients and six normal subjects were studied. Study 3: ten normal subjects and ten hyperthyroid patients were given 75 g oral glucose or water 30 minutes before GHRH. Study 4: 11 normal subjects and eight hyperthyroid patients were studied. TRH or vehicle were dissolved in 250 ml of saline solution and infused at a rate of 400 micrograms/h for 150 minutes. Thirty minutes after the beginning of the infusions, L-arginine (30 g infused over 45 min i.v.) was administered.. Hyperthyroid patients were compared to normal subjects.. Growth hormone was measured by RIA at 15-minute intervals.. GH responses to GHRH were subnormal in hyperthyroid patients. Following antithyroid drug treatment with methimazole, GH responses to GHRH increased in these patients in comparison to pretreatment values. Serum IGF-I levels, which were elevated before treatment, decreased after methimazole administration. Exogenous GH administration induced a clear decrease of GH responses to GHRH in both control and hyperthyroid subjects. On the other hand, oral glucose load decreased the GH responses to GHRH in normal but not in hyperthyroid subjects. TRH administration did not modify the GH responses to arginine in either normal subjects or hyperthyroid patients.. Hyperthyroidism is associated with increased serum IGF-I levels and marked alterations in the neuroregulation of GH secretion. These changes involve decreased GH responsiveness to GHRH at the pituitary level and, at the hypothalamic level, a lack of suppressive effect of an oral glucose load. The normal inhibitory effect of exogenous GH administration but not of an oral glucose load in hyperthyroid patients suggests that these two feedback signals act through different mechanisms. The lack of effect of a TRH infusion on GH responses to L-arginine in normal and hyperthyroid patients makes an inhibitory role for TRH in GH secretion unlikely, at least in Caucasian subjects.

Topics: Adult; Arginine; Female; Glucose; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Hyperthyroidism; Hypothalamus; Insulin-Like Growth Factor I; Male; Methimazole; Pituitary Gland; Radioimmunoassay; Thyrotropin-Releasing Hormone

Endothelin (ET) and its receptor characteristics were studied in hyper- and hypo-thyroid states in the rats. Hyperthyroidism was induced by daily administration of thyroxine (0.1 mg/kg i.p.) for 8 weeks, while hypothyrodism was induced by daily administration of methimazole (10 mg/kg i.p.) for 8 weeks. The chronic administration of thyroxine to rats decreased their rate of gain of body weight, increased serum T3 and T4 concentration, blood pressure and heart rate. The chronic administration of methimazole decreased the rate of gain of body weight, serum T3 and T4 concentration, blood pressure and heart rate as compared to vehicle-treated control. Plasma ET-1 levels were found to be similar in control and methimazole-treated rats, while the levels were found to be significantly (P < 0.002) increased in thyroxine-treated rats as compared to control rats. Binding studies showed that [125I]ET-1 bound to a single, high affinity binding site in the cerebral cortex, hypothalamus and pituitary. The density (Bmax) and the affinity (Kd) of [125I]ET-1 binding in the cerebral cortex and hypothalamus were found to be similar in control, methimazole- and thyroxine-treated rats. The pituitary of thyroxine-treated rats showed a decrease in the binding (34.3% decrease in the density) of [125I]ET-1 as compared to control rats. No difference was observed in the binding of [125I]ET-1 to pituitary membranes from control and methimazole-treated rats. Competition studies showed that the IC50 and Ki values of ET-3 for [125]ET-1 binding were about 8 to 11 times higher than ET-1 in cerebral cortex, hypothalamus and pituitary.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Binding, Competitive; Blood Pressure; Body Weight; Cerebral Cortex; Endothelins; Heart Rate; Hyperthyroidism; Hypothalamus; Hypothyroidism; Iodine Radioisotopes; Kinetics; Male; Methimazole; Pituitary Gland; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Receptors, Endothelin; Thyroxine; Triiodothyronine

Coronary angiography (CA) is followed by an iodine load of 15 to 20 mg for the thyroid and may be the cause of iodine-induced hyperthyroidism. 60 consecutive patients hospitalized for CA without any thyroid history were examined and 56 had thyroid diseases with normal thyroid function. 33 patients still showed a significant decrease of 20 min Technetium uptake (TcU) and an increase of urine iodine excretion because of iodine excess 12 weeks after CA. 3 patients developed latent hyperthyroidism. 27 patients received medication of 1 g natrium-perchlorate and 60 mg methimazole 24 hours before and on the day of CA. These patients showed normal TcU and urine iodine excretion 4 and 12 weeks after CA. 1 out of these 27 patients developed overt hyperthyroidism but had PTCA without premedication 2 weeks after CA. Since Iodine excess leads to iodine-induced hyperthyroidism even in euthyroids a prophylaxis with perchlorate and methimazole is generally recommended in patients with CA.

Topics: Adult; Aged; Aged, 80 and over; Contrast Media; Coronary Angiography; Female; Humans; Hyperthyroidism; Iodine; Male; Methimazole; Middle Aged; Perchlorates; Premedication; Sodium Compounds; Thyroid Function Tests

A 30-year-old woman, who had had two episodes of distal dominant sensorimotor disorders in the extremities, developed again sensorimotor involvement in the distal portion of all limbs. She was also found to have hyperhidrosis, tachycardia and goiter. Neurological and endocrinological examinations led to a diagnosis of coexistence of recurrent polyradiculoneuropathy and hyperthyroidism. Treatment with thiamazole resulted in improvement of the neurological features as well as of hyperthyroidism. The relationship between polyradiculoneuropathy and hyperthyroidism is discussed.

Topics: Adult; Autoantibodies; Diagnosis, Differential; Female; Humans; Hyperthyroidism; Methimazole; Neurologic Examination; Polyradiculoneuropathy; Recurrence

In 7 hyperthyroid patients on the one hand thyroxine-binding globulin (TBG) was determined by commercially available radioimmunoassay and on the other hand TBG-isovariants were established by means of isoelectric focusing. For assessment blood samples were taken upon admittance to our hospital and 2 and 4 weeks thereafter, respectively, during antithyroid drug treatment. A comparative series of 10 euthyroid subjects were equally evaluated. Both groups showed no significant differences of TBG values at onset and in the course of antithyroid treatment. However, TBG isovariants showed significant decreases in anionic bands (pH 4.25 to 4.45) whereas a significant increase in cathodic bands (pH 4.55 to 4.65) at onset of treatment compared to the euthyroid control group could be observed. During the course of antithyroid treatment the values of TBG-isobands reversed reaching the pattern of normal group. In contrast to the recent research by Hashizume et al. we observed no reduction in TBG level in hyperthyroid patients although a significant shift in the TBG isovariants could be established. Due to the antithyroid treatment prescribed, the TBG isovariants finally reached the normal pattern of euthyroid controls.

Topics: Female; Humans; Hyperthyroidism; Male; Methimazole; Propranolol; Reference Values; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine

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

The aim of the study was answering the question whether determination of psychical reaction time may be useful for the monitoring of treatment of hypothyreosis and hyperthyreosis. The correlation of disease symptoms (diagnostic index for hypothyroidism after Murray and for hypothyroidism according to Crooks), concentration of triiodothyronine, thyroxine, index of free thyroxine in blood serum and Achilles tendon reflex--with the simple reaction time (srt) as well as with the choice reaction time (chrt) before and during treatment was investigated in 18 patients with primary hypothyroidism and in 24 with hyperthyroidism caused by Graves-Basedow's disease. Two control groups comprised 84 healthy persons. Either in hypothyroidism or in hyperthyroidism the srt and chrt was significantly prolonged. The substitution therapy in hypothyroidism resulted in a normalization of both parameters. On the other hand, administration of thiamazole, especially in the early period of treatment of hyperthyroidism, further prolonged the srt and chrt. A shortening of the time of each of the two reactions occurred, however, when the restoration of euthyroidism was achieved, which was accompanied by reduction of thiamazole dosage. The obtained data point to the usefulness of srt and chrt determination for the diagnosis and therapy monitoring of functional disturbances of the thyroid gland.

Topics: Adult; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Middle Aged; Reaction Time

Erythrocyte sodium pump is decreased in hyperthyroid patients. We described the effect of untreated hyperthyroidism on Na+K+ATPase activity, ouabain binding sites and intracellular sodium concentration. We found a reduction in Na+K+ATPase activity and in number of ouabain binding sites with a concomitant increase in intracellular sodium. B-blockade therapy failed to restore normal pump activity and sodium concentration, where only thionamide treatment was successful when it was able to decrease free T3.

Topics: Adult; Erythrocytes; Female; Heart Rate; Humans; Hyperthyroidism; Male; Methimazole; Potassium; Propranolol; Receptors, Drug; Sodium; Sodium-Potassium-Exchanging ATPase; Thyroid Function Tests

Four hundred and fifty two patients having clinical features of thyrotoxicosis have been studied for their hormonal (T4, T3 and TSH) content, I131 uptake levels and FNAB at repeated intervals. Four hundred and twenty seven had presented with diffuse enlargement and rest 25 cases with nodular enlargements. Of the primary hyperthyroidism cases 342 (82.4%) were of Grave's disease without exophthalmos and 73 (17.6%) with exophthalmos. T4, T3 and I131 uptake levels have correlated well with the degree of morphological changes as observed on FNAB. Degree of nuclear pleomorphism has correlated well with the duration of disease. Critical evaluation of morphological changes on FNAB has been done in all cases of primary hyperthyroidism being treated with neomercazole and radioactive iodine therapy. Treatment with neomercazole had shown, good correlation between time lag and the retrogressive changes. This was not so in cases treated with radioactive iodine therapy. Various known complications of radioactive treatment e.g. development of hypothyroidism, refractory and recurrent hyperthyroidism, exacerbation of the disease, radiation thyroiditis, and severe degree of dysplastic changes could be demonstrated in some cases on serial aspirations.

Topics: Biopsy, Needle; Female; Humans; Hyperplasia; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Thyroid Hormones; Thyrotoxicosis

Cyclic AMP (cAMP) is the major intracellular second messenger of thyrotropin (TSH) action on thyroid cells. It stimulates growth as well as the function and differentiation of cultured thyrocytes. The adenosine A2 receptor, which activates adenylyl cyclase via coupling to the stimulating G protein (Gs), has been shown to promote constitutive activation of the cAMP cascade when transfected into various cell types. In order to test whether the A2 receptor was able to function similarly in vivo and to investigate the possible consequences of permanent adenylyl cyclase activation in thyroid cells, lines of transgenic mice were generated expressing the canine A2 adenosine receptor under control of the bovine thyroglobulin gene promoter. Thyroid-specific expression of the A2 adenosine receptor transgene promoted gland hyperplasia and severe hyperthyroidism causing premature death of the animals. The resulting goitre represents a model of hyperfunctioning adenomas: it demonstrates that constitutive activation of the cAMP cascade in such differentiated epithelial cells is sufficient to stimulate autonomous and uncontrolled function and growth.

Topics: Adenosine; Animals; Blotting, Northern; Brain; Cattle; Cell Membrane; Cyclic AMP; Dogs; Hyperplasia; Hyperthyroidism; Kinetics; Methimazole; Mice; Mice, Transgenic; Phenethylamines; Poly A; Promoter Regions, Genetic; Receptors, Purinergic; Receptors, Thyrotropin; Reference Values; RNA; RNA, Messenger; Thyroglobulin; Thyroid Gland; Thyroxine; Triiodothyronine

Plasma atrial natriuretic hormone (ANH) values were evaluated in 28 hyperthyroid patients and in 11 hypothyroid patients and compared with 20 healthy subjects. In hyperthyroid patients plasma ANH basal levels were significantly (p less than 0.01) higher (14.2 +/- 1.6 pmol/l) than in controls (7.8 +/- 0.4 pmol/l) and in hypothyroid patients (6.4 +/- 0.3 pmol/l). No significant differences were found between controls and hypothyroid patients. The propranolol-induced decrease in heart rate in hyperthyroid patients did not significantly affect the plasma ANH values. Conversely, after the methimazole-induced euthyroidism a return within the normal range of ANH values was observed. The thyroxine replacement in hypothyroid patients determined a small but significant (p less than 0.05) increase in plasma ANH values. Observed data suggest that in humans thyroid hormones may influence plasma ANH concentrations independently of their effect on heart rate.

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Female; Heart Rate; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Middle Aged; Propranolol; Thyroxine

We undertook this study to investigate respiratory muscle strength in relation to thyroid function in 20 thyrotoxic patients and in a group of 20 normal subjects matched for age and sex. Global respiratory muscle strength was assessed by measuring mouth pressure during maximal static inspiratory (PImax) and expiratory (PEmax) efforts. We also measured VC, FVC, and FEV1 as well as thyroid-related hormones (T3, T4, TSH). Measurements were made once in normal subjects and twice in thyrotoxic patients, before and 3 months after medical treatment. Our results showed that both maximal pressures were significantly reduced (p less than 0.0001) before treatment in thyrotoxic patients in relation to the mean values of the normal subjects (p less than 0.0001), and they increased significantly (p less than 0.0003) after treatment. Lung volumes were significantly reduced (p less than 0.0001) before and increased significantly (p less than 0.008) after treatment. The ratio FEV1/FVC did not change. A statistically significant linear relationship was found when PImax of patients with thyrotoxicosis before treatment and of normal subjects were plotted against thyroid hormones (T3, T4) (r = -0.746 and r = -0.745, respectively, p less than 0.001). Similarly, a statistically significant linear relationship was found between PEmax and T3 and T4 (r = -0.837 and r = -0.838, respectively, p less than 0.001). No relationship was found between maximal pressures and TSH. Finally, a significant linear relationship was found between PImax and PEmax (r = 0.872, p less than 0.001). Our results confirm that in thyrotoxicosis respiratory muscle weakness occurs that affects both inspiratory and expiratory muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Female; Humans; Hyperthyroidism; Lung Volume Measurements; Male; Methimazole; Propylthiouracil; Respiratory Function Tests; Respiratory Muscles; Thyroid Gland; Thyroid Hormones; Time Factors

A highly sensitive, specific, and reproducible RIA has been developed to measure rat type I iodothyronine 5'-monodeiodinase (5'-MD). A 16-amino acid peptide (LAP-744) corresponding to a portion of the carboxy-terminal region of the rat liver 5'-MD, as predicted from its cDNA, was synthesized, and rabbits were immunized with the peptide-BSA conjugate. In a final dilution of 1:15,000, our anti-5'-MD antibody bound about 30-35% of a tracer amount of [125I]LAP-744. The detection threshold of the RIA approximated 0.08 pmol LAP-744 or an equivalent amount of 0.08 pmol 5'-MD. Rat liver and kidney microsomes produced dose-response curves that were essentially parallel to that of LAP-744. No inhibition of binding of [125I]LAP-744 to antibody was produced by 0.3 mg or less rat microsomal proteins from testes, heart, brain, muscle, spleen, intestine, lung, placenta, or fetal liver. Recovery of nonradioactive LAP-744 added to spleen microsomes averaged 103%. The coefficient of variation averaged 4% within an assay and 11% between assays. In 16 normal rats studied, the mean (+/- SD) 5'-MD content was 2.4 +/- 0.22 pmol/mg protein in liver microsomes and 2.5 +/- 0.27 pmol/mg protein in kidney microsomes. Fasting of the rat for 2-4 days was associated with a significant reduction in both the activity and the content of the 5'-MD in liver and kidney. Hypothyroidism was also associated with a significant decrease in the activity and content of 5'-MD in both tissues. Significant opposite changes were observed in these parameters in hyperthyroidism. Treatment of the rat with sodium ipodate for 3 days was associated with a significant decrease in both the activity and the content of 5'-MD in liver and kidney. A similar treatment of the rat with propylthiouracil induced a clear reduction in the activity of 5'-MD in liver and kidney, but the content of the enzyme was significantly increased in both tissues. Rats treated with aurothioglucose for 3 days exhibited a significant decrease in 5'-MD activity in liver and kidney microsomes, whereas the tissue content of 5'-MD was not affected. A similar treatment of the rat with methimazole had no significant effect on either the activity or the content of 5'-MD.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Amino Acid Sequence; Animals; Fasting; Female; Hyperthyroidism; Hypothyroidism; Iodide Peroxidase; Ipodate; Kidney; Liver; Male; Methimazole; Microsomes; Microsomes, Liver; Molecular Sequence Data; Organ Specificity; Peptide Fragments; Propylthiouracil; Radioimmunoassay; Rats; Rats, Sprague-Dawley

To understand the regulation by thyroid hormone, 3,3',5-triiodo-L-thyronine (T3), of the synthesis of a cytosolic thyroid hormone binding protein (p58-M2) during liver regeneration, the synthesis of p58-M2 was evaluated. The synthesis of p58-M2 was measured by metabolic labeling of primary cultures derived from the regenerating liver of euthyroid, hypo- or hyperthyroid rats. During regeneration, the increase in the liver/body weight ratio is approximately 25% higher in hyper- than in hypothyroid rats. However, T3 has no effect on the rate of overall liver regeneration observed in four days. In mature liver, T3 increased the synthesis of p58-M2 by approximately 2.5-fold. During regeneration, however, the change in the synthesis of p58-M2 varied with the thyroid status. In euthyroid rats, the synthesis of p58-M2 continued to increase up to 2-fold during liver regeneration. In hyperthyroid rats, after an initial increase by 1.5-fold on day 1, the synthesis of p58-M2 subsequently declined during regeneration. In hypothyroid rats, the synthesis of p58-M2 remained virtually unchanged during regeneration. These results indicate that T3 regulates the synthesis of p58-M2 in mature and regenerating liver.

Topics: Animals; Autoradiography; Cells, Cultured; Cytosol; Hepatectomy; Hyperthyroidism; Hypothyroidism; Isoenzymes; Liver; Liver Regeneration; Male; Methimazole; Methionine; Pyruvate Kinase; Rats; Rats, Sprague-Dawley; Reference Values; Sulfur Radioisotopes; Triiodothyronine

We report on 2 newborn infants with esophageal atresia and tracheoesophageal fistula (EA + TEF) born to hyperthyroid mothers receiving methimazole (Tapazol) before and during their entire pregnancies. Both mothers were euthyroid during gestation and developed hydramnios diagnosed during weeks 34 and 33 of gestation. Premature delivery (36.2 weeks of gestation) occurred in one case, and both newborn infants were small for date with palpable goiter; one of them had other associated malformations. Hypothyroidism was diagnosed by laboratory tests in both cases. Corrective surgery was undertaken, but both newborn infants developed septicemia and renal insufficiency and died in the first week of life. The EA + TEF and a normally placed enlarged thyroid gland were confirmed at necropsy. These cases represent a previously unreported example of the association of maternal ingestion of methimazole during pregnancy and EA + TEF.

Topics: Abnormalities, Drug-Induced; Adult; Esophageal Atresia; Female; Humans; Hyperthyroidism; Infant, Newborn; Male; Maternal-Fetal Exchange; Methimazole; Pregnancy; Pregnancy Complications; Tracheoesophageal Fistula

In the cytoenzymatic investigations of peripheral blood neutrophils in patients with hyperthyroidism there was found the increase of acid phosphatase activity, beta-glucuronidase, leucine aminopeptidase, and catalase moreover there was found the decrease of the activity of alkaline phosphatase. After a two-week treatment with thiamazole (methimazole++) 50 mg in 24-hour dose there was observed the decrease of acid phosphatase activity in neutrophils. During incubation of plasma containing leucocytes, from healthy persons, with L-thyroxine there was observed the increase of the activity for acid phosphatase and beta-glucuronidase. In patients with hyperthyroidism there appear many changes of enzymic equipment of neutrophils which are concerned with lysosomal and connected with cell membrane enzymes. The results of cytochemical investigations after application of thiamazole and no difference, with exception of catalase, between patients with Graves-Basedow disease and with toxic goitre and the results of investigations in vitro with L-thyroxin point out, that there is the possibility of connection between the observed changes in the range of enzymic equipment of neutrophils and the hormonal state of the investigated group of patients.

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Catalase; Culture Media; Enzyme Activation; Female; Glucuronidase; Humans; Hyperthyroidism; In Vitro Techniques; Leucyl Aminopeptidase; Methimazole; Middle Aged; Neutrophils; Thyroxine

Hyperthyroidism is invariably accompanied by nervous system dysfunctions. Irritability, emotional lability and hyperkinesia are the signs and symptoms most frequently observed. Chorea or choreoathetosis are only rarely associated with hyperthyroidism. It is the purpose of this work to describe the case of a young girl in whom chorea was the main manifestation of thyrotoxicosis. The chorea receded and disappeared as the patient became euthyroid. Hyperthyroidism, therefore, is to be considered an unusual cause of chorea and every patient with choreiform movements should be examined also for thyroid function.

Topics: Adolescent; Chorea; Female; Humans; Hyperthyroidism; Methimazole; Thyroid Function Tests

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

1. Urinary excretion of digoxin-like immunoreactive factor and arginine-vasopressin and other parameters related to salt and water metabolism were studied in hyper- and hypo-thyroid rats after different tests. 2. Urinary excretion of arginine-vasopressin was increased in hyperthyroid and reduced in hypothyroid rats with respect to controls, in response to water deprivation or a hypertonic saline load. 3. Control and hypothyroid rats showed the highest urinary excretion of digoxin-like immunoreactive factor after a hypertonic saline load. However, hyperthyroid rats had the highest urinary levels of digoxin-like immunoreactive factor under normal conditions. 4. From these results it is suggested that: (a) hyper- and hypo-thyroid rats exhibit hyper- and hypo-responsiveness of arginine-vasopressin secretion to osmotic stimuli, respectively; (b) an unidentified digoxin-like immunoreactive factor measured in unextracted rat urine may be related to diuresis and natriuresis in control and hypothyroid rats; however, dissociation between this factor and natriuresis is observed in hyperthyroid rats.

Topics: Animals; Arginine Vasopressin; Blood Proteins; Cardenolides; Digoxin; Hyperthyroidism; Hypothyroidism; Kidney; Male; Methimazole; Rats; Rats, Inbred Strains; Saline Solution, Hypertonic; Saponins; Sodium-Potassium-Exchanging ATPase; Thyroxine; Water Deprivation

Three female patients with cholestatic jaundice related to methimazole therapy are presented. The jaundice appeared after more or less 30 days of therapy. Markers for hepatitis A and B were negative in all. None of them had previous history of alcoholism or ingestion of potentially hepatotoxic drugs. Characteristically there was a marked elevation of alkaline phosphatase and gamma-glutamyltranspeptidase with only moderate increase of the aminotransferases. Liver biopsy performed in all showed intensive cholestasis with low degree of inflammatory reaction confined to the portal tracts. The three patients presented a prolonged duration of the liver injury in spite of the interruption of the drug lasting in one of them up to one year, but all ultimately resolved.

