methimazole and Thyroid-Diseases

Thyroid autoimmunity is characterized by a large number of identified factors, and determining the relative importance of genetics and environment, for instance, can be difficult. In addition, the definition and progression of the individual diseases can also be challenging, and questions such as "when to begin treatment" or even "should treatment be begun" can be problematic. One approach to handling situations in which there are many factors is utilizing mathematical modeling. In a model, quantities that are clinically measurable are related through equations, based on known and inferred relationships between the systems involved.

Topics: Antithyroid Agents; Autoimmune Diseases; Autoimmunity; Computer Simulation; Humans; Methimazole; Models, Immunological; Thyroid Diseases; Thyroid Gland

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

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

Thyroid dysfunction can influence the physiological disposition of drugs. Depending on the pharmacokinetic properties of the individual drug, changes in the rate of metabolism ranging from profound to moderate or negligible have been observed. Since renal function is also influenced by thyroid disease, changes in renal elimination of drugs which are excreted in the urine mainly as unchanged drugs have to be considered as another reason for altered drugs disposition in thyroid disease. In patients with thyrotoxicosis lower, and in patients with myxoedema, higher, digitalis plasma levels have been observed. The altered disposition of cardiac glycosides in thyroid dysfunction can be attributed to changes in renal elimination and metabolism. These findings may be the kinetic correlate for the clinical observation that larger than the usual dose of digitalis is required in thyrotoxic patients and lower in hypothyroid patients. Antipyrene half-lives are very much shortened during hyperthyroidism and prolonged appreciably during hypothyroidism. The alterations in the disposition of these drugs seen during thyroid dysfunction can be ascribed to changes in its rate of metabolism which is controlled by the levels of circulating thyroid hormones. N-demethylation of aminopyrine is depressed both in hyper- and hypothyroid patients as compared with euthyroid subjects. Changes in the half-life of this drug were observed only during hypothyroidism. The physiological disposition of the antithyroid drug propylthiouracil is not changed during thyrotoxicosis. A decrease in plasma half-life of methimazole is however, observed during hyperthyroidism, whereas in hypothyroid patients half-life is increased. The few data available so far do not allow general prediction of how thyroid disease could alter drug metabolism in man.

Topics: Administration, Oral; Aminopyrine; Anticoagulants; Antipyrine; Digitalis Glycosides; Hormones; Humans; Kinetics; Methimazole; Pharmaceutical Preparations; Propylthiouracil; Riboflavin; Steroids; Thyroid Diseases; Tolbutamide

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

To date, there is no agreement about the frequency or the features of thyroid abnormalities in McCune-Albright syndrome (MAS). The aim of our study was to detect thyroid abnormalities in a cohort of MAS children and adolescents and to give indications for their treatment and follow-up.. In 36 patients, 22 females and 14 males, thyroid function and sonographic features of thyroid were evaluated every 6-12 months.. Three males and 1 female had hyperthyroidism: 2 with nodular, 2 with diffuse goiters. They were treated with methimazole (0.2-0.5 mg/kg/day) with good clinical and biochemical responses. The remaining 32 patients were euthyroid, even if 7 displayed sonographic alterations, of whom 5 had nodular goiter with nodules >1 cm, and 2 micronodular goiter. Fine-needle aspiration biopsy was performed in 2 patients with nodules >1 cm, 1 showing hemorrhagic nodule and 1 colloid cystic nodule.. Prevalence of thyroid alterations in the studied MAS series was 31%. 64% of 11 patients with thyroid alterations had nodular goiters, with nodules >1 cm. As the onset of thyroid disease ranged from 1 to 20 years, a strict monitoring of thyroid function is recommended every 6 months. Satisfactory treatment can be obtained and maintained with antithyroid drugs.

