methimazole and Goiter

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

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

A 15-year-old girl had a history of diffuse goiter and received methimazole treatment 2 months before admission to the hospital. She developed bilateral lower leg edema 5 days before admission and the laboratory examinations revealed leukopenia, anemia, proteinuria, and granular cast. Positive antinuclear antibodies and anti-double strand (anti-ds) DNA antibodies were noted, although complement levels were not reduced. Myeloperoxidase antineutrophil cytoplasmic antibody was positive. A renal biopsy disclosed that there was focal segmental glomerulosclerosis. Methimazole was discontinued, and she was treated with prednisolone and Plaquenil, after which the symptoms and laboratory tests became normal within 40 days. The prednisolone was discontinued after treatment for seven months. Currently, the anti-dsDNA, C3, C4, CBC, urinalysis, and thyroid function tests are within normal limits. With hydroxychloroquine and levothyroxine, she was free of symptoms after discontinuation of methimazole until now (about 21 months).

Topics: Adolescent; Antibodies; Antibodies, Antinuclear; DNA; Female; Glucocorticoids; Goiter; Humans; Hydroxychloroquine; Lupus Nephritis; Methimazole; Prednisolone; Thyroxine

Topics: Animals; Carbimazole; Choanal Atresia; Ectodermal Dysplasia; Female; Goiter; Guinea Pigs; Humans; Hypothyroidism; Methimazole; Mice; Pregnancy; Propylthiouracil; Rabbits; Rats; Teratogens; Thyroid Gland

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

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

It is possible to raise the rate of the uptake of. Thirty-one patients with NMG received. Radioiodine treatment of NMG preceded with appropriate application of MMI is efficient thanks to increased RAIU, shorter period of treatment, and lower frequency of

Topics: Goiter; Goiter, Nodular; Humans; Iodine Radioisotopes; Methimazole; Thyrotropin

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

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

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

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

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

Accelerated metabolism is a hallmark of thyrotoxicosis, but the underlying biochemical mechanisms are incompletely understood. In order to elucidate these metabolic events further, we studied 12 patients with newly diagnosed diffuse (10 patients) or nodular (two patients) toxic goitre (ten women, two men; age 42.8 +/- 3.2 yr; BMI: 21.6 +/- 0.7 kg/m2) before ("TOX") and after ("TRE") 11.2 +/- 1.0 weeks treatment with methimazole and compared these patients to a control group ("CTR") of 11 subjects (nine women, two men; age 40.5 +/- 3.9 yr; BMI 22.5 +/- 1.0 kg/m2). All were studied for three hours in the basal state, using indirect calorimetry, isotope dilution for measurement of glucose turnover and the forearm technique for assessment of muscle metabolism. Prior to treatment patients with thyrotoxicosis were characterized by: Increased (p < 0.05) levels of T3 (3.75 +/- 0.23 [TOX], 1.89 +/- 0.08 [TRE] and 1.75 +/- 0.11 [CTR] nmol/l), resting energy expenditure (130.5 +/- 3.5 [TOX], 107.7 +/- 2.7 [TRE] and 106.3 +/- 3.1 [CTR] percent of predicted), protein oxidation (0.67 +/- 0.03 [TOX], 0.54 +/- 0.06 [TRE] and 0.46 +/- 0.05 [CTR] mg/kg/min), lipid oxidation (1.34 +/- 0.08 [TOX], 1.00 +/- 0.06 [TRE] and 1.02 +/- 0.04 [CTR] mg/kg/min), endogenous glucose production (2.51 +/- 0.13 [TOX], 1.86 +/- 0.12 [TRE] and 1.85 +/- 0.12 [CTR] mg/kg/min), non-oxidative glucose turnover (1.28 +/- 0.16 [TOX], 0.75 +/- 0.18 [TRE] and 0.71 +/- 0.11 [CTR] mg/kg/min) and a 50% increase in total forearm blood flow. Glucose oxidation (1.23 +/- 0.09 [TOX], 1.13 +/- 0.10 [TRE] and 1.13 +/- 0.09 [CTR] mg/kg/min), exchange of substrates in the muscles of the forearm and circulating levels of insulin, C-peptide, growth hormone or glucagon were not influenced by hyperthyroidism. Propranolol (20 mg thrice daily) given to seven of the patients for two days did not affect circulating levels of thyroid hormones, energy expenditure or glucose turnover rates. These results suggest that all major fuel sources contribute to the hypermetabolism of thyrotoxicosis and that augmented non-oxidative glucose metabolism may further aggravate the condition. All abnormalities recede with medical treatment of the disease.

Topics: Adult; Antithyroid Agents; Energy Metabolism; Female; Glucose; Goiter; Goiter, Nodular; Humans; Male; Methimazole; Substrate Cycling; Thyroid Hormones; Thyrotoxicosis

Accelerated metabolism is a hallmark of thyrotoxicosis, but the underlying biochemical mechanisms are incompletely understood and the majority of studies have investigated normal subjects rendered only modestly hyperthyroid for a brief period of time. We have therefore studied a group of thyrotoxic patients using several different techniques.. Twelve patients with newly diagnosed diffuse (10 patients) or nodular (2 patients) toxic goitre (10 women, 2 men; age 42.8 +/- 3.2 years; BMI 21.6 +/- 0.7 kg/m2) before ('pretreatment') and after ('treated') 11.2 +/- 1.0 weeks treatment with methimazole and compared these patients to a control group ('control') of 11 subjects (9 women, 2 men; age 40.5 +/- 3.9 years; BMI 22.5 +/- 1.0 kg/m2). All were studied for 3 hours in the basal state, using indirect calorimetry, isotope dilution for the measurement of glucose turnover and the forearm technique for assessment of muscle metabolism.. Prior to treatment patients with thyrotoxicosis were characterized by increased (P < 0.05) levels of T3 (3.75 +/- 0.23 nmol/l (pretreatment), 1.89 +/- 0.08 (treated) and 1.75 +/- 0.11 (control)), resting energy expenditure (130.5 +/- 3.5 (pretreatment), 107.7 +/- 2.7 (treated) and 106.3 +/- 3.1 (control), % of predicted), protein oxidation (0.67 +/- 0.03 (pretreatment), 0.54 +/- 0.06 (treated) and 0.46 +/- 0.05 (control), mg/kg/min), lipid oxidation (1.34 +/- 0.08 (pretreatment), 1.00 +/- 0.06 (treated) and 1.02 +/- 0.04 (control), mg/kg/min), endogenous glucose production (2.51 +/- 0.13 (pretreatment), 1.86 +/- 0.12 (treated) and 1.85 +/- 0.12 (control), mg/kg/min), non-oxidative glucose turnover (1.28 +/- 0.16 (pretreatment), 0.75 +/- 0.18 (treated) and 0.71 +/- 0.11 (control), mg/kg/min) and a 50% increase in total forearm blood flow. Glucose oxidation (1.23 +/- 0.09 (pretreatment), 1.13 +/- 0.10 (treated) and 1.21 +/- 0.11 (control) mg/kg/min), exchange of substrates in the muscles of the forearm and circulating levels of insulin, C-peptide, growth hormone or glucagon were not influenced by hyperthyroidism. Propranolol (20 mg thrice daily) given to 7 of the patients for 2 days did not affect circulating levels of thyroid hormones, energy expenditure or glucose turnover rates.. These results suggest that all major fuel sources contribute to the hypermetabolism of thyrotoxicosis and that augmented non-oxidative glucose metabolism may further aggravate the condition. All abnormalities diminish with medical treatment of the disease.

Topics: Adrenergic beta-Antagonists; Adult; Antithyroid Agents; Calorimetry, Indirect; Drug Therapy, Combination; Female; Forearm; Glucose; Goiter; Humans; Male; Methimazole; Middle Aged; Muscle, Skeletal; Oxygen Consumption; Propranolol; Radioisotope Dilution Technique; Regional Blood Flow; Thyrotropin; Thyroxine; Triiodothyronine

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

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

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

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

Diffuse toxic goiter accounts for about 15% of all childhood thyroid diseases. There is great controversy over the management of Graves' disease in children and adolescents. This article reports our experience in 304 children and juvenile patients with Graves' disease.. Between 1981 and 2015, 304 patients aged 5-19 years with diffuse toxic goiter were studied, of whom 296 patients were treated with antithyroid drugs (ATD) for 18 months. Patients with persistent or relapsed hyperthyroidism who refused ablative therapy with surgery or radioiodine were managed with continuous methimazole (MMI) treatment.. In 304 patients (245 females and 59 males), the mean age was 15.6±2.6 years. After 18 months of ATD therapy, 37 remained in remission and of the 128 who relapsed, two, 29 and 97 patients chose surgery, continuous ATD and radioiodine therapy, respectively. Of the 136 patients who received radioiodine, 66.2% became hypothyroid. Twenty-nine patients received continuous ATD therapy for 5.7±2.4 years. The mean MMI dose was 4.6±12 mg daily, no serious complications occurred and all of them remained euthyroid during the follow-up. Less abnormal thyroid-stimulating hormone (TSH) values were observed in these patients, as compared to patients who were on a maintenance dose of levothyroxine after radioiodine induced hypothyroidism.. Original treatment with ATD and subsequent radioiodine therapy remain the mainstay of treatment for juvenile hyperthyroidism. Continuous ATD administration may be considered as another treatment modality for hyperthyroidism.

