methimazole and Thyroid-Neoplasms

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

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

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

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

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

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

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

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

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

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

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

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

The 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

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

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

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

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

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

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

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

Diffuse toxic goiter, as the most common cause of hyperthyroidism, is usually initially treated with thyrostatic drugs such as methimazole, followed by radioiodine therapy or surgery which may be indicated as definitive treatment. Radioactive iodine therapy has a known association with various histopathologic features including cytologic atypia, but herein we present a rare example of morphological thyrocyte changes induced by long-term pharmacological treatment with methimazole that mimicked thyroid malignancy in a pathohistological sample.

Topics: Antithyroid Agents; Humans; Iodine Radioisotopes; Methimazole; Thyroid Neoplasms

Topics: Anaplastic Lymphoma Kinase; Animals; Antithyroid Agents; Calmodulin-Binding Proteins; Cell Dedifferentiation; Cell Differentiation; Disease Models, Animal; Disease Progression; Membrane Proteins; Methimazole; Mice; Mice, Knockout; Mice, Transgenic; Nerve Tissue Proteins; Oncogene Proteins, Fusion; Perchlorates; RNA-Seq; Sodium Compounds; Symporters; Thyroglobulin; Thyroid Cancer, Papillary; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms; Transcriptome; Tumor Suppressor Protein p53

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

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

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

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

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

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

Chronic administration of acrylamide has been shown to induce thyroid tumors in rat. In vitro acrylamide also causes DNA damage, as demonstrated by the comet assay, in various types of cells including human thyroid cells and lymphocytes, as well as rat thyroid cell lines. In this work, mice were administered acrylamide in their drinking water in doses comparable with those used in rats, i.e., around 3-4 mg/kg per day for mice treated 2, 6, and 8 months. Some of the mice were also treated with thyroxine (T(4)) to depress the activity of the thyroid. Others were treated with methimazole that inhibits thyroid hormone synthesis and consequently secretion and thus induces TSH secretion and thyroid activation. These moderate treatments were shown to have their known effect on the thyroid (e.g. thyroid hormone and thyrotropin serum levels, thyroid gland morphology...). Besides, T(4) induced an important polydipsia and degenerative hypertrophy of adrenal medulla. Acrylamide exerted various discrete effects and at high doses caused peripheral neuropathy, as demonstrated by hind-leg paralysis. However, it did not induce thyroid tumorigenesis. These results show that the thyroid tumorigenic effects of acrylamide are not observed in another rodent species, the mouse, and suggest the necessity of an epidemiological study in human to conclude on a public health policy.

Topics: Acrylamide; Adrenal Medulla; Animals; Body Weight; Female; Methimazole; Mice; Thyroid Gland; Thyroid Neoplasms; Thyrotropin; Thyroxine

High basal levels of TLR3 and Wnt5a RNA are present in papillary thyroid carcinoma (PTC) cell lines consistent with their overexpression and colocalization in PTC cells in vivo. This is not the case in thyrocytes from normal tissue and in follicular carcinoma (FC) or anaplastic carcinoma (AC) cells or tissues. The basally expressed TLR3 are functional in PTC cells as evidenced by the ability of double-strand RNA (polyinosine-polycytidylic acid) to significantly increase the activity of transfected NF-kappaB and IFN-beta luciferase reporter genes and the levels of two end products of TLR3 signaling, IFN-beta and CXCL10. Phenylmethimazole (C10), a drug that decreases TLR3 expression and signaling in FRTL-5 thyrocytes, decreases TLR3 levels and signaling in PTC cells in a concentration-dependent manner. C10 also decreased Wnt5a RNA levels coordinate with decreases in TLR3. E-cadherin RNA levels, whose suppression may be associated with high Wnt5a, increased with C10 treatment. C10 simultaneously decreased PTC proliferation and cell migration but had no effect on the growth and migration of FC, AC, or FRTL-5 cells. C10 decreases high basal phosphorylation of Tyr705 and Ser727 on Stat3 in PTC cells and inhibits IL-6-induced Stat3 phosphorylation. IL-6-induced Stat3 phosphorylation is important both in up-regulating Wnt5a levels and in cell growth. In sum, high Wnt5a levels in PTC cells may be related to high TLR3 levels and signaling; and the ability of phenylmethimazole (C10) to decrease growth and migration of PTC cells may be related to its suppressive effect on TLR3 and Wnt5a signaling, particularly Stat3 activation.