Topics: Adolescent; Adult; Antithyroid Agents; Child; Child, Preschool; Female; Fibrous Dysplasia, Polyostotic; Follow-Up Studies; Humans; Infant; Male; Methimazole; Prevalence; Retrospective Studies; Thyroid Diseases; Thyroid Gland

35S-methimazole (MMI), 35S-carbimazole or 35S-propylthiouracil (PTU) were given orally to fifty-five patients at various times up to 12 h before surgical thyroidectomy. The amount of 35S radioactivity and labelled drug in thyroid and plasma samples was measured. Intrathyroidal inhibition or organic binding of iodine by MMI, carbimazole and PTU was measured after intravenous administration of 131I, 132I or 125I-iodide. After administration of 35S-carbimazole or 35S-MMI the thyroid to serum (T/S) ratio of 35S radioactivity was greater in thyrotoxic glands than in non-toxic adenoma tissue. 35S-MMI was found in thyroid and plasma samples after administration of 35S-carbimazole. The T/S 35S-MMI was greater than 1 in most but not all patients. 35S radioactivity was also concentrated in the thyroid after administration of 35S-PTU. In thyrotoxic glands there was an 80% inhibition of iodine organification in patients receiving MMI and 60% for those receiving PTU. It is suggested that carbimazole and MMI can be given once or twice daily in some patients but PTU would be less suitable for this dose schedule.

Topics: Antithyroid Agents; Carbimazole; Clinical Trials as Topic; Female; Humans; Iodine; Male; Methimazole; Propylthiouracil; Thyroid Diseases; Thyroid Gland; Time Factors

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

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

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

This chapter represents a selection of 8 clinical scenarios that may commonly be encountered. They help summarize some of the literature and teaching points of the previous chapters. They are not meant to represent every possible presentation of thyroid disease, but rather to present common symptoms and findings that may aid a clinician in making a diagnosis or in selecting initial treatment.

Topics: Adult; Antithyroid Agents; Diabetic Ketoacidosis; Female; Humans; Methimazole; Preconception Care; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Diseases; Thyroid Function Tests

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

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

Myasthenia gravis (MG) is an acquired autoimmune disorder causing skeletal muscle fatigue and weakness. This is a report of one woman and her daughter presenting with myasthenia and gravis and Grave's disease. It highlights possible hereditary component of this condition which has not been commonly reported in our setting.

Topics: Adult; Antithyroid Agents; Autoimmune Diseases; Cholinesterase Inhibitors; Female; Graves Disease; Humans; Methimazole; Middle Aged; Myasthenia Gravis; Pyridostigmine Bromide; Thyroid Diseases

This study investigates the effect of thyroid hormones on the morphology of hippocampal neurons in adult rats. Hypo- and hyperthyroidism were induced by adding 0.02% methimazole and 1% l-thyroxine, in drinking water from 40 days of age, respectively. When the rats were 89 days old their brains were removed and stained by a modified Golgi method and blood samples were collected in order to measure T4 serum levels. Neurons were selected and drawn using a camera lucida. Our results show that methimazole administration reduces the dendritic branching of the apical shafts of CA3 and CA1 pyramidal neurons mainly by increasing the distance to the first branch point in both types of neurons, and reducing branch points in the radius of 50 microm from the soma in CA1 neurons. Nevertheless, it was observed an increase of apical spine density in CA3 neurons from this group. Thyroxine reduces apical and basal tree of CA3 pyramidal neurons increasing the distance to the first branch point, reducing branch points in the radius of 50 microm from the soma and increases their apical and basal spine density. In CA1 field, thyroxine reduces the number of basal branch points. Both treatments seems to provoke alterations in the same direction reducing the dendritic branching and increasing spine density, although no significances appeared in some of the parameters analyzed. The effects are more evident in thyroxine than methimazole group; and in CA3 neurons than in CA1 neurons. In discussion it is pointed that the increase of spine density could be a mechanism to compensate the functionality reduction that can be provoke by the treatment effect on dendritic branching.

Topics: Analysis of Variance; Animals; Disease Models, Animal; Hippocampus; Male; Methimazole; Neurons; Random Allocation; Rats; Rats, Wistar; Silver Staining; Thyroid Diseases; Thyroxine