Topics: Adolescent; Adult; Antithyroid Agents; Child; Child, Preschool; Combined Modality Therapy; Female; Follow-Up Studies; Goiter; Hospitals, University; Humans; Iodine Radioisotopes; Iran; Male; Methimazole; Outpatient Clinics, Hospital; Patient Acceptance of Health Care; Radiopharmaceuticals; Recurrence; Remission Induction; Retrospective Studies; Thyroid Gland; Thyrotoxicosis; Young Adult

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

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

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

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

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

Although thyroid-stimulating hormone (TSH) is known to be a major regulator of thyroid hormone biosynthesis and thyroid growth, insulin-like growth factor 1 (IGF-1) is required for mediating thyrocyte growth in concert with TSH in vitro. We generated mice with thyrocyte-selective ablation of IGF-1 receptor (TIGF1RKO) to explore the role of IGF-1 receptor signaling on thyroid function and growth. In 5-wk-old TIGF1RKO mice, serum thyroxine (T4) concentrations were decreased by 30% in concert with a 43% down-regulation of the monocarboxylate transporter 8 (MCT8), which is involved in T4 secretion. Despite a 3.5-fold increase in circulating concentrations of TSH, thyroid architecture and size were normal. Furthermore, thyrocyte area was increased by 40% in WT thyroids after 10 d TSH injection, but this effect was absent in TSH-injected TIGF1RKO mice. WT mice treated with methimazole and sodium perchlorate for 2 or 6 wk exhibited pronounced goiter development (2.0 and 5.4-fold, respectively), but in TIGF1RKO mice, goiter development was completely abrogated. These data reveal an essential role for IGF-1 receptor signaling in the regulation of thyroid function and TSH-stimulated goitrogenesis.

Topics: Animals; Antithyroid Agents; Down-Regulation; Goiter; Membrane Transport Proteins; Methimazole; Mice; Mice, Knockout; Monocarboxylic Acid Transporters; Perchlorates; Receptor, IGF Type 1; Sodium Compounds; Symporters; Thyroid Gland; Thyrotropin; Thyroxine

Studies on the role of thyroid hormones (THs) in teleost fish physiology have deployed the synthetic goitrogens, methimazol (MMI), propilthiouracil (PTU) and thiourea (TU) that are used to treat human hyperthyroidism. However, the action of the goitrogens, MMI, PTU and TU at different levels of the hypothalamic-pituitary-thyroid (HPT) axis in teleosts is largely unknown. The central importance of the hypothalamus and pituitary in a number of endocrine regulated systems and the cross-talk that occurs between different endocrine axes makes it pertinent to characterize the effects of MMI, PTU and TU, on several endpoints of the thyroid system. The marine teleost, sea bream (Sparus auratus) was exposed to MMI, PTU and TU (1mg/kg wet weight per day), via the diet for 21days. Radioimmunoassays (RIA) of plasma THs and ELISA of the TH carrier transthyretin (TTR) revealed that MMI was the only chemical that significantly reduced plasma TH levels (p<0.05), although both MMI and PTU significantly (p<0.05) reduced plasma levels of circulating TTR (p<0.05). Histological analysis of the thyroid tissue revealed modifications in thyrocyte activity that explain the reduced circulating levels of THs. MMI also significantly (p<0.05) up-regulated transcript abundance of liver deiodinase 1 and 2 while significantly (p<0.05) decreasing TRβ expression in the pituitary, all hallmarks of HPT axis action of goitrogens in vertebrates. The results indicate that in the sea bream MMI is the most effective goitrogen followed by PTU and that TU (1mg/kg wet weight for 21days) failed to have a goitrogenic effect. The study highlights the non-uniform effect of goitrogens on the thyroid axis of sea bream and provides the basis for future studies of thyroid disrupting pollutants.

Topics: Animals; Goiter; Methimazole; Phenylthiourea; Prealbumin; Radioimmunoassay; Sea Bream; Thioamides; Thiourea; Thyroid Gland; Thyroid Hormones

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

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

Thyroid autoregulation has been related to intraglandular content of an unknown putative iodocompound. The thyroid is capable of producing different iodolipids such as 6-iodo-deltalactone (ILdelta) and 2-iodohexadecanal (2-IHDA). Data from different laboratories have shown that these iodolipids inhibit several thyroid parameters. ILdelta has an antigoitrogenic action but no data about the action of 2-IHDA on this parameter has been published.. to study the action of 2-IHDA on methimazole (MMI)-induced goiter and analyze if this compound can cause the involution of preformed goiter.. Administration of MMI to rats during 10 days increased thyroid weight by 112%. This effect was significantly inhibited by the simultaneous injection of 20mug/day of 2-IHDA (51% vs. MMI) while iodine or non iodinated hexadecanal were without action. Thyroidal proliferating cell nuclear antigen (PCNA) content was increased by MMI while 2-IHDA decreased this value (control: 100%; MMI: 190+/-11; MMI+2-IHDA: 134+/-10). Serum TSH was increased after MMI administration and 2-IHDA did not modify this parameter (control: 1.89+/-0.10; MMI: 8.19+/-0.93ng/ml; MMI+2-IHDA: 7.38+/-0.72). Treatment with MMI increased thyroidal cAMP content (control: 16.1+/-0.82, MMI: 42.4+/-4.6 fmol/mg protein) while injection of 2-IHDA significantly decreased this value (22.3+/-2.0). Goiter prevention by 2-IHDA was also observed at 30 days of treatment reducing total number of cells (51% inhibition) and epithelial height (81% inhibition). Goiter involution was induced after withdrawal of MMI and injection with 2-IHDA, KI or saline. 2-IHDA led to a reduction of 74.5% in thyroid weight after 3 days while spontaneous involution (saline) was only of 32%. KI failed to alter this value. This significant involution was accompanied by a reduction in the number of cells (66%). Administration of the iodolipids did not produce significant changes in several serum parameters such as total T(3) and T(4), cholesterol, transaminases, urea and creatinine.. 2-Iodohexadecanal, as 6-iodo-deltalactone, prevents goiter growth in rats and opens a potential therapeutic application of iodolipids.

Topics: Aldehydes; Animals; Cyclic AMP; Goiter; Methimazole; Proliferating Cell Nuclear Antigen; Rats; Rats, Wistar; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

A major problem with antithyroid drug (ATD) therapy in Graves' disease is the high relapse rate. Therefore, clinicians have sought prognostic indicators of permanent remission. Suppression of serum thyrotropin (TSH) when ATD therapy is stopped carries a poor prognosis, but little is known regarding the significance of elevated serum TSH concentrations in the course of ATD therapy. The objective of this study was to determine if elevated serum TSH concentrations during methimazole (MMI) therapy is associated with a favorable long-term prognosis.. We retrospectively studied patients with Graves' disease who were initially on MMI, in whom this drug was stopped because they had undetectable thyroid-stimulating antibodies (TSAbs) or were euthyroid after at least 24 months on MMI treatment. A strategy of high MMI doses plus T4 was not used in these patients. We identified 40 patients with elevated serum TSH concentration (>10 microIU/mL) during MMI therapy (H-TSH group). Eighty-five percent of the H-TSH group had negative tests for TSAb. The H-TSH group was sex- and age-matched with 37 patients who had similar selection criteria, but did not have elevated serum TSH concentration during MMI therapy (N-TSH group). The H-TSH and N-TSH groups were similar in gross thyroid size, percentage of patients with exophthalmos, serum free thyroxine, duration of MMI treatment, TSAb status, duration that their TSAb tests remained negative, and thyroid peroxidase antibody titers. The patients were followed for 24 months after stopping MMI.. In the H-TSH group, MMI-associated hypothyroidism typically occurred after 7-8 months of treatment with daily doses of 10-15 mg MMI. No patient had severe symptoms of hypothyroidism. The percentage of patients in remission at 6, 12, and 24 months after discontinuation of MMI was 90.0, 87.5, and 85.0, respectively, in the H-TSH group and 70.3, 67.6, and 54.1, respectively, in the N-TSH group (p  <  0.05 for the comparison of groups at 6 and 12 months and p  <  0.001 for comparison of the groups at 24 months).. In patients with Graves' disease who are treated with MMI for at least 2 years and become euthyroid, the occurrence of elevated serum TSH concentrations during MMI treatment is a favorable indicator for long-term remission and is independent of multiple other factors including TSAb status, duration of MMI treatment, and gross parameters of goiter size.