Topics: Carcinoma, Papillary; Cell Division; Cell Line, Tumor; Cell Movement; Humans; Methimazole; Proto-Oncogene Proteins; Thyroid Neoplasms; Toll-Like Receptor 3; Wnt Proteins; Wnt-5a Protein

Five chemicals that are known to induce in rats thyroid follicular-cell adenomas and carcinomas were assayed for their ability to induce DNA damage and DNA repair synthesis in primary cultures of human thyroid cells. Significant dose-dependent increases in the frequency of DNA single-strand breaks and alkali-labile sites, as measured by the same Comet assay, were obtained after a 20-h exposure to the following subtoxic concentrations of the five test compounds: methimazole from 2.5 to 10mM; nitrobenzene, potassium bromate, N,N'-diethylthiourea and ethylenethiourea from 1.25 to 5mM. Under the same experimental conditions, DNA repair synthesis, as evaluated by quantitative autoradiography, was present in potassium bromate-exposed thyroid cells from all the three donors and in those from two of three donors with either nitrobenzene or ethylenethiourea, but did not match the criteria for a positive response in thyroid cells from any of the donors with methimazole and N,N'-diethylthiourea. Consistently with their ability to induce thyroid tumors, all the five test compounds, administered p.o. in rats in a single dose corresponding to 1/2 LD50, induced a statistically significant degree of DNA fragmentation in the thyroid. These findings suggest that the five test compounds might be carcinogenic to thyroid in humans.

Topics: Adenocarcinoma, Follicular; Adenoma; Animals; Bromates; Carcinogens; Cells, Cultured; DNA Damage; DNA Fragmentation; DNA Repair; Ethylenethiourea; Humans; In Vitro Techniques; Kidney; Liver; Male; Methimazole; Nitrobenzenes; Rats; Rats, Sprague-Dawley; Thiourea; Thyroid Gland; Thyroid Neoplasms

Hydrogen peroxide (H(2)O(2)) is necessary for thyroid hormone production and also for intracellular signalling purposes. Owing to its oxidative properties, however, it is harmful to cells, and deregulation of thyroid oxidative state has been implicated in the pathology of thyroid cancer. In this project, we studied the effects of H(2)O(2) on morphology and histochemical indicators of differentiated function (intracellular thyroglobulin), ability to generate NADPH (glucose-6-phosphate dehydrogenase (G6PD) activity) and vitality (apoptosis assay) in human thyroid epithelial cells. We further evaluated whether methimazole, an antithyroid drug reported to have antioxidative properties, could counteract the effects of H(2)O(2). Our data demonstrate tolerance to H(2)O(2) in concentrations less than 0.3mM and harmful effects at higher concentrations. 10mM methimazole sensitizes the cells towards H(2)O(2), possibly due to a dose-dependent inhibition of G6PD. Our data demonstrate the importance of this antioxidative system and point towards a relevant, but seldom recognized, influence of methimazole.

Topics: Antithyroid Agents; Cells, Cultured; Dose-Response Relationship, Drug; Drug Synergism; Epithelial Cells; Glucosephosphate Dehydrogenase; Humans; Hydrogen Peroxide; Methimazole; Oxidants; Oxidation-Reduction; Oxidative Stress; Thyroid Gland; Thyroid Hormones; Thyroid Neoplasms

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

Topics: Adenoma; Aged; Antithyroid Agents; Female; Humans; Methimazole; Radionuclide Imaging; Radiopharmaceuticals; Sodium Pertechnetate Tc 99m; Thyroid Function Tests; Thyroid Neoplasms

Activins are dimeric proteins of the transforming growth factor beta superfamily, which exhibit multiple functions in gonadal and extragonadal tissues. Expression of activin A, composed of two betaA subunits, has been shown in the thyroid, whereas there has been no study regarding activin B (betaBbetaB) in this gland. In other tissues, such as the gonads, pancreas, and adrenal cortex, expression of both activin betaA and activin betaB has been described. In this study, we detected activin betaB mRNA and protein expression using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry in rat experimental goiter and in human thyroid, including multinodular goiter, follicular adenoma, papillary carcinoma, and follicular carcinoma. Activin betaA mRNA and protein expression was also investigated in rat and human thyroid tissue. The expression of both activin betaB and activin betaA was highest in rat methimazole-induced goiter and in human follicular adenoma, and papillary and follicular carcinomas when compared with multinodular goiter and normal thyroid tissue. The increased expression of activin betaB as well as activin betaA, observed in this study, suggests that activin B and activin A may be involved in the proliferative and neoplastic processes of the thyroid.