Topics: Adult; Alkaline Phosphatase; Bilirubin; Cholestasis; Female; gamma-Glutamyltransferase; Humans; Hyperthyroidism; Methimazole

Seven patients with hyperthyroidism due to a TSH-secreting pituitary macroadenoma have been observed of a total of 800 patients with pituitary tumors over a period of 15 yr. Serum TSH levels varied between 1.1-36.3 mU/L. The serum alpha-subunit level was low in 1 case, while in 4 other cases the concentration was elevated and varied between 3.7-7.8 micrograms/L. Serum TSH beta levels were normal in the 4 cases in which it was determined. Serum GH or PRL levels were elevated in 5 cases. In 1 patient the cosecretion of TSH, GH, and PRL was confirmed by immunocytochemical examination. Serum TSH and alpha-subunit responses to TRH, GnRH, CRF, GRF, dexamethasone, methimazole, T3, and bromocriptine administration were variable when studied. Serum TSH and alpha-subunit circadian rhythms were absent in 1 case and inverted in another. A serum alpha-subunit pulsatility without TSH pulses was observed in 1 patient. Five patients underwent transsphenoidal adenomectomy. Three of 4 patients operated on in our center were cured, but a recurrence of the adenoma was found in 1 of them after 5 yr. The fifth patient was not cured. Treatment with octreotide in 3 patients resulted in normalization of serum TSH, GH, and thyroid hormones levels. Cosecretion of PRL in 1 case and alpha-subunit in 2 cases was also inhibited. Partial tachyphylaxis occurred in 1 patient. In summary, heterogeneity in clinical presentation, hormonal expression, and therapeutic response appears to characterize these TSH-secreting adenomas.

Topics: Adenoma; Adolescent; Adult; Aged; Aged, 80 and over; Bromocriptine; Circadian Rhythm; Female; Glycoprotein Hormones, alpha Subunit; Growth Hormone; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Octreotide; Pituitary Neoplasms; Prolactin; Thyrotropin; Thyrotropin-Releasing Hormone

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Female; Glucose Tolerance Test; Humans; Hyperthyroidism; Insulin; Male; Methimazole; Middle Aged; Thyroid Hormones; Thyroxine; Triiodothyronine

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

Topics: Drug Therapy, Combination; Humans; Hyperthyroidism; Methimazole; Recurrence; Thyroxine

Serum bone gamma-carboxyglutamic acid-containing (Gla) protein (BGP) was measured before and with initially 2 weeks, later 4-8 weeks intervals for 20-58 weeks during treatment of patients with hyperthyroidism (n = 10) and hypothyroidism (n = 4). Biochemical euthyroidism was obtained in the hyperthyroid patients after a median of 3 weeks (range 1-8 weeks), and in the hypothyroid patients after a median of 17 weeks (range 10-27 weeks). Serum BGP levels closely followed the thyroid state, being high respectively low in the hyperthyroid and hypothyroid state and reaching a stable plateau just at the time biochemical euthyroidism was obtained. These data suggest that osteoblastic activity is enhanced in hyperthyroidism and reduced in hypothyroidism, and that normalization occurs in close conjunction with the normalization of the thyroid state, without any delay, indicating a direct effect on the function of the excisting osteoblasts by the thyroid hormones.

Topics: Aged; Female; Follow-Up Studies; Humans; Hyperthyroidism; Hypothyroidism; Longitudinal Studies; Male; Methimazole; Osteocalcin; Radioimmunoassay; Thyrotropin; Thyroxine; Triiodothyronine

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

The intravenous and oral disposition of the antithyroid drug methimazole was determined in 10 clinically normal cats and nine cats with naturally occurring hyperthyroidism. After intravenous administration of 5 mg methimazole, the mean residence time was significantly (P less than 0.05) shorter in the cats with hyperthyroidism than in the normal cats, but there was no significant difference between the mean values for total body clearance (CL), steady state volume of distribution (Vdss), terminal elimination rate constant (ke), or serum terminal half-life (t1/2) in the two groups of cats. After oral administration, the mean bioavailability of methimazole was high in both the normal cats (77.6 per cent) and cats with hyperthyroidism (79.5 per cent). The values for mean residence time, ke and serum terminal t1/2 after oral dosing were significantly shorter in the cats with hyperthyroidism than in the normal cats. However, after oral administration of methimazole there were no significant differences between the mean values for CL, Vdss, bioavailability and maximum serum concentrations or the time for maximal concentrations to be reached in the two groups of cats. Overall, most pharmacokinetic parameters for methimazole were not altered by the hyperthyroid state. However, the cats with hyperthyroidism did show a trend toward faster elimination of the drug compared with the normal cats, similar to what has been previously described for the antithyroid drug propylthiouracil in cats. These results also indicate that methimazole is well absorbed when administered orally and has a higher bioavailability than that of propylthiouracil in cats with hyperthyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Absorption; Administration, Oral; Animals; Biological Availability; Cat Diseases; Cats; Female; Hyperthyroidism; Injections, Intravenous; Male; Methimazole; Tissue Distribution

Topics: Adolescent; Adult; Atrioventricular Node; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Middle Aged; Sinoatrial Node

Ten hyperthyroid patients were assessed for muscle strength before and after a period of medical treatment that averaged 12 months. The subjects did not change their habitual level of physical activity between the two test occasions. Maximal voluntary isokinetic knee extensor muscle strength was determined during various concentric, eccentric and isometric conditions. Average increases in strength from before to termination of treatment ranged from 25 to 41% for the concentric and isometric tests (P less than 0.01, n = 10), and from 19 to 35% for the eccentric tests (P less than 0.01, n = 6). The present study demonstrates that medical treatment of hyperthyroid patients results in a marked increase in muscle strength.

Topics: Adult; Analysis of Variance; Body Weight; Female; Humans; Hyperthyroidism; Male; Methimazole; Muscles; Propranolol; Thiouracil

Thyroid scintigrams of two women (aged 48 and 58) with Plummer's disease showed unusual radioiodine accumulation during treatment with methimazole (MMI). Before MMI therapy, the scintigrams revealed most of the radioiodine uptake only in the nodules of the patients and very little uptake in the non-nodular portions of the thyroid. After initiation of MMI therapy, scintigrams performed at three and eight months revealed that the hot nodules had become hypofunctional and that the surrounding tissues had normal radioiodine accumulation. The findings indicate that the nodules in Plummer's disease continue to concentrate MMI selectively compared with normal surrounding thyroid tissue during therapy.

Topics: Adenoma; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Middle Aged; Radionuclide Imaging; Syndrome; Thyroid Gland; Thyroid Neoplasms

Prenatal plus neonatal administration of methimazole (MMI), a procedure provoking marked hypothyroidism in rats, increased by about 100% the thymic content of oxytocin and severely (by approximately 80%) decreased the thymus weight, compared to euthyroid counterparts. Adult-onset, propylthiouracyl (PTU)-induced hypothyroidism, while provoking thymic involution, or thyroxine (T4) hyperthyroidism, did not affect oxytocin concentrations. Thymic involution and increases in thymus oxytoxin could also be obtained with repeated administration of the potent glucocorticoid dexamethasone. However, since corticosterone, unless subchronically injected at largely supraphysiological doses, was previously shown to have no influence on thymic parameters of young adult rats, a major involvement of the neonatal adrenal axis in oxytocin alterations could be excluded. It is suggested that the ontogenesis of thymic oxytocin production is under thyroid control.

Topics: Aging; Animals; Animals, Newborn; Dexamethasone; Female; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Organ Size; Oxytocin; Propylthiouracil; Rats; Rats, Inbred Strains; Thymus Gland; Thyroxine

Oxygen consumption (VO2) and mitochondrial guanosine diphosphate (GDP) binding of interscapular brown adipose tissue (BAT) were measured in hypothyroid, hyperthyroid and euthyroid rats after stimulations with selective and nonselective beta-adrenoceptor agonists: BRL 35135A (BRL) and Isoprenaline (ISO). Resting VO2, VO2 increment and mitochondrial GDP binding after beta-adrenergic stimulations were lower in hypothyroid rats than in the euthyroid group. The reduced responses were more marked for ISO than for BRL. Restion VO2 and VO2 increment after beta-adrenergic stimulations were higher in hyperthyroid rats than in the eurthyroid group; the increment was more marked for BRL than for ISO. In hyperthyroidism, mitochondrial GDP binding after BRL and after ISO was in the same magnitude; it was higher in the hyperthyroid than in the euthyroid group after BRL but not after ISO. The different thermogenic responses after ISO and BRL stimulations suggest that BRL is acting on a beta-adrenoceptor differing from the beta-1 and beta-2 adrenoceptors responsible for the effects of ISO. Activation of thermogenesis via the beta-3 adrenoceptor seems to be less dependent on the permissive levels of thyroid hormones than activation via beta-1 and/or beta-2 adrenoceptors. The beta-3 adrenoceptor may be more sensitive to increased levels of thyroid hormones.

Topics: Adipose Tissue, Brown; Animals; Body Weight; Guanosine Diphosphate; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Mitochondria; Organ Size; Oxygen Consumption; Rats; Rats, Inbred Strains; Reference Values; Thyroid Gland

A very rare case of granulomatous hepatitis in a 56-year old woman with hyperthyroidism, under long-term treatment with methimazole, is reported. Liver biopsy showed multiple non caseous granulomas in the portal triads, consisted of epithelioid and multinucleated cells, lymphocytes and isolated eosinophils. The presence of eosinophils in granulomas, could indicate an iatrogenic aethiology.

Topics: Chemical and Drug Induced Liver Injury; Female; Granuloma; Humans; Hyperthyroidism; Methimazole; Middle Aged

Carbonic anhydrase (CA) and Mg2(+)-dependent ATPase and Mg2(+)-dependent, HCO3(-)-stimulated ATPase (Mg2(+)-HCO3(-)-ATPase) activities in rat duodenal mucosa and kidney cortex were examined with respect to thyroidal status. Administration of 50 and 150 micrograms thyroxine (T4)/kg per day s.c. for 7 days decreased duodenal cytosol CA activity to 66% of control with the former and 43% with the latter dose, while Mg2(+)-HCO3(-)-ATPase activity in brush borders of duodenal mucosa was increased to 116% of control by 150 micrograms T4/kg. CA and Mg2(+)-HCO3(-)-ATPase activities in the cytosol and brush border of kidney cortex did not change after administration of T4. Hypothyroidism induced by thyroidectomy for 2 and 4 weeks or administration of methimazole (2.5-20 mg/kg per day s.c. or peroral) for 2, 3 and 4 weeks all increased duodenal cytosol CA activity, to about 140% at 2 weeks and 153% at 4 weeks after thyroidectomy, and to about 136% after the oral administration of 10 mg methimazole/kg per day for 4 weeks, while brush border Mg2(+)-HCO3(-)-ATPase activity was decreased to 56% of control 4 weeks after thyroidectomy and to 74% after the s.c. administration of 20 mg methimazole/kg day for 3 weeks. The increase in CA activity and the decrease in ATPase activity after thyroidectomy were restored to normal levels by replacement with T4. Neither enzyme activity in the kidney changed in hypothyroidism. Serum concentrations of T4 and cortisol-like material increased after administration of T4, and serum concentrations of T4, aldosterone and cortisol-like material all decreased in hypothyroidism. Correlations were observed between duodenal CA and Mg2(+)-HCO3(-)-ATPase activities and serum concentrations of T4 (P less than 0.01). These results reveal that the decrease in CA activity and the increase in Mg2(+)-HCO3(-)-ATPase activity of duodenal mucosa in hyperthyroidism are reversed in hypothyroidism, while both enzyme activities in the kidney are unrelated to thyroidal status.

Topics: Adenosine Triphosphatases; Animals; Anion Transport Proteins; Ca(2+) Mg(2+)-ATPase; Carbonic Anhydrases; Duodenum; Enzyme Activation; Hyperthyroidism; Hypothyroidism; Intestinal Mucosa; Kidney Cortex; Male; Methimazole; Rats; Rats, Inbred Strains; Thyroidectomy; Thyroxine

The serum ACE activity was determined in male Fischer 344 rats at 2, 6, 13, and 25 months of age to determine whether serum angiotensin converting enzyme (ACE) activity is a potential biomarker of tissue hypothyroidism in aged rats. Since rodent serum contains an ACE activity inhibitor, the measurements were done in both undiluted and 1:8 diluted sera. The highest serum inhibitor activity was found in the 2-month-old animals. The serum ACE activity measured in the diluted serum of the aged rats (77.6 +/- 2.9 units/ml) was significantly reduced compared to 2-month-old (178.2 +/- 6.4 units/ml), 6-month-old (101.5 +/- 6.1 units/ml) and 13-month-old rats (84.9 +/- 8.6 units/ml); (p less than 0.001). Hyperthyroidism induced by injecting L-triiodothyronine (T3) 15 micrograms/100 gm body weight intraperitoneally for 10 days increased the serum ACE activity in the older rats, but reduced the levels in 2-month-old rats. There was no significant change in 6-month-old rats. The levels of serum ACE activity in hypothyroid 6-month-old rats (95.5 +/- 3.5 units/ml) and in 2-month-old-rats (94.2 +/- 4.0 units/ml) were similar to the level seen in hypothyroid old rats (88.9 +/- 5.8 units/ml). Pair feeding of young rats (8 months old) with old did not alter the baseline ACE level (117.4 +/- 3.7 units/ml) or the T3 stimulated (105.2 +/- 10.2 units/ml) serum ACE activity. It is concluded that the reduced serum ACE activity in aged rats cannot be accounted for by the reduced caloric intake or reduced serum thyroid hormone levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aging; Animals; Eating; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Peptidyl-Dipeptidase A; Rats; Rats, Inbred F344; Triiodothyronine

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

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

Red blood cell (RBC) zinc (Zn) concentration was measured by atomic absorption spectrophotometry in 28 healthy volunteers, in 46 patients with hyperthyroidism, and in 6 patients with hypothyroidism. The mean (+/- SD) RBC Zn concentration in euthyroid controls was 11.4 +/- 1.5 mg/L RBC, and the normal range defined as the mean +/- 2 SD was 8.5 to 14.3 mg/L RBC. The mean RBC Zn in patients with hyperthyroidism was decreased to 6.4 +/- 1.6 mg/L RBC, and 43 (93%) had low values. The mean RBC Zn in patients with hypothyroidism was not different from that in the controls. There was a significant negative correlation between the concentrations of RBC Zn and those of both plasma thyroxine (T4; r = -0.73) and plasma 3,5,3'-triiodothyronine (T3; r = -0.70). After the treatment of 17 hyperthyroid patients with antithyroid drugs, both mean plasma T4 and T3 levels became normal within 4 weeks, but the normalization of RBC Zn lagged about 2 months behind them. The RBC Zn levels significantly correlated with both the plasma T4 and T3 levels obtained 0, 4, 8, and 12 weeks prior to the RBC sampling, and the highest correlation was observed between the RBC Zn levels and plasma T4 and T3 levels measured 8 weeks previously. These data suggest that RBC Zn concentration in hyperthyroid patients reflects a patient's mean thyroid hormone level over the preceding several months as glycosylated hemoglobin level does in diabetic patients.

Topics: Adult; Erythrocytes; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Middle Aged; Propylthiouracil; Testosterone; Thyroid Hormones; Thyrotropin; Time Factors; Zinc

Dietary carbohydrate and thyroid hormone (T3) interact to regulate rat liver S14 gene expression. The molecular basis for this interaction was examined by analysis of hepatic mRNAS14 levels, S14 gene transcription, and chromatin structure. While starvation of euthyroid rats inhibited hepatic S14 gene transcription greater than or equal to 90%, sucrose administration induced mRNAS14 and S14 transcription to 82% of euthyroid-fed levels within 4 h. In contrast, administration of sucrose or T3 to starved hypothyroid animals restored S14 gene transcription to only 30% of euthyroid-fed values. Both T3 and sucrose were required to restore S14 run-on activity and mRNAS14 to euthyroid-fed levels within 4 h. Thus, T3 and sucrose interact synergistically and rapidly to induce S14 gene transcription. Analysis of S14 chromatin structure showed that starvation of hypothyroid rats inhibited the formation of three DNase I-hypersensitive sites flanking the 5'-end of the S14 gene (Hss-1 at -65 to -265 base pairs; Hss-2 at -1.2 kilobases and Hss-3 at -2.67 kilobases). The loss of these sites correlated with the repression of S14 gene transcription in starved hypothyroid rats. Whereas administration of sucrose to starved hypothyroid rats consistently induced the Hss-1 and Hss-2 sites, T3 consistently induced all three DNase I-hypersensitive sites. Yet, neither treatment alone induced S14 gene transcription to euthyroid levels. The combination of T3 and sucrose induced no additional change in S14 chromatin structure over that induced by T3 alone. Thus, regulation of S14 chromatin structure alone is not the sole mechanism by which these stimuli regulate S14 gene transcription. We speculate that the synergistic regulation of S14 gene transcription by T3 and dietary carbohydrate involves a complex interaction between factors which regulate the accessibility of putative cis-regulatory elements through changes in chromatin structure and the regulation of "transcription factors" which interact with these elements.

Topics: Animals; Base Sequence; Deoxyribonuclease I; Dietary Carbohydrates; DNA Probes; Gene Expression Regulation; Genes; Hyperthyroidism; Hypothyroidism; Liver; Male; Methimazole; Molecular Sequence Data; Nuclear Proteins; Proteins; Rats; Rats, Inbred Strains; RNA, Messenger; Transcription Factors; Transcription, Genetic; Triiodothyronine

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

To determine whether age-related differences in body weight loss in hyperthyroidism could be related to caloric intake, the body weight and food consumption of Fischer 344 male rats were monitored every other day for four weeks. Six-month-old (young) rats were compared to 16-month-old rats (intermediate age) and 25-month-old (aged) rats. Hypothyroidism was induced with 0.025% methimazole in the drinking water for four weeks. Hyperthyroidism was induced with triiodothyronine (T3) injections (15 micrograms/100 g body weight i.p.) for the last 10 days of observation. A group of young rats pair fed with aged rats was included as a control group. The body weight changes of aged rats were similar to hypothyroid young rats. An index of T3 catabolic effect was calculated based on the net weight loss and food intake. This index was not different in aged rats compared to young rats. The apparent hypersensitivity of aged rats to T3 as evidenced by excessive weight loss could totally be attributed to decreased caloric intake. It is concluded that aged rats compared to the young are not more sensitive to the overall catabolic effects of thyroid hormones.

Topics: Aging; Animals; Energy Intake; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Rats; Rats, Inbred F344; Thyroid Hormones; Triiodothyronine; Weight Loss

Data of 196 patients treated for hyperthyroidism exclusively with antithyroid drugs were analyzed retrospectively concerning the relapse rate within a follow-up period of four years. Patients were subdivided for primary or recurrent disease, and for immunogenic or non-immunogenic hyperthyroidism, respectively. In immunogenic as well as in non-immunogenic hyperthyroidism, the relapse rate was significantly lower for patients with primary disease (35% and 52%, respectively) compared to those with recurrent hyperthyroidism (82%, p less than 0.001 and 83%, p less than 0.001, respectively). In patients with primary disease, clinical, biochemical and scintigraphic parameters were tested with respect to their capability of predicting a relapse. For immunogenic hyperthyroidism the highest relapse rates were observed in young patients and in those with large goitres, whereas for non-immunogenic hyperthyroidism they were highest in old patients, in those with nodular goitres and in those without an increased urinary iodine excretion at the time of diagnosing hyperthyroidism.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Drug Therapy, Combination; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Recurrence; Risk; Thyroxine

A literature review of individual pregnancies and recent surveys involving large cohorts reveal an association between congenital malformation and maternal hyperthyroidism, suggesting that some aspect of hyperthyroidism or its treatment might compromise the development of the fetus. Experiments have shown that the thyroid antagonist, ethylenethiourea (ETU), causes fetal malformations when administered to pregnant rats, but it is not known whether it is ETU or the imbalance in maternal thyroid hormone which it causes which is the teratogenic agent. Here we employ in vitro culture to determine the possible direct effects on rat embryos of two thyroid antagonists, ETU and methimazole (MMI), the latter being one which is used for treatment of thyrotoxicosis in humans. It was found that ETU can compromise the development of rat embryos in vitro, confirming that ETU has a direct effect on the rat embryo. It was also found that MMI can cause abnormal development of rat embryos in vitro, although the concentration at which MMI disturbs rat embryogenesis is higher than that which is reached in hyperthyroid patients treated with clinical doses of MMI or carbimazole.

Topics: Abnormalities, Drug-Induced; Animals; Embryo, Mammalian; Ethylenethiourea; Hyperthyroidism; Imidazoles; In Vitro Techniques; Methimazole; Rats; Rats, Inbred Strains

A case of extremely severe hyperthyroidism due to bone metastasis of papillary thyroid cancer is described. Hyperthyroidism began in this patient soon after the discovery of pelvic metastasis and worsened after total thyroidectomy and after the first dose of radioiodine. The administration of methimazole, prednisone and multiple, fractioned and small doses of radioiodine cured the hyperthyroidism and stabilized the neoplastic growth. Hyperthyroidism lasted for at least six months and hypothyroidism appeared only after seven months. Thus, the fractionation of the doses of radioiodine together with antithyroid drugs appears to be an effective treatment in patients with hyperthyroidism due to metastatic thyroid cancer.

Topics: Aged; Bone Neoplasms; Carcinoma, Papillary; Dose-Response Relationship, Drug; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Prednisone; Prognosis; Thyroid Neoplasms

Topics: Adult; Extremities; Humans; Hyperthyroidism; Male; Methimazole; Nephrotic Syndrome; Paralysis; Periodicity; Recurrence; Remission Induction

Side effects of antithyroid treatment were retrospectively analysed in 1256 patients with hyperthyroidism. Overall rate of side effects was 14.3%. Skin reactions were the most frequent ones (5.6%), followed by arthropathies (1.6%). The incidence of agranulocytosis was 0.14%. Median duration of all side effects was 1.5 months. In half the cases the side effects were controllable so that treatment was continued, although at a changed dosage. The rate of cross-reaction between carbimazole and thiamazole, on the one hand, and propylthiouracil, on the other, was 13.8% and 15.2%, respectively. The side effects became apparent after a mean of one month's treatment, almost always (in 97.1%) within the first year of treatment. There was a significant dose dependence for an initial thiamazole dose of over 20 mg (relative side effect risk of 2.3), and for an initial dose of over 30 mg for carbimazole (relative side effect risk of 1.6). Although most side effects were not dangerous, in normal instances the lowest possible dosage should be administered to control hyperthyroid metabolism. Long-term treatment with low doses seem to be without problems.

Topics: Adult; Antithyroid Agents; Carbimazole; Dose-Response Relationship, Drug; Drug Evaluation; Drug Interactions; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Propylthiouracil; Retrospective Studies; Time Factors

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

Hyperthyroidism is difficult to diagnose in the elderly because at this age thyroid disorders are often insidious and atypical with non-specific symptoms. The diagnosis of thyroid disease may be particularly difficult in the presence of a multiple age-associated pathology which may mask the signs or symptoms of thyroid disease. The paper presents the clinical findings in 18 patients in whom the diagnosis of thyrotoxicosis was established at the age of 65 or later.

Topics: Age Factors; Aged; Aged, 80 and over; Antithyroid Agents; Diagnosis, Differential; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Thyroid Hormones; Thyrotropin; Thyrotropin-Releasing Hormone

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 a retrospective study about 276 clinically and paraclinically ascertained cases of hyperthyroidism in 34% of the patients above all mild anaemias could be proved which under thyreostatic therapy with thiamazol which after repeated incidence of an euthyroid metabolic situation vastly normalized themselves also without an anaemia-specific additional medication. Leukocytopenias (5.8%) and thrombocytopenias (3.3%) had only a low frequency in untreated hyperthyroidism. Nevertheless an unequivocal parallelity of the haematologic changes was to be observed in erythro-, granulo- and thrombopoiesis. There was a clear correlation between the activity of hyperthyroidism, measured at the T3- or T4 level, and anaemia and haemocytopenia, respectively. Lacking substance deficiency conditions and signs of haemolysis let us first of all think of a causal thyrotoxic bone-marrow damage on account of the dependence of the haematologic changes on the activity of hyperthyroidism and their immediate influencibility by aimed thyrostatic therapy. A relatively low dosed thiamazol therapy has influence on haematopoiesis and peripheral blood picture only at a very small percentage, in which cases the changes mostly are fully reversible. Thereby the initial haematologic situation before the therapy does not provide any predictability for perhaps appearing haematotoxic or allergic side-effects under thyreostatic treatment. The thiamazol therapy does not show any recognizable side-effects in the dosage administered on the investigated leukocytic functions agglomeration, adhesion and phyagocytosis. Only for the adhesion of leukocytes was proved a significant functional disturbance of leukocytes, which was, however, reversible with normalization of metabolism and with high probability was also directly thyreotoxically induced.