Topics: Adult; Antithyroid Agents; Autoantibodies; Exophthalmos; Female; Goiter; Graves Disease; Humans; Hypothyroidism; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Prognosis; Retrospective Studies; Thyrotropin; Thyroxine

We have demonstrated that the administration of delta-iodolactone (i.e., 5-iodo-delta lactone) of arachidonic acid (IL-delta), a mediator in thyroid autoregulation, prevents goiter induction by methylmercaptoimidazol (MMI) in rats. Other studies have shown that transforming growth factor beta-1 (TGF-beta1) mimics some of the actions of excess iodide, but its participation in autoregulation is disputed. The present studies were performed to test the hypotheses that IL-delta decreases thyroid growth by inhibition of cell proliferation and/or by stimulation of apoptosis due to oxidative stress, that TGF-beta is stimulated by an excess of iodide and by IL-delta, and that c-Myc and c-Fos expression are upregulated during goiter induction and downregulated during goiter inhibition.. Rats were treated with MMI alone or together with iodide or IL-delta. Thyroid weight, cell number, cell proliferation, apoptosis, and oxidative stress were determined. Proliferating cell nuclear antigen (PCNA), TGF-beta1, TGF-beta3, c-Myc, and c-Fos were measured by Western blot.. MMI caused a progressive increase in thyroid weight accompanied by an increase in cell number, asymmetry of the ploidy histograms, and PCNA, c-Fos, and c-Myc expression. In addition, an early increase of apoptosis was observed. Peroxides as well as glutathione peroxidase and catalase activities were also increased in goitrous animals. The inhibitory action of IL-delta on goiter formation was accompanied by the inhibition of cell proliferation evidenced by a significant decrease in cell number, PCNA expression, and asymmetry of the ploidy histograms. A transient stimulation of apoptosis after 7 days of treatment was also observed. MMI administration stimulated TGF-beta1 but not TGF-beta3 synthesis. IL-delta alone caused a slight increase of TGF-beta3 but not TGF-beta1, whereas potassium iodide (KI) stimulated both isoforms and MMI reversed KI effect on TGF-beta1 expression but not on TGF-beta3.. The goiter inhibitory action of IL-delta is due to the inhibition of cell proliferation and the transient stimulation of apoptosis. This latter action does not involve oxidative stress. TGF-beta1 does not play a role in the autoregulatory pathway mediated by IL-delta. Iodide stimulates TGF-beta3 without the need of being organified. These results suggest that there may be more than one pathway involved in the autoregulatory mechanism.

Topics: Animals; Apoptosis; Arachidonic Acids; Catalase; Cell Proliferation; Female; Glutathione Peroxidase; Goiter; Methimazole; Oxidative Stress; Peroxides; Proliferating Cell Nuclear Antigen; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-myc; Rats; Rats, Wistar; Thyroid Gland; Transforming Growth Factor beta1; Transforming Growth Factor beta3

Kang-Jia-Wan (KJW), a traditional Chinese herbal medicine, is widely used to treat goiter in the clinics in China.. The mechanisms by which KJW treats goiter are unclear. It is known that insufficient apoptosis of thyrocytes is involved in the formation of goiter. Here, we investigated whether KJW could induce apoptosis in goiter of rats given methimazole (MMI).. Fifty-six Wistar rats were randomly separated into four groups: normal, MMI, MMI+low-dose KJW and MMI+hig h-dose KJW. Except for the normal group (20 rats), all groups (each with 12 rats) were given 0.04% (w/v) MMI in their drinking water. One week later, the rats in MMI+low- and high-dose KJW groups were orally supplemented with KJW at 250 mg/kg d(-1) and 1000 mg/kg d(-1), respectively.. After KJW treatment for 12 weeks, the relative thyroid weight (mg/100g body weight) of the MMI+high-dose KJW group decreased significantly. Features of apoptosis were also apparent in thyroid tissues of rats given KJW treatment. Importantly, KJW markedly increased the caspase-3 and Fas protein expression, in a dose-dependent manner, in the thyroid specimens.. These results showed that KJW played a therapeutic role via apoptosis induction in the goitrous glands.

Topics: Animals; Antithyroid Agents; Apoptosis; Caspase 3; Drugs, Chinese Herbal; fas Receptor; Goiter; Magnoliopsida; Methimazole; Organ Size; Plant Extracts; Plants, Medicinal; Rats; Rats, Wistar; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

Topics: Adult; Antithyroid Agents; Female; Goiter; Graves Disease; Humans; Methimazole; Tomography, X-Ray Computed

We present 4 patients with Graves' disease who developed spontaneous hypothyroidism during follow-up. The two most plausible physiopathologic mechanisms for this development were progressive autoimmune-mediated destruction of the thyroid follicular epithelium and a predominance of blocking antibodies to the thyroid-stimulating hormone (TSH) receptor at the expense of stimulating antibodies in the same patient. Description of these patients not only illustrates the heterogeneous nature of this disease, but also the interrelation among its distinct clinical forms.

Topics: Adult; Aged; Autoantibodies; Disease Progression; Female; Goiter; Graves Disease; Humans; Hypothyroidism; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Middle Aged; Receptors, Thyrotropin; Thyroid Hormones; Thyrotoxicosis; Thyroxine

To investigate the inhibitory effects of Kangjia Pill (KJP) on the cell proliferation in rat goiter model induced by methimazole (MMI).. Fifty-six Wistar rats were randomly divided into four groups: the normal group, MMI model group (MMI), low dose of KJP group (LKJP), and high dose of KJP (HKJP). Except the normal group (20 rats), the other groups (12 rats in each) were given 0.04% (w/v) MMI through the drinking water until the end of the experiment. One week later, the rats in the LKJP and HKJP groups were given KJP by gastrogavage at the dose of 250 mg/(kg x d) and 1,000 mg/(kg x d), respectively for 12 weeks. The relative thyroid weight (mg/100 g body weight) of each rat was accessed. The expression of proliferating cell nuclear antigen (PCNA) was determined by immunohistochemistry, and the correlation analysis between the PCNA positive thyrocytes and the relative thyroid weight was performed. The expressions of PCNA and cyclin D1 were examined with Western blotting.. After KJP treatment for 12 weeks, compared with the MMI group, the relative thyroid weight of the HKJP group decreased significantly, and the positive thyrocyte populations of PCNA in the two KJP groups reduced markedly (all P<0.05). The correlation analysis showed that PCNA was closely correlated with thyrocyte proliferation (r=0.685, P<0.05). KJP significantly decreased the protein expression of PCNA and cyclin D1 in the thyroid specimens (P<0.05), the high dose showed better effects.. KJP played a therapeutic role via inhibiting cell proliferation in the rat goitrous glands.

Topics: Animals; Cell Proliferation; Cyclin D1; Disease Models, Animal; Down-Regulation; Drug Evaluation, Preclinical; Drugs, Chinese Herbal; Goiter; Male; Methimazole; Organ Size; Proliferating Cell Nuclear Antigen; Random Allocation; Rats; Rats, Wistar; Tablets; Thyroid Gland

A unique case of fetal goiter accompanied by bilateral ovarian cysts in a mother treated with methimazole for Graves'disease is reported. The abnormal findings were detected by ultrasound at 31 weeks of gestation. Umbilical fetal blood sampling revealed elevated serum TSH, normal concentrations of free T 4 , normal FSH and LH and high concentrations of E 2 . A series of weekly amniocenteses and intra-amniotic injections of levothyroxine was initiated, along with a reduction of the mother's methimazole dosage. The level of TSH in amniotic fluid was initially high, but was considerably reduced by each injection and followed by a gradual reduction of fetal goiter as well as the left ovarian cyst. The right cyst ruptured spontaneously. At 36 weeks + 4 days, the patient underwent elective caesarean section and gave birth to a female, weighing 2,880 g with 1- and 5-min Apgar scores of 10. The thyroid gland appeared normal in size, and cord blood TSH and free T 4 were both within normal limits. At ultrasound control 6 days later, the right ovarian cyst was not visible, while the left cyst was still present. Thus, our report supports previous findings that fetal goiter can be treated successfully with intra-amniotic injection of levothyroxine.More importantly, it shows that fetal hypothyroidism with elevated levels of TSH can be accompanied by ovarian cysts,suggesting interference between thyreotropic and gonadotropic hormones.

Topics: Amniocentesis; Amniotic Fluid; Antithyroid Agents; Cesarean Section; Female; Fetal Blood; Follicle Stimulating Hormone; Goiter; Graves Disease; Humans; Infant, Newborn; Luteinizing Hormone; Maternal-Fetal Exchange; Methimazole; Ovarian Cysts; Pregnancy; Pregnancy Complications; Thyrotropin; Thyroxine; Ultrasonography

Insulin receptor substrate-1 (IRS-1) is the main intracellular substrate for both insulin and insulin-like growth factor I (IGF-I) receptors and is critical for cell mitogenesis. Thyrotropin is able to induce thyroid cell proliferation through the cyclic AMP intracellular cascade; however, the presence of either insulin or IGF-I is required for the mitogenic effect of thyroid-stimulating hormone (TSH) to occur. The aim of the present study was to determine whether thyroid IRS-1 content is modulated by TSH in vivo. Strikingly, hypothyroid goitrous rats, which have chronically high serum TSH levels (control, C = 2.31 +/- 0.28; methimazole (MMI) 21d = 51.02 +/- 6.02 ng/mL, N = 12 rats), when treated with 0.03% MMI in drinking water for 21 days, showed significantly reduced thyroid IRS-1 mRNA content. Since goiter was already established in these animals by MMI for 21 days, we also evaluated IRS-1 expression during goitrogenesis. Animals treated with MMI for different periods of time showed a progressive increase in thyroid weight (C = 22.18 +/- 1.21; MMI 5d = 32.83 +/- 1.48; MMI 7d = 31.1 +/- 3.25; MMI 10d = 33.8 +/- 1.25; MMI 14d = 45.5 +/- 2.56; MMI 18d = 53.0 +/- 3.01; MMI 21d = 61.9 +/- 3.92 mg, N = 9-15 animals per group) and serum TSH levels (C = 1.57 +/- 0.2; MMI 5d = 9.95 +/- 0.74; MMI 7d = 10.38 +/- 0.84; MMI 10d = 17.72 +/- 1.47; MMI 14d = 25.65 +/- 1.23; MMI 18d = 35.38 +/- 3.69; MMI 21d = 31.3 +/- 2.7 ng/mL, N = 9-15 animals per group). Thyroid IRS-1 mRNA expression increased progressively during goitrogenesis, being significantly higher by the 14th day of MMI treatment, and then started to decline, reaching the lowest values by the 21st day, when a significant reduction was detected. In the liver of these animals, however, a significant decrease of IRS-1 mRNA was detected after 14 days of MMI treatment, a mechanism probably involved in the insulin resistance that occurs in hypothyroidism. The increase in IRS-1 expression during goitrogenesis may represent an important event associated with the increased rate of cell mitosis promoted by TSH and indicates that insulin and IGF-I are important co-mitogenic factors in vivo, possibly acting through the activation of IRS-1.