Topics: Animals; Base Sequence; DNA Primers; Goiter; Humans; Immunohistochemistry; Inhibin-beta Subunits; Male; Methimazole; Molecular Sequence Data; Rats; Rats, Wistar; RNA, Messenger; Thyroid Gland; Thyroid Neoplasms

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

We report a case of pulmonary metastatic thyroid carcinoma complicated with Graves' disease. A 56-year-old Japanese woman was referred to the Niigata Cancer Center Hospital for isotope therapy for pulmonary metastatic thyroid carcinoma. In 1993, she received a left-hemithyroidectomy. In 1999, the remnant thyroid was resected for isotope therapy of metastatic lesions in the lungs. Although she had been receiving suppressive therapy with levothyroxine, her general condition was good, and TRAb was positive before the operation. After a total thyroidectomy, the patient became thyrotoxic. For functioning metastatic lesions, the patient was treated with 5550 MBq of 131I and methimazole. Thyroid function was normalized after the therapy but TRAb and TSAb levels remained high.

Topics: Antithyroid Agents; Autoantibodies; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Iodine Radioisotopes; Lung Neoplasms; Methimazole; Middle Aged; Receptors, Thyrotropin; Thyroid Neoplasms; Thyroidectomy; Thyrotropin; Thyroxine; Tomography, X-Ray Computed; Triiodothyronine

Sarcoidosis is a systemic chronic granulomatous disease of unknown etiology most commonly affecting young females. The disease was first described in the thyroid gland in 1938. Our patient, a 27-year-old male with known sarcoidosis, was referred to the National University Hospital for acute symptoms of thyrotoxicosis (weight loss of 6 kg, tremor, thyroid enlargement, and tachycardia). Laboratory findings showed suppressed serum thyrotropin (TSH, <0.03 mU/L [0.5-4.20]), increased total thyroxine (T4) (223 nmol/L, [60-140]), and triiodothyronine (T3) (8.5 nmol/L, [1.5-2.7]). Furthermore, Tc-99m pertechnetate scintigraphy disclosed diffuse accumulation of the isotope confirming the diagnosis of Graves' disease. During the next 18 months of antithyroid treatment (thiamazole, Thycapzol) hyperthyroidism was difficult to control, the thyroid gland gradually enlarged, and surgery was recommended. Initially, the patient declined surgery but after an additional 18 months, he accepted surgery. During the 36-month period of antithyroid drug treatment TSH was suppressed (<0.01 mU/L) and T3 often elevated despite high doses of thiamazole. Total thyroidectomy was performed, and histologic examination of the removed thyroid tissue confirmed the diagnosis of Graves' disease and also the presence of sarcoid granuloma and metastatic papillary adenocarcinoma with spread to neck lymph nodes. Four months later, a modified radical neck dissection was performed with removal of neck lymph nodes followed by external radiation therapy (2 Gy x 32 fractions to the neck). The concomitant presence of sarcoidosis, papillary carcinoma, and Graves' disease in a thyroid gland, to our knowledge, has not previously been described in the literature.

Topics: Adult; Antithyroid Agents; Carcinoma, Papillary; Granuloma; Graves Disease; Humans; Lymphatic Metastasis; Male; Methimazole; Sarcoidosis; Thyroid Diseases; Thyroid Neoplasms; Thyrotropin; Thyroxine; Triiodothyronine

Here we report three cases of hyperthyroid Graves' disease that occurred after partial thyroidectomy for papillary carcinoma. In Case 1, the patient first developed hyperthyroidism 2 years after resection of left thyroid lobe, was treated for 2 years with antithyroid drug which was then discontinued, and relapsed with periodic paralysis after 8 years of remission. In Case 2, a hyperfunctioning remnant thyroid was noted 22 years after right hemithyroidectomy. In Case 3, where thyrotoxic symptoms became evident 7 weeks after right hemithyroidectomy, autoantibodies to thyroglobulin and thyroid microsome were positive in preoperative serum, in line with a report by others detecting these antibodies in 2 out of 3 such cases examined. Later bioassay revealed activity of thyroid stimulating antibodies in that serum, with further increase in titer in the sample taken at the clinical manifestation. Hence in Case 3, surgical stress may have altered immunological homeostasis, promoting a preclinical Graves' disease to full-blown hyperthyroidism.