We investigated whether thyroid receptor antibodies (TRAb) could result in transient neonatal thyroid disease by transfer through milk from mothers treated for thyrotoxicosis.. To analyse whether breast milk content of TRAb in euthyroid mothers with treated thyrotoxicosis resulted in neonatal thyroid disease and whether extended breastfeeding prolonged the neonatal disease.. We tested three TRAb-positive mothers and the course, treatment and outcome for their offspring with neonatal thyrotoxicosis, and six healthy and two TRAb-negative euthyroid mothers with treated thyrotoxicosis during breastfeeding.. TRAb was analysed in serum and breast milk by a radioreceptor assay.. TRAb in serum was detectable in all treated mothers, in one mother during her four pregnancies, resulting in all neonates requiring treatment for thyrotoxicosis. Serum TRAb concentration in neonates decreased continuously with time after birth. Breast milk TRAb was detectable in all cases but not in the controls or in TRAb-negative mothers treated for thyrotoxicosis. The calculated half-life for offspring serum and breast milk TRAb was calculated as approx. 3 weeks and 2 months, respectively.. Euthyroid TRAb-positive mothers may cause transient neonatal thyroid disease which seems to be worse and more prolonged during breastfeeding as a consequence of TRAb in breast milk.

Topics: Adult; Autoantibodies; Control Groups; Female; Humans; Immunoglobulins, Thyroid-Stimulating; Infant, Newborn; Male; Maternal-Fetal Exchange; Methimazole; Milk, Human; Pregnancy; Receptors, Thyrotropin; Reproducibility of Results; Risk; Thyroid Diseases; Thyrotoxicosis

Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antithyroid Agents; Autoantibodies; B-Lymphocytes; Female; Glucocorticoids; Graves Disease; Graves Ophthalmopathy; Humans; Immunoglobulins, Thyroid-Stimulating; Methimazole; Middle Aged; Recurrence; Remission Induction; Rituximab; Thyroid Diseases

Activation of cell-mediated immunity by soluble interleukin-2 receptor alpha (sIL-2Ralpha) release is well documented. The aim of this study was to measure serum concentrations of sIL-2Ralpha in patients with autoimmune and non-autoimmune thyroid disorders in different stages of thyroid function, before and after administration of l-thyroxine (l-T4) and its discontinuation as well as before and during methimazole administration.. The study included 80 females: 16 with Graves' disease, 15 with Hashimoto's thyroiditis and subclinical hypothyroidism, 14 with Hashimoto's thyroiditis with fibrosis and clinical hypothyroidism, 20 after subtotal thyroidectomy following nodular non-toxic goitre and 15 healthy controls. Patients were examined at two different time points. Serum concentrations of sIL-2Ralpha were measured with the use of enzyme immunoassay technique.. Souble IL-2Ralpha serum concentration increased in patients with untreated Graves' disease and decreased after methimazole treatment. In Hashimoto's thyroiditis, the sIL-2Ralpha level was within the normal range, in Hashimoto's thyroiditis with clinical hypothyreosis it was low and after l-T4 administration it increased in both patient groups. After thyroidectomy, patients treated with l-T4, had increased levels of sIL-2Ralpha which decreased after discontinuation of therapy. There were a significant positive correlation between sIL-2Ralpha and free thyroxine in patients with (i). Graves' disease both before and after methimazole administration, (ii). Hashimoto's thyroiditis (with subclinical hypothyroidism) both before and after l-T4 therapy, (iii). Hashimoto's thyroiditis with fibrosis and (iv). overt hypothyroidism before l-T4 administration and in individuals during long-term l-T4 treatment (after subtotal thyroidectomy).. Serum sIL-2Ralpha concentration in autoimmune thyroid diseases depends on thyroid function. In both autoimmune and non-autoimmune thyroid diseases, thyroxine stimulates the release of sIL-2Ralpha.

Topics: Adult; Antithyroid Agents; Case-Control Studies; Female; Graves Disease; Humans; Hypothyroidism; Interleukin-2 Receptor alpha Subunit; Male; Methimazole; Middle Aged; Receptors, Interleukin; Thyroid Diseases; Thyroidectomy; Thyroiditis, Autoimmune; Thyroxine