Topics: Adolescent; Adult; Aged; Anemia, Aplastic; Anemia, Hypochromic; Erythrocyte Count; Female; Hemoglobinometry; Humans; Hyperthyroidism; Leukocyte Count; Leukopenia; Long-Term Care; Male; Methimazole; Middle Aged; Platelet Count; Thrombocytopenia; Thyroid Function Tests

The effect of thyroid hormone on circulating levels of atrial natriuretic peptide (ANP) was studied in experimental hyperthyroid and hypothyroid rats. Plasma ANP was 102 +/- 5 pg/ml in euthyroid rats, 82 +/- 4 pg/ml in hypothyroid rats, and 138 +/- 11 pg/ml in hyperthyroid rats. We have also measured immunoreactive ANP in the atria of euthyroid, hypothyroid, and hyperthyroid rats. ANP content and concentration in the atria were lower (546 +/- 32 pg/mg tissue) in hyperthyroid rats than in hypothyroid rats (802 +/- 74 pg/mg tissue). Right atrium from euthyroid, hypothyroid, and hyperthyroid rats was superfused with a modified Langendorff preparation. Spontaneous release of ANP was significantly higher from the hyperthyroid rats (20 +/- 2 pg.min-1.mg-1) than from the hypothyroid rats (5.6 +/- 0.5 pg.min-1.mg-1). ANP release from the euthyroid rats was 9.3 +/- 1.2 pg.min-1.mg-1. These results indicate hyperthyroidism causes an increase in ANP secretion and a decreased release occurs during hypothyroidism.

Topics: Animals; Atrial Natriuretic Factor; Heart Atria; Hyperthyroidism; Hypothyroidism; In Vitro Techniques; Male; Methimazole; Myocardium; Rats; Rats, Inbred Strains; Thyroxine

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

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

To exploit the antiarrhythmic effect of amiodarone when patients develop the side effect of thyrotoxicosis three patients with hyperthyroidism induced by amiodarone were given simultaneously 1 g potassium perchlorate a day for 40 days and a starting dose of 40 mg methimazole a day while they continued to take amiodarone. As hyperthyroidism might have recurred after potassium perchlorate treatment was stopped the dose of methimazole was not reduced until biochemical hypothyroidism (raised thyroid stimulating hormone concentrations) was achieved. The patients became euthyroid (free triiodothyronine concentration returned to normal values) in two to five weeks and hypothyroid in 10 to 14 weeks. One patient became euthyroid while taking 5 mg methimazole a day and 600 mg amiodarone weekly; the two others required substitution treatment with thyroxine sodium while taking 5 mg methimazole or 50 mg propylthiouracil (because of an allergic reaction to methimazole) and 2100 or 1400 mg amiodarone weekly. Hyperthyroidism induced by amiodarone may be treated with potassium perchlorate and methimazole given simultaneously while treatment with amiodarone is continued.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Drug Evaluation; Drug Therapy, Combination; Humans; Hyperthyroidism; Methimazole; Middle Aged; Perchlorates; Potassium; Potassium Compounds; Thyroid Gland

Acylphosphatase activity and content were measured in erythrocytes from hyperthyroid patients and healthy controls. In addition, the soluble enzymes glucose-6-phosphate dehydrogenase, hexokinase, and the membrane bound (Na+ + K+)-ATPase and Ca2+-ATPase were assayed. Our results confirmed previous studies indicating a decrease of (Na+ + K+)-ATPase and an increase of Ca2+-ATPase activity in hyperthyroid erythrocytes. While glucose-6-phosphate dehydrogenase was not significantly changed, hexokinase and acylphosphatase activities were significantly higher in the hyperthyroid group. Both activities and content of acylphosphatase returned to normal levels in erythrocytes from treated patients, when they were euthyroid. These findings suggest that an excess of thyroid hormones may stimulate acylphosphatase biosynthesis in erythroid cells and indicate a potential clinical usefulness of this enzyme in hyperthyroidism.

Topics: Acid Anhydride Hydrolases; Acylphosphatase; Adenosine Triphosphatases; Adult; Erythrocyte Membrane; Erythrocytes; Female; Glucosephosphate Dehydrogenase; Hexokinase; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Phosphoric Monoester Hydrolases; Thyrotropin; Thyroxine; Triiodothyronine

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

Investigations of the heart automatism were carried out in 10 patients with hyperthyreoidism before thiamazol therapy and after restoration of the euthyroid status. A control group was comprised of 34 healthy subjects. In order to determine the electrophysiologic parameters the transoesophageal atrium extrastimulus technique and the over-driving stimulation were applied. Restoration of the euthyroid status was accompanied by a significant prolongation of the atrial refraction, the border interval, the border conductivity and the sinus rhythm recurrence time. In a half of the patients were atrioventricular and intraventricular conductibility disturbances observed. The authors conclude, that in the early period of the euthyroid status restoration after thiamazole therapy there still exists a risk of cardiologic complications.

Topics: Adult; Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Dose-Response Relationship, Drug; Electrocardiography; Female; Heart Conduction System; Heart Rate; Humans; Hyperthyroidism; Male; Methimazole; Thyroid Function Tests

A case is reported of neoplastic TSH hypersecretion in a 62-year-old man with severe hyperthyroidism and cardiovascular disease. He had been known to be hyperthyroid for 14 yr, and had been treated by thyreostatic drugs and subtotal thyroidectomy without satisfactory results. When he was referred to our Center, he was frankly hyperthyroid with both TSH (14 microU/ml) and thyroid hormone serum levels (TT4 24 micrograms/dl, TT3 370 ng/dl, FT41 7.9) above the normal range. alpha-subunit serum level was markedly increased (7.2 ng/ml), while beta-subunit was only 0.3 ng/ml. Skull X-ray showed an enlarged sella turcica with destruction of the dorsum and an intrasellar tumor was visualized on conventional and computer tomography. TSH response was absent after TRH and domperidone, while TSH serum levels decreased by 25% after bromocriptine. Methimazole therapy temporarily decreased serum thyroid hormones to normal levels, while TSH levels rose to 34 microU/ml, thus indicating that pituitary-thyroid feed-back was maintained at a higher set point. Surgical attempt failed because of cardiac problems during anesthesia. Radiotherapy plus methimazole was begun and TSH serum levels first increased markedly, up to 140 microU/ml, and then progressively decreased without reaching normal values. After methimazole withdrawal hyperthyroidism recurred.

Topics: Bromocriptine; Cardiovascular Diseases; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Pituitary Gland; Pituitary Neoplasms; Thyrotropin; Thyroxine; Triiodothyronine

Investigations of heart automatism have been performed in 10 patients with hyperthyreosis prior and after the euthyreosis obtaining with the methizol therapy. The control group consisted of 34 healthy volunteers. The electrophysiologic parameters of heart were determined by the transoesophageal stimulation of atrium using the method of single impulse and rapid stimulation. Instantly after obtaining the remission the normorhytmia has been observed; moreover, the significant elongation of the effective time of atium refraction and of the border interval, has been noted; the last two parameter were shorter than in the control group. The normalization of the border atrioventricular conduction and the sinusal rhythmus return as well as appearance in half of patients treated of latent block of intracardial conductivity has also been stated. According to the authors' opinion the early period after the obtaining of euthyreosis by the use of methizol is characterized by cardiological risk.

Topics: Adult; Cardiac Pacing, Artificial; Female; Heart Conduction System; Heart Rate; Humans; Hyperthyroidism; Male; Methimazole

In a patient with hyperthyroidism and newly diagnosed insulin-dependent diabetes mellitus (IDDM), insulin action and clearance were studied before the initiation of antithyroid treatment and at 3-mo intervals for 1 yr thereafter. The sequential euglycemic clamp technique (5 mM) was used with insulin infusion rates of 0.5, 1.0, 2.0, and 5.0 mU.kg-1.min-1 in four steps of 2 h. The data were compared with nine control subjects and nine newly diagnosed euthyroid IDDM patients treated with insulin for 0.5 mo. Insulin sensitivity was increased in the patients (ED50 40 vs. 52 mU/L, range 43-70, in controls and 70 mU/L, range 59-120, in IDDM subjects). Insulin responsiveness was markedly elevated; the steady-state glucose infusion rate (SSGIR) of step 4 was 104 vs. 64 mumol.kg-1.min-1 (range 50-79) in controls and 61 mumol.kg-1.min-1 (range 47-69) in IDDM subjects. Insulin clearance was elevated in all steps (1-3, 20-23 vs. 9-15 ml.kg-1.min-1; 4, 18 vs. 6-12 ml.kg-1.min-1 in control and IDDM subjects). Parallel to the normalization of thyroid metabolism, insulin action (ED50 60 mU/L, SSGIR in step 4, 51 mumol.kg-1.min-1) and insulin clearance (steps 1-3, 11-14 ml.kg-1.min-1; step 4, 7 ml.kg-1.min-1) returned to the normal range in 6 mo. Both remained within the normal range until 12 mo. In the patient with newly diagnosed IDDM, the initial marked increases of insulin action and clearance were due to coexistent hyperthyroidism. With the amelioration of the hyperthyroid state, both processes became normal. The parallelism between insulin action and clearance suggests a functional relationship.

Topics: Adult; Diabetes Mellitus, Type 1; Follow-Up Studies; Glucose Clamp Technique; Humans; Hyperthyroidism; Insulin; Insulin, Regular, Pork; Male; Methimazole; Reference Values

Topics: Adult; Body Weight; Energy Intake; Female; Humans; Hyperthyroidism; Male; Methimazole; Methylthiouracil; Middle Aged

A 30-year-old twin pregnant woman complicated with hyperthyroidism was scheduled to receive anesthesia for cesarean section. During the early months of pregnancy, her thyroid status was stimulated, being positive for TSH-binding inhibitor immunoglobulins (TBII). Because maternal positiveness of TBII correlates with neonatal hyperthyroidism, she was treated with antithyroid drugs (methimazole). Her thyroid status was suppressed gradually and her TBII level became negative. On the 38th week of pregnancy, she underwent cesarean section by lumbar spinal anesthesia and twin girls were delivered with Apgar scores of 9. The thyroid statuses of the twins were measured, showing that their thyroid functions to be almost equal, although they were dizygotic twins. T3 and free-T3 were below the normal limits for adults, but they did not require any therapy. Maternal level of TBII is considered to be a useful index for management of patients with hyperthyroidism during the perianesthetic period for cesarean section. In this type of patients the thyroid status of both the mother and fetus should be carefully followed.

Topics: Adult; Anesthesia, Obstetrical; Anesthesia, Spinal; Cesarean Section; Female; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy, Multiple; Twins

Topics: Adult; Drug Administration Schedule; Heart Rate; Humans; Hyperthyroidism; Methimazole; Middle Aged; Prospective Studies; Random Allocation; Thyroid Hormones; Thyroxine; Triiodothyronine

A 68-year-old woman who, for the first time, had a generalized tonic-clonic seizure and persisting confusional state was found to have nodular enlargement of the thyroid and a tachycardic arrhythmia. Electroencephalography (EEG) demonstrated a continuous irregular polyspike wave pattern. Total T4 concentration was elevated to 23 micrograms/dl. Consecutive Administration of 250 mg phenytoin, 4 mg clonazepam and 7.5 mg midazolam changed neither the clinical nor the EEG findings. But after general intensive care measures and high-dose thyrostatic treatment (40 mg thiamazole intravenously every four hours) the clinical and neurological status became normal. Serial EEGs over the subsequent weeks and months showed gradual disappearance of the abnormal changes with increasingly prolonged periods of normal activity.

Topics: Aged; Electroencephalography; Female; Humans; Hyperthyroidism; Injections, Intravenous; Methimazole; Status Epilepticus; Thyroxine; Time Factors

This paper reports a case of agranulocytosis that developed in a patient with hyperthyroidism two months after the administration of methimazole. The patient manifested symptoms of fever, sore throat, profound leukopenia, and oral complications such as generalized gingival necrosis and mucosa ulceration, which subsequently abated upon withdrawal of the drug. Dental practitioners should be aware of the potential of agranulocytosis associated with methimazole therapy. The oral manifestations should be kept in mind.

Topics: Adult; Agranulocytosis; Female; Gingivitis, Necrotizing Ulcerative; Humans; Hyperthyroidism; Methimazole

Topics: Adolescent; Adult; Aged; Female; Humans; Hyperthyroidism; Methimazole; Middle Aged; Platelet Count

Hyperthyroidism was induced in two burn patients (one a 34-year-old male, with burns covering 80 per cent BSA and the other a 22-year-old female with a 45 per cent BSA burn) by topical treatment with povidone-iodine. Both patients had no history of thyroid disease and their post-burn examination revealed normal thyroid glands. In both patients 1 per cent povidone-iodine was applied onto granulation tissue and a marked increase in circulating thyroid hormones occurred. After topical treatment with povidone-iodine was discontinued circulating thyroid hormones returned to normal values within weeks. In the second patient povidone-iodine treatment had to be repeated again resulting in hyperthyroidism which was also readily reversible.

Topics: Administration, Topical; Adult; Burns; Female; Humans; Hyperthyroidism; Male; Methimazole; Povidone; Povidone-Iodine; Thyroid Hormones

20 patients with hyperthyroidism were observed with repeated EEG measurements before and during treatment (ObsidanR; MethimazolR). 17 patients, before starting antithyroid therapy, had slight to moderate EEG abnormalities. A prevalence for moderate disturbances occurred for patients with a higher degree of hyperthyroidism. The dominant EEG frequency was higher than in euthyroid controls, but no exact correlation to T3-values could be observed. 16 patients showed abnormal reactivity to photic stimulation. One-week therapy by propranolol produced only a slight synchronizing effect in EEG's, where T3-values decreased. After 4 weeks selective therapy by MethimazolR all patients were euthyroid, but some EEG abnormalities persisted in 12 patients in a lower degree. The dominant EEG frequency decreased to control-group ranges and abnormal photic reactivity was reduced. After 6 months some EEG disturbances re-increased tentiatively, in 3 relapses excessively. These observations confirm the prognostic value of EEG measurements for the recognition of occurrence and persistence of cerebral disturbances in severe metabolic dysfunctions.

Topics: Adult; Brain; Electroencephalography; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Propranolol; Remission Induction

Topics: Aged; Autoimmune Diseases; Female; Humans; Hyperthyroidism; Hypoglycemia; Insulin Antibodies; Methimazole

Since the effectiveness of 30 mg methimazole in a single daily dose in gaining initial control of hyperthyroidism may depend largely on patient characteristics, 52 patients (34 with diffuse and 18 with nodular goitre) were investigated in an attempt to determine the relative importance of a number of pretreatment variables. Return to normal thyroid hormone levels after 2 to 6 weeks of treatment appeared to be the rule, although eight of these patients formed notable exceptions (6-20 weeks). The individual duration of treatment until achievement of biochemical euthyroidism correlated with the initial free thyroxine index (r = 0.75, P less than 0.001) and the free triiodothyronine index (r = 0.70, P less than 0.001). For patients with a diffuse goitre it was also related to the thyroid volume estimated by ultrasound (r = 0.73, P less than 0.001). According to multiple linear regression analysis however these variables were found to have no independent prognostic value. The decrease in thyroid volume during initial therapy, the nature of the goitre, a medication compliance score and various other patient variables did not correlate with the effect of treatment. In 12 cases perchlorate discharge tests were performed. The results suggest continued hormone synthesis in patients with highly active iodine trapping as an important mechanism of the postponed attainment of euthyroidism.

Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Thyroxine; Triiodothyronine

The serum BGP level was assayed in patients with hyperthyroidism (untreated and remittent cases) and hypothyroidism. The mean serum BGP concentration was 9.7 +/- 0.90 ng/ml in 30 patients with untreated hyperthyroidism which was significantly higher than the 2.7 +/- 0.38 ng/ml in 15 remittent patients and 1.3 +/- 0.31 ng/ml in 13 patients with hypothyroidism (p less than 0.001, p less than 0.001). Serum BGP had a significant positive correlation with the concentrations of free triiodothyronine and alkaline phosphatase in the serum, while it had a significant negative correlation with serum PTH. In the patients with hypothyroidism, serum BGP increased significantly in parallel with increases in serum free triiodothyronine with thyroxine therapy. In the patients with hyperthyroidism, serum free triiodothyronine decreased significantly after the first month of methimazole treatment, and fluctuated within the normal range after two months. Serum alkaline phosphatase and BGP did not show significant changes during the first six months of treatment, although they were eventually reduced significantly at the end of one year. These results suggest that thyroid hormone directly stimulates the synthesis and secretion of BGP in existent osteoblasts and also acts on the bone remodeling cycle, therapy accelerating the rate of bone formation; the latter action may occur over a long period.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Bone and Bones; Calcium; Calcium-Binding Proteins; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Middle Aged; Osteocalcin; Parathyroid Hormone; Thyroid Gland; Thyroxine; Triiodothyronine

To investigate the dose-response relationship between thyroid hormone and linear growth, we studied 10 castrated prepubertal cynomolgus monkeys. Hypothyroidism was induced by administration of methimazole (0.0125% in drinking water) and was confirmed by high serum TSH levels (greater than 40 mU/L) in all animals. Subsequently, each animal received 1, 2, 4, or 8 micrograms/kg.day T4, im, for 9 weeks. The sequence of T4 doses was random, and 6 weeks elapsed between successive T4 doses. Serum T4, T3, TSH, and insulin-like growth factor I (IGF-I) levels and lower leg length were measured every 3 weeks. Methimazole administration decreased thyroid hormone and IGF-I levels and lower leg growth rate. With increasing doses of exogenous T4, serum T4, T3, and IGF-I as well as lower leg growth rate increased significantly. Animals not given T4 had a 65% decrease in lower leg growth rate (P less than 0.01). Animals given 4 and 8 micrograms/kg.day T4 had 56% and 73% increases, respectively, in lower leg growth rate compared to baseline (P less than 0.05 and P less than 0.01, respectively). Lower leg growth rate correlated better with serum T3 (r = 0.50; P less than 0.001) than with serum T4 (r = 0.29; P less than 0.05). Lower leg growth rate also correlated with serum IGF-I levels (r = 0.53; P less than 0.001). Serum IGF-I correlated with serum T3 (r = 0.47; P less than 0.001), but not with serum T4. We conclude that increased serum T4 and T3 levels cause progressive increases in growth velocity and IGF-I levels over a range from moderate hypothyroidism to moderate hyperthyroidism. Growth velocity and IGF-I levels correlated more strongly with the serum T3 than with the serum T4 level.

Topics: Animals; Castration; Dose-Response Relationship, Drug; Female; Growth; Hyperthyroidism; Hypothyroidism; Macaca fascicularis; Male; Methimazole; Somatomedins; Thyroid Hormones; Thyroxine; Triiodothyronine

We treated a 78-year-old patient with hyperthyroidism and atrial fibrillation with amiodarone 1200 mg/day for 3 days and methimazole 60 mg/day. Sinus rhythm was restored within 3 days and serum levels of triiodothyroxine returned to normal within 4 days. A transient increase in serum rT3 concentrations was observed. Amiodarone associated with methimazole was useful in the management of atrial fibrillation and hyperthyroidism in our patient.

Topics: Aged; Amiodarone; Atrial Fibrillation; Drug Therapy, Combination; Female; Humans; Hyperthyroidism; Methimazole; Thyroid Hormones

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

Topics: Acupuncture Therapy; Adult; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Hyperthyroidism; Male; Methimazole; Recurrence

Previous studies have suggested that thyroid hormones influence the number of membrane-bound cardiac adrenoceptors, but their effect on the intracellular distribution of adrenoceptors has not been examined. A plasma cell membrane and a vesicular fraction devoid of membrane markers were prepared from hearts of euthyroid and hyperthyroid rats and were used to compare beta- and alpha-adrenoceptors. During daily injection of l-thyroxine, cardiac hypertrophy developed within 4 days and remained unchanged thereafter. The number of membrane-bound beta-receptors increased progressively and plateaued within 2 weeks of thyroxine administration. Vesicular beta-receptors, on the other hand, increased more gradually and to a lesser extent so that after 2 weeks of l-thyroxine injection, they constituted a smaller proportion of the total beta-receptor population compared to normal rats. In contrast, the number of cardiac alpha 1-adrenoceptors declined rapidly to about 80% of that in euthyroid animals and did not change further for the duration of the study. Membrane-bound and vesicular alpha 1-adrenoceptors were affected to the same extent in hyperthyroidism. During regression of cardiac hypertrophy following cessation of thyroxine administration, alpha 1-adrenoceptors rose rapidly (within 2 days) to normal values while beta-receptors declined more gradually to normal levels within 2 weeks. In hypothyroid rats, there was a significant decline in the density of both alpha 1- and beta-adrenoceptors, with a shift away from the vesicular fraction. These results indicate that both the total numbers of cardiac adrenoceptors and their distribution between the plasma membrane and vesicular fraction are influenced by the thyroid status.

Topics: Animals; Cardiomegaly; Cell Membrane; Dihydroalprenolol; Hyperthyroidism; Hypothyroidism; Kinetics; Male; Methimazole; Myocardium; Rats; Rats, Inbred Strains; Receptors, Adrenergic, alpha; Receptors, Adrenergic, beta; Thyroid Hormones; Thyroxine

Plasma concentrations of atrial natriuretic peptides were measured in 32 normal control subjects, 25 patients with hyperthyroidism, and 18 patients with hypothyroidism. Atrial natriuretic peptide values were measured before and after successful therapy with methimazole or 1-thyroxine. Plasma atrial natriuretic peptide concentration was increased in patients with hyperthyroidism (48.0 +/- 19.5 pg/ml) but was decreased in patients with severe hypothyroidism (16.3 +/- 5.7 pg/ml) compared with values in normal control subjects (31.2 +/- 9.5 pg/ml). There was no significant difference between values in normal control subjects and mildly hypothyroid patients (35.0 +/- 12.2 pg/ml). The plasma atrial natriuretic peptide concentration was correlated with the serum thyroxine level and heart rate. The elevated atrial natriuretic peptide concentration in hyperthyroidism decreased, whereas the reduced atrial natriuretic peptide concentration in severe hypothyroidism increased, compared with the initial value after successful therapy. These results suggest that plasma atrial natriuretic peptide concentration is frequently increased in hyperthyroidism and is frequently decreased in severe hypothyroidism, and that thyroid hormone is one of the regulatory factors for circulating atrial natriuretic peptides.