Topics: Adult; Antithyroid Agents; Autoantibodies; Carcinoma, Papillary; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Receptors, Thyrotropin; Recurrence; Sodium Pertechnetate Tc 99m; Thyroid Neoplasms; Thyroidectomy; Thyrotropin

Radioiodine treatment use is frequent in patients with benign hyperfunctioning thyroid diseases and the side-effects are rare. In this paper we described the appearance of TSH-receptor antibodies and the concomitant development of persistent hyperthyroidism in a patient with hyperfunctioning thyroid adenoma after 131I treatment. A 70-year-old man presented a hyperfunctioning thyroid adenoma with suppressed uptake in the adjacent normal gland. Antibodies against the thyroglobulin (TgAb), thyroid peroxidase (TPOAb) and TSH-receptor (TRAb) were absent. One year after remission by radioiodine therapy the patient developed severe and persistent hyperthyroidism associated with diffuse 131I uptake in the gland. TgAb and TPOAb remained absent, but TRAb were present. Although spontaneous development of Graves' disease cannot be excluded, the time sequence and the negative familial and personal history for autoimmune diseases suggest a possible connection between the two phenomena. The release of TSH-receptor antigen from follicular cells damaged by 131I may have triggered the autoimmune response turning a toxic nodular goiter patient into a Graves' disease patient.

Topics: Adenoma; Aged; Antithyroid Agents; Autoantibodies; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Iodine Radioisotopes; Male; Methimazole; Receptors, Thyrotropin; Thyroid Neoplasms; Thyrotropin; Thyroxine; Triiodothyronine

A case of a very rare association of toxic adenoma and papillary carcinoma with Graves' disease is presented. A 34-year-old woman developed Graves' disease with mild ophthalmopathy. An ultrasound revealed diffuse thyroid enlargement with a hypoechoic pattern and a hypoechoic nodule with regular edges of 1.6 cm in diameter at the lower pole of the left lobe. A thyroid 131I scintiscan showed a diffuse and homogeneous 131I distribution. The 131I uptake (RAIU) was elevated. One year later, while still on a low dose of methimazole, the patient had a recurrence of hyperthyroidism following an iodine load from a contrast agent. A further thyroid ultrasound confirmed the previously described pattern but showed a new hypoechoic nodule of 1.1 cm with irregular edges in the left lobe. A thyroid 131I scintiscan this time demonstrated a hyperactive area localised in the larger nodule and a lower diffuse uptake of the remaining tissue. Because of the worsening of the symptoms of hyperthyroidism, the patient had a left lobectomy. On histological examination, the larger nodule was well encapsulated and showed the characteristics of a hyperfunctioning follicular adenoma. The smaller nodule was a typically unencapsulated papillary carcinoma. Several other microfoci of papillary carcinoma were also found in the adjacent tissue. Completion of thyroidectomy was therefore performed, followed by 131I ablative therapy and thyroxine suppressive treatment. This observation suggests that the chronic abnormal stimulation of the thyroid gland by the thyroid-stimulating antibody (TSAb) may facilitate the neoplastic transformation of the thyrocytes in individuals with a critical genetic background.

Topics: Adenoma; Adult; Antithyroid Agents; Carcinoma, Papillary; Female; Graves Disease; Humans; Iodine Radioisotopes; Methimazole; Thyroid Neoplasms; Thyroidectomy; Thyroxine; Ultrasonography

We describe a 75-year-old man who had had a lump in his neck for about 15 years. At his first visit to our hospital, poorly differentiated papillary carcinoma of the thyroid was diagnosed by means of aspiration cytology; x-rays revealed the presence of lung metastases. He was thyrotoxic with positive thyroid stimulating antibody (TSAb). He was reluctant to undergo surgery. In an early stage of the treatment for Graves' disease, he became hypothyroid with decreased TSAb activity and strongly positive thyroid stimulation blocking antibody (TSBAb), and rapid growth of the thyroid carcinoma with anaplastic transformation was observed. The increase in the size of the transformed thyroid carcinoma was shown to be exponential by ultrasonography. This is a rare case in which anaplastic transformation of the thyroid papillary carcinoma became apparent during treatment of Graves' disease with varied activity of thyrotropin receptor antibodies.