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

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

During radiolabeled metaiodobenzylguanidine (MIBG) administration in children with neuroblastoma, the thyroid is protected from (123/131)I uptake by potassium iodide. Despite this protection, up to 64% of patients develop thyroid dysfunction. The authors introduce a new method of radiation protection for the thyroid gland.. In a prospective cohort study, 34 children with neuroblastoma who received MIBG were given thyroxine, methimazole, and potassium iodide for protection of the thyroid gland. Protection started 1 day before the start of diagnostic 123I-MIBG and was continued until 4 weeks after the last therapeutic 131I-MIBG dose. Follow-up measurements were performed every 3 months after the protection was stopped. Visualization of the thyroid on MIBG images was reviewed by three nuclear medicine physicians. Results were compared with a historic control group of children who had received potassium iodide for thyroid protection during MIBG administration.. After a mean follow-up of 19 months, there were 23 evaluable patients. Thyroid function was normal in 86% of survivors compared with 44% of children in the historic control group (P=0.011; Pearson chi-square test). Scintigraphic visualization of the thyroid diminished substantially after the new protection (21.5% vs. 5.3%, respectively; P=0.000).. The results of the current study indicate that compared with potassium iodide alone, combined thyroxine, methimazole, and potassium iodide protect the thyroid more effectively against radiation damage from (123/131)I during diagnostic and therapeutic MIBG administration in children with neuroblastoma.

Topics: 3-Iodobenzylguanidine; Antineoplastic Agents; Child; Child, Preschool; Female; Humans; Infant; Male; Methimazole; Neuroblastoma; Potassium Iodide; Radiation-Protective Agents; Thyroid Diseases; Thyroid Function Tests; Thyroxine; Treatment Outcome

Topics: Antithyroid Agents; Female; Graves Disease; Humans; Hypothyroidism; Methimazole; Middle Aged; Psychotic Disorders; Recurrence; Thyroid Diseases; Thyroxine; Treatment Outcome

The aim of the present study was to determine the influence of thyroid hormones on the anxiety of male Wistar rats. Dysthyroidism was induced by adding 20 mg of methimazole (100 ml) to their drinking water or by adding 0.3 mg of L-thyroxine (100 ml) to their drinking water from the ninth day of gestation. After weaning, the drugs were administered to young rats until the end of the experiment. Anxious behavior was measured using the elevated plus maze and social interaction tests when the animals were 85 days old. Chronic methimazole administration produced a significant anxiolytic pattern in both tests. In the plus maze test, the methimazole-treated animals entered and remained more time in the open arms than the control animals. In the social interaction test, they spent more time in bodily contact, and did this more frequently than those in the control group did. Results from this experiment suggest that chronic thyroid deficiency produces an anxiolytic-like effect in both tests.

Topics: Animals; Anxiety; Female; Interpersonal Relations; Male; Maze Learning; Methimazole; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Thyroid Diseases; Thyroid Hormones; Thyroxine

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

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

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

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

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

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

To determine drug-induced hyperfunction of marmoset thyroids due to inhibition of synthesis or enhancement of metabolic elimination of thyroid hormones, males were orally administered 10 and 30 mg/kg/day methimazole (MMI), 30 and 100 mg/kg/day spironolactone (SPL), or 50 mg/kg/day phenobarbital (PB) for 4 weeks. MMI caused marked hypertrophy of follicular epithelial cells in accordance with a significant decrease in the plasma thyroxin (T4) level. Hypertrophied epithelial cells were filled with dilated rough endoplasmic reticulum and reabsorbed intracellular colloids, and the luminal surface was covered with abundant microvilli. The colloid included vacuoles positive to anti T4 immuno-staining. SPL and PB also caused similar histomorphological changes, although they were less severe than those due to MMI and were not clearly associated with decrease in the plasma T4 levels. Hepatic T4 UDPGT activities tended to increase due to SPL and PB treatment, however, which were not so significant as increases in microsomal cytochrome P-450 contents. Some animals treated with SPL and PB showed marked increases in thyroid weights due to inactive dilated follicles. In conclusion, hyperactivity of thyroid follicles was induced in marmosets not only due to inhibition of T4 synthesis produced by MMI but also because of enhancement of hepatic T4 elimination produced by SPL and PB. However, hypertrophic effects of SPL and PB were less severe than MMI, because plasma T4 levels were maintained at almost pretreatment or control levels after SPL or PB treatment.