Topics: Adult; Atrial Natriuretic Factor; Female; Heart Rate; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Reference Values; Thyroxine

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: Adult; Humans; Hyperthyroidism; Male; Methimazole; Papilledema; Pyramidal Tracts

Topics: Anemia, Aplastic; Bone Marrow; Child; Colony-Forming Units Assay; Female; Humans; Hyperthyroidism; Methimazole

Three groups of male Sprague Dawley rats received methimazole without or with Na-thyroxine in drinking water (3 and 0.33 mg T4/l, respectively) to induce characteristic alterations of their thyroid status (hypothyroid, hyperthyroid, euthyroid). A fourth group served as an untreated control without any additive to the drinking water. With respect to the different thyroid status, the following changes in the blood parameters were found: increasing plasma-T3-levels caused a reduction in plasma viscosity, in total plasma protein and in alpha 1-globulin, but an increase in hematocrit, whole blood viscosity, the number of erythrocytes and leukocytes, alpha 2-globulin and beta-globulin. It was concluded that the increase in the plasma viscosity in the hypothyroid status is mainly due to an alteration of the plasma protein pattern, and that the increase in whole blood viscosity in the hyperthyroid rat is a consequence of increased hematocrit.

Topics: Animals; Blood Proteins; Blood Viscosity; Hyperthyroidism; Hypothyroidism; Methimazole; Rats; Rats, Inbred Strains; Thyroxine; Triiodothyronine

Topics: Adult; Carbimazole; Female; Humans; Hyperthyroidism; Methimazole; Smell; Taste Disorders

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

An infant girl with choanal atresia, athelia, minor anomalies, and mild to moderate mental retardation was born to a woman treated for hyperthyroidism throughout pregnancy with methimazole and propranolol. The patient's defects may be due to methimazole teratogenicity or could represent a previously undescribed syndrome affecting ectodermal structures.

Topics: Abnormalities, Drug-Induced; Adult; Breast; Child, Preschool; Choanal Atresia; Female; Follow-Up Studies; Humans; Hyperthyroidism; Infant; Infant, Newborn; Methimazole; Nipples; Pregnancy; Pregnancy Complications; Syndrome

We have experienced two cases (Case 1: 21-year-old female, Case 2: 26-year-old female) of systemic lupus erythematosus (SLE) associated with hyperthyroidism. Case 1 had been treated with methimazole (MMI) and betamethasone for approximately two years. Although thyroid function improved with the treatment, laboratory data of SLE deteriorated. She was successfully treated with betamethasone alone. Case 2, who had severe side effect (severe hemorrhage due to gastric ulcer) during prednisolone treatment for SLE, was found to have an additional hyperthyroidism. She was treated with intermittent prednisolone administration alone. Physical findings as well as laboratory data of both SLE and hyperthyroidism improved by the therapy.

Topics: Adult; Betamethasone; Female; Humans; Hyperthyroidism; Lupus Erythematosus, Systemic; Methimazole; Prednisolone

Topics: Carbimazole; Female; Humans; Hyperthyroidism; Maternal-Fetal Exchange; Methimazole; Pregnancy; Pregnancy Complications; Scalp

We have used a method based on a perchlorate discharge test to estimate the duration of antithyroid effect of two doses of methimazole (MMI). Six patients with diffuse toxic goitre took 5 mg MMI twice daily and six took 20 mg twice daily over the study period of 12 weeks. Biochemical control of hyperthyroidism was achieved in all patients and thyroid hormone supplementation was required by all of the patients in the higher dose group to avoid hypothyroidism. Discharge of radioiodine from the thyroid by perchlorate diminished in both groups with time after MMI. After 5 mg MMI, perchlorate discharge as a percentage of the 30-min uptake (mean +/- SD), was 81.7 +/- 3.3% at 2.2 h, 69.3 +/- 18.9% at 5.9 h, 22.6-23.4% at 13.4 h and 2.7-6.7% at 25.1 h. After 20 mg MMI, the discharge was 92.5 +/- 1.9% at 2.2 h, 84.3 +/- 8.8% at 6.3 h, 64.8 +/- 24.1% at 13.3 h and 26.9-29.4% at 25.1 h. Only four patients (one in the lower dose group) showed a detectable discharge at 25 h and one of the patients treated with the lower dose showed no discharge at 13 h. These estimates of the effect of MMI on thyroidal iodide organification are not in keeping with published thyroidal MMI concentrations which do not show a fall between 3-6 h and 17-20 h after carbimazole. The explanation for this disparity is not clear but may be based on a redistribution of thioureylenes within the thyroid with time after dosage.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Humans; Hyperthyroidism; Iodides; Iodine Radioisotopes; Methimazole; Middle Aged; Thyroid Gland; Time Factors

Topics: Antithyroid Agents; Female; Graves Disease; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil

Topics: Adrenal Cortex Hormones; Amiodarone; Antithyroid Agents; Humans; Hyperthyroidism; Ipodate; Lithium; Methimazole; Propranolol; Propylthiouracil; Thyroxine; Triiodothyronine

Seven hyperthyroid patients were studied by repeated muscle biopsies (vastus lateralis) before and after a period of medical treatment which averaged 10 months. The biopsies were analysed with regard to fibre-type composition, fibre area, capillary density, glycogen content and enzyme activities representing the glycolytic capacity (hexokinase, 6-phosphofructokinase), oxidative capacity (oxoglutarate dehydrogenase, citrate synthase) and Ca2+- and Mg2+-stimulated ATPase in muscle. In the pretreatment biopsy (hyperthyroid state), there was a significantly lower proportion of type I fibres (30% vs. 41%), a higher capillary density (23%), lower glycogen content (33%), and higher hexokinase activity (32%) compared with the post-treatment biopsy. No significant changes in the activity of the remaining enzymes were observed. The present study indicates that hyperthyroidism induces a transformation from type I to type II fibres in human skeletal muscle. The increase in hexokinase activity probably reflects a higher glucose utilization by skeletal muscle in order to compensate partially for the reduced glycogen content.

Topics: Adult; Biopsy; Ca(2+) Mg(2+)-ATPase; Calcium-Transporting ATPases; Citrate (si)-Synthase; Female; Glycogen; Hexokinase; Humans; Hyperthyroidism; Ketoglutarate Dehydrogenase Complex; Male; Methimazole; Middle Aged; Muscles; Phosphofructokinase-1; Thiouracil

Nuclear binding of [125I]T4 in human mononuclear blood cells was examined in six hyperthyroid and six hypothyroid patients before and after treatment. In hypothyroid patients the nuclear T4 binding was initially increased and subsequently normalized as the patients became euthyroid suggesting a homeostatic counter-regulation. The thyroid state did not affect the nuclear T4 binding in hyperthyroid patients. Treatment with methimazol however increased the nuclear T4 binding, suggesting either a direct effect of methimazol on the hormone-receptor interaction or that the patients had become slightly hypothyroid during the treatment. The TSH was shown not to affect nuclear T4 binding. The thyroid state of the patients did not significantly affect the nuclear accumulation of the T3 produced intracellularly by deiodination of T4.

Topics: Adult; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Middle Aged; Monocytes; Receptors, Cell Surface; Receptors, Thyroid Hormone; 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

A 40 year-old woman with a rapidly progressive proximal muscle deficit of all four limbs had an acute myopathy secondary to hyperthyroidism. Biopsy of the quadriceps femoris revealed signs of non specific muscle impairment with type II fiber atrophy. Treatment with methimazole and correction of the thyroid condition led to rapid disappearance of the disorders. Eighteen months later the clinical status was normal and a second quadriceps femoris biopsy showed that the muscle had normalized.

Topics: Acute Disease; Adult; Female; Humans; Hyperthyroidism; Methimazole; Muscles; Muscular Diseases

In 20 patients with hyperthyroidism the behaviour of the agglomeration of leucocytes as well as of the adhesivity before and after the methimazol therapy was investigated. The agglomeration of leucocytes was directly inhibited neither by the overfunction of the thyroid gland nor by methimazol. By means of a stimulation test an undisturbed ability of leucocytic activation in hyperthyroidism could be proved. The adhesivity at the glass slide, however, was slightly restricted in untreated hyperthyroidism. It normalized under thyrostatic therapy.

Topics: Adolescent; Adult; Aged; Female; Humans; Hyperthyroidism; Leukocyte Count; Leukocytes; Male; Methimazole; Middle Aged; Thyroid Hormones

Topics: Adolescent; Adult; Aged; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Plasmapheresis; Preoperative Care

Topics: Female; Humans; Hyperthyroidism; Infant, Newborn; Maternal-Fetal Exchange; Methimazole; Pregnancy; Pregnancy Complications; Thyrotropin

Blood urea nitrogen (BUN/creatinine ratio was abnormally high (24.8 +/- 0.6) in untreated hyperthyroid patients due to both increase in BUN and decrease in creatinine concentration. BUN, creatinine and BUN/creatinine ratio were all completely normalized after restoration of euthyroid status. On the other hand, BUN/creatinine ratio was slightly suppressed in hypothyroidism before treatment and it was reversed by thyroxine treatment (12.6 +/- 4.0 and 16.3 +/- 3.3, before and after treatment, respectively). An age-related increase in BUN/creatinine ratio, which was primarily due to an age-related increase in BUN, was also found in hyperthyroid subjects (21.9 +/- 2.8 vs 27.7 +/- 9.0; first vs fifth decade) and in normal controls (13.7 +/- 2.8 vs 16.0 +/- 2.9; first vs fifth decade). To elucidate reasons for abnormal increase in BUN/creatinine ratio in hyperthyroidism, measurement of cardiac output and kinetic analysis on urea nitrogen (UN) and creatinine were performed. The results indicated a marked increase in cardiac output. Serum creatine concentration was clearly increased in hyperthyroid patients. Thus, serum creatinine concentration was suppressed due to a decrease in creatinine synthesis and an increase in renal creatinine excretion. BUN was high, primarily due to an increase in UN production secondary to excessive protein catabolism together with insufficient excretion of UN.

Topics: Adolescent; Adult; Age Factors; Blood Urea Nitrogen; Cardiac Output; Creatinine; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Thyroxine; Triiodothyronine

The authors report a further case of methimazole-associated liver damage and present a brief review of eleven previous cases found in the literature. The main clinical features of this 58-year-old female patient were laboratory evidence of leucopenia and cholestasis, and biopsy features of fatty liver parenchyma degeneration with granulocytic portal infiltration and bile stasis, demonstrated 20 days after the initiation of antithyroid therapy with 20 mg methimazole daily. An immediate cholestatic liver reaction was also provoked by drug rechallenge, with spontaneous amelioration of signs and symptoms after drug discontinuation.

Topics: Cholestasis, Intrahepatic; Female; Humans; Hyperthyroidism; Liver; Methimazole; Middle Aged

Serum and urinary concentrations of methimazole (MMI) were measured by high-performance liquid chromatography (HPLC) with an electrochemical detector (ECD) in 10 normal subjects and 43 hyperthyroid patients after intravenous and oral administration of the drug. The pharmacokinetic parameters of MMI were estimated in 5 normal subjects and 15 hyperthyroid patients according to a two-compartment model after intravenous injection of a 10 mg dose. The mean half-life of the distribution phase (T1/2 alpha) was 2.7 +/- 1.0 h (mean +/- SD) and 3.1 +/- 1.4 h and that of the slower-phase (T1/2 beta) was 20.7 +/- 9.6 h and 18.5 +/- 12.9 h in normal subjects and hyperthyroid patients, respectively. There were no significant differences between pharmacokinetic parameters of normal subjects and those of hyperthyroid patients. No correlations between free T4 index (FT4I) and pharmacokinetic parameters were observed. Maximum serum MMI concentrations (Cmax) (213 +/- 84 and 299 +/- 92 ng/ml) were attained 1.8 +/- 1.4 h and 2.3 +/- 0.8 h after a single dose of 10 mg in 5 normal subjects and in 15 hyperthyroid patients, respectively. In hyperthyroid patients the time taken to reach the peak concentration (Tmax) after a single dose of 10 mg was similar to that after a single 15 mg and 30 mg dose. The pharmacokinetic parameters, except Cmax and the area under the curve (AUC), were not affected by the administered dose and those, except Cmax, were not affected by the thyroid function. All urine was collected at intervals of 3 h for the first 12 h and then at 24 h and 48 h after intravenous and oral administration of MMI. In all subjects, MMI rapidly appeared in the urine and the rate of excretion was highest in the first 3 h. The cumulative urinary excretion of MMI was 5.5-8.5% of administered doses in normal subjects and hyperthyroid patients. These findings in the present study are compatible with the assumption that the extent of absorption of MMI is high, if not complete, and hyperthyroidism does not affect the kinetics of MMI, and that interindividual variation is observed in the time taken to reach the peak concentration after oral administration.

Topics: Administration, Oral; Adolescent; Adult; Aged; Chromatography, High Pressure Liquid; Female; Humans; Hyperthyroidism; Injections, Intravenous; Kinetics; Male; Metabolic Clearance Rate; Methimazole; Middle Aged

Topics: Female; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil

Two cases of the apathetic form of thyrotoxicosis in women aged 39 and 54 were described. The disease was characterized by the absence of typical signs of thyrotoxicosis in the presence of ptosis, cardiovascular disorders and thyrotoxic myopathy confirmed by EMG findings. Clinical symptoms were not registered after surgical therapy or chemotherapy with mercazolyl.

Topics: Adult; Face; Female; Humans; Hyperthyroidism; Methimazole; Middle Aged; Thyroidectomy

Topics: Antithyroid Agents; Humans; Hyperthyroidism; Methimazole; Postoperative Complications; Premedication; Thyroid Crisis; Thyroid Hormones

The thyreostatic therapy of a hyperthyroidism in coincident chronic hepatopathy is problematic. On the one hand, this therapy may be an additional load, particularly by the development of a cholestasis for the ill liver. On the other hand, due to the hyperthyroidism disturbance of the liver function and liver diseases up to cholestatic hepatitis may develop. At the instance of two patients with liver cirrhosis, whose simultaneous hyperthyroidism was treated thyreostatically, the therapeutic problems are represented. On the basis of the treatment of a not small number of patients with this constellation of findings we recommend the use of Thiamazol as therapy of choice in the at present, usual lower initial dosage. If functional disturbances of the liver and other side effects appear under this therapy, the radio-iodine therapy offers itself as alternative.

Topics: Adult; Antithyroid Agents; Female; Humans; Hyperthyroidism; Liver Cirrhosis; Male; Methimazole; Middle Aged

The effects of thyroid and gonadal status on the content of substance P in the anterior pituitary (AP-SP) were examined in prepubertal rats. A sex difference in AP-SP is evident by age 50 days [males, 287 +/- 35 fmol/mg protein (mean +/- SE); females, 103 +/- 17; P less than 0.05], and this difference becomes greater by 75 days (males, 543 +/- 54; females, 146 +/- 11.5; P less than 0.01). Hypothyroidism was induced in male and female pups by giving lactating dams 0.1% methimazole (wt/vol) in their drinking water after parturition. There was a marked and significant increase in AP-SP in 21-day-old hypothyroid compared to euthyroid control pups. Male pups were made thyrotoxic by daily treatment with T4 (10 micrograms/rat, sc) from age 8 to 15 days. AP-SP was 4 times lower in the thyrotoxic than in the euthyroid pups (P less than 0.001). Rats ovariectomized at age 22 days and killed on day 35 revealed no change in AP-SP, in contrast to the rise in AP-SP in the ovariectomized adult rat. Female pups were treated with dihydrotestosterone (DHT; 50 micrograms/day) or testosterone (50 micrograms/day) from age 8-20 days. Neither androgen induced a change in AP-SP. Female pups which received estradiol (E2; 0.5 micrograms/day) or testosterone (75 micrograms/day) from age 8-20 days also had no change in AP-SP. As opposed to the lack of effect of E2 and DHT on AP-SP in female rats younger than 22 days, E2 (1 microgram/100 g BW daily) caused a decrease and DHT (100 micrograms/100 g BW daily) caused an increase in AP-SP in female rats treated from 22-35 days of age [E2, 91 +/- 6.9; DHT, 226 +/- 31 (P less than 0.05 vs. control for both); control, 154 +/- 13]. We conclude that the responsiveness of AP-SP to alterations in thyroid status is present at the youngest age studied. In contrast, the responsiveness of AP-SP to changes in the levels of gonadal steroids is absent in the infantile period and requires a maturational process that becomes evident during the juvenile state of sexual development.

Topics: Androgens; Animals; Diethylstilbestrol; Dihydrotestosterone; Estradiol; Estrogens; Female; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Orchiectomy; Ovariectomy; Pituitary Gland, Anterior; Rats; Sex Factors; Sexual Maturation; Substance P; Testosterone; Thyroid Hormones; Thyroxine

Topics: Animals; Antithyroid Agents; Autoantibodies; Autoimmune Diseases; Carbimazole; Graves Disease; Humans; Hyperthyroidism; Immunity, Cellular; Immunosuppressive Agents; Methimazole; Propylthiouracil; Thiourea; Thyroid Hormones

Thyroidal binding of iodide was studied by kinetic analysis of [123I]iodide uptake and its discharge by perchlorate in 80 hyperthyroid subjects receiving antithyroid drug therapy. Five dosage regimens ranging from 5 mg carbimazole twice daily to 15 mg methimazole twice daily were studied. Binding inhibition was estimated at 5-7 h after drug as an index of the mean effect of the 12 hourly regimen. In all cases, except one in the lowest dose group, binding was found to be markedly reduced with mean binding rates ranging from 0.002 to 0.020 min-1 (normal greater than 0.15 min-1). The net clearance of iodide in the lowest dose group was reduced to a mean value near the upper limit of the euthyroid range, whereas in the highest dose group it lay at the lower limit of the euthyroid range. These results were reflected in the serum thyroid hormone response. There was a reducing incidence of inadequate control of hyperthyroidism and an increasing incidence of hypothyroidism with increasing thiourylene dose. The exit rate constant of free iodide for the various doses showed values from 0.048 to 0.055 min-1. Corresponding mean values for the discharge rate constant after perchlorate were 0.087 to 0.105 min-1. This suggests that perchlorate increases the rate of iodide release from the thyroid gland. Studies at a later interval after drug (12-14 h) showed no change in discharge rate constant. This leads to the conclusion that perchlorate may further inhibit iodide binding in subjects receiving antithyroid drug therapy.

Topics: Antithyroid Agents; Carbimazole; Dose-Response Relationship, Drug; Humans; Hyperthyroidism; Iodides; Iodine Radioisotopes; Kinetics; Methimazole; Perchlorates; Sodium Compounds; Thyroid Gland; Thyroid Hormones

Hyperthyroidism occurred following primary hypothyroidism in a 46-year-old man with serologically and histologically proved chronic lymphocytic thyroiditis. Repeated thyroid biopsy specimens revealed that histologic features compatible with chronic lymphocytic thyroiditis seen at the initial hypothyroid state subsequently underwent a remarkable resolution, with titers of circulating antithyroid antibodies being reduced in correspondence with the histologic improvement. This case shows that primary hypothyroidism in adults can spontaneously evolve into a hyperthyroid state, as has been suggested previously, and that the histologic abnormalities in chronic lymphocytic thyroiditis may not necessarily be irreversible.

Topics: Antibodies; Follow-Up Studies; Humans; Hyperthyroidism; Hypothyroidism; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Thyroid Gland; Thyroiditis; Thyroxine

Topics: Autoantibodies; Graves Disease; Humans; Hyperthyroidism; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Methimazole; Receptors, Cell Surface; Receptors, Thyrotropin; Thyroid Gland; Thyroidectomy

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

Plasma fibronectin concentrations up to 85 mg/100 ml were found in hyperthyroid patients. There was a significant correlation between free thyroxine index and plasma fibronectin values. Hypothyroid patients had low to normal fibronectin concentrations. Parallel decreases of thyroid hormones and plasma fibronectin concentrations were noted during treatment with thiamazole. A direct effect of thyroid hormones on fibronectin synthesis seems probable.

Topics: Adult; Aged; Female; Fibronectins; Humans; Hyperthyroidism; Hypothyroidism; Methimazole; Middle Aged; Prealbumin; Thyroid Diseases; Thyroid Function Tests; Thyroxine

The modification of behavior caused by hypo and hyperthyroidism were studied when the schedule of reinforcement was changed from a fixed ratio to a fixed interval. The conditions of hypo and hyperthyroidism were obtained with a chronic administration of methimazole and of 1-thyroxine. The level of the modifications of thyroid activity was determined by evaluation of the basal metabolic rate and of the plasma levels of T4. Hyperthyroidism caused no modification of the rat behaviour. A difficulty in adapting to the new experimental situation (learning) was found in hypothyroidism. This effect is evident in high hypothyroidism. In low hypothyroidism a depression of the rat behaviour may interfere with the modification of the learning process.

Topics: Animals; Behavior, Animal; Hyperthyroidism; Hypothyroidism; Kinetics; Male; Methimazole; Rats; Rats, Inbred Strains; Reinforcement Schedule; Thyroxine

Topics: Agranulocytosis; Female; Humans; Hyperthyroidism; Methimazole; Middle Aged; Thyroid Crisis

Topics: Carbimazole; Female; Humans; Hyperthyroidism; Infant, Newborn; Methimazole; Pregnancy; Pregnancy Complications; Scalp; Teratogens

Topics: Adolescent; Adult; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Middle Aged

Topics: Adrenal Cortex Hormones; Adult; Aged; Drug Therapy, Combination; Female; Humans; Hyperthyroidism; Length of Stay; Male; Methimazole; Middle Aged; Preoperative Care; Prospective Studies; Thyroid Hormones; Thyrotropin

Topics: Adult; Antithyroid Agents; Arthritis, Rheumatoid; Complement System Proteins; Female; Humans; Hyperthyroidism; Methimazole; Propylthiouracil; Thyroxine; Triiodothyronine

Topics: Abortion, Spontaneous; Adolescent; Adult; Anovulation; Antithyroid Agents; Female; Humans; Hyperthyroidism; Infertility, Female; Menstruation Disturbances; Methimazole; Ovulation; Pregnancy

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 patient with inappropriate thyrotrophin (TSH) secretion is described. She initially presented with classical hyperthyroidism during pregnancy, responded to propylthiouracil and, subsequently, had a normal delivery. Hyperthyroidism persisted and 7.5 months later a subtotal thyroidectomy was performed. After a further 16 months, mild symptoms of hyperthyroidism recurred. She again responded to propylthiouracil, but developed galactorrhoea. At that stage, it was noted that she had persistently elevated circulating TSH in the presence of elevated T4 and T3 levels. Her symptomatology was mild, although objective indices of thyroid activity, including pulse rate, BMR, sex hormone binding globulin and cholesterol, were indicative of hyperthyroidism. CT scan and tomography of the sella were normal. She had a markedly exaggerated TSH response to thyrotrophin releasing hormone (TRH). Basal TSH and responsiveness to TRH was suppressed by high dose dexamethasone. The TSH response to TRH was partially suppressed by exogenous T3, but there was no effect on basal TSH levels. TSH also decreased slightly with L-dopa and bromocriptine. Circulating TSH rose markedly during methimazole administration. TSH alpha and beta subunits were elevated and appropriate for the high TSH. In addition, both subunits increased following TRH. The patient had basal hyperprolactinaemia with an impaired prolactin (PRL) response to TRH and metoclopramide. PRL suppressed with L-dopa and bromocriptine. The remaining anterior pituitary function was intact. Most of the laboratory findings argue against the presence of a TSH producing pituitary tumour and the most likely cause for inappropriate TSH secretion in this patient is selective resistance of the thyrotroph to thyroid hormones. A mild element of peripheral resistance might also be present. The hyperprolactinaemia could be related to lactotroph resistance to thyroid hormone. The complexities of treatment in this patient are stressed. Therapy was initially attempted with low dose dexamethasone, but this had no effect. T3 treatment produced an exacerbation of her symptomatology and did not influence basal TSH, thyroid hormones, or 131I uptake. Bromocriptine administration for 11 months partially suppressed basal TSH without influencing T3 and there was an increase in T4. Methimazole did decrease her T4 and T3, but TSH and PRL rose to even greater levels. Her hyperthyroidism was eventually controlled with an ablative dose of 131I. Thyroid horm

Topics: Adult; Bromocriptine; Dexamethasone; Female; Humans; Hyperthyroidism; Methimazole; Prolactin; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

Six hundred and forty-three neonates from mothers with Graves' disease were examined for major malformations of external organs to compare the influence of maternal hyperthyroidism vs. ingestion of methimazole (MMI) during the first trimester on the incidence of congenital malformations. The subjects were divided into four groups according to maternal therapy and thyroid status during the first trimester as follows: (1) infants whose mothers did not receive MMI and were hyperthyroid (Group 1), (2) infants whose mothers did not receive MMI and were euthyroid (Group 2), (3) infants whose mothers received MMI and were hyperthyroid (Group 3) and (4) infants whose mothers received MMI and were euthyroid (Group 4). The prevalence of malformed infants in these four groups was 6.0% (three of 50), 0.3% (one of 350), 1.7% (two of 117) and 0.0% (none of 126), respectively. The incidence in Group 1 was significantly higher than that in Group 2 (P less than 0.01). There was no discernible dose dependency of MMI on the occurrence of malformations. These findings suggest that maternal uncontrolled hyperthyroidism may cause congenital malformations and that the beneficial role of MMI treatment outweighs its teratogenic effect, if any.