Topics: Aged; Antibodies; Antithyroid Agents; Carcinoma; Carcinoma, Papillary; Graves Disease; Humans; Hypothyroidism; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Receptors, Thyrotropin; Thyroid Neoplasms; Ultrasonography

Two cases are reported in which a rare hyperthyroidism appeared: in a female after radioiodine therapy for toxic multinodular goiter and in a male after spontaneous regression of a toxic adenoma. Both subjects showed a relapse of hyperthyroidism after a period of well-being lasting almost eight months in the first and three years in the second. Thyroid scans were consistent with an immunogenic hyper-thyroidism because there was a diffuse trapping of 131I in the thyroids while the previous autonomously functioning nodules became "cold". Serum TSH was undetectable, free thyroid hormones were increased, TgAb and TRAb were always normal in both patients, TPO became moderately positive only in the female. TRAb were evaluated only by radioimmunoassay. In these patients a diagnosis of Graves'-like disease was made because of the clinical and scintigraphic pattern. Moreover US did not reveal nodular areas different from those highlighted by scans. None of the subjects developed ophthalmopathy and/or dermopathy. Our remarks show that in particular subjects, genetically susceptible to autoimmunity, the release of antigenic materials secondary to destruction of thyroid nodules can trigger an autoimmune thyroid response resembling Graves' disease. Therefore all patients carrying autonomous nodules should be carefully evaluated for a possible autoimmune disposition before treatment and after admission. Radionuclide imaging is a simple, reliable, non invasive technique which can be applied in the evaluation of the etiology of the relapses.

Topics: Adenoma; Aged; Antithyroid Agents; Autoimmune Diseases; Female; Goiter, Nodular; Graves Disease; Humans; Male; Methimazole; Middle Aged; Radionuclide Imaging; Thyroid Neoplasms

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

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

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

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

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

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

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

The proliferation pattern of some scattered clones of naturally occurring follicular cells with an exceedingly high intrinsic growth potential was investigated in the mouse thyroid gland. In particular, evidence was sought to demonstrate that the high propensity to replicate is a stable trait transmitted from the progenitor cells to their offspring. We hypothesize that these cell clones are at the origin of the multiple adenomas that invariably arise in chronically stimulated thyroid. Growth stimulation was induced either by hemithyroidectomy or by methimazole feeding. In a first series of experiments, involving hemithyroidectomized animals, [3H]thymidine was administered continuously for 3 weeks by means of osmotic minipumps, so that all cells entering the mitotic cycle during that time were labeled. Hemithyroidectomy led to a 3-fold increase of the fraction of labeled cells in the remaining lobe. The increase was prevented by thyroxine treatment in thyroid-stimulating hormone-suppressing doses. Autoradiographs of contiguous serial sections across whole follicles showed that roughly 75% of the labeled cells were clustered in groups of 3 or more, rather than being randomly distributed. In a second set of experiments, glands stimulated by methimazole-induced thyroid-stimulating hormone hypersecretion were pulse-labeled by a single i.p. injection of [3H]thymidine. Animals were sacrificed either 2 h or 3 weeks after the administration of the label. The thyroids were excised and the fate of labeled thyroid cells was analyzed autoradiographically. In the 2-h exposure, about 95% of all labeled follicular cells were single and the remaining 5% were in pairs. In contrast, about 50% of all labeled cells were clustered in groups of 3 to 12 cells 3 weeks after the pulse labeling. The number of silver grains per nucleus was compared to that of the identically exposed controls. The intensity of label per cell appeared to be decreased in proportion to the size of the labeled clusters, indicating that clusters had generated several subsequent generations of cells. The results support previously produced evidence that highly growth-prone cells naturally occur within the normal thyroid and demonstrate, in addition, that their high intrinsic growth rate is a stable, inheritable trait. Cells which replicate at a rate faster than that of the average epithelial cell have a tendency to overgrow during goitrogenesis. They may be at the very origin of the nodules and adenomas co