Topics: Adaptor Proteins, Signal Transducing; Animals; Goiter; Hypothyroidism; Insulin Receptor Substrate Proteins; Male; Methimazole; Mitosis; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Thyroid Gland; Thyrotropin

Topics: Aged, 80 and over; Antithyroid Agents; Diuretics; Echocardiography; Electrocardiography; Female; Furosemide; Goiter; Humans; Methimazole; Treatment Outcome; Ultrasonography

Topics: Adult; Female; Follow-Up Studies; Goiter; Humans; Intraoperative Complications; Methimazole; Necrosis; Plastic Surgery Procedures; Surgical Flaps; Surgical Wound Infection; Thyroid Crisis; Trachea; Treatment Outcome

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

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

Necrosis and apoptosis coexist in the thyroid during goitre development and involution, but little is known about their respective causes. To test the possible role of free radicals, we analysed separately necrosis and apoptosis in male Wistar rats with depressed or normal antioxidant protection. Vitamin E-deficient and -sufficient rats were made goitrous with perchlorate in drinking water; involution was induced by repeated injection of NaI, without or with methimazole. Increase of thyroid malondialdehyde concentration and decrease of glutathione peroxidase activity confirmed the depressed antioxidant protection in vitamin E-deficient rats. Plasma thyroxine and TSH levels were not modified. Necrosis (swollen cells) and apoptosis (pyknotic cells) were quantified on histological sections. In vitamin E-sufficient rats, dead cells were very rare in control thyroids, increased 3-fold in goitre and still further during involution. Necrotic epithelial cells predominated in the goitre and their number declined after iodide supplementation, without or with methimazole. In contrast, the number of apoptotic cells and the caspase-3 activity were increased in goitre and further increased after involution, with two-thirds of pyknotic cells being observed in the interstitium. Apoptosis was prevented by methimazole. Vitamin E deficiency significantly increased total cell death and epithelial cell necrosis and induced the occurrence of much cell debris in the follicular lumen during involution, with no modification of the apoptotic reaction. These results show that the type of cell death is differentially regulated during goitre development and involution: necrosis is related to the oxidative status of the cells, while apoptosis comes with iodine-induced involution.

Topics: Analysis of Variance; Animals; Antioxidants; Apoptosis; Cell Death; Glutathione Peroxidase; Goiter; Iodides; Male; Malondialdehyde; Methimazole; Rats; Rats, Wistar; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine; Vitamin E

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

We report the case of a 31-year-old man with Graves' disease who manifested malignant hyperthermia during subtotal thyroidectomy. His past medical history and family history were unremarkable. Before surgery, his condition was well controlled with propylthiouracil, beta-adrenergic blocker and iodine. During the operation, anesthesia was induced by intravenous injection of vecuronium and thiopental, followed by suxamethonium for endotracheal intubation. Anesthesia was maintained with nitrous oxide and sevoflurane. One hour after induction of anesthesia, his end tidal carbon dioxide concentration (ET(CO2)) increased from 40 to 50 mmHg, heart rate increased from 90 to 100 beats per min and body temperature began to rise at a rate of 0.3 degrees C per 15 min. Suspecting thyroid storm, propranolol 0.4 mg and methylprednisolone 1,500 mg were administered, which, however, had little effect. Despite the lack of muscular rigidity, the diagnosis of malignant hyperthermia was made based on respiratory acidosis. Sevoflurane was discontinued and dantrolene was given by intravenous bolus. Soon after the treatment, ET(CO2), heart rate and body temperature started to fall to normal levels. His laboratory findings showed abnormally elevated serum creatine phosphokinase and myoglobin but normal thyroid hormone levels. Since dantrolene is efficacious in thyrotoxic crisis and malignant hyperthermia, an immediate intravenous administration of dantrolene should be considered when a hypermetabolic state occurs during anesthesia in surgical treatment for a patient with Graves' disease.

Topics: Acidosis, Respiratory; Adult; Anesthetics; Antithyroid Agents; Carbon Dioxide; Creatine Kinase; Dantrolene; Diagnosis, Differential; Goiter; Graves Disease; Heart Rate; Humans; Male; Malignant Hyperthermia; Methimazole; Methyl Ethers; Muscle Relaxants, Central; Myoglobin; Nitrous Oxide; Propylthiouracil; Sevoflurane; Succinylcholine; Thiopental; Thyroidectomy; Thyroxine; Triiodothyronine; Vecuronium Bromide

Radioiodine is used to treat thyroid cancer and hyperthyroidism. In order to reduce radiation hazard to the patient and to people in contact with the patient it would be desirable to obtain the same therapeutic effect with lower activities of the radioisotope. This could be achieved by the simultaneous administration of a compound that increases tissue radiosensitivity. In this study we analyzed the use of nicotinamide (NA) as a radiosensitizer to radioiodine, to increase 131I efficacy. NA administered during 30 days to Wistar rats failed to alter thyroid weight. The influence of NA on radiothyroidectomy induced by increasing doses of 131I was examined in otherwise nontreated rats. NA produced a significant increase in the ablation caused by radioiodine. Goiter was then induced by the administration of methylmercaptoimidazol (MMI) to rats, followed by the treatment with radioiodine with and without simultaneous administration of NA. Thyroid weight per 100 g of body weight ratio was not changed by NA alone; 131I administration caused a 25% decrease in goiter size, while 131I plus NA produced a reduction of the ratio of 46% (p < 0.01 vs. NA). No changes were observed in adenosine diphosphate (ADP)-ribosilation of thyroid nuclear protein in NA-treated rats. Thyroid blood flow (determined by 86Rb uptake) was increased by 84% by NA. In conclusion, nicotinamide has a significant radiosensitizing effect to 131I both in normal and goitrous rats. This action is because of an increase in thyroid blood flow, which probably enhances tissue oxgenation.

Topics: Adenosine Diphosphate Ribose; Animals; Antithyroid Agents; Cell Nucleus; Female; Goiter; Iodine Radioisotopes; Methimazole; Niacinamide; Radiation Tolerance; Rats; Rats, Wistar; Regional Blood Flow; Rubidium Radioisotopes; Thyroid Gland

Previously, we observed that excess iodide rapidly suppressed the elevated ornithine decarboxylase activity in the thyroid of propylthiouracil (PTU)-pretreated rats. Excess iodide also induces involution of goitrous thyroids. These findings led us to study effects of excess iodide on apoptosis of rat thyroids. When given to PTU-pretreated rats, excess potassium iodide (KI) (13 mg/kg body weight, 10 mg as iodine) induced DNA fragmentation in the thyroid at the first 3 hours after its treatment. The percentage of DNA fragmentation was also maximal at 3 hours after KI treatment. In methimazole-pretreated rats, the kinetic of DNA fragmentation was nearly the same; apoptosis increased for the first 6 hours and then decreased at 12 hours after KI administration. Other iodinated compounds such as amiodarone and diiodotyrosine have also shown apoptosis-inducing activity, but their effect was observed later than KI. Iopanoic acid had no such effect. Apoptotic changes were also observed with the use of flow cytometry. PTU or methimazole alone had some stimulatory effect on thyroid apoptosis. Iodine effect was not observed in rats treated with either perchlorate or thiocyanate. These results suggest that excess iodine induces thyroid involution in goitrogen-treated rats at least partially by apoptosis.

Topics: Amiodarone; Animals; Antithyroid Agents; Apoptosis; Diiodotyrosine; DNA Fragmentation; Goiter; Male; Methimazole; Potassium Iodide; Propylthiouracil; Rats; Rats, Wistar; Thyroid Gland

In hyperthyroid Graves' disease, short-term methimazole is sufficient to induce lasting remission in some patients, but even long-term treatment fails to do so in others. We have evaluated the role of autoimmune abnormalities in the helper T cell type 2 (TH2)-interleukin-13 (IL-13)-TSH receptor system in maintaining hyperthyroidism by comparing IgE levels in patients with various thyroid diseases. One hundred and ninety-three patients with hyperthyroid Graves' disease were treated with methimazole, and blood samples were obtained to measure serum levels of T4, T3, TSH, thyroglobulin, antimicrosomal antibody, TSH binding inhibitory Ig (TBII), thyroid-stimulating antibody, thyroid stimulation-blocking antibody, IgE, interferon-gamma, IL-4, and IL-13. Elevation of serum IgE (> or = 170 U/mL) was found in 35.5% of patients with hyperthyroid Graves' disease, and serum levels of T4, T:1, antimicrosomal antibody, and TBII were significantly greater in patients with IgE elevation than in those with normal serum IgE. During methimazole treatment, there was a parallel decrease in the serum T4 concentration in the presence or absence of an IgE elevation. However, there was a significantly smaller decrease in TBII in patients with elevated IgE than in those with normal IgE. As a result, the remission rate was significantly greater in patients with normal IgE than in those with IgE elevation. Serum levels of IL-13 were elevated in 64.7% of patients with IgE elevation in the absence of detectable TH1 marker, interferon-gamma. These findings suggest that in one third of patients with hyperthyroid Graves' disease, TH2 cells are stimulated and secrete excess amounts of IL-13, which subsequently stimulates B cells to synthesize more TSH receptor antibody and IgE, so that during methimazole treatment TBII decreases less in patients with IgE elevation, producing a lower remission rate.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antithyroid Agents; Biomarkers; Female; Goiter; Goiter, Nodular; Graves Disease; Humans; Immunoglobulin E; Male; Methimazole; Middle Aged; Reference Values; Th2 Cells; Thyroiditis, Autoimmune; Thyroxine; Time Factors; Triiodothyronine