Topics: Abnormalities, Drug-Induced; Congenital Abnormalities; Dose-Response Relationship, Drug; Female; Humans; Hyperthyroidism; Infant, Newborn; Maternal-Fetal Exchange; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First

Psychopathology, psychometric variables, central arousal and time experience were studied in 30 hyperthyroid female outpatients. While these patients could be significantly discriminated in several of the above-described measures during the acute state of the disease, the intergroup differences disappeared after thyreostatic therapy. The thyroxine level was correlated with elevated beta-activity and the latter with variables of psychopathology and time experience. Hormonal dysbalance in hyperthyroidism is discussed as a biological substrate for neurophysiological changes which in turn causes deterioration in mood and behavior.

Topics: Adult; Arousal; Electroencephalography; Female; Flicker Fusion; Humans; Hyperthyroidism; Methimazole; Middle Aged; Neurocognitive Disorders; Psychopathology; Time Perception; Trail Making Test

An improved method for plasma methimazole assay using high performance liquid chromatography is described. The plasma samples were treated with sodium bisulfite and ammonium sulfate prior to extraction with chloroform. This pretreatment of the samples raised the extraction coefficient to 90%, while simple extraction yielded only 55%. The minimal detection limit was 0.02 microgram/ml, and the coefficient of variation at the level of 0.2 and 1.0 microgram/ml was less than 5%. Pharmacokinetics of methimazole was studied after a single oral dose (20 mg/m2) in six subjects including two healthy adults and four thyrotoxic children. Plasma levels of methimazole showed a peak concentration of 1.03 +/- 0.25 microgram/ml approximately one hour after the drug administration. Plasma half-life, area under the curve and distribution volume were 4.56 +/- 0.71 hr, 7.05 +/- 0.95 microgram/ml X hr, and 630 +/- 110 ml/kg respectively.

Topics: Adolescent; Adult; Child; Chromatography, High Pressure Liquid; Drug Stability; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged

Topics: Adult; Aldosterone; Angiotensin II; Humans; Hyperthyroidism; Methimazole; Middle Aged

In the antithyroid drug therapy, an initial treatment with low doses (10-15 mg) of methimazole (MMI) leads to satisfactory improvement in nearly all cases and even 5 mg MMI are sufficient in more than 50% of all patients. Additional intake of thyroid hormones (Th) is not necessary, if the MMI-dosage is reduced accordingly to the individual course of treatment. Consequent follow -up is to recommend anyway, particularly under the higher MMI-doses and in the first time, respectively. Consecutive measurement of total T-3 helps in assessment of euthyroidism under treatment, whereas the response to MMI is indicated more correct by total T-4. Serial determinations of serum-TSH are very helpful to decide about the cessation of treatment. If any goitre growth occurs, it seems not to be TSH-mediated in every case. Skin reactions as side-effect of high MMI-doses can be prevented by use of low doses.

Topics: Adult; Aged; Female; Goiter; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Propranolol; Thyrotropin; Thyroxine

A combination of antithyroid drugs and thyreoidine appears to be the optimal preoperative treatment for patients with thyrotoxicosis. A combination of methimazole and thyroid in adequate dosages can eliminate thyrotoxicosis and prevent postoperative reactions and increased intraoperative bleeding.

Topics: Adrenal Cortex Hormones; Adrenal Insufficiency; Humans; Hyperthyroidism; Iodine; Methimazole; Postoperative Complications; Preoperative Care; Thyroid Crisis; Thyroid Hormones; Time Factors

Using a quantitative immunocytochemical technique, antral gastrin cell populations in the rat were studied in various states of thyroid function. Simultaneous determinations of circulating serum gastrin were made by RIA. Rats made hypothyroid by ingestion of methimazole (0.01% solution in drinking water for 30 days) demonstrated a significant 32% decrease in gastrin cell density (306 +/- 9/cm vs. 207 +/- 11/cm for controls) associated with a significant 50% decrease in serum gastrin (143 +/- 12 vs. 307 +/- 20 pg/ml for controls). Induction of hypothyroidism and hypoparathyroidism by surgical thyroparathyroidectomy resulted in similarly significant decreases in gastrin cell numbers (229 +/- 12/cm) and serum gastrin (169 +/- 14 pg/ml). Animals that underwent thyroparathyroidectomy followed by T4 replacement (2.5 micrograms/100 g X day, ip) for 30 days had a mean gastrin cell density that was not significantly different from that of controls; serum gastrin was decreased to 207 +/- 11 pg/ml. The administration of excess T4 (200 micrograms/100 g X day, ip) for either 15 or 30 days was associated with a significant increase in gastrin cell numbers (413 +/- 23/cm at 15 days; 352 +/- 21/cm at 30 days). Mean serum gastrin was increased by 82% after 15 days of T4 administration (558 +/- 51 pg/ml) and by 65% at 30 days (506 +/- 36 pg/ml). We conclude that T4 is trophic for gastrin cells in the rat.

Topics: Animals; Calcium; Female; Gastric Mucosa; Gastrins; Hyperthyroidism; Hypothyroidism; Methimazole; Pyloric Antrum; Rats; Rats, Inbred Strains; Thyroid Gland; Thyroxine

Topics: Abnormalities, Drug-Induced; Female; Humans; Hyperthyroidism; Infant, Newborn; Methimazole; Pregnancy; Pregnancy Complications; Skin Abnormalities

Topics: Antithyroid Agents; Female; Humans; Hyperthyroidism; Mental Disorders; Methimazole; Middle Aged

In discussing undesirable therapy effects by thyrostatics one must issue from the fact that the possible side effects have a different genesis and appear in different frequency. While pharmacodynamically caused therapy effects are generally to be avoided, when considering the pathophysiology of the regulation of the thyroid gland, this is not the case as to allergic side effects and only to a limited extent with regard to toxic side effects. Allergic side effects abruptly and suddenly appear and do not show any dependence on dosage. But for the greater part these side effects are harmless. Severe side effects are nearly without exception of toxic genesis. The decrease of the initial dose and the early transition to a still effective maintenance dose reduce the possibility of toxic complications. In case that side effects lead to a discontinuation of the corresponding thyrostatic, a change to a thyrostatic of another chemical group is possible and necessary.

Topics: Antithyroid Agents; Dose-Response Relationship, Drug; Humans; Hyperthyroidism; Methimazole; Methylthiouracil; Thyroid Hormones

A 47-yr-old woman who had previously received methimazole (MMI) treatment for hyperthyroidism was found to have glucagon binding autoantibodies in plasma. She had never received glucagon. The binding substances were detected in plasma at the time of a glucagon RIA. [125I]Glucagon binding was inhibited only by porcine glucagon and porcine glicentin, and dissociated at acid pH. The substances proved to be glucagon binding antibodies (immunoglobulin G, L-chain K-type), as determined by ammonium sulfate and radioprecipitation. There were no clinical manifestations related the presence of these autoantibodies. In a survey of 91 patients with thyroid disease, 3 patients whose plasma bound [125I]glucagon were identified among 41 with hyperthyroidism who were receiving MMI treatment. Such binding was not found in plasma from untreated hyperthyroid patients, those receiving propylthiouracil or those with chronic thyroiditis. These findings suggest that the development of glucagon antibodies in hyperthyroidism may be associated with MMI treatment.

Topics: Autoantibodies; Chromatography, Gel; Female; Glucagon; Humans; Hyperthyroidism; Immunosorbent Techniques; Methimazole; Middle Aged; Thyroiditis

A case of hyperthyroidism associated with pancytopenia has been reported. A 51-year-old woman was hospitalized for the investigation of struma, peripheral edema and fatigue. Hormonal studies revealed hyperfunction of the thyroid gland. Hematological examinations showed normocytic normochromic anemia, leukopenia and thrombocytopenia with hyperplastic bone marrow and increased serum iron levels. Elevations of the anti-thyroidal antibody and anti-microsomal antibody, and a decrease in CH50 titer were observed. A Coombs' test and anti-leukocytic antibody and anti-thrombocytic antibody tests were negative. The numbers of erythrocyte and thrombocyte were normalized after the administration of methimazole for three months as were the findings of the bone marrow and the serum iron level. However, leukopenia was maintained due to the effect of methimazole. It should be suggested that the etiology of pancytopenia might be due to hyperthyroidism. Although the mechanism of pancytopenia in a patient with hyperthyroidism is unclear, it might be related to the reduced life-span of whole blood components and/or partially to the autoimmune mechanism.

Topics: Female; Humans; Hyperthyroidism; Methimazole; Middle Aged; Pancytopenia

Long-Evans, male and female rats born of mothers kept on an iodide-rich diet prior to delivery and during lactation, were fed this diet after weaning, thus becoming slightly hypothyroid. A more severe hypothyroidism was also provoked with the chronic administration of methimazole to Long-Evans iodide-supplemented, or Charles River iodine-deprived pups through the first month of age. Additional Long-Evans rats were made hyperthyroid with a daily injection of triiodothyronine (T3) through the first 29 days of age. Severe hypothyroidism in both strains of rats markedly increased the density of serotonin type 1 (5-HT1) and type 2 (5-HT2) receptors in the brain (less cerebellum, corpus striatum and olfactory bulbs) at 31-32 days of age. Receptor alterations were not correlated to either the rise in thyrotropin (TSH) levels in hypothyroidism or the direct influence of residual methimazole after the last treatment, or to neonatal malnutrition. This increase in 5-HT receptor density might represent an adaptive (supersensitivity) postsynaptic response to the state of central serotonergic hypofunction occurring in hypothyroidism. Though receptor alterations might be important, their precise functional role in the etiogenesis of hypothyroid-associated mental disturbances is difficult to ascertain.

Topics: Animals; Animals, Newborn; Brain; Female; Hyperthyroidism; Hypothyroidism; Iodides; Male; Methimazole; Rats; Rats, Inbred Strains; Receptors, Serotonin; Spiperone; Triiodothyronine

2-Mercapto-1-methyl-5-methylmercapto-imidazole (13) was found in urine samples of man and rat after intake of thiamazole (1). It is assumed that the metabolite is produced via a N-oxidation intermediate enabling a nucleophilic attack at carbon-5 in the thiazole ring.

Topics: Animals; Dose-Response Relationship, Drug; Humans; Hyperthyroidism; Male; Methimazole; Methylation; Models, Biological; Oxidation-Reduction; Rats; Rats, Inbred Strains

Topics: Adult; Female; Humans; Hyperthyroidism; Methimazole; Serum Sickness

A 45-year-old woman with thyrotoxicosis developed agranulocytosis after treatment with propylthiouracil. When the thyrotoxicosis recurred, accompanied by a severe psychotic reaction, administration of antithyroid medication was recommenced. The patient was given methimazole instead of propylthiouracil but, 10 weeks later, agranulocytosis again occurred. This is, to the best of our knowledge, the first report of a case in which agranulocytosis followed treatment with both propylthiouracil and methimazole in the same patient.

Topics: Agranulocytosis; Female; Humans; Hyperthyroidism; Methimazole; Middle Aged; Propylthiouracil; Recurrence

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

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Thermography

Topics: Antithyroid Agents; Carbimazole; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Perchlorates; Propylthiouracil; Sodium Compounds

Subtotal tumour removal had been performed in a 34-year-old female patient for an extensive intra- and suprasellar expansive process. The considerably increased prolactin level did not decrease postoperatively, but normalised only after a three months bromocriptine treatment. The primary hyperthyroidism has been recovering after administering methimazolum. In a second case was reported on a 65-year-old female patient, suffering from rachitic dwarfism, stenosis of the aortic valve and tumour of the hypophysis, causing acromegaly, whose diabetes mellitus of contrainsular type could have been hardly balanced with insulin of a 128-unit-dose daily, and whose hyperthyroidism was due to an autonomous adenoma of the thyroid gland, first I-131 treatment was administered and she got into an euthyroid state. Six weeks following the removal of the acidophilic adenoma of the hypophysis administration of insulin could have been ceased, and the results of her growth hormone became normal. The clinical picture partly corresponds with Troell-Junet's syndrome.

Topics: Acromegaly; Adenoma; Adenoma, Acidophil; Adenoma, Chromophobe; Adult; Aged; Diabetes Complications; Female; Humans; Hyperthyroidism; Methimazole; Pituitary Neoplasms; Thyroid Neoplasms

During antithyroid drug therapy hyperthyroid patients with border-line elevated serum T3 had shortening of pre-ejection period (PEP) and QKd interval (period between the onset of QRS complex and the onset of the Korotkoff arterial sound). There was a significant relationship between PEP and QKd interval with serum T3 concentration in a group of patients under medical therapy; PEP and QKd were normalized later than serum thyroid hormone concentration in such patients. Propranolol induced a prolongation of PEP and QKd interval in hyperthyroid patients. PEP and QKd are sensitive measures of metabolic status in thyrotoxic patients during antithyroid treatment.

Topics: Heart Auscultation; Heart Sounds; Humans; Hyperthyroidism; Methimazole; Myocardial Contraction; Propranolol; Systole; Thyroid Function Tests; Thyroxine; Triiodothyronine

Topics: Carbimazole; Female; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Second; Propylthiouracil; Thyroidectomy

The kinetic profiles of oral methimazole 40 mg, propranolol 80 mg, metoprolol 100 mg and atenolol 100 mg were compared in hyperthyroid patients both during the hyper- and euthyroid states. for methimazole, neither the peak concentration (Cmax), the time to reach peak concentration (tmax), the elimination half-life (t 1/2) nor the area under the curve (AUC) value was affected by the hyperthyroid state. For propranolol and metoprolol, which undergo extensive presystemic clearance, the AUC values were lower (p less than 0.02) when the patients were hyperthyroid than when they had become euthyroid, but the t 1/2's were not significantly altered. For atenolol, there were no significant kinetic differences between the hyperthyroid and euthyroid states. The findings are compatible with the assumption that hyperthyroidism does not affect the kinetics of methimazole or atenolol, but that it may enhance presystemic clearance of propranolol and metoprolol.

Topics: Administration, Oral; Atenolol; Female; Humans; Hyperthyroidism; Kinetics; Male; Metabolic Clearance Rate; Methimazole; Metoprolol; Middle Aged; Propanolamines; Propranolol

In thyreostatic treatment the loss of taste combined with discreetly increasing hepatic enzymes has been observed as a toxic effect of thiamazole in a female patient. Sense and hepatic enzymes normalized rapidly after discontinuing use of thiamazole.

Topics: Adult; Ageusia; Female; Humans; Hyperthyroidism; Liver; Methimazole; Taste Disorders

Topics: Adult; Creatine Kinase; Humans; Hyperthyroidism; Male; Methimazole; Muscle Spasticity; Recurrence

Topics: Adult; Female; Humans; Hyperthyroidism; Methimazole; Propranolol; Urticaria

Two patients with overproduction of thyroid-stimulating hormone (TSH) are described. The first patient, a 25-year-old man with recurrent hyperthyroidism, had a pituitary adenoma and highly elevated levels of TSH. While the patient was receiving 0.3 mg of thyroid daily, and basal TSH level was 161 microM/ml. Despite an increase in the thyroid hormone therapy, serum TSH levels remained elevated. The administration of thyrotropin-releasing hormone (TRH) or dexamethasone resulted in no changes in TSH level. The second patient was an 18-year-old man who had inappropriately elevated levels of TSH 3 months after radioiodine therapy for hyperthyroidism. A gradual increase in thyroid hormone replacement therapy decreased the serum TSH levels from 250 to 14.8 microM/ml. The administration of TRH led to huge increases of TSH. Dexamethasone inhibited basal TSH but not TRH-stimulated TSH levels. The overproduction of TSH was attributed to autonomous, neoplastic secretion in the first case and to partial, selective pituitary thyrotroph resistance to thyroid hormone in the second.

Topics: Adenoma; Adolescent; Adult; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Pituitary Neoplasms; Sphenoid Sinus; Thyrotropin; Thyroxine; Triiodothyronine

Topics: Bis-Trimethylammonium Compounds; Humans; Hyperthyroidism; Methimazole; Postoperative Care; Preoperative Care; Propranolol

Nine healthy female controls and 10 hyperthyroid female patients were studied. The intravenous administration of 200 mg cimetidine, an H2-receptor antagonist, was followed by a significant and marked rise in serum prolactin levels in all control subjects. There was no significant difference in serum PRL response to cimetidine injection between the euthyroid controls and hyperthyroid patients. But max delta PRL, the change from basal to peak values, is significantly lower in the hyperthyroid patients than in the controls. There was a significant negative correlation between max delta PRL and serum T4 or T3 levels in hyperthyroid patients before and after treatment with MMI or PTU. It appears from our data that cimetidine induced PRL release was blunted in hyperthyroid patients.

Topics: Adult; Cimetidine; Female; Guanidines; Humans; Hyperthyroidism; Kinetics; Methimazole; Prolactin; Propylthiouracil; Thyroxine; Triiodothyronine

Topics: Aged; Autoimmune Diseases; Chemical and Drug Induced Liver Injury; Female; Humans; Hyperthyroidism; Insulin Antibodies; Methimazole; Propylthiouracil

Topics: Adult; Agranulocytosis; Colony-Forming Units Assay; Humans; Hyperthyroidism; Lymphocyte Activation; Male; Methimazole

Topics: Adult; Aged; Cholestasis, Intrahepatic; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Propranolol

A patient experienced three separate episodes of apathetic hyperthyroidism. Each time, this clinical picture appeared after the patient had been euthyroid for one to three months and within one to three weeks of discontinuing antithyroid drug therapy. This rapid recurrence of apathetic hyperthyroidism represents evidence against the concept that this disorder represents "burnt-out," or exhaustion of, body reserves in long-standing, untreated hyperthyroidism. Initial recognition and diagnosis of thyrotoxicosis was delayed by contamination of her serum from therapeutic radioactive iodine and possible interference with thyroxine radioimmunoassay. The solution to this problem with double isotope counting is discussed.

Topics: Aged; Antithyroid Agents; Exophthalmos; Face; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Middle Aged; Personality Disorders; Recurrence; Thyroid Function Tests

Topics: Antithyroid Agents; Carbimazole; Female; Fetus; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Infant, Newborn, Diseases; Methimazole; Pregnancy; Pregnancy Complications; Propranolol; Propylthiouracil; Thyroid Diseases; Thyroid Gland

Topics: Antithyroid Agents; Drug Therapy, Combination; Humans; Hyperthyroidism; Methimazole; Premedication; Preoperative Care; Thyroid Hormones

Topics: Adult; Antithyroid Agents; Carbimazole; Female; Fetus; Humans; Hyperthyroidism; Infant, Newborn; Male; Methimazole; Pregnancy; Pregnancy Complications

Total hexokinase levels (units/g tissue) have been measured during postnatal development of the cerebellum in control, hypothyroid, and hyperthyroid rats. In addition. distribution of hexokinase in the developing cerebellum has been observed with an immunofluorescence method. Hypothyroidism delays the normally observed postnatal increase in total hexokinase activity, whereas hyperthyroidism accelerates the increase. In normal animals, hexokinase levels in maturing Purkinje cells pass through a transient increase, with maximal levels at approximately 8 days postnatally followed by rapid decline to relatively low levels by 12 days; hypothyroidism delays this transient increase and subsequent decline, but hyperthyroidism does not appear to affect markedly the timing of this phenomenon. Cerebellar glomeruli are relatively enriched in hexokinase content, as judged by their intense fluorescence. Hypothyroidism delays the development of intensely stained glomeruli. Hyperthyroidism did not appear to cause precocious increase in numbers of glomeruli but may have increased the rate at which the hexokinase was assimilated by newly formed glomeruli. The effects of hypo- and hyperthyroidism on total cerebellar hexokinase levels are interpreted in terms of the effect of thyroid hormone on the biochemical maturation of synaptic structures rich in hexokinase.

Topics: Animals; Cerebellum; Fluorescent Antibody Technique; Hexokinase; Hyperthyroidism; Hypothyroidism; Methimazole; Purkinje Cells; Rats; Thyroxine

Topics: Adult; Female; Humans; Hyperthyroidism; Methimazole; Middle Aged; Myotonic Dystrophy

Myelinogenesis was studied in controls and in rats treated since birth with Methimazole (hypothyroid) or thyroxine (hyperthyroid). The amount of myelin in forebrain and its protein composition were determined between 13 and 40 days of age, the period of most rapid myelin accumulation. Hypothyroid rats had reduced on both and brain weights relative to controls and the yield of myelin was reduced on both a per brain and a per milligram brain protein basis. Developmental changes in the protein composition of isolated myelin followed the pattern of control animals (the percentage of total myelin protein present as proteolipid protein, large basic protein, and small basic protein increased, as did the ratio of proteolipid/large basic protein) but were delayed temporally by 1-2 days. Hyperthyroid rats also had reduced body and brain weights. At 13 days myelin accumulation was greater than that of controls, corresponding to an earlier initiation of myelination. At later ages myelin yield was reduced on a per brain basis but not on a per milligram brain protein basis. The developmental pattern of myelin protein composition was accelerated temporally by 1-2 days. Myelination in optic nerve, assayed by proteolipid protein content, also was slightly delayed in hypothyroid animals and somewhat accelerated in hyperthyroid animals. The relative synthesis of myelin proteins (determined as incorporation of intracranially injected [(3)H]glycine into myelin protein relative to incorporation into whole brain protein), as well as distribution of radioactivity among individual myelin proteins, was determined. The results supported the conclusion of the myelin protein accumulation study; hypothyroidism retards the developmental program for myelinogenesis, whereas in the hyperthyroid state myelin synthesis is initiated earlier but is also terminated earlier.