Topics: Animals; Cell Division; Clone Cells; Epithelial Cells; Methimazole; Mice; Mice, Inbred BALB C; Thymidine; Thyroid Gland; Thyroid Neoplasms; Thyrotropin; Tritium

A follicular adenoma of the thyroid was 'hot' one hour after 99mTc pertechnetate administration, but 'cold' 24 h after 131I iodide administration. Incubation of the tissue in vitro demonstrated a defect in iodide binding to proteins that was abolished by addition of an H2O2 generating system. In this tissue iodide failed to inhibit TSH-induced cyclic AMP accumulation. The results show that iodide oxidation is required for its inhibitory action on cyclic AMP accumulation in human thyroid.

Topics: Adenoma; Adult; Cyclic AMP; Female; Humans; In Vitro Techniques; Iodine Radioisotopes; Methimazole; Potassium Iodide; Protein Binding; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Technetium; Thyroid Neoplasms; Thyrotropin

The human Sipple syndrome associates a thyroid-C-cell tumor and a pheochromocytoma. A treatment with the antithyroid drug thiamazole allows obtaining experimentally a similar syndrome in rat. Present paper seeks to analyse changes which happened in the medullary zone of adrenal glands before and during the development of the tumors. During the treatment by thiamazole both adrenal cortex and medulla were atrophied. After the treatment was stopped, the weight of the gland increased, as compared with its previous state, and this was chiefly due to the hyperplasia of medullary cells, from which pheochromocytomas originate. The initial atrophy of adrenal gland depends on the thiamazole-induced hyperthyroidism, but the mechanism of the medullary hyperplasia subsequent to the treatment ending is unknown. It results probably from a secondary hyperthyroidism.

Topics: Adrenal Gland Neoplasms; Adrenal Medulla; Animals; Male; Methimazole; Neoplasms, Experimental; Pheochromocytoma; Rats; Rats, Inbred Strains; Syndrome; Thyroid Neoplasms

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

When rats are treated by an antithyroid drug as the thiamazole, an hyperplasia of the parafollicular thyroideal cells can occur during the treatment, as shown in our previous works, or not, as in the present experiment. This difference depends on the dose of drug used, but it both cases parafollicular tumours never appear during this treatment. Whatever was the initial reaction of the parafollicular cells during the treatment, an important hyperplasia of these cells always expands after its stop and is frequently followed by the development of parafollicular tumours. Then, the initial hyperplasia sometimes obtained is not prerequisite for the formation of neoplasm. The mechanism of tumoral formation must be investigated in the disorders which follow the stop of the treatment.

Topics: Animals; Antithyroid Agents; Hyperplasia; Male; Methimazole; Rats; Thyroid Gland; Thyroid Neoplasms; Time Factors

Sipple syndrome, associating a C cells or parafollicular thyroid tumor and a pheochromocytoma of the medullary part of adrenal gland, can be experimentally induced with the use of an antithyroid drug, the thiamazole, in the rat. The treatment is applied here either between 3 and 11 months, or between 6 and 14 months of age. Tumors appear a long time after the treatment is stopped. Hypotheses are proposed to explain this phenomenon.

Topics: Adrenal Gland Neoplasms; Animals; Male; Methimazole; Neoplasms, Experimental; Pheochromocytoma; Rats; Syndrome; Thyroid Neoplasms

We have investigated the thyroid uptake of Tl-201 in 37 patients with various types of goiter, and in six with normal thyroids. Significant thallium uptake was found in all cases in which there was thyroid enlargement, including Graves' disease, toxic thyroid nodule, primary hypothyroidism, simple goiter, Hashimoto's disease, thyroid carcinoma, and thyroid adenoma. If goiter was absent, however, there was no demonstrable uptake--e.g., in secondary hypothyroidism, subacute thyroiditis, and the normal controls. Thallium uptake did not correlate with thyroid function tests such as BMR, T3-RU, T3, T4, TSH, antithyroid antibodies, or the 24-hr I-131 uptake. In 23 patients with diffuse goiter, on the other hand, maximum Tl-201 uptake correlated well with thyroid weight: r = 0.836 (p less than 0.001); y = 0.02 x + 0.06.