Hyperthyroidism of Graves' disease (Morbus Basedow) is known to involve the thyroid gland in toto, unlike Graves' ophthalmopathy which clinically may either be unilateral or bilateral. We report a 31-year-old Caucasian female patient who presented with unilateral goiter and clinical and laboratory evidence for hyperthyroidism. High-resolution ultrasonography of the thyroid gland revealed a morphology indicative of an autoimmune thyroid disease strictly limited only to the right lobe. 123I-scintiscanning showed a homogenous but several fold increased uptake of the radionuclide in the right lobe of the thyroid gland, whereas the uptake in the left lobe did not differ from the uptake in normal controls. Cytology of the fine needle aspirate of the right lobe revealed a remarkable inflammatory background mainly by presence of lymphocytes, a finding which was not seen in the cytology of the left lobe. Furthermore, both serum antibodies to TSH-receptors and thyroid peroxidase were significantly increased. Consequently, hyperthyroidism of Graves' disease with the involvement of only one lobe of the thyroid gland was diagnosed.

Topics: Adult; Antithyroid Agents; Autoantibodies; Biopsy, Needle; Female; Goiter; Graves Disease; Humans; Iodide Peroxidase; Methimazole; Radionuclide Imaging; Receptors, Thyrotropin; Thyroglobulin; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine; Ultrasonography

The factors mediating the accumulation of thyroglobulin are of great importance to the understanding of the pathogenesis of human and experimentally induced colloid goiters. To elucidate further the underlying cellular mechanism, thyroid fragments from newborn rats were incorporated into semisolid alginate beads and were cultured as three-dimensional organoids for up to 21 d. In five parallel cultures, the medium contained either no supplements (group A), Nal (group B), thyroid-stimulating hormone (TSH) (group C), Nal plus TSH in the same concentrations as B and C (group D), or Nal and TSH (as in group D) plus methimazole (MMI, group E). The thyroid organoids maintained morphological integrity, functional activity, and ability to proliferate in vitro. Addition of iodine to the cultures significantly increased mean (+/-SEM) follicular diameters from 19.5 +/- 0.7 microm in controls to 33.9 +/- 2.2 microm (p < 0.0001) when NaI was added alone (group B), and 30.4 +/- 1.7 microm (p < 0.0001) when combined with TSH (group D). The effect of NaI on follicular size was abolished by MMI (group E, follicular diameter 23.5 +/- 1.3 microm). The results presented support the recent finding, using a rat colloid goiter model, that not only TSH but also iodine organification or its inhibition are important factors in modulating follicular morphology.

Topics: Animals; Animals, Newborn; Culture Techniques; Goiter; Humans; Iodine; Methimazole; Rats; Rats, Wistar; Thyroglobulin; Thyroid Gland; Thyrotropin

Angiogenesis is an important component in the development of thyroid goitre. Vascular endothelial growth factor (VEGF) represents a family of specific endothelial cell mitogens involved in normal angiogenesis and in tumour development. The purpose of this study was to determine the distribution of VEGF in thyroid tissues during goitre formation, and to study the actions of VEGF on the regulation of thymidine incorporation and iodine uptake by thyroid follicular cells. Goitre was induced in adult rats by administration of methimazole together with a low iodine diet. Thyroid from normal or goitrous rats was removed, fixed and sectioned. Immunocytochemistry performed for VEGF using the avidin-biotin system showed that VEGF is present in normal thyroid and is located mainly in the vascular endothelium and interfollicular stromal tissue. After administration of goitrogen for 2 weeks, which caused a two- to threefold increase in thyroid weight, staining of VEGF was less apparent within the interfollicular stroma, but strongly increased throughout the thyroid follicular and endothelial cells. Uptake of [125I] and incorporation of [3H]thymidine by Fisher rat thyroid cells (FRTL-5) were measured after 72 h culture with or without TSH or VEGF, or both. In the absence of TSH, incubation with VEGF caused a significant reduction in [3H]thymidine incorporation, but did not significantly alter [125I] uptake. Incubation with TSH (1 mU/ml) caused a fourfold increase in [3H]thymidine incorporation that was diminished by co-incubation with 10 ng/ml or greater VEGF. Similarly, 10 ng/ml or greater VEGF significantly reduced the ability of TSH to increase [125I] uptake. The antagonistic effects of VEGF on TSH-stimulated [3H]thymidine incorporation or [125I] uptake were significantly reduced in the presence of an anti-VEGF antiserum. A DNA fragment representing mRNA encoding the VEGF receptor, flt-1, was identified in FRTL-5 cells by reverse transcription PCR analysis, and the abundance of this fragment was increased in FRTL-5 cells cultured in the medium containing TSH (1 mU/ml) or fibroblast growth factor (FGF)-2 (25 ng/ml). These results indicated that VEGF and one of its receptors, Flt-1, are present in epithelial cells of the thyroid, and that VEGF could contribute to the regulation of development and function of thyroid epithelial cells.

Topics: Animals; Antithyroid Agents; Cells, Cultured; Endothelial Growth Factors; Goiter; Immunohistochemistry; Iodine; Lymphokines; Male; Methimazole; Polymerase Chain Reaction; Proto-Oncogene Proteins; Rats; Rats, Wistar; Receptor Protein-Tyrosine Kinases; RNA, Messenger; Thymidine; Thyroid Gland; Thyrotropin; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factors

To assess the involvement of cellular inhibition and the appearance of apoptosis in regression of the hyperplastic thyroid gland towards normality, an experimental design was used to elicit non-toxic goiter by inducing hyperplastic goiter in rats by treatment with methimazole. We performed a morphological and PCNA immunocytochemical study together with in situ end labelling with bromodeoxyuridine in thyroid glands of rats receiving methimazole in their drinking water over 21 days after which they were allowed a recovery period of 0, 12, 24, 36, 48 and 72 h and 7, 14, 21 and 44 days. Serum T3 and T4 levels were found to be very low in the methimazole-treated animals although they increased after the goitrogenic compound had been withdrawn. Inhibition of cell proliferation and the burst of apoptosis play important roles in the regression of hyperplastic goiter in rats. Cell proliferation, which was strongly stimulated during goiter, fell significantly at 24 h, thereafter decreasing gradually as the recovery period progressed. Isolated cases of thyrocyte necrosis were observed ultrastructurally. Light and transmission electron microscopy revealed the existence of thyroid apoptosis with respect to the development of the study over time. Most apoptotic thyrocytes became detached from the follicular epithelium and later underwent cellular degeneration in the follicular lumen. The remaining apoptotic cells retracted their cytoplasm, lost contact with the follicular lumen and became located at the base of the follicles. The percentage of apoptosis showed that during the first week of thyroid involution apoptosis was already present but with low percentages while maximum values were attained at 21 days of survival. Our results suggest that, in the rat, during the return of thyroid follicular cells to normality after methimazole-induced hyperplastic goiter a balance arises between proliferation and cell death and that this balance is due to the inhibition of cellular proliferation and, secondarily, to the appearance of apoptosis, which becomes particularly evident towards the end of the first week after withdrawing the goitrogenic agent.

Topics: Animals; Antithyroid Agents; Apoptosis; Bromodeoxyuridine; Cell Division; Epithelial Cells; Female; Goiter; Hyperplasia; Immunoenzyme Techniques; In Situ Nick-End Labeling; Male; Methimazole; Proliferating Cell Nuclear Antigen; Rats; Rats, Sprague-Dawley; Thyroid Gland; Thyroxine; Triiodothyronine

Administration of a goitrogen (methimazole) and a low iodine diet to rats over a two-week period resulted in hypothyroidism and thyroid hyperplasia compared with controls (control: total serum thyroxine (T4) 66 +/- 4 nmol/l, thyroid weight 5 +/- 1 mg/100 g body weight; experimental: T4 undetectable, thyroid weight 27 +/- 4 mg/100 g body weight after 2 weeks of treatment; mean +/- S.D., n = 10). Immunohistochemistry carried out using a specific endothelial cell marker, CD31, and morphometric analysis (point counting of immunopositive cells) revealed that the progression of goitre in the rat thyroid is accompanied by an increase in capillary endothelial cell growth (neovascularisation). Fibroblast growth factor-2 (FGF-2) immunohistochemistry revealed widespread staining for the protein in the follicular cells of control glands. Less intense staining was found in the stroma and follicular cell nuclei. During hyperplasia and subsequent neovascularisation there was a progressive increase in the FGF-2 immunoreactivity at all locations during the two-week treatment period. Thrombospondin-1 (TSP1) immunoreactivity in the control rat thyroid was found in the stroma and in the endothelial cells, while weak follicular cell staining was also present. In the goitrous rat thyroid the TSP immunoreactivity was present after 1 week of treatment in the endothelial cells and most follicular cells, whilst stroma localisation was weak. After week 2 of treatment the endothelial cell and stromal localisation was no longer apparent, although a follicular localisation was still present. Transforming growth factor-beta 1 (TGF beta 1) immunoreactivity was present in the cytoplasm of a minority of the follicular cells in control rat thyroids, while their nuclei were unstained. In the goitrous rat thyroid an increase intensity of staining for TGF beta 1 was seen in all follicular cells, many of which now also demonstrated immuno-positive nuclei, within one week of goitrogen administration. These results show that in the hyperplastic thyroid increases in FGF-2 and TGF beta 1, and decreases in TSP1 accompany angiogenesis. These factors may interact in an autocrine/paracrine relationship to stimulate the neovascularisation that occurs during goitre formation.