Topics: Animals; Anticonvulsants; Antithyroid Agents; Biopsy; Callithrix; Cytochrome P-450 Enzyme System; Immunohistochemistry; Liver; Male; Methimazole; Microscopy, Electron; Mineralocorticoid Receptor Antagonists; Phenobarbital; Radioimmunoassay; Spironolactone; Thyroid Diseases; Thyroid Gland; Thyroxine; Triiodothyronine

To investigate the possible participation of immunoglobulin E (IgE) in the autoimmune process of Graves' disease, incidence of elevation of serum IgE level, TSH receptor antibody (TRAb), and thyroid status were studied in 66 patients with hyperthyroid Graves' disease, 54 patients with Hashimoto's thyroiditis, 19 patients with bronchial asthma, and 15 patients with pollen allergy. In hyperthyroid Graves' patients, elevation of serum IgE levels (> or = 170 U/mL) was found in 19 of 66 patients (29%), 11 of whom had hereditary and/or allergic conditions. Elevations of serum IgE levels were found in 63% of patients with bronchial asthma and in 40% of patients with pollen allergy. Mean values of serum IgE were the same in patients with hyperthyroid Graves' disease and with bronchial asthma. During methimazole treatment TRAb decreased without fluctuation of IgE levels in both groups. The decrease in TRAb was significantly greater in patients with normal IgE than in patients with IgE elevation. After prednisone administration, reduction in TRAb was greater in patients with normal IgE than that in patients with IgE elevation. High incidence of IgE elevation in hyperthyroid Graves' disease and slower reduction in TRAb in association with IgE elevation suggest a difference in the autoimmune processes in Graves' disease with and without elevation of IgE.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Asthma; Female; Glucocorticoids; Graves Disease; Humans; Hypersensitivity; Immunoglobulin E; Male; Methimazole; Middle Aged; Pollen; Prednisone; Thyroid Diseases; Thyroid Gland

This study investigated T-cell activation markers HLA-DR and CD69 in both naive (CD45RA+) and memory (CD45RA-) CD4+ as well as CD8+ T cells in peripheral blood of patients with autoimmune thyroiditis (AT, N = 28) or hyperthyroid untreated Graves' disease (GDH, N = 34) using three-color flow cytometry. It was demonstrated that patients with AT, but not those with GDH, expressed increased amounts of HLA-DR antigen compared to healthy subjects (HS, N = 26) on total CD4+ (AT: 14.1%; GDH: 11.3%; HS: 10.9%) and CD8+ cells (AT: 31.9%; GDH: 23.5%; HS: 19.4%) as well as on CD45RA- CD4+ cells (AT: 11.2%; GDH: 7.7%; HS: 7.9%). In GDH (+71%) and AT (+91%) only the proportion of HLA-DR+ CD45RA+ CD8+ cells was increased vs HS. Furthermore, euthyroid GD patients on methimazole (GDE, N = 22) displayed greater HLA-DR+ expression on total and CD45RA- cells within both CD4+ (+37 and 40%, respectively) and CD8+ cells (+47 and 93%, respectively) than GDH. In addition, total and CD45RA+ CD4+ and CD8+ cells were increased vs HS. In contrast, proportions of CD69 positive T cells were increased in AT and GDH on total CD4+ (+97 and 74%, respectively) and CD8+ (+95 and 68%, respectively) cells and all subsets thereof (except for CD45RA- cells in GDH), but normalized upon thyrostatic treatment. We conclude that patients with autoimmune thyroid disease harbor an almost twofold greater proportion vs HS of (a) HLA-DR+ CD45RA+ CD8+ T cells, and of (b) CD69 on total CD4+ and CD8+ cells, and an even more marked elevation on their CD45RA+ subset in AT and untreated GD. In addition, (c) thyrostatic treatment by methimazole in GD is accompanied by a further increase in circulating HLA-DR+ CD4+ and CD8+ cells and their CD45RA- subsets, but decreased CD69 expression. These data suggest association of HLA-DR expression with ongoing autoimmunity, while increased CD69 expression relates in part also to elevated thyroid hormone concentration in GDH.