Topics: Adenoma; Antithyroid Agents; Contrast Media; Goiter; Goiter, Nodular; Graves Disease; Humans; Hypothyroidism; Iodipamide; Methimazole; Radioisotopes; Radionuclide Imaging; Syndrome; Thallium; Thyroid (USP); Thyroid Diseases; Thyroid Function Tests; Thyroid Neoplasms; Thyroiditis; Thyroiditis, Autoimmune; Thyrotropin

Hyperthyroidism of Graves' disease may be treated very effectively by antithyroid pills, such as PTU and Tapazole, by radioactive iodine therapy, and by subtotal thyroidectomy. Each form of therapy has advantages and disadvantages, and thus treatment should be individualized. While therapy with radioactive iodine would appear to be ideal since it does not require an operation and is less expensive than surgical management, it suffers from a high rate of progressive hypothyroidism and from the fact that the time until a euthyroid state is obtained is often prolonged. In addition, the long-term carcinogenic risk of the therapy for thyroid neoplasia has never been completely defined since the data most often quoted have a mean follow-up time of only eight years. Furthermore, new "low-dose" radioiodine regimens may be more dangerous in this regard. Subtotal thyroidectomy, while not totally without complications, remains a rapid, safe, and effective treatment for Graves' disease. The careful use of propranolol has facilitated the preparation of some patients and has lessened the risk of operation. Thyroidectomy should remain the treatment of choice for young adults with this disease.

Topics: Graves Disease; Humans; Iodine Radioisotopes; Leukemia, Radiation-Induced; Methimazole; Neoplasms, Radiation-Induced; Premedication; Propranolol; Propylthiouracil; Risk; Thyroid Neoplasms; Thyroidectomy

Hypothyroidism is induced in rats treated with thiamazole, an antithyroid drug. If this phase lasts long enough, the follicular cells develop adenomas. Within the same period, the number of parafollicular or C cells increases threefold on an average, but without producing corresponding adenomas, the formation of which is inhibited. When treatment is stopped, a second phase appears during which thyroid function reverts to normal. The previously observed inhibition disappears, and, after a period of latency, the hyperplastic C cells develop parafollicular adenomas. The type of tumors to be found in treated rats (either of them, or both simultaneously) is determined by respective durations of the two phases. The endocrine mechanisms of these phenomena are discussed.

Topics: Adenoma; Animals; Antithyroid Agents; Hypothyroidism; Male; Methimazole; Neoplasms, Experimental; Rats; Thyroid Gland; Thyroid Neoplasms; Time Factors

The nature of tumors appearing in the thyroid gland and in the lungs of mice fed two standard goitrogenic drugs (MTU and MII) has been studied. These tumors have been considered malignant on the basis of their morphological appearance and their occurrence in abnormal locations. Some investigatiors, however, have questioned that they are actually malignant. The present results indicate that these tumors are most likely not malignant even if it is shown that the pulmonary nodules are of thyroid origin. The thyroid adenomas disappear once the goitrogen is withdrawn, but thryoid enlargement pesists, and event 6 months after discontinuation of the goitrogenic treatment , pulmonary nodules are still produced. Evidence is presented that these nodules are emoli from hyperplastic thyroid tissue and not tumors.

Topics: Adenoma; Animals; Carcinoma, Hepatocellular; Diet; Glycolysis; Hyperplasia; Iodine; Liver Neoplasms; Lung Neoplasms; Male; Methimazole; Methylthiouracil; Mice; Mice, Inbred Strains; Oxygen Consumption; Thyroid Gland; Thyroid Neoplasms