Topics: Animals; Cell Adhesion Molecules; Cytoplasm; Endothelium; Fibroblast Growth Factor 2; Goiter; Growth Substances; Hyperplasia; Immunohistochemistry; Male; Membrane Glycoproteins; Methimazole; Neovascularization, Pathologic; Rats; Rats, Inbred Strains; Thrombospondins; Thyroid Gland; Transforming Growth Factor beta

We have reevaluated the prevalence and pathogenetic importance of TSH receptor blocking antibodies (TRBAb) in autoimmune hypothyroidism, and investigated the changes in TRBAb activities during thyroxine and antithyroid drug treatment.. Serum TSH binding inhibitor immunoglobulin (TBII) and thyroid stimulation blocking antibody (TSBAb) were measured serially in all patients with non-goitrous autoimmune thyroiditis (AT) and measured monthly during methimazole treatment in 6 patients.. Ninety patients with non-goitrous AT and 95 patients with goitrous AT were entered consecutively into this study. All patients with non-goitrous AT were treated with thyroxine and followed at intervals of 6 months for 2 years initially and then yearly intervals. The duration of follow-up was 1-8 years. Six patients from the TRBAb-positive non-goitrous AT group who were treated with thyroxine were randomly selected and given additional treatments with methimazole (40 mg per day) for 6 months.. Serum TBII was measured by a radioreceptor assay, TSBAb by using FRTL-5 cells, and antithyroid peroxidase and antithyroglobulin antibodies by radioimmunoassay.. The prevalences of TBII and TSBAb is non-goitrous AT were 47.8 and 58.9%, respectively, which were significantly higher than those in goitrous AT (6.3% for TBII, 10.5% for TSBAb). All but one patient showed persistent TBII and TSBAb activities during the thyroxine treatment for up to 8 years. A high dose of methimazole (40 mg per day) did not affect the titres of TBII and TSBAb in 5 out of 6 patients with non-goitrous AT tested. However, antithyroid peroxidase and antithyroglobulin antibodies activities were significantly decreased during the methimazole treatment.. The high prevalence of TSH receptor blocking antibodies (TRBAb) suggests that TRBAb may play a major role in the development of hypothyroidism and thyroid atrophy in the vast majority of patients with non-goitrous autoimmune thyroiditis. Most TRBAb activities are stable for at least 8 years and are now affected by thyroxine and antithyroid drug treatment.

Topics: Adult; Autoantibodies; Drug Therapy, Combination; Female; Follow-Up Studies; Goiter; Humans; Immunoglobulins, Thyroid-Stimulating; Iodide Peroxidase; Male; Methimazole; Middle Aged; Prevalence; Receptors, Thyrotropin; Thyroglobulin; Thyroiditis, Autoimmune; Thyroxine

We have investigated changes in the synthesis and localization of insulin-like growth factor (IGF)-I and IGF binding proteins (IGFBPs) in thyroid tissues during the induction of goitre in iodine-deficient rats, and during the subsequent involution of the gland following goitrogen withdrawal. Goitre was induced in adult rats by acute (1 or 2 weeks) or chronic (4 or 10 weeks) administration of methimazole together with a low iodine diet. After twelve weeks the goitrogenic stimuli were removed and thyroids examined 4 weeks later. Circulating T4 levels became undetectable within two weeks of goitrogen administration while thyroid weight had increased five-fold. The thyroids continued to increase in size up to 10 weeks, but at a slower growth rate. IGF-I mRNA, detected by ribonuclease protection assay, was present in the control rat thyroid and increased in abundance after both 1 and 2 weeks of goitrogen administration. Levels of IGF-I mRNA showed a relative decline with prolonged goitrogen administration, and following thyroid involution the hybridization signal was similar to that seen in control glands. Northern blot hybridization showed that IGFBP-2, -3 and -5 mRNAs were all present in growth-quiescent, control thyroids and those encoding IGFBP-2 and -3 were elevated in the goitrous glands and remained so as long as goitrogen was administered, thereafter declining during thyroid involution. IGF-I and IGFBP-2 and -3 mRNAs and synthesized peptides, detected by in situ hybridization and immunohistochemistry respectively, were found to co-localize predominantly in follicular epithelial cells. IGFBP-5 mRNA abundance was unaltered during goitre formation, but was increased in the involuting thyroid. Both IGFBP-5 mRNA and peptide were localized to the parafollicular cells (C-cells) which were increased in number during involution. The results suggest that an increased expression of IGF-1 may contribute to early goitre formation, but that a relative increase in the abundance of IGFBP-2 and -3 may limit IGF availability at later times, and facilitate a slowing of thyroid growth rate. The discrete expression of IGFBP-5 by C-cells suggests that it could contribute indirectly to goitre formation or involution by acting in a paracrine fashion.

Topics: Animals; Carrier Proteins; Gene Expression Regulation, Neoplastic; Goiter; Hyperplasia; Hypertrophy; Immunoenzyme Techniques; In Situ Hybridization; Insulin-Like Growth Factor Binding Protein 5; Insulin-Like Growth Factor I; Male; Methimazole; Rats; Rats, Wistar; RNA, Messenger; Thyroid Gland; Thyroxine

The targeting and recruitment of inflammatory cells to vascular endothelium in Graves' disease (GD) is mediated by intercellular adhesion molecule-1 (ICAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1), and vascular cell adhesion molecule-1 (VCAM-1). We have studied serum levels of soluble ICAM-1 (sICAM-1), soluble ELAM-1 (sELAM-1), and soluble VCAM-1 (sVCAM-1) in patients with GD (n = 21) and in patients with iodine-deficient goitre (IDG) (n = 23). The serum levels of sICAM-1 were markedly elevated in patients with GD before treatment with thiamazole (median 560 ng/ml versus 185 ng/ml in patients with IDG). In addition, elevated serum concentrations of sELAM-1 (median 85 ng/ml versus 33 ng/ml, respectively) and sVCAM-1 (median 42 ng/ml versus 15 ng/ml, respectively) were observed in patients with GD (P < 0.01 for all). The serum levels of sELAM-1 and sVCAM-1 dropped significantly after initiation of therapy and were within the normal range after 4, and 8 weeks of therapy, respectively. Serum levels of sICAM-1 were elevated even after 8 weeks of therapy. Serum levels of sVACM-1 and sICAM-1 correlated with the serum concentrations of anti-thyroid-stimulating hormone (TSH)-receptor antibodies (TSHR-R) (n = 21; r = 0.929 and r = 0.810, respectively) and anti-thyroid peroxidase antibodies (TPO-Ab) (n = 21; r = 0.673 and r = 0.750, respectively). However, no correlation between sELAM-1 and TPO-Ab, TSHR-R, and anti-thyroglobulin antibodies (Tg-Ab), respectively, could be found. In addition to thyroid hormones and autoantibodies, serum concentrations of sELAM-1 and sVCAM-1, but not sICAM-1, could be useful as clinical markers for disease activity.

Topics: Autoantibodies; Cell Adhesion Molecules; E-Selectin; Endothelium, Vascular; Female; Goiter; Graves Disease; Humans; Immunoenzyme Techniques; Intercellular Adhesion Molecule-1; Iodine; Male; Methimazole; Thyroid Hormones; Thyroxine; Vascular Cell Adhesion Molecule-1

The thyroid gland synthesizes 6-delta-iodolactone, a compound shown to inhibit goiter growth in vivo and cell proliferation in culture. The present studies were performed to characterize this effect further with the aim of exploring the possible therapeutic action of iodolactones. Prevention assay: rats were treated simultaneously with a goitrogen, methylmercaptoimidazole, and either 6-delta-iodo-lactone or 14-iodo-omega-lactone, a synthetic derivative, given either i.p. or p. o. Both compounds caused a significant decrease in thyroid weight irrespective of the route of administration, but oral administration was less effective. A dose-response relationship was observed, the minimal effective dose (i.p.) being 3 micrograms/day. Involution assay: goiter was first induced with methylmercaptoimidazole and then the iodolactones were injected. Both compounds caused a significant involution, which was dose-related. Acute (10 days) administration of the iodolactones did not produce significant changes in several serum parameters (total T3 and T4, cholesterol, total protein, urea and acetylcholinesterase). These results give further support to the potential therapeutic application of iodolactones.

Topics: Administration, Oral; Animals; Arachidonic Acids; Cells, Cultured; Dose-Response Relationship, Drug; Female; Goiter; Hydroxyeicosatetraenoic Acids; Injections, Intraperitoneal; Methimazole; Rats; Rats, Wistar; Thyroid Gland

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

Previous studies have shown that iodoarachidonates (IAs) prevent goiter production in rats. In the present studies we show that both IL-d and IL-w (IAs bearing the iodine atom at the positions 6 and 14, respectively), cause a significant involution of preformed goiter. This effect was evident when IAs were administered either orally or via i.p., although the first one required larger doses to obtain the same degree of inhibition. No changes were observed in serum protein, urea, cholesterol, cholinesterase, T3 or T4. In vitro studies with FRTL-5 cells showed that both IAs inhibit iodide and alpha-AIB uptake, as well as ATPase activity.