Topics: Animals; Brain; Hyperthyroidism; Hypothyroidism; Methimazole; Myelin Proteins; Myelin Sheath; Optic Nerve; Rats; Thyroxine

1 The effect of small doses of carbimazole on the binding rate constant of intrathyroidal iodide, plasma methimazole concentrations and circulating thyroid hormone concentrations in five hyperthyroid patients is presented. 2 In all patients there was a marked reduction in iodide binding with carbimazole doses as low as 5 to 10 mg daily. 3 In three patients little further reduction in the observed binding rate occurred with daily doses in excess of 10 mg despite progressive increases in plasma methimazole concentrations. 4 At the end of 4 weeks' treatment with 10 mg carbimazole daily, the reduction in thyroid hormone concentrations and clinical improvement were such as to suggest that this dose may be an effective starting dose in many patients.

Topics: Adult; Carbimazole; Female; Humans; Hyperthyroidism; Iodides; Methimazole; Middle Aged; Thyroid Gland

Topics: Amitriptyline; Animals; Caffeine; Diazepam; Hyperthyroidism; Hypothyroidism; Male; Memory; Methimazole; Rats; Rats, Inbred Strains; Thyroid Hormones; Thyroxine

Topics: Female; Humans; Hyperthyroidism; Male; Methimazole; Technetium; Thyroid Function Tests; Triiodothyronine

Topics: Child; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Methods; Prognosis; Technetium; Thioamides

The results of medical and surgical therapy were determined in 107 hyperthyroid children. After surgery, 85% of patients were rendered free of hyperthyroidism; however, 62% became hypothyroid. After medical treatment, 30% of patients were euthyroid and 2% became hypothyroid. The relapse rate, however, was higher after medical (22%) than after surgical (9%) therapy. Serious drug-related complications (arthritis-, hepatitis-, and collagen disease-like syndromes) occurred in 14% of patients. Complications occurred in 9% of surgically treated patients, but recurrent laryngeal nerve injury or permanent hypoparathyroidism did not occur. In medically treated patients, both a goiter size less than three times normal prior to treatment and a reduction in goiter size to less than two times normal at the completion of therapy correlated with a successful outcome.

Topics: Adolescent; Arthritis; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Collagen Diseases; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Postoperative Complications; Propylthiouracil; Thyroidectomy

Topics: Adult; Amylases; Female; Humans; Hyperthyroidism; Methimazole

Topics: Adolescent; Adult; Aged; Antibodies; Antithyroid Agents; Carbimazole; Female; Follow-Up Studies; Humans; Hyperthyroidism; Hypothyroidism; Iodine; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Recurrence; Thyroid Gland; Thyroidectomy

Topics: Adult; Aged; Autoimmune Diseases; Carbimazole; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Middle Aged; Thyroidectomy; Thyroxine

Topics: Humans; Hyperthyroidism; Iodine; Lithium; Mercaptopurine; Methimazole; Postoperative Care; Preoperative Care; Propranolol; Propylthiouracil; Thyroidectomy

Topics: Adult; Blood Coagulation; Blood Coagulation Tests; Esterases; Female; Fibrinolysis; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Thyroidectomy

1 Methimazole plasma concentrations were measured in two groups of hyperthyroid subjects after the oral administration of either carbimazole or methimazole. 2 With the HPLC method it was also possible to measure the concentration of a methimazole metabolite, 3-methyl-2-thiohydantoin in one patient. 3 Large interindividual differences were observed, especially within the carbimazole group. 4 Incomplete absorption of carbimazole could explain particular high apparent volumes of distribution and apparent clearances.

Topics: Administration, Oral; Adolescent; Adult; Carbimazole; Female; Humans; Hyperthyroidism; Kinetics; Male; Methimazole; Middle Aged

1 A high performance liquid chromatographic (HPLC) method was used to study the pharmacokinetics of methimazole after oral administration of carbimazole to women in various stages of pregnancy. 2 In one patient it was possible to conduct the study in the first and third timesters: there was an appreciable increase in the apparent clearance of methimazole. 3 Based on the assumption of complete absorption and hydrolysis of carbimazole to methimazole the mean apparent clearance was found to be significantly higher in pregnant patients receiving 10 mg carbimazole than in non-pregnant patients receiving the same dose.

Topics: Administration, Oral; Adult; Carbimazole; Female; Humans; Hyperthyroidism; Kinetics; Methimazole; Pregnancy; Pregnancy Complications

Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Prognosis; Propylthiouracil; Retrospective Studies; Sex Factors; Time Factors; Triiodothyronine

The effectiveness of methimazole used in a single daily dose was studied in 47 patients during their initial episode of hyperthyroidism, and in an additional eight patients during a relapse of hyperthyroidism. All patients become euthyroid using this method. Mean time required to achieve a euthyroid state was 16.7+/-1.1 weeks in the former group, and 14.9+/-2.9 weeks in the latter. In one patient there was an initial response to single daily dose therapy, but subsequently split dosage was required for control. The single daily dose regimen of antithyroid drugs will control hyperthyroidism in most patients. We have found that propylthiouracil will achieve this more rapidly than methimazole.

Topics: Adolescent; Adult; Aged; Child; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged

rT3 metabolism in patients treated for thyrotoxicosis with prophylthiouracil (PTU), or methimazole (MMI) was studied by infusion of rT3 and measurements of the increase in serum rT3 and serum 3,3'-diiodothyronine. The results indicate that the high serum rT3 observed during treatment with PTU is not due to an increase in rT3 production, but to a decrease in the metabolic clearance rate of rT3. rT3 infusion was followed by an increase in serum 3,3'-T2 which was similar whether PTU or MMI was given. However, after stopping rT3 infusion there was a more rapid fall serum 3,3'-T2 during MMI treatment, compatible with an inhibitory effect of PTU on 3,3'-T2 degradation.

Topics: Adult; Aged; Diiodothyronines; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Propylthiouracil; Thyronines; Triiodothyronine; Triiodothyronine, Reverse

Topics: Adult; Drug Therapy, Combination; Humans; Hyperthyroidism; Iodine; Lithium; Methimazole; Middle Aged; Secretory Rate; Thyroid Hormones

Topics: Adult; Female; Follow-Up Studies; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Prospective Studies; Thyroid Function Tests; Thyroxine; Triiodothyronine

Topics: Acromegaly; Female; Growth Hormone; Humans; Hyperthyroidism; Menopause; Methimazole; Middle Aged; Prednisolone; Prolactin; Propylthiouracil; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

In 65 elderly hyperthyroid patients (age range 50-78 years), sex differences, signs and symptoms and thyroid function were studied and the data were compared with those on 48 young hyperthyroid patients (age range 20-29 years). The incidence of hyperthyroidism was 3.5 times higher in females than in males among the young patients, whereas it was approximately equal in males and females among the elderly patients. Signs and symptoms conformed with the textbook description in the young subjects but not in the elderly ones. Measurements of serum triiodothyronine (T3) and thyroxine (T4) proved useful in preventing false diagnoses in elderly patients with atypical symptoms. In some elderly subjects with marginal increases of serum T3 and T4 concentrations, measurement of serum thyroid-stimulating hormone (TSH) after administration of thyrotropin-releasing hormone (TRH) was required to achieve an accurate diagnosis. Serum T3 and T4 levels and the thyroidal uptake of radioiodine were slightly but not significantly lower in the elderly than in the young patients. A high titer of circulating thyroid auto-antibody in the elderly may be related to this slight decrease in thyroid function. Serum T3 levels were significantly lower in the elderly than in the young subjects; this suggests impairment of peripheral monodeiodination of T4. Any abnormal serum levels of T4, T3, and TSH before and after administration of TRH could easily be restored to normal by treatment with antithyroid drugs in the elderly patients.

Topics: Adult; Aged; Diagnosis, Differential; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

A 9-yr-old boy is described in whom increased serum T4 concentration, increased T3 uptake, and increased free T4 index were associated with a euthyroid clinical state with normal total serum T3. T4-binding globulin (TBG), measured by RIA, was decreased. Reverse flow paper electrophoresis of serum proteins after reaction with radioactively labeled T4 demonstrated increased binding of T4 to a protein with electrophoretic mobility corresponding to albumin. Displacement of serum protein-bo-nd [125I]T4 activity by increasing concentrations of T4 revealed the presence of a low affinity, high binding capacity system with an association constant similar to that of T4-binding prealbumin. This low affinity binding protein cochromatographed with TBG on a DEAE-Sephadex column which normally separates TBG from T4-binding prealbumin. At free T4 concentrations equivalent to those present in the plasma of normal individuals, the T4 bound to free ratio is higher in the patient than in normals and the total serum T4 level is increased in the presence of normal free T4 concentrations. The relative affinity of this abnormal T4-binding protein for T3 is low compared to that of TBG. The patient's father had the same abnormal binding protein, which was not found in his mother or fraternal twin brother. These data suggest an autosomal dominant mode of inheritance of an aberration leading to synthesis of a new protein instead of normal TBG. The new protein is different from TBG in electrophoretic mobility, T4 and T3 binding, and antigenic properties.

Topics: Child; Humans; Hyperthyroidism; Male; Methimazole; Methylphenidate; Thyroid Gland; Thyrotropin; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

Topics: Adolescent; Adult; Child; Female; Humans; Hyperthyroidism; Methimazole; Middle Aged; Myasthenia Gravis; Preoperative Care; Thymectomy

Thionamide drugs are widely used in the management of hyperthyroidism and are infrequently associated with adverse reactions. We report the development of the nephrotic syndrome during methimazole (Tapazole) therapy in a young man with Graves' disease. His proteinuria remitted promptly with discontinuance of the drug, and renal histologic features bore a striking resemblance to the toxic nephrosis induced in animals by the aminonucleoside of puromycin. In view of the histologic similarities, we propose that methimazole acted as a direct glomerular toxin, inducing the nephrotic syndrome in this patient.

Topics: Adult; Humans; Hyperthyroidism; Male; Methimazole; Nephrotic Syndrome

Topics: Adult; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Propylthiouracil; Thyroidectomy

The treatment of benign forms of thyroid disease is reviewed. Endemic goiter is a public health problem preventable by the addition of iodine to the food or water supply. Endemic and familial goiters are treated with replacement doses of I-thyroxine, as are sporadic colloid goiters and goiters resulting from chronic thyroiditis. Hyperfunctioning autionomous nodules without thyrotoxicosis and cystic nodules require no specific therapy. Prophylaxis against diffuse or nodular goiter after radiation to the head or neck for therapeutic purposes with thyroxine replacement therapy is debatable. All forms of hypothyroidism, including incipient types, require replacement thyroxine therapy, but this should be undertaken cautiously in older patients and in those with evidence of ischemic myocardial disease. Myxedema coma requires vigorous treatment and detailed supervision because of dismal mortality rates. Iodine 131 is the treatment of choice in diffuse toxic goiter, but alternative forms.

Topics: Adolescent; Adult; Female; Goiter; Humans; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Methimazole; Pregnancy; Propylthiouracil; Radiation Dosage; Thyroid Diseases; Thyroxine

The effect of endogenous thyroid stimulating hormone (TSH) on the thyroid secretion of triiodothyronine (T3) and thyroxine (T4) was evaluated by serial determinations of serum T3. T4 and TSH concentrations in the following groups of patients: a) three patients submitted to surgical removal of a solitary, autonomous thyroid nodule which had completely inhibited the extranodular tissue; b) five subjects, with the same disease, in whom functional recovery of the extranodular tissue was induced by increased circulating TSH levels, produced by treatment with methimazole; c) one patient submitted to hemithyroidectomy for multinodular goitre; d) two hyperthyroid patients who had been treated with methimazole. In all these patients serum T3 and T4 levels progressively decreased, with a consequent progressive increase in serum TSH concentrations, leading to stimulation of the thyroid gland. During this TSH-induced stimulation of thyroid tissue, a significant positive correlation was found between the serum TSH concentrations and the corresponding ratio between the serum levels of T3 and T4 (T3/T4), both within each patient group (P less than 0.001) and among all patients (P less than 0.001). The same correlation also governs the relationship between the TSH and the T3/T4 values of 34 euthyroid control subjects and one patient with incipient hypothyroidism. These data strongly suggest that endogenous TSH can induce a preferential secretion of T3 over T4 by the human thyroid.

Topics: Goiter; Goiter, Nodular; Humans; Hyperthyroidism; Methimazole; Thyroid Gland; Thyroidectomy; Thyrotropin; Thyroxine; Triiodothyronine

A hyperthyroid patient treated with methimazole for three weeks developed proximal muscle weakness, myalgia, arthralgia, and fever, and thyrotoxic myopathy was diagnosed. The signs and symptoms spontaneously abated when antithyroid medication was discontinued. This case identified a complication of thionamide treatment mimicking thyrotoxic myopathy and points to the therapeutic necessity of making such a differentiation.

Topics: Adult; Diagnosis, Differential; Female; Fever; Humans; Hyperthyroidism; Joint Diseases; Methimazole; Muscular Diseases; Pain

An account is given of incidence, diagnosis, therapy, and clinical peculiarities of hyperthyreosis in gravidity, with reference being made to literature as well as to the authors' own experience. It is strongly suggested that thyreostatic treatment may yield good success even under the conditions of gravidity, provided that certain peculiarities are taken into due consideration. Conclusions then are drawn for efficient organisation of medical attention to pregnant patients with thyroid diseases.

Topics: Abortion, Spontaneous; Body Weight; Female; Fetal Diseases; Fetus; Humans; Hyperthyroidism; Meningocele; Methimazole; Pregnancy; Pregnancy Complications; Thyroid Hormones

This paper deals with the activity of glucose-6-phosphate dehydrogenase in patients with hyper- and hypothyroidism as well as in hyperthyroxinaemic rats. The activity of glucose-6-phosphate dehydrogenase is enhanced in red blood cells of hyperthyreotic patients and hyperthyroxinaemic animals. The activity will be decreased to normal range in patients by administration of antithyreotic drugs, such as thiamazole. Patients with hypothyroidism exhibit decreased enzymatic activity. It is suggested that thyroid hormones stimulate the HMP-shunt in red blood cells as a defence mechanism against additional oxidative stress.

Topics: Animals; Erythrocytes; Female; Glucosephosphate Dehydrogenase; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Rats; Thyroid Diseases; Thyroxine

The "grasping reflex" test was performed in adult rats with altered thyroid function. Any modification of the thyroid activity (hyper or hypothyroidism) caused a prolongation of the grasping time. Our data indicate that the condition of hypo or hyperthyroidism induces behavioural modifications in the adult rats.

Topics: Animals; Foot; Forelimb; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Rats; Reflex; Thyroxine

A case of thyrotoxicosis associated with neuropathy and encephalomyelitis is reported which gradually improved as regards the hyperthyroidism and the neurological deficit during treatment with Tapazole. The possible role of the nervous system of an excess of thyroxine or an autoimmune factor as a cause of the involvement is discussed.

Topics: Adult; Encephalomyelitis; Humans; Hyperthyroidism; Male; Methimazole; Syndrome

In a young woman who presented with hyperthyroidism and autoimmune thrombocytopenic purpura, the platelet count returned to normal following successful treatment of the hyperthyroidism. Thromboagglutinins were present, the titer declining as the patient became euthyroid. A survey of the literature revealed 48 reports of hyperthyroidism and thrombocytopenia, these disorders coexisting in 37 patients and there being no apparent cause for the lowered platelet counts in 28 of them. The clinical features and response to treatment in the latter group and in our patient are reviewed, comprising a series of 29. Of 22 patients whose hyperthyroidism was adequately treated, platelet counts returned to normal in 18 (82%). In three patients the purpura remitted despite persistent thrombocytopenia. It is estimated that in 7% of patients with autoimmune thrombocytopenic purpura, thrombocytopenia responds to treatment of an underlying thyrotoxicosis and in many of these patients the thrombocytopenia will prove resistant to other forms of therapy.

Topics: Adult; Autoimmune Diseases; Female; Humans; Hyperthyroidism; Methimazole; Prednisone; Purpura, Thrombocytopenic; Thyroidectomy

Blood samples for determination of serum total and free reverse triiodothyronine (rT3), triiodothyronine (T3) and thyroxine (T4) were obtained daily in 6 previously untreated thyrotoxic patients during periods of propylthiourazil (PTU) (600 mg per day) or methimazol (MMI) (45 mg per day) administration. PTU induced about 60 per cent increase in both total and free serum rT3. This was accompanied by a rapid decrease in serum T3 and a more gradual decline in serum T4. MMI administration to untreated patients was followed by a gradual parallel decrease in rT3, T3 and T4. Turn from PTU to MMI produced a rapid decrease in serum rT3 and increase in serum T3 in all 6 patients. The relative variations in the free and total concentrations of iodothyronines were practically identical. The increase in serum rT3 after PTU is most likely explained either by enhanced deiodination of T4 to rT3 or by an inhibitory effect of PTU on rT3 degradation.

Topics: Adult; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Propylthiouracil; Thyroxine; Triiodothyronine

Lithium acetate treatment of 6 patients with hyperthyroid Graves' disease and 6 patients with toxic nodular goiter is reported. Lithium acetate was administered either as monotherapy (group A) or combined with 45 mg carbimazole or methimazole (group B). A control group of 8 patients received methimazole or carbimazole only (group C). Lithium either alone or combined with thionamide drugs consistently lowered serum thyroxine and triiodothyronine with marked clinical improvement. After 7 days of treatment thyroxine was reduced by 28% (group A), 43% (group B) and 36% (group C). The respective decrease in triiodothyronine was 42%, 50% and 46%. The differences between three groups were not statistically significant. We conclude that lithium is a useful antithyroid agent for selected patients, since it is safe and effective even in severe cases, does not interfere with radioiodine uptake for diagnostic or therapeutic purposes and provides an alternative for patients allergic to thionamides.

Topics: Acetates; Adult; Aged; Carbimazole; Drug Evaluation; Drug Therapy, Combination; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Lithium; Methimazole; Middle Aged

Absolute activity measurement of I-123 by coincidence counting was used to study the early thyroidal iodide uptake in 20 hyperthyroid children. Patients were pretreated either with methimazole or propylthiouracil before injection of Na123I. The usual method of analysis of the early uptake was modified to account for a rapidly equilibrating compartment, to give thyroidal iodide trapping rate constant (K1) and absolute iodide uptake (AIU). The suppressibility of the early uptake by triiodothyronine (T3) was evaluated in some patients. The upper limit of normal for K1 was 0.03 min-1 and for AIU was 0.04 microgram/min. In the hyperthyroid subjects, K1 and AIU were in the hyperthyroid range before and after T3 suppression. For patients with suppressible uptake, remission from hyperthyroidism was maintained for 6 mo to 2 1/2 yr. Only two patients with nonsuppressible uptake achieved remission from hyperthyroidism, perhaps because of coexistence of thyroiditis.

Topics: Adolescent; Child; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Propylthiouracil; Triiodothyronine

Topics: Adult; Carbimazole; Child; Congresses as Topic; Female; Germany, West; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Prednisone; Pregnancy; Prognosis; Propylthiouracil

Topics: Adjustment Disorders; Adolescent; Adrenocortical Hyperfunction; Adult; Dexamethasone; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Psychotic Disorders

Topics: Adolescent; Child; Humans; Hyperthyroidism; Methimazole; Methylthiouracil; Perchlorates; Potassium

Topics: Drug Therapy, Combination; Female; Humans; Hyperthyroidism; Male; Methimazole; Time Factors; Triiodothyronine

Topics: Animals; Body Weight; Cold Temperature; Heart; Hyperthyroidism; Hypothyroidism; In Vitro Techniques; Kinetics; Male; Methimazole; Muscles; Myocardium; Norepinephrine; Organ Size; Rats; Thyroid Hormones; Thyroidectomy; Thyroxine; Time Factors

Topics: Antibody Specificity; Female; Fetal Blood; Humans; Hyperthyroidism; Hypothyroidism; Isomerism; Methimazole; Myocardial Infarction; Pregnancy; Propylthiouracil; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine

Topics: Acute Disease; Aged; Agranulocytosis; Antithyroid Agents; Female; Humans; Hyperthyroidism; Methimazole

The possibilities of the treatment of hyperthyroidism are mentioned, in which cases the author especially deals with the medicamentous therapy, taking into consideration the different chemical groups (imidazol derivations, thiourazil derivations, perchlorates) and their therapeutic mechanisms. The indications and contraindications of this treatment and the possible side effects are compiled in form of a table. The in-vitro-parameters which are necessary for the observation of the course are estimated in their significance. The author deals with the problems of the additional treatment. Taking into consideration indications and contraindications as well as controls of the course of functional parameters the medicamentous therapy concerned is a treatment with a good prognosis. It is promising particularly in such cases, when suitable parameters are used for the solution of the question concerning the end of the therapy. For this purpose nowadays two tests are at our disposal: 1. modified Alexander's test (radioiodine-test and suppression test under thyreostatic therapy) and 2. TRH-test with radioimmunological determination of TSH. The treatment should be carried out in adequate endocrinological dispensaries, as there are certain risks in not optimal therapy.

Topics: Conjunctivitis; Drug Eruptions; Fever; Humans; Hyperthyroidism; Methimazole; Nausea; Perchlorates; Thiouracil

Eight patients with active thyrotoxicosis have been followed up to one year after the onset of antithyroid treatment. At different time intervals during the investigation period, TRH tests were performed and total T4 and T3 basal levels were measured. The TRH-induced TSH release was delayed in all patients in spite of a normalization of the circulating levels of thyroid hormones. The delay varied according to the patients and lasted, in some cases, for as long as 24 weeks after the normalization of the thyroid hormone levels. Administration of thyroid hormones, together with methimazole, did not seem to prevent the pituitary thyrotropes responsiveness; moreover, it did not provoke an inhibition of the TRH-induced TSH release once the thyrotropes reactivity was fully restored. The feed-back mechanism does not seem to be the main modulator of the pituitary responsiveness to TRH in these circumstances.

Topics: Adolescent; Adult; Aged; Child; Female; Follow-Up Studies; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Propranolol; Thyrotropin-Releasing Hormone; Thyroxine

Responsiveness to synthetic thyrotropin-releasing hormone (TRH), thyroid suppressibility by triiodothyronine (T3) and the outcome of hyperthyroidism following prolonged therapy with thionamides were studied in a group of 35 patients with toxic diffuse goiter. TRH and T3 suppression tests were performed 10 days to 24 months (mean 4 months) after withdrawal of antithyroid drugs. Nineteen patients were euthyroid and had a normal thyrotropin (TSH) response to TRH, while 4 were recovering from mild hypothyroidism due to overtreatment and had an exaggerated response. No response was observed in 12 patients with recurrent hyperthyroidism. Positive T3 suppression tests were found only in 10 of the 30 cases examined. Peak and net 2 h secretion responses of TSH to TRH exhibited a significant inverse correlation with the levels of serum thyroxine and serum triiodothyronine, but were unrelated to the degree of thyroid suppressibility. Relapse or recurrence of thyrotoxicosis occurred in at least 9 of the 23 patients having no evidence of hyperthyroidism at the time of TRH test. Each of them was found to be responsive to TRH, while the T3 suppression test was negative in 8 and had to be discontinued in one because of thyrotoxic symptoms. The present data indicate that during the early period after completion of a prolonged course of antithyroid drug therapy responsiveness to TRH in toxic diffuse goiter is: a) correlated with circulating thyroid hormones, b) unrelated to the degree of thyroid suppressibility by T3 and c) of little value in predicting the long-term results of treatment.