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

To determine if propylthiouracil (PTU) inhibited extrathyroidal thyroxine (T4) to triiodothyronine (T3) conversion in man, PTU was administered to T4-treated hypothyroid patients and serial measurements of T4, T3, and thyrotropin (TSH) carried out. All patients had proven thyroidal hypothyroidism and had been receiving 0.1 or 0.2 mg T4 daily for at least 2 mo before study. Hormone measurements were made for 5 consecutive days before and daily during a 7-day treatment period with PTU, 1,000 mg/day. In eight patients receiving 0.1 mg T4 daily, administration of PTU resulted in a prompt fall in mean serum T3 concentrations from 78 plus or minus 6 ng/100 ml (SEM) to 61 plus or minus 3 ng/100 ml after 1 day. The mean serum T3 concentrations ranged from 55 to 60 ng/100 ml during the remainder of the PTU treatment period (P less than 0.01). The mean control serum TSH concentration was 29.6 muU/ml and it increased to a peak of 40 muU/ml on the 5th and 6th days. In five patients receiving 0.2 mg T4 daily, the mean control serum T3 concentration was 84 plus or minus 7 NG/100ML. It fell to 70 plus or minus 5 ng/100 ml after 1 day and 63 plus or minus 7 ng/100 ml after 2 days of PTU administration and thereafter ranged from 6) to 69 ng/100 ml (P LESS THAN 0.01). Serum TSH concentrations did not increase. No changes in serum T4 concentrations were found in either group. In five patients who received 100 mg methimazole (MMI) daily for 7 days there were no changes in serum T4, T3, or TSH concentrations. These results indicate that PTU, but not MMI, produces a prompt and sustained, albeit modest, reduction in serum T3 concentrations in patients whose sole or major source of T3 is ingested T4. These findings most likely result from inhibition of extrathyroidal formation of T3 from T4.

Topics: Administration, Oral; Adult; Aged; Depression, Chemical; Female; Humans; Hypothyroidism; Male; Methimazole; Middle Aged; Propylthiouracil; Thyroid Neoplasms; Thyroidectomy; Thyroiditis, Autoimmune; Thyrotropin; Thyroxine; 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

Topics: Adenoma; Antithyroid Agents; Carbimazole; Humans; Hyperthyroidism; Iodides; Methimazole; Propylthiouracil; Sulfur Isotopes; Thyroid Gland; Thyroid Neoplasms

Topics: Adenoma; Aged; Chemical and Drug Induced Liver Injury; Cholangiography; Drug Hypersensitivity; Female; Humans; Hyperthyroidism; Liver; Liver Function Tests; Methimazole; Thyroid Neoplasms

Topics: Adenocarcinoma; Adenoma; Animals; Female; Hyperplasia; Hypertrophy; Male; Methimazole; Neoplasms; Rats; Thyroid Diseases; Thyroid Gland; Thyroid Neoplasms

Topics: Animals; Antithyroid Agents; Carbimazole; Chromatography, Paper; Chromatography, Thin Layer; Humans; Imidazoles; Male; Methimazole; Methylthiouracil; Propylthiouracil; Rats; Sulfur Isotopes; Thiouracil; Thyroid Gland; Thyroid Neoplasms; Thyroidectomy

Topics: Adenoma; Humans; Iodine Isotopes; Methimazole; Radionuclide Imaging; Thyroid Neoplasms

Topics: Adenoma; Animals; Antithyroid Agents; Carcinogens; Carcinoma, Hepatocellular; Cysts; Female; Glucose; Goiter; Imidazoles; Kidney Diseases; Lactates; Liver Neoplasms; Male; Methimazole; Methylthiouracil; Mice; Mice, Inbred Strains; Ovarian Cysts; Oxygen Consumption; Thyroid Diseases; Thyroid Gland; Thyroid Neoplasms; Triiodothyronine

Topics: Adenoma; Animals; Antithyroid Agents; Hypercalcemia; Hyperparathyroidism; Iodine Isotopes; Methimazole; Parathyroid Glands; Rats; Thyroid Neoplasms

Topics: Adenoma; Animals; Antithyroid Agents; Carcinogens; Carcinoma; Carcinoma, Hepatocellular; Female; Goiter; Imidazoles; Liver Neoplasms; Methimazole; Mice; Neoplasms, Experimental; Ovarian Neoplasms; Oxygen Consumption; Thyroid Gland; Thyroid Neoplasms

Topics: Aged; Chromatography, Paper; Diagnosis, Differential; Electrocardiography; Female; Humans; Iodine Isotopes; Iodine Radioisotopes; Methimazole; Neoplasm Metastasis; Radiography; Radionuclide Imaging; Thoracic Neoplasms; Thyroid Crisis; Thyroid Function Tests; Thyroid Neoplasms; Thyroidectomy; Triiodothyronine