Topics: Adenosine Triphosphatases; Administration, Oral; Animals; Arachidonic Acids; Cells, Cultured; Deoxyglucose; Goiter; Hydroxyeicosatetraenoic Acids; Injections, Intraperitoneal; Iodides; Methimazole; Rats; Thyroid Gland

Myeloperoxidase (MPO), which displays considerable amino acid sequence homology with thyroid peroxidase (TPO) and lactoperoxidase (LPO), was tested for its ability to catalyze iodination of thyroglobulin and coupling of two diiodotyrosyl residues within thyroglobulin to form thyroxine. After 1 min of incubation in a system containing goiter thyroglobulin, I-, and H2O2, the pH optimum of MPO-catalyzed iodination was markedly acidic (approximately 4.0), compared to LPO (approximately 5.4) and TPO (approximately 6.6). The presence of 0.1 N Cl- or Br- shifted the pH optimum for MPO to about 5.4 but had little or no effect on TPO- or LPO-catalyzed iodination. At pH 5.4, 0.1 N Cl- and 0.1 N Br- had a marked stimulatory effect on MPO-catalyzed iodination. At pH 4.0, however, iodinating activity of MPO was almost completely inhibited by 0.1 N Cl- or Br-. Inhibition of chlorinating activity of MPO by Cl- at pH 4.0 has been previously described. When iodination of goiter thyroglobulin was performed with MPO plus the H2O2 generating system, glucose-glucose oxidase, at pH 7.0, the iodinating activity was markedly increased by 0.1 N Cl-. Under these conditions iodination and thyroxine formation were comparable to values observed with TPO. MPO and TPO were also compared for coupling activity in a system that measures coupling of diiodotyrosyl residues in thyroglobulin in the absence of iodination. MPO displayed very significant coupling activity, and, like TPO, this activity was stimulated by a low concentration of free diiodotyrosine (1 microM). The thioureylene drugs, propylthiouracil and methimazole, inhibited MPO-catalyzed iodination both reversibly and irreversibly, in a manner similar to that previously described for TPO-catalyzed iodination.

Topics: Animals; Catalysis; Cattle; Goiter; Humans; Iodide Peroxidase; Iodides; Kinetics; Lactoperoxidase; Methimazole; Peroxidase; Propylthiouracil; Serum Albumin, Bovine; Swine; Thyroglobulin; Thyroid Gland

In patients with Graves' disease, thyrostatic drug treatment may induce definitive remission without the need of more aggressive measures such as surgery or radioiodine. Following drug therapy, however, relapses often occur. In the present study, a multivariate analysis of pretreatment variables was performed, in order to identify individuals running a high risk of an unfavourable outcome of thyrostatic drug therapy. We studied 109 consecutive patients with a mean age of 38 years, range 20-70, over a mean follow-up period of 5.3 years after cessation of therapy. The analysis showed that goitre size, age, thyroid hormone levels, HLA-DR 3 haplotype, and TSH receptor antibody levels were of prognostic significance, whereas HLA-B8 haplotype, a lymphocytic infiltrate at fine needle biopsy, thyroglobulin, and microsomal antibodies had no such value. In particular, patients characterized by young age, large goitre and high hormone values were found to be associated with an unfavourable course.

Topics: Adult; Age Factors; Aged; Drug Therapy, Combination; Female; Goiter; Graves Disease; HLA Antigens; Humans; Male; Methimazole; Middle Aged; Multivariate Analysis; Receptors, Thyrotropin; Thyroglobulin; Thyroxine; Triiodothyronine

In this experiment, goiter was successfully induced in rat with MMI, and the antigoiter effect of 25% and 50% casein diet was observed. The results showed that the diet with 50% casein is more effective than that with 25% casein in counteracting MMI and preventing goiter in rat. The antigoiter mechanisms of high protein nutrition might be as follows: Protecting the mechanism of thyroid iodine transportation through the follicular cell, and therefore accelerating thyroid iodine metabolism; Relieving thyroid peroxidase (TPO) from the inhibitive effect of MMI and facilitating thyroid hormone synthesis; Coordinating the function of hypothalamus-pituitary-TSH-thyroid axis and protecting the wholeness of thyroid cell and thus avoiding the occurrence of pathological changes.

Topics: Animals; Caseins; Female; Goiter; Iodine; Methimazole; Rats; Rats, Inbred Strains

A study of system of cellular and humoral immunity, unspecific defense in 187 patients with diffuse toxic goiter before and after treatment with mercasolyl revealed that despite the clinical effect, the agent did not essentially influence the content and functional activity of T-lymphocytes. The effect was more favourable on the content of immunoglobulins, titer of antithyroid antibodies. This was observed in mild and average severe course of the disease. It is suggested that mercasolyl effects lymphocytes synthesizing autoantibodies to the thyroid gland.

Topics: Adult; Autoantibodies; Drug Therapy, Combination; Female; Goiter; Humans; Immunity, Cellular; Male; Methimazole; Middle Aged; Thyroid Gland

In 16 untreated patients with hyperthyroidism due to Graves' disease, serum antidouble stranded DNA antibody, measured by RIA, was positive (greater than 20 U/ml) in 14. In methimazole-treated patients with T3-suppressible thyroid uptake, anti-DNA antibody was found in 9% (3 of 35). The frequency of positive tests in methimazole-treated patients with T3-nonsuppressible thyroid uptake and in surgically treated patients was 24% (5 of 21) and 57% (4 of 7), respectively. Among anti-DNA antibody-negative (less than 9 U/ml) and weakly positive (10-19 U/ml) patients, those with T3-suppressible thyroid uptake had lower anti-DNA antibody titers than those with T3-nonsuppressible thyroid uptake. Among 32 patients with Hashimoto's thyroiditis, anti-DNA antibody was positive in 7. None of the patients with simple goiter had positive or weakly positive anti-DNA antibody results. Although the quantity of antibodies did not correlate well in individual patients, the rates of positive TSH binding-inhibiting immunoglobulin and anti-DNA antibody tests were roughly comparable in these patient groups. None of these patients with thyroid disease associated with anti-DNA antibody had clinical or other serological evidence suggestive of systemic lupus erythematosus or related collagen vascular disorders. The finding of anti-DNA antibody provides a new aspect of immunological abnormality associated with hyperthyroidism of Graves' disease.

Topics: Antibodies, Antinuclear; Autoimmune Diseases; Female; Goiter; Graves Disease; Humans; Lupus Erythematosus, Systemic; Male; Methimazole; Thyroiditis, Autoimmune; Thyroxine; Triiodothyronine

Amiodarone iodine induced thyrotoxicosis occurs frequently in patients residing in areas of mild iodine deficiency and in patients with preexisting goiter. Drug therapy of the hyperthyroidism is often unsuccessful. Twenty-three patients with amiodarone induced thyrotoxicosis were either not treated, treated with 40 mg methimazole daily or with methimazole and 1 gm potassium perchlorate daily for up to 40 days and then with methimazole alone. Thyrotoxicosis was more likely to spontaneously remit in patients without goiter. Therapy with methimazole alone was unsuccessful in inducing euthyroidism in 5 patients with goiter. However, combined therapy with methimazole and potassium perchlorate rapidly alleviated hyperthyroidism in almost all patients with goiter. This drug combination is successful because perchlorate inhibits the active transport of iodine into the thyroid and methimazole blocks the intrathyroidal synthesis of thyroid hormones.

Topics: Adult; Aged; Amiodarone; Drug Synergism; Drug Therapy, Combination; Female; Goiter; Humans; Male; Methimazole; Middle Aged; Perchlorates; Potassium; Potassium Compounds; Thyrotoxicosis

Functional and morphologic heterogeneity of human multinodular goiters was investigated in 300 samples from "cold" and "hot" regions of 20 goiters transplanted onto nude mice. Transplants were labeled with [3H]thymidine and radioiodine, while the host's thyroid-stimulating hormone (TSH) secretion was either stimulated or suppressed. Proliferation and function of follicular cells were assessed in whole follicles reconstructed from autoradiographs of serial sections. Hot transplants had a higher autonomous iodine uptake than those of cold tissue in TSH-suppressed hosts. Functional autonomy widely varied among the follicles, but even more so among individual cells. Hot grafts differed from cold ones only by a comparatively larger fraction of autonomous cells. Intercellular differences of iodinating activity were not abolished by TSH. Grafts faithfully reproduced the individual growth pattern of the original tissue. Between 0.5% and 7% of all follicular cells replicated despite suppression of TSH. Up to 70% of these cells were clustered, forming scattered foci of autonomously growing tissue. Other cells only started replicating after long-term TSH stimulation. Thus, goiters contained subsets of cells with high and others with low growth response. Progenies of replicating cells remained clustered, sometimes budding outwards to form new follicles. Autonomy of growth and autonomy of function are independent traits of epithelial cells. Epithelial cells have their individual growth pattern, replication rate, and functional capacity. These traits are passed on from a mother cell to its progeny during follicle neogenesis. To this main mechanism accounting for the morphologic and functional heterogeneity of human goiters, inheritable modifications of gene expression must probably be added.