Topics: Adult; Carbimazole; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Middle Aged; Propylthiouracil; Radioimmunoassay; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Time Factors; Triiodothyronine

The radioimmunoassay for T3 is now widely available and is a useful diagnostic tool for hyperthyroidism, especially in T3-thyrotoxicosis. It is an essential tool in the management of hyperthyroidism that persists after treatment with normal T4 serum levels or, in euthyroid cases, with low T4 serum levels. In these conditions, it reflects the metabolic state more accurately than serum levels of T4. A promising new test is the response of radioimmunoassayable TSH to protirelin (TRH) administration. An absent response indicates pituitary suppression and thyroid autonomy as seen in frank hyperthyroidism or euthyroid Graves disease, treated or untreated. It is safer and quicker than the conventional T3 suppression test of thyroid radioactive iodine uptake and may replace it at least partly in the future.

Topics: Adult; Female; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Propylthiouracil; Thyroid Function Tests; Thyroidectomy

Seventy-three cases of thyrotoxicosis were treated at Lloyd Noland Hospital with methimazole, propylthiouracil or both. Two cases of agranulocytosis occurred (2.7%) secondary to methimazole. Both responded to hospitalization, reverse isolation, and antibiotic coverage with complete recovery of the peripheral blood picture. The toxicity of methimazole is noted. The need for careful monitoring of blood counts during therapy and immediate discontinuance of the drug at the first clinical sign of granulocytopenia is stressed.

Topics: Adult; Agranulocytosis; Anti-Bacterial Agents; Blood Cell Count; Female; Humans; Hyperthyroidism; Methimazole; Pharyngitis

Topics: Adult; Female; Humans; Hyperthyroidism; Libido; Methimazole

The authors made an analysis of clinical materials pertaining to 1234 patients with thyrotoxicosis, who were given different preoperative management and operated upon under local and general anesthesia. It is noted, that there is less number of postoperative thyrotoxic crises after mercosolyl administration in combination with reserpine and nonspecific drugs than after Plummer preoperative preparation (0.1% versus 1.2%).

Topics: Adult; Aged; Anesthesia; Anesthesia, Endotracheal; Anesthesia, Inhalation; Anesthesia, Local; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Preanesthetic Medication; Preoperative Care; Reserpine; Thyroid Crisis

Hyperthyroidism is a clinically dramatic but usually benign syndrome that is most commonly associated with the clinical triad known as Graves' disease. Although the diagnosis and treatment usually are straightforward and clinically rewarding, there are occasional patients in whom considerable clinical and laboratory expertise are required before the problem is identified and solved. Although among the most common endocrine disorders, the etiology of the hyperfunction of the thyroid gland in Graves' disease remains unknown and the mechanism by which thyroid hormones produce their effect is equally obscure. However, if the rate of progress in the past decade is typical, both these questions may well be answered before another 10 years have elapsed.

Topics: Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Propylthiouracil; Thyroid Neoplasms; Thyroxine; Triiodothyronine

Marked, and in some cases long-lasting, taste disturbances occurred in three patients on thiamazole. In addition, all three had a rise in serum transaminases and alkaline phosphatase levels, due to associated liver parenchymal damage. Cause of these changes was the high thiamazole dosage (160 and 120 mg/d). Reduction in dosage restored normal taste sense in all three, but in two the drug had to be discontinued because of persisting high transaminase levels.

Topics: Adult; Chemical and Drug Induced Liver Injury; Female; Humans; Hyperthyroidism; Methimazole; Middle Aged; Taste Disorders; Time Factors

The rate of disappearance of antipyrine from the plasma is a useful indicator for the in vivo capacity of mixed function oxidation. The half-life of antipyrine was measured before and after treatment in three hypothyroid and three hyperthyroid children, aged three months to 14 years, in order to examine the effect on drug metabolism of thyroid disorders in children. The half-life of antipyrine decreased in all three hypothyroid subjects and increased in all three hyperthyroid subjects after treatment. The mean half-life decreased from 34.5 h to 8.6 h after treatment of the hypothyroid subjects and increased from 6.1 to 10.1 h after treatment of the hyperthyroid subjects. The mean metabolic clearance rate of antipyrine increased from 11.7 to 25 ml/h in the hyothyroid patients while in the hyperthyroid children there was a decrease from 43 to 25 ml/h. The apparent volume of distribution did not change significantly in the treatment, thus changes in the half-life of antipyrine were most likely attributable to alterations in the metabolic clearance rate of antipyrine.

Topics: Adolescent; Antipyrine; Child; Child, Preschool; Half-Life; Humans; Hyperthyroidism; Hypothyroidism; Infant; Methimazole; Propylthiouracil; Thyroidectomy; Thyrotropin; Thyroxine; Time Factors

Thyrotoxicosis is associated with hypomagnesemia. Therapy leads to restoration of serum magnesium concentration. The clinical significance of the disturbance in magnesium metabolism is discussed on results of two groups of patients with hyperthyroidism. One group of 7 patients with high serum thyroxine levels and mild clinical signs of thyrotoxicosis showed a normal magnesium concentration in serum. In a second group with further 7 patients serum magnesium level did not increase during therapy while thyroxine decreased in spite of lack of clinical improvement. The results suggest that serum magnesium concentration is primarily determined by 1-triiodothyronine.

Topics: Adult; Aged; Drug Therapy, Combination; Female; Humans; Hyperthyroidism; Iodine Isotopes; Iodine Radioisotopes; Magnesium; Male; Methimazole; Middle Aged; Thyroid Function Tests; Thyroxine; Triiodothyronine

A patient with hyperthyroidism is described who developed grand mal seizures when anth-thyroid medication was withdrawn. Pyramidal signs were also present. The EEG reverted to normal and the clinical signs and symptoms disappeared when his thyroid status was again controlled.

Topics: Adult; Humans; Hyperthyroidism; Male; Methimazole; Phenytoin; Seizures

Topics: Animals; Antithyroid Agents; Chromatography; Drug Interactions; Drug Therapy, Combination; Half-Life; Humans; Hyperthyroidism; Injections, Intraperitoneal; Male; Methimazole; Protein Binding; Rats; Sulfur Radioisotopes; Thyroid Gland; Thyroxine

Twenty-one women were studied who had received propylthiouracil or methimazole during 26 pregnancies. Four of the infants had a goiter at birth, and 3 of these had neonatal thyrotoxicosis. In 2 children neonatal thyrotoxicosis was not evident at birth because of maternal antithyroid therapy. Five children had congenital defects. Two mothers were responsible for 4 of the children with abnormalities, and both mothers had been treated with thiourea drugs for long periods, ranging from 7 to 11 years. The majority of children who are exposed to these drugs in utero appear to have no subsequent ill effects. However, prolonged therapy with these agents may be undesirable.

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Adult; Female; Fetal Blood; Fetal Death; Goiter; Humans; Hyperthyroidism; Infant; Infant, Newborn; Infant, Newborn, Diseases; Long-Acting Thyroid Stimulator; Male; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Scalp; Thyroid Function Tests; Thyroxine

From 1959 to 1970, 272 operations for thyrotoxicosis were performed. Most of the patients received anti-thyroid drugs and thyroid hormones preoperatively. The patients were continuously followed up. The primary results with low morbidity and no mortality as well as the long term results with a low rate of recurrence and a relatively high incidence of thyroid substitution are discussed. A safe and effective programme for surgical treatment of thyrotoxicosis is described. Anti-thyroid drugs and thyroid hormones should be administered as the method of choice in preparing these patients for surgery.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Carbimazole; Child; Female; Goiter; Humans; Hyperthyroidism; Hypocalcemia; Hypothyroidism; Laryngoscopy; Length of Stay; Male; Methimazole; Middle Aged; Paralysis; Postoperative Complications; Preoperative Care; Propylthiouracil; Recurrent Laryngeal Nerve; Thyroxine; Triiodothyronine

In nine patients with thyrotoxicosis (three patients with ophthalmopathy, one patient with T3 thyrotoxicosis) we followed plasma levels of triiodothyronine (T3) and thyroxine (T4) and the TRH induced TSH release before and under treatment with propythiouracil (PTU), carbimazole or methimazol. The patients were observed for 2-8 months and did not receive any thyroid hormones during this time. Before treatment the TSH responses to TRH were absent in all patients. After commencement of antithyroid drug therapy the T3 and T4 plasma values decreased to normal (T3) or subnormal levels (T4) within 1-5 weeks and the patients became euthyroid, but at that time the TRH test was still negative in all patients. Moreover, there was a lag between 2 weeks and 4 months in five of the patients before the TRH test became positive. The duration of this lag could not be correlated with any data of the history or the clinical signs. Several possible explanations for this observation are discussed. Our results suggest that the TRH-test is not suited for the control of the therapeutic effect of antithyroid drug therapy.

Topics: Adult; Carbimazole; Female; Humans; Hyperthyroidism; Methimazole; Middle Aged; Propylthiouracil; Thyroid Function Tests; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

In normal, nonmedicated volunteers and in patients with thyroid disorders the plasma half-lives of antipyrine, propylthiouracil, and methimazole were determined after single oral doses. The plasma half-liver plus or minus S.D. of antipyrine, propylthiouracil, and methimazole were 11.9 plus or minus 1.4 hr, 6.7 plus or minus 1.0 hr, and 9.3 plus or minus 1.4 hr, respectively, in normal volunteers, but were shortened to 7.7 plus or minus 1.2 hr, 4.3 plus or minus 0.7 hr, and 6.9 plus or minus 0.6 hr, respectively, in hyperthyroid patients. In hypothyroid patients the plasma half-lives of these drugs were prolonged to 26.4 plus or minus 4.0 hr, 24.7 plus or minus 34.5 hr, and 13.6 plus or minus 4.8 hr, respectively. Return to the euthyroid state restored plasma half-lives to or toward normal. Alterations in plasma drug half-lives during thyroid dysfunction appear to result mainly from accelerated hepatic microsomal drug metabolism in hyperthyroidism and retarded drug biotransformation during hypothyroidism.

Topics: Adult; Aged; Antipyrine; Biotransformation; Female; Half-Life; Humans; Hyperthyroidism; Hypothyroidism; Kinetics; Male; Methimazole; Middle Aged; Propylthiouracil; Spectrophotometry; Thyroid Diseases; Thyroid Function Tests

Topics: Adolescent; Adult; Child; Female; Guanethidine; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Phenobarbital; Propranolol; Propylthiouracil; Reserpine; Thyroidectomy

An 18-yr-old woman with clinical and laboratory features of hyperthyroidism had persistently elevated serum levels of immunoreative thyrotropin (TSH). During 11 yr of follow-up there had been no evidence of a pituitary tumor. After thyrotropin-releasing hormone (TRH), there was a marked increase in TSH and secondarily in triiodothyronine (T3), the latter observation confirming the biologic activity of the TSH. Exogenous T3 raised serum T3 and several measurements of peripheral thyroid hormone effect, while decreasing serum TSH, thyroxine (T4), and thyroidal radioiodine uptake. After T3, the TRH-stimulated TSH response was decreased but was still inappropriate for the elevated serum T3 levels. Dexamethasone reduced serum TSH but did not inhibit TRH stimulation of TSH. Propylthiouracil reduced serum T4 and T3 and raised TSH. This patient represents a new syndrome of TSH-induced hyperthyroidism, differing from previous reports in the absence of an obvious pituitary tumor and in the responsiveness of the TSH to TRH stimulation and thyroid hormone suppression. This syndrome appears to be caused by a selective, partial resistance of the pituitary to the action of thyroid hormone. This case is also compared with previous reports in the literature of patients with elevated serum levels of immunoreactive TSH in the presence of elevated total and free thyroid hormones. A classification of these cases, termed "inappropriate secretion of TSH," is proposed.

Topics: Adolescent; Child; Depression, Chemical; Dexamethasone; Female; Humans; Hyperthyroidism; Metabolism, Inborn Errors; Methimazole; Pituitary Gland; Prolactin; Syndrome; Thyroid Function Tests; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine

Topics: Humans; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Methimazole; Propylthiouracil

Effect of 1-methyl-2-mercaptoimidazole (MMI) on the serum triiodothyronine (T3) and thyroxine (T4) was studied in six patients with hyperthyroidism. From 30 to 60 mg of MMI per day were administered to the patients orally. Serum T3 was measured by radioimmunoassay and T4 by radioimmunoassay of Tetrasorb Kit (Abbott Lab.). Serum T4/T3 ratios in these patients were low initially, but increased to normal range in two cases immediately after the administration of MMI. But they were unchanged at first in the other four cases. When high serum T3 values decreased abruptly to normal at a later course of medication, the serum T4/T3 ratios increased to normal range in almost all cases. Even though the serum T4/T3 ratio became normal, serum T3 and T4 values remained high in some cases. Elevated serum T4 values in all cases decreased to normal faster than serum T3 with the administration of MMI. When MMI was administered to the patents concinuously, the T4/T3 ratios, once increased to normal, then decreased again gradually in five cases. And serum T3 which decreased to normal sometimes gave high values. After the discontinuation of MMI, serum T3 increased over the normal range more rapidly than did T4.

Topics: Adult; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Radioimmunoassay; Thiouracil; Thyroxine; Time Factors; Triiodothyronine

Over a 7-yr period from January 1967 to January 1974, 141 patients underwent thyroid surgery for various pathology at the Bexar County Hospital - University of Texas Medical School at San Antonio. Of these, 113 patients underwent subtotal thyroidectomy for benign diseases, including 28 of thyrotoxic patients who underwent subtotal thyroidectomy as definitive treatment. In this group of patients special interest and emphasis was placed in the preoperative and intraoperative management of the difficult and complicated hyperthyroid patient. Preoperative treatment was accomplished by the utilization of multiple drug combinations - including antithyroid drugs, adrenergic blocking agents, and iodine - which resulted in significant decrease in preparation time for surgery. Furthermore, this short intensive preoperative management of complicated hyperthyroid patients allowed satisfactory correction of their problems with little or no morbidity which otherwise would have been extremely difficult if not impossible to resolve. At operation, 28 patients were diagnosed to have malignant disease; 23 underwent total thyroidectomy and the other 5 had subtotal thyroidectomy. In addition to total or subtotal thyroidectomy, 23 patients had either classical or modified radical neck dissection including 9 patients who had bilateral neck dissection. The various surgical techniques utilized, the rationale for rapid preoperative preparation of complicated hyperthyroid patients, morbidity, and long-term follow-up are discussed.

Topics: Adolescent; Adult; Aged; Child; Dexamethasone; Female; Follow-Up Studies; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Neck Dissection; Potassium Iodide; Propylthiouracil; Reserpine; Thyroid Diseases; Thyroid Neoplasms; Thyroidectomy

In homogenate supernatants of kidneys of male rats the extent of deiodination of L-diiodotyrosine (L-DJT) and L-thyroxine (L-T4) was investigated in dependence on the thyroid function (hypo- and hyperthyroidized) and also in dependence on age. In rats hypothyroidized by loading with Methylthiouracil (MTU) or Methimazol (MMI) the deiodination for L-DJT and L-T4 was significantly reduced, in rats loaded with 40 mug T4 sc. for 10 days, the deiodination was significantly enhanced compared with untreated control animals. With advancing age (6 weeks, 3 or 12 month) the deiodination activity is highly significantly reduced. The results underline relations between thyroid gland function and deiodination activity in kidney.

Topics: Age Factors; Animals; Diiodotyrosine; Hyperthyroidism; Hypothyroidism; Iodine; Kidney; Male; Methimazole; Methylthiouracil; Monoiodotyrosine; Rats; Thyroid Diseases; Thyroid Hormones; Thyroxine; Triiodothyronine

In 66 untreated patients with hyperthyroidism, serum triiodothyronine (T(3)) and thyroxine (T(4)) concentrations were measured by immunoassay. The mean T(3) level was 478+/-28 ng/100 ml (all values mean+/-SEM) and the T(4) was 20.6+/-0.6 mug/100 ml. The serum T(4)/T(3) ratio by weight was 48+/-2 as opposed to a value of 71+/-3 in euthyroid adults. There was a significant inverse correlation of the T(4)/T(3) ratios with serum T(3) (r=0.77; P<0.01) but not with serum T(4)(r=0.21). These results suggested that relative overproduction of T(3) is consistently present in patients with hyperthyroidism. To examine the acute effects of various antithyroid agents on serum T(3) and T(4) concentrations, iodide, propylthiouracil (PTU), and methylmercaptoimidazole (MMI) were given alone to mine patients, and serial T(3) and T(4) measurements were made. There was an acute decrease in serum T(3) over the first 5 days in the three iodide and three PTU-treated patients which was greater than that seen in the MMI group. This suggested that PTU and MMI had different effects on T(3) production. To compare the effects of PTU and MMI under conditions in which thyroidal hormone release was minimized, these drugs were given in combination with iodide. The mean daily dosage of PTU was 827 (n=11) and of MMI was 88 (n=8). In the PTU+iodide group, the initial serum T(3) concentration was 586+/-61 ng/100 ml and decreased significantly to 326+/-41 on day 1 and to 248+/-21 on days 2 and 3, respectively, and did not change further on days 4 and 5. In the MMI + iodide group, basal serum T(3) was 645+/-90 ng/100 ml and decreased to 568+/-81, 452+/-73, and 344+/-51 on days 1, 2, and 3, respectively, and did not change thereafter. While the initial T(3) concentrations in serum were not different in the PTU and MMI groups, the T(3) concentrations in the PTU patients were significantly lower on days 1 and 2 and during the apparent plateau period on days 3-5. Serum T(4) concentrations decreased gradually in both groups, from 23.9+/-2.0 mug/100 ml, initially, to 17.5+/-1.6 on day 5 in the PTU group and from 22.0+/-2.6 to 14.6+/-2.0 in the MMI-treated patients. The T(4) values were not significantly different at any time. These changes resulted in increases in the serum T(4)/T(3) ratios in both groups, but these ratios were substantially higher in the patients treated with PTU + iodide. The initial serum T(4)/T(3) ratio was 43+/-3 and increased to 74+/-7 and 88+/-7 on days 1 and 2 in the PTU grou

Topics: Antithyroid Agents; Dose-Response Relationship, Drug; Humans; Hyperthyroidism; Iodine; Methimazole; Propylthiouracil; Thyroid Gland; Thyroxine; Triiodothyronine

Topics: Antithyroid Agents; Congenital Hypothyroidism; Female; Goiter; Humans; Hyperthyroidism; Hypothyroidism; Infant; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Iodine Radioisotopes; Long-Acting Thyroid Stimulator; Male; Maternal-Fetal Exchange; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Function Tests; Thyroid Hormones; Thyrotropin; Thyroxine; Twins

Topics: Antithyroid Agents; Exophthalmos; Female; Graves Disease; Humans; Hyperthyroidism; Long-Acting Thyroid Stimulator; Male; Methimazole; Ophthalmoplegia; Prednisone; Thyroid Function Tests; Thyrotropin-Releasing Hormone

Topics: Animals; Antithyroid Agents; Child; Goiter; Graves Disease; Humans; Hyperthyroidism; Methimazole; Phenylthiourea; Propylthiouracil; Rats; Sulfaguanidine; Thioglycosides; Thyroid Gland; Vegetables

Topics: Blood Glucose; Diabetes Complications; Diabetic Coma; Diabetic Ketoacidosis; Electrocardiography; Female; Glucose Tolerance Test; Humans; Hyperthyroidism; Insulin; Iodine; Iodine Radioisotopes; Methimazole; Middle Aged; Prednisolone; Thyroid Crisis

Topics: Diazepam; Dihydroxyphenylalanine; Drug Therapy, Combination; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Parkinson Disease; Propranolol; Thyroidectomy; Trihexyphenidyl

Topics: Animals; Blood Glucose; Disease Models, Animal; Gluconeogenesis; Glucose Tolerance Test; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Methylthiouracil; Rats; Thyroid Gland; Thyroxine

Topics: Animals; Exophthalmos; Goldfish; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Methimazole; Muscles; Orbit; Sulfates; Sulfur Radioisotopes; Thyroid Diseases; Thyrotropin

Topics: Female; Fetus; Humans; Hyperthyroidism; Hypothyroidism; Intelligence Tests; Iodine; Maternal-Fetal Exchange; Methimazole; Patient Care Team; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

Topics: Adolescent; Female; Growth Hormone; Half-Life; Humans; Hyperthyroidism; Methimazole; Secretory Rate

Topics: Adult; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged

Topics: Antithyroid Agents; Child; Female; Humans; Hyperthyroidism; Iodine Isotopes; Methimazole; Methods

Topics: Adenoma; Antithyroid Agents; Carbimazole; Humans; Hyperthyroidism; Iodides; Methimazole; Propylthiouracil; Sulfur Isotopes; Thyroid Gland; Thyroid Neoplasms

Topics: Adolescent; Adult; Antithyroid Agents; Erythrocytes; Female; Follow-Up Studies; Glucosephosphate Dehydrogenase; Humans; Hyperthyroidism; Iodine Isotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Thyroid Function Tests

Topics: Alpha-Globulins; Animals; Blood Proteins; Carbon Isotopes; Dose-Response Relationship, Drug; Fibrinogen; Glycoproteins; Haptoglobins; Hydrocortisone; Hyperthyroidism; Hypothyroidism; Insulin; Liver; Male; Methimazole; Perfusion; Rats; Serum Albumin; Thyroid Gland; Thyroidectomy; Thyroxine

Topics: Adult; Animals; Antibodies; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Long-Acting Thyroid Stimulator; Long-Term Care; Male; Methimazole; Mice; Prognosis; Recurrence; Triiodothyronine

Topics: Depression, Chemical; Female; Follow-Up Studies; Humans; Hyperthyroidism; Male; Methimazole; Recurrence; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones

Topics: Half-Life; Hyperthyroidism; Iodides; Methimazole; Plasmapheresis; Thyroid Crisis; Thyroxine; Triiodothyronine

Topics: Adult; Female; Humans; Hyperthyroidism; Iodine; Iodine Isotopes; Lithium; Male; Methimazole; Middle Aged; Protein Binding; Radioimmunoassay; Thyrotropin; Thyroxine

Topics: Adult; Female; Humans; Hyperthyroidism; Iodine; Male; Methimazole; Middle Aged; Peritoneal Dialysis; Postoperative Care; Prednisolone; Preoperative Care; Thyroid Crisis

Topics: Adenoma; Aged; Chemical and Drug Induced Liver Injury; Cholangiography; Drug Hypersensitivity; Female; Humans; Hyperthyroidism; Liver; Liver Function Tests; Methimazole; Thyroid Neoplasms

Topics: Female; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones

Topics: Adolescent; Child; Female; Graves Disease; Humans; Hyperthyroidism; Hypocalcemia; Laryngeal Edema; Male; Methimazole; Methods; Postoperative Complications; Potassium Iodide; Propranolol; Propylthiouracil; Thyroid Hormones; Thyroidectomy

Topics: Abortion, Spontaneous; Adolescent; Adult; Cesarean Section; Cholesterol; Female; Fetal Death; Gestational Age; Goiter; Humans; Hyperthyroidism; Infant, Newborn; Iodine; Iodine Radioisotopes; Maternal Mortality; Methimazole; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Function Tests; Thyroid Hormones; Thyroidectomy; Triiodothyronine

Topics: Adult; Cardiac Catheterization; Electrocardiography; Female; Heart Ventricles; Humans; Hyperthyroidism; Methimazole; Mitral Valve Insufficiency; Myocardial Infarction; Phonocardiography; Radiography

Topics: Adenoma; Adult; Female; Humans; Hypercalcemia; Hyperparathyroidism; Hyperthyroidism; Methimazole; Parathyroid Neoplasms; Thyroid Gland

Topics: Adult; Antibody Formation; Antibody Specificity; Humans; Hyperthyroidism; Hypothalamus; Methimazole; Middle Aged; Oxygen Consumption; Thyroid Function Tests

Topics: Antipyrine; Carbimazole; Humans; Hyperthyroidism; Methimazole; Thyroid Diseases; Triiodothyronine

Topics: Child; Diabetes Mellitus, Type 1; Female; Humans; Hyperthyroidism; Methimazole; Thyroiditis, Autoimmune

Topics: Adult; Female; Humans; Hyperthyroidism; Methimazole; Nephrotic Syndrome

Topics: Antithyroid Agents; Humans; Hyperthyroidism; Long-Acting Thyroid Stimulator; Methimazole; Neoplasms; Propylthiouracil; Thyroidectomy

Topics: Albumins; Animals; Antibody Specificity; Binding Sites; Globulins; Humans; Hyperthyroidism; Hypothyroidism; Immune Sera; Iodine Isotopes; Methimazole; Methods; Propylthiouracil; Rabbits; Radioimmunoassay; Thyroid Function Tests; Thyroxine; Thyroxine-Binding Proteins

Topics: Adult; Dexamethasone; Female; Humans; Hyperthyroidism; Hypothalamo-Hypophyseal System; Iodine Isotopes; Iodine Radioisotopes; Methimazole; Pituitary Hormones, Anterior; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

Topics: Antithyroid Agents; Follow-Up Studies; Humans; Hyperthyroidism; Iodine Isotopes; Methimazole; Propylthiouracil; Radioimmunoassay; Thyroxine; Triiodothyronine

Topics: Agranulocytosis; Antithyroid Agents; Drug Eruptions; Humans; Hyperthyroidism; Imidazoles; Male; Methimazole; Pruritus; Urticaria

Since lithium has been shown to inhibit release of iodine from the thyroid, we have investigated its therapeutic potential in thyrotoxicosis. Eight detailed (131)I kinetic studies were performed on seven thyrotoxic women and data was analyzed using a computer program. Lithium at serum levels of about 1 mEq liter decreased the loss of (131)I from the thyroid, led to a fall in serum (131)I levels and diminished urinary (131)I excretion. Computer simulation of the lithium effect required, in every case, that lithium inhibit hormonal and nonhormonal thyroid iodine release. In five cases a second lithium effect was required for a satisfactory fit of the model soluton with observed data: namely, an inhibition of hormone disappearance from serum. NEITHER INHIBITION OF RELEASE NOR OF HORMONE DISAPPEARANCE SEEMED TO BE AFFECTED BY METHIMAZOLE (RELEASE: 52% decrease without methimazole, 60% with methimazole; hormone disappearance: approximately 60% decrease in both). When Li(+) was discontinued, recovery of the iodine release rate and hormone disappearance rate over the observed time span was variable, ranging from no recovery to rates that exceeded pre-Li(+) values. When Li(+) is used alone its effect on serum hormone levels is diminished due to continued accumulation of iodide by the thyroid. Thus, serum thyroxine-iodine levels fell 21-30% in 6-8 days in patients who did not receive methimazole and 15-67% in the methimazole-treated subjects. For prolonged therapy, therefore, a thiocarbamide drug must be used in conjunction with Li(+). The similarity of inhibition of iodine release from the thyroid produced by Li(+) and iodides is discussed.