Topics: Animals; Cell Division; Epithelium; Goiter; Humans; Iodine; Methimazole; Mice; Mice, Nude; Thyrotropin; Thyroxine; Transplantation, Heterologous

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

The role of the sympathetic nervous system in the control of the goitrogenic response was examined in adult male rats subjected to unilateral superior cervical ganglionectomy 12-30 days earlier. A spontaneous goiter as well as an increased thyroid growth after the administration of the goitrogenic agents methylmercaptoimidazole and thyrotropic stimulating hormone (TSH) were found in the ipsilateral lobe. Norepinephrine and epinephrine content decreased significantly by 80 and 31%, and thyroxine (T4) and triiodothyronine (T3) content by 24 and 15%, in the ipsilateral lobe. After the injection of a tracer dose of 125I, percent radioactivity incorporation to diiodotyrosine (DIT) was higher, and that to monoiodotyrosine (MIT) lower, in the ipsilateral lobe; additionally a lower ratio "labeled T3 + T4/labeled DIT" was found in the denervated thyroid lobe. These results suggest that the sympathetic nerve terminals in the thyroid gland modulate the organ's response to circulating TSH.

Topics: Animals; Epinephrine; Goiter; Iodine Radioisotopes; Male; Methimazole; Norepinephrine; Rats; Rats, Inbred Strains; Sympathectomy; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

Naturally occurring euthyroid goitres in man and goitres produced in experimental animals by iodine deficiency or goitrogen feeding both have in common a thyroglobulin of low iodine content. The latter experimental goitres are always depleted of colloid and thyroglobulin. In contrast, natural goitres often contain excessive amounts of colloid which may accumulate because of endocytosis becoming refractory to TSH. We tested the hypothesis that minute doses of goitrogens could lower the iodine content of thyroglobulin without colloid depletion. We then examined whether such a low-dose 'classical' goitrogen could induce excessive colloid storage rather than depletion if acting in concert with lithium, a cation which blocks endocytosis. Rats on an adequate iodine intake were fed minimal doses of methimazole either alone or combined with lithium chloride. Chronic minimal-dose methimazole treatment lowered the iodine content of thyroglobulin without changing thyroglobulin content and thyroid weight. In contrast, addition of lithium to methimazole, produced goitres containing supranormal amounts of poorly iodinated thyroglobulin. We conclude that borderline doses of goitrogens can lower iodination of thyroglobulin without causing hyperplasia and colloid depletion. Thyroglobulin-rich goitres can be obtained by adding a second goitrogen which inhibits endocytosis. As an alternative to Marine's hypothesis of colloid goitre formation we suggest that inhibition of endocytosis, e g by goitrogens of the lithium type, could cause colloid and thyroglobulin accumulation in human iodine deficiency goitre.

Topics: Animals; Colloids; Endocytosis; Female; Goiter; Iodine; Lithium; Male; Methimazole; Organ Size; Rats; Rats, Inbred Strains; Thyroglobulin; Thyroid Gland; Thyrotropin

Topics: Animals; Body Weight; Goiter; Hypothyroidism; Iodide Peroxidase; Isoenzymes; Kinetics; Liver; Male; Methimazole; Peroxidases; Rats; Thyroid Gland; Thyroid Hormones; Thyrotropin

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

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

Epidemiological findings from the city of Cali, Colombia, support the hypothesis that water supply and iodine intake are not the only dietary factors which influence the magnitude of the goitre endemia. Experiments were conducted in rats to determine whether casein has a counteracting effect on the goitrogenic and antithyroid activities of methimazole (MMI) and goitrogenic water extracts (GWE) from the endemic area of the Cauca Valley. Female albino rats (Charles River, DC strain) 100-110 g initial weight, receiving 12 mug of iodine daily, were divided into three groups annd put on special diets: protein-free, 8 % casein, or 60 % casein, respectively. Each group (24 rats) was then divided into three subgroups. Subgroup one received goitrogen-free water and was used as a control. Subgroup two was administered MMI, 50 mug/day/rat. Subgroup three was given per animal a daily amount of GWE equivalent in antithyroid potency to 50 mug of MMI. At 77 days, the thyroid glands were studied for weight, 131I uptake, and 127I concentration. Animals on the protein-free diet showed significantly (P less than 0.05 - less than 0.01) larger thyroid glands per 100 g body weight and lower thyroidal 4 h 131I uptake and 127I-concentrations than rats on casein diets. These differences were significantly increased (P less than 0.01) by the administration of MMI and GWE. All the effects were completely reversed by the 60 % casein diet showing no differences between control rats and those on MMI or GWE. Rats on 8 % casein showed intermediate values between those of animals on protein-free and 60 % casein diets; differences were still present between the control as against the MMI or GWE groups, The results indicate that under these experimental conditions, a poor-protein diet impairs the thyroidal transport of iodine, decreases its concentration in the thyroid and is accompanied by an enlargement of the gland. Under these circumstances, the action of thiourea-like antithyroid agents is enhanced. The administration of protein reverses these alterations and decreases the action of such antithyroid agents. Whether the changes observed are due to a direct action of casein on the thyroid and/or to effects of malnutrition on the metabolism of antithyroid compounds remains to be determined.

Topics: Animals; Body Weight; Caseins; Dietary Proteins; Drug Evaluation, Preclinical; Female; Goiter; Iodine; Methimazole; Organ Size; Rats; Thyroid Gland

The effect of BHDB, an analogue of thyroxine, on the pituitary-thyroid system was studied in the rat. BHDB produced low plasma T4 and T3 concentrations similar to those produced by methimazole, but failed to elevate plasma TSH and to produce goiter because of displacement of T4 from the binding protein. Low plasma thyroid hormone concentrations were due to an increase of fecal loss of thyroid hormones. By releasing excess iodide, BHDB blocked the development of goiter produced by methimazole.

Topics: Animals; Antithyroid Agents; Feces; Goiter; Iodine; Iodobenzoates; Male; Methimazole; Organ Size; Pituitary Gland; Rats; Thyroid Gland; Thyroidectomy; Thyrotropin; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine

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

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: Animals; Antithyroid Agents; Child; Goiter; Graves Disease; Humans; Hyperthyroidism; Methimazole; Phenylthiourea; Propylthiouracil; Rats; Sulfaguanidine; Thioglycosides; Thyroid Gland; Vegetables

Topics: Adult; Female; Goiter; Humans; Iodides; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Thyroid Gland; Time Factors; Triiodothyronine

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: Esterases; Fasting; Female; Glycerides; Goiter; Graves Disease; Heparin; Humans; Hyperthyroidism; Insulin; Iodine Isotopes; Lipase; Lipoprotein Lipase; Male; Methimazole; Propranolol; Propylthiouracil; Triglycerides

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: Animals; Antithyroid Agents; Carbon Isotopes; Cattle; Centrifugation, Density Gradient; Freezing; Goiter; Guanidines; Humans; Imidazoles; In Vitro Techniques; Iodine; Iodine Isotopes; Methimazole; Protein Denaturation; Solubility; Thiocyanates; Thyroglobulin; Thyroid Gland; Ultracentrifugation; Valine

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: Adult; Antithyroid Agents; Female; Goiter; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Imidazoles; Male; Methimazole; Middle Aged; Thyroid Function Tests

Topics: Animals; Biological Assay; Blood Proteins; Body Weight; Chickens; Goiter; Hybrid Vigor; Hybridization, Genetic; Iodine; Methimazole; Organ Size; Protein Binding; Secretory Rate; Thyroid Function Tests; Thyroid Gland; Thyroidectomy; Thyroxine

Topics: Animals; Antithyroid Agents; Blood Proteins; Body Weight; Goiter; Hypothyroidism; Insulin; Iodine; Male; Methimazole; Organ Size; Perchlorates; Propylthiouracil; Protein Binding; Rats; Rhenium; Thiocyanates; Thyroid Gland; Thyroidectomy; Thyrotropin; Thyroxine

Topics: Adult; Antithyroid Agents; Female; Glucagon; Goiter; Humans; Hypothyroidism; Imidazoles; Iodides; Male; Methimazole; Pituitary Gland; Radioimmunoassay; Stimulation, Chemical; Thyroid Function Tests; Thyrotropin; Time Factors; Vasopressins

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: 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: 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

Topics: Adipose Tissue; Animals; Anticholesteremic Agents; Blood Proteins; Clofibrate; Epididymis; Glycerolphosphate Dehydrogenase; Goiter; Growth; Iodine; Kidney; Liver; Malate Dehydrogenase; Male; Methimazole; Muscles; Myocardium; Organ Size; Pancreas; Propionates; Protein Binding; Rats; Spleen; Stimulation, Chemical; Testis; Thyroidectomy; Thyroxine

Topics: Chronic Disease; Diet; Goiter; Humans; Iodine; Iodine Isotopes; Methimazole; Methods; Perchlorates; Potassium; Thyroid Gland; Thyroiditis

Topics: Antithyroid Agents; Goiter; Humans; Methimazole; Methylthiouracil; Reserpine

Topics: Antithyroid Agents; Goiter; Imidazoles; Iodine Isotopes; Methimazole; Pathology; Pharmacology; Rats; Research; Thyroid Function Tests; Toxicology

Topics: Antineoplastic Agents, Hormonal; Antithyroid Agents; Goiter; Goiter, Nodular; Hyperthyroidism; Methimazole; Thyrotoxicosis