Topics: Adolescent; Adult; Computers; Female; Humans; Hyperthyroidism; Iodine; Iodine Radioisotopes; Kinetics; Lithium; Mathematics; Methimazole; Models, Biological; Thyroid Function Tests; Thyroid Gland; Thyroxine

Topics: Antithyroid Agents; Female; Half-Life; Humans; Hyperthyroidism; Male; Methimazole; Methods; Perchlorates; Potassium; Propylthiouracil

Topics: Adult; Arrhythmia, Sinus; Atrial Fibrillation; Cardiac Complexes, Premature; Electrocardiography; Heart Block; Heart Ventricles; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Mitral Valve Insufficiency; Myocardial Infarction; Propranolol; Respiration

Topics: Animals; Electron Transport Complex IV; Histocytochemistry; Hyperthyroidism; Hypothyroidism; Kidney; Male; Methimazole; Rats; Succinate Dehydrogenase; Thyroid Gland; Thyroidectomy; Triiodothyronine

Topics: Aged; Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Bilirubin; Cholestasis; Clinical Enzyme Tests; Enzyme Induction; Female; gamma-Glutamyltransferase; Humans; Hyperthyroidism; Isoenzymes; Leucyl Aminopeptidase; Methimazole; Middle Aged

Topics: Agranulocytosis; Chemical and Drug Induced Liver Injury; Cholestasis; Humans; Hyperthyroidism; Liver; Male; Methimazole; Middle Aged

Topics: Humans; Hyperthyroidism; Iodine Isotopes; Methimazole; Propylthiouracil; Radioimmunoassay; Thyroidectomy; Thyrotropin; Thyroxine; Triiodothyronine

Topics: Adult; Arrhythmias, Cardiac; Back; Chronic Disease; Electromyography; Extremities; Female; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Methylthiouracil; Middle Aged; Muscular Diseases; Paralyses, Familial Periodic; Sex Factors

Topics: Humans; Hyperthyroidism; Methimazole; Prognosis; Remission, Spontaneous; Thyroid Function Tests; Time Factors

Topics: Esterases; Fasting; Female; Glycerides; Goiter; Graves Disease; Heparin; Humans; Hyperthyroidism; Insulin; Iodine Isotopes; Lipase; Lipoprotein Lipase; Male; Methimazole; Propranolol; Propylthiouracil; Triglycerides

Topics: 17-Hydroxycorticosteroids; Adenoma, Chromophobe; Adult; Biological Assay; Blood Pressure; Cerebral Angiography; Gonadotropins; Hemangioma; Humans; Hyperthyroidism; Insulin; Iodine; Iodine Isotopes; Lysine; Male; Methimazole; Middle Aged; Pituitary Neoplasms; Radioimmunoassay; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine; Vasopressins

Topics: Eye Manifestations; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Iodides; Iodine Isotopes; Male; Methimazole; Neurotic Disorders; Pregnancy; Pregnancy Complications; Propylthiouracil; Psychotic Disorders; Skin Manifestations; Thyroidectomy; Triiodothyronine

Topics: Adult; Graves Disease; Humans; Hyperthyroidism; Methimazole; Methylthiouracil; Propylthiouracil; Radioimmunoassay; Thyroxine; Triiodothyronine

Topics: Adolescent; Child; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Thyroxine; Triiodothyronine

Topics: Adolescent; Adult; Aged; Blood Glucose; Depression, Chemical; Diazepam; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Goiter; Goiter, Nodular; Half-Life; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Thyroid Function Tests; Thyroid Gland; Time Factors

Topics: Adult; Aged; Catecholamines; Child; Female; Humans; Hyperthyroidism; Iodine Isotopes; Methimazole; Middle Aged; Pruritus; Thyroid Function Tests; Urticaria

Topics: Adolescent; Adult; Antithyroid Agents; Autoanalysis; Drug Synergism; Female; Half-Life; Humans; Hyperthyroidism; Imidazoles; Injections, Intravenous; Iodides; Male; Methimazole; Middle Aged; Thyroid Gland; Thyroxine

Topics: Adult; Graves Disease; Humans; Hyperthyroidism; Injections, Intravenous; Kinetics; Male; Metabolic Clearance Rate; Methimazole; Middle Aged; Models, Biological; Stereoisomerism; Thyroid Function Tests; Triiodothyronine

Topics: Adrenergic beta-Antagonists; Antithyroid Agents; Carbimazole; Chemical Phenomena; Chemistry; Humans; Hyperthyroidism; Hypothyroidism; Imidazoles; Iodine Isotopes; Methimazole; Methylthiouracil; Myocardial Infarction; Perchlorates; Potassium; Potassium Iodide; Propranolol; Propylthiouracil; Psychotic Disorders; Thiourea; Thyroxine; Time Factors

Topics: Adult; Aged; Antithyroid Agents; Diet; Female; Graves Disease; Humans; Hyperthyroidism; Imidazoles; Iodine; Iodine Isotopes; Male; Methimazole; Middle Aged; Thyroid Diseases; Thyroid Gland; Time Factors

Topics: Adult; Antithyroid Agents; Female; Goiter; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Imidazoles; Male; Methimazole; Middle Aged; Thyroid Function Tests

Topics: Acclimatization; Adrenal Glands; Animals; Body Temperature Regulation; Body Weight; Catecholamines; Cold Temperature; Epinephrine; Glycols; Hot Temperature; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Myocardium; Norepinephrine; Normetanephrine; Rats; Rats, Inbred Strains; Thyroid Gland; Thyroxine; Time Factors

Topics: Humans; Hyperthyroidism; Iodine; Iodine Isotopes; Methimazole; Propylthiouracil

Topics: Alkaline Phosphatase; Glutamine; Humans; Hyperthyroidism; Methimazole; Peptide Hydrolases

Topics: Adolescent; Adult; Brain; Female; Humans; Hydroxyindoleacetic Acid; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Middle Aged; Monoamine Oxidase; Serotonin; Thyroidectomy; Triiodothyronine

Topics: Achilles Tendon; Adolescent; Diagnosis, Differential; Female; Humans; Hyperthyroidism; Hypophysectomy; Hypothyroidism; Male; Methimazole; Methods; Middle Aged; Obesity; Reflex, Stretch; Statistics as Topic; Thyroid Diseases; Thyroid Function Tests; Triiodothyronine

Topics: Adult; Antisocial Personality Disorder; Expert Testimony; Humans; Hyperthyroidism; Male; Methimazole; Reserpine

Topics: Blood Proteins; Circadian Rhythm; Humans; Hyperthyroidism; Iodine; Iodine Radioisotopes; Kinetics; Methimazole; Protein Binding; Secretory Rate; Thyroid Gland; Thyroxine

Topics: Acute Disease; Administration, Oral; Adult; Antithyroid Agents; Female; Humans; Hyperthyroidism; Imidazoles; Injections, Intravenous; Male; Methimazole; Middle Aged; Propranolol

Topics: Antithyroid Agents; Humans; Hyperthyroidism; Imidazoles; Methimazole; Thyroid Function Tests; Thyroxine; Thyroxine-Binding Proteins

Topics: Adolescent; Adult; Antithyroid Agents; Drug Synergism; Humans; Hyperthyroidism; Imidazoles; Methimazole; Middle Aged; Reserpine

Topics: Adolescent; Arthritis, Rheumatoid; Female; Humans; Hyperthyroidism; Indians, North American; Lupus Erythematosus, Systemic; Methimazole; Neutrophils

Topics: Adult; Anemia, Aplastic; Antithyroid Agents; Female; Humans; Hyperthyroidism; Imidazoles; Methimazole

Topics: Adolescent; Choriocarcinoma; Chorionic Gonadotropin; Dactinomycin; Female; Hormones, Ectopic; Humans; Hydatidiform Mole; Hyperthyroidism; Methimazole; Methotrexate; Neoplasm Metastasis; Pregnancy; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Thyroxine

Topics: Adult; Antithyroid Agents; Diagnosis, Differential; Electrocardiography; Heart Block; Humans; Hyperthyroidism; Male; Methimazole; Penicillins; Reserpine; Rheumatic Fever; Salicylates; Thyroid Function Tests

Topics: Adult; Aged; Basal Metabolism; Ethchlorvynol; Female; Goiter; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Serum Globulins; Thyroid Function Tests; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Female; Follow-Up Studies; Goiter; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Radionuclide Imaging; Thyroid Function Tests; Thyroidectomy; Triiodothyronine

A method has been devised which is free of many of the shortcomings of serial epithyroid counting techniques as an index of the rate of thyroid hormone secretion. By means of this method, the effect of treatment with Lugol's iodine on the rate of thyroidal secretion of thyroxine (T(4)) has been assessed in eight patients with thyrotoxicosis due to diffuse or multinodular goiter. The technique involves administration of a tracer dose of inorganic (125)I followed several days later by an intravenous tracer dose of (131)I-labeled T(4). Serial observations of serum protein-bound (PB) (125)I and (131)I are accompanied by frequent measurements of endogenous serum T(4) (T(4)-(127)I) concentration. Regardless of whether or not its administration was anteceded and accompanied by the administration of large doses of methimazole, iodine induced a rapid decrease in serum T(4)-(127)I concentration which could not be explained by an increase in the peripheral turnover of T(4), as judged from the metabolism of the (131)I-labeled hormone. Hence, the decreased serum T(4) concentration could only have resulted from decreased secretion of the hormone by the gland. Analyses of specific activity relationships between PB(125)I or T(4)-(127)I and PB(131)I made possible estimations of the extent to which iodine had decreased the rate of secretion of T(4). From such analysis, and in view of other considerations, it is concluded that the rapid decrease in T(4) secretion induced by iodine is not the result of an acute, sustained inhibition of T(4) synthesis, but rather results from an abrupt decrease in the fractional rate of thyroidal T(4) release.

Topics: Adult; Aged; Blood Proteins; Female; Goiter; Humans; Hyperthyroidism; Iodine; Iodine Radioisotopes; Male; Mathematics; Methimazole; Methods; Middle Aged; Protein Binding; Thyroid Gland; Thyroxine

Topics: Adult; Diabetes Complications; Female; Humans; Hyperglycemia; Hyperthyroidism; Methimazole; Osmolar Concentration

Topics: Adolescent; Adult; Aged; Goiter; Humans; Hyperthyroidism; Immunoglobulin G; Iodine Radioisotopes; Long-Acting Thyroid Stimulator; Methimazole; Middle Aged; Propylthiouracil; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Triiodothyronine

In order to assess the contribution of 3.3',5-triiodo-L-thyronine (T(3)) to overall thyroid hormone economy, conjoint measurements of the kinetics of peripheral T(3) metabolism and the total concentration of T(3) in serum were made in a group of normal subjects and in a group of patients with hyperthyroid Graves' disease. As judged from the disappearance of trichloroacetic acid-precipitable (131)I from serum after a single intravenous dose of labeled T(3), the following mean values were obtained in the normal subjects: volume of distribution, 43 liters or 0.62 liter/kg; fractional turnover rate. 52% per 24 hr: clearance rate, 22.3 liters/24 hr: and absolute disposal rate, 60 mug/24 hr. In the patients with untreated hyperthyroidism, values for all these functions were greatly increased. After treatment, the volume of T(3) distribution returned to normal but the fractional turnover rate remained abnormally rapid.

Topics: Acetates; Adult; Basal Metabolism; Chemical Precipitation; Chlorine; Female; Graves Disease; Humans; Hyperthyroidism; Kinetics; Male; Methimazole; Middle Aged; Serum Albumin, Radio-Iodinated; Triiodothyronine

Topics: Adenoma, Chromophobe; Craniotomy; Hemianopsia; Humans; Hyperthyroidism; Iodides; Male; Methimazole; Middle Aged; Pituitary Neoplasms; Radioimmunoassay; Thyrotropin; Visual Fields

Topics: Adolescent; Child; Child, Preschool; Diagnosis, Differential; Germany, East; Humans; Hyperthyroidism; Hypothyroidism; Infant; Infant, Newborn; Methimazole; Methylthiouracil; Thyroid Diseases; Thyroid Hormones; Thyroidectomy

Topics: Humans; Hyperthyroidism; Long-Acting Thyroid Stimulator; Methimazole; Pituitary Gland; Radioimmunoassay; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Thyroxine

Topics: Adult; Eye Manifestations; Female; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Long-Acting Thyroid Stimulator; Methimazole; Propylthiouracil; Skin Manifestations; Thyroid Diseases

Differences in the metabolic fate of antithyroid drugs influence the optimal frequency of administration and their therapeutic efficacy. (35)S propylthiouracil differed from the (35)S imidazoles (carbimazole and methimazole) in the more rapid absorption and excretion and the shorter biological half-life in the plasma of the former. Renal function may have a more important influence on the biological half-life of the drugs than thyroid status. Further work is required to determine the optimal frequency of administration for each compound.

Topics: Antithyroid Agents; Carbimazole; Chromatography, Thin Layer; Female; Humans; Hyperthyroidism; Imidazoles; Kidney Failure, Chronic; Methimazole; Propylthiouracil; Sulfur Isotopes

Topics: Antithyroid Agents; Female; Humans; Hyperthyroidism; Imidazoles; Methimazole; Middle Aged; Parotid Gland; Salivary Gland Diseases

Topics: Adult; Aerospace Medicine; Agranulocytosis; Antithyroid Agents; Female; Humans; Hyperthyroidism; Imidazoles; Male; Methimazole; Middle Aged

Topics: Acid Phosphatase; Adenosine Triphosphatases; Animals; Antithyroid Agents; Histocytochemistry; Hyperthyroidism; Male; Methimazole; Mitochondria, Liver; Oxidoreductases; Rats; Succinate Dehydrogenase; Thyroxine

Topics: Adult; Antithyroid Agents; Electromyography; Humans; Hyperthyroidism; Hypokalemia; Male; Methimazole; Paralysis; Periodicity; Propylthiouracil; Reserpine; Thyroid Function Tests

Topics: Adult; Aged; Antibodies; Chronic Disease; Female; Humans; Hyperthyroidism; Hypothyroidism; Iodine Isotopes; Male; Methimazole; Middle Aged; Myxedema; Propranolol; Propylthiouracil; Pulse; Thiocyanates; Thyroid Diseases; Thyroid Function Tests; Thyroiditis; Time Factors; Triiodothyronine

Topics: Adult; Antithyroid Agents; Female; Humans; Hyperthyroidism; Imidazoles; Kidney; Methimazole; Nephrotic Syndrome; Prednisolone

Topics: Agranulocytosis; Animals; Antibodies; Antigen-Antibody Complex; Antithyroid Agents; Basophils; Cytoplasm; Cytoplasmic Granules; Drug Eruptions; Eosinophilia; Eosinophils; Female; Guinea Pigs; Heart Failure; Humans; Hyperthyroidism; Imidazoles; Immunoassay; Jaundice; Leukocyte Count; Methimazole; Middle Aged; Neutrophils

Topics: Adolescent; Adult; Depression, Chemical; Female; Humans; Hyperthyroidism; Iodine; Iodine Radioisotopes; Methimazole; Middle Aged; Potassium Iodide; Protein Binding; Thyroglobulin; Thyroid Gland; Thyroid Hormones

Topics: Adult; Aged; Blood Pressure; Cholesterol; Female; Humans; Hypertension; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Middle Aged; Myxedema; Norepinephrine; Thyroid Hormones

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Anesthesia, Spinal; Anti-Bacterial Agents; Child; Cortisone; Female; Guanethidine; Humans; Hyperthyroidism; Iodides; Liver; Lung; Male; Methimazole; Middle Aged; Myocardium; Propylthiouracil; Reserpine; Sex Factors; Sodium; Thyroid Crisis; Thyroid Gland

Topics: Animals; Gluconeogenesis; Glucose-6-Phosphatase; Histocytochemistry; Hyperthyroidism; Hypothyroidism; Islets of Langerhans; Kidney; Liver; Male; Methimazole; Potassium Iodide; Rats; Staining and Labeling; Thyroidectomy; Thyroxine; Triiodothyronine

Topics: Antithyroid Agents; Humans; Hyperthyroidism; Methimazole; Preoperative Care; Reserpine; Thyroidectomy; Thyrotoxicosis

Topics: Agranulocytosis; Drug Therapy; Hyperthyroidism; Imidazoles; Methimazole; Toxicology

Topics: Antithyroid Agents; Humans; Hyperthyroidism; Iodine; Iodine Isotopes; Methimazole; Thyroid Function Tests; Thyrotoxicosis

Topics: Agranulocytosis; Antithyroid Agents; Humans; Hyperthyroidism; Methimazole; Toxicology

Topics: Agranulocytosis; Antithyroid Agents; Humans; Hyperthyroidism; Methimazole; Toxicology

Topics: Antithyroid Agents; Hyperthyroidism; Iodine; Methimazole; Thyrotoxicosis

Topics: Antineoplastic Agents, Hormonal; Antithyroid Agents; Goiter; Goiter, Nodular; Hyperthyroidism; Methimazole; Thyrotoxicosis

Topics: Antineoplastic Agents, Hormonal; Antithyroid Agents; Hyperthyroidism; Methimazole

Topics: Antineoplastic Agents, Hormonal; Antithyroid Agents; Hyperthyroidism; Methimazole; Thyrotoxicosis

Topics: Antithyroid Agents; Hyperthyroidism; Methimazole

Topics: Antithyroid Agents; Carbimazole; Double-Blind Method; Humans; Hyperthyroidism; Methimazole

Topics: Antithyroid Agents; Humans; Hyperthyroidism; Iodides; Methimazole

Topics: Antithyroid Agents; Hyperthyroidism; Methimazole

Topics: Antithyroid Agents; Hyperthyroidism; Methimazole

Topics: Antithyroid Agents; Blood Cells; Bone Marrow; Humans; Hyperthyroidism; Methimazole; Sternum; Vegetables

Topics: Antithyroid Agents; Carbimazole; Humans; Hyperthyroidism; Methimazole

Topics: Antithyroid Agents; Hyperthyroidism; Methimazole

Topics: Aging; Antithyroid Agents; Hyperthyroidism; Methimazole

Topics: Antithyroid Agents; Humans; Hyperthyroidism; Methimazole

Topics: Antithyroid Agents; Hyperthyroidism; Methimazole; Thiouracil

Topics: Antithyroid Agents; Hyperthyroidism; Methimazole

Topics: Antithyroid Agents; Hyperthyroidism; Methimazole

Topics: Antithyroid Agents; Humans; Hyperthyroidism; Methimazole

Topics: Anemia; Anemia, Aplastic; Antithyroid Agents; Cortisone; Female; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications

Topics: Antithyroid Agents; Hyperthyroidism; Methimazole

Topics: Antithyroid Agents; Hyperthyroidism; Methimazole

Topics: Antithyroid Agents; Hyperthyroidism; Methimazole; Thyrotoxicosis

Topics: Antithyroid Agents; Hyperthyroidism; Methimazole

Topics: Antithyroid Agents; Hyperthyroidism; Methimazole

Topics: Antithyroid Agents; Hyperthyroidism; Methimazole; Thyrotoxicosis

Topics: Hyperthyroidism; Imidazoles; Methimazole; Thyrotoxicosis

Topics: Humans; Hyperthyroidism; Imidazoles; Methimazole

Topics: Antithyroid Agents; Hyperthyroidism; Methimazole

Topics: Antithyroid Agents; Humans; Hyperthyroidism; Methimazole; Propylthiouracil; Thiouracil

Topics: Antithyroid Agents; Humans; Hyperthyroidism; Iodine; Iodine Radioisotopes; Methimazole; Propylthiouracil; Sodium Iodide

Topics: Humans; Hyperthyroidism; Imidazoles; Methimazole; Thyrotoxicosis

Topics: Hyperthyroidism; Methimazole; Thyrotoxicosis

Topics: Antithyroid Agents; Hyperthyroidism; Imidazoles; Methimazole

Topics: Agranulocytosis; Humans; Hyperthyroidism; Imidazoles; Methimazole

Topics: Hyperthyroidism; Methimazole; Thiourea

Topics: Humans; Hyperthyroidism; Methimazole

Topics: Antithyroid Agents; Hyperthyroidism; Methimazole

Topics: Hyperthyroidism; Imidazoles; Methimazole; Thyroid Gland