Topics: Adult; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; Antithyroid Agents; Autoimmune Diseases; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Female; Graves Disease; HLA-DR Antigens; Humans; Lectins, C-Type; Leukocyte Common Antigens; Lymphocyte Activation; Male; Methimazole; Middle Aged; Thyroid Diseases

We evaluated the concentration of epidermal growth factor (EGF) in platelets, serum and plasma obtained from 47 patients with Graves' disease, 7 with hypothyroidism and 20 healthy subjects. The platelets of the subjects were collected from platelet rich plasma and lysed by freezing and thawing. Subsequently the platelet debris was treated with Triton X-100. The EGF concentration was determined by homologous radioimmunoassay. The concentration of EGF in the platelets in 14 patients with untreated Graves' disease was significantly higher than that in the healthy controls. After treating these 14 patients with antithyroid agents, the EGF concentration in the platelets decreased to the level of the healthy controls. The EGF concentration in the platelets in the 7 untreated hypothyroid patients decreased after replacement therapy with thyroxine. The mean volume of the platelets in the 14 patients with untreated Graves' disease was significantly larger than in the control and decreased after treatment with antithyroid agents. The serum and plasma levels of EGF in the 7 untreated hypothyroid increased after replacement therapy. In conclusion, thyroid function affected the concentration of EGF in the platelets of patients with thyroid disorders.

Topics: Adult; Blood Platelets; Epidermal Growth Factor; Female; Graves Disease; Humans; Hypothyroidism; Male; Methimazole; Middle Aged; Platelet Count; Propylthiouracil; Thyroid Diseases; Thyroxine

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

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

The aim of this study was to evaluate through the auditory brainstem responses (ABRs) the electrical events generated along the auditory pathway in 56 adult patients affected with hyper- and hypothyroidism. Twenty-four normal-hearing hyperthyroid patients affected with Graves' disease and 32 normal-hearing hypothyroid patients (9 with subclinical and 23 with overt hypothyroidism) were subjected to standard (clicks at 21 pps) and sensitized ABR with masking wide-band (masking noise). In addition, thyroid scintiscan and ultrasonography, free T3 and T4, total T3 and T4, TSH, antimicrosomal and antithyroglobulin antibodies, audiogram and impedance tests were performed in all the patients. This study was repeated after 6-12 months of treatment in conditions of euthyroidism. The results showed changes of ABRs both in the standard procedure as well as in the sensitized test in 6 hyperthyroid (25%) and 8 hypothyroid patients (25%). All the patients with abnormal ABRs had overt hypothyroidism (8/23; 34.7%). The ABRs became normal in 5 out of 6 Graves' patients after 6-12 months of methimazole treatment. ABRs remained abnormal in all the hypothyroid patients despite their having been on L-thyroxine treatment for 6-12 months and were euthyroid for at least 5 months before the study was repeated. These findings suggest that ABR abnormalities are indicative only of a nonspecific injury in the bulbo-ponto-mesencephalic centers. Alterations of ABRs in thyroid diseases are not specific in relation to hyper- or hypothyroidism. Lastly, there is a relationship between ABR abnormalities and the degree of hypothyroidism, even if ABR alterations are not always reversible after long-term therapy.

Topics: Adult; Evoked Potentials, Auditory, Brain Stem; Female; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Middle Aged; Thyroid Diseases; Thyroxine

A 90-day gavage study was performed to evaluate the subchronic toxicity of 1-methyl-3-propylimidazole-2-thione (PTI) when administered to Crl:CD BR rats. PTI is a chemical catalyst and is structurally similar to the thioureas, which are known to adversely affect the thyroid. Therefore, this study was designed to investigate the effects of PTI on the thyroid. Male and female rats were dosed with 0, 5, 10, 25, or 75 mgPTI/kg/day for 13 weeks. Clinical pathology examinations and pathology examination were performed and the following were measured periodically: serum T3, T4, and TSH, hepatic UDP-glucuronyltransferase activity, and cell proliferation of the thyroid and liver. Under the conditions of this study, the overall no-observed-adverse-effect level (NOAEL) for the subchronic effects of PTI in male and female rats was 10 mg PTI/kg/day. The NOAEL was based on the effects on the thyroid gland in male and female rats dosed with 25 and 75 mg PTI/kg/day, as well as the hepatic centrilobular fatty change, increased severity of chronic progressive nephropathy, fatty change in the adrenal medulla, and the substantial reduction in body weight and body weight gain. The primary target organs were the thyroid and liver. Alterations in thyroid hormones (T3, T4, and TSH) occurred predominantly at 25 and 75 mg/kg/day. Toxicologically significant alterations in T3, T4, and TSH levels, cell proliferation, and UDP-glucuronyltransferase activity occurred in rats dosed with 25 and 75 mg/kg/day, which correlated with organ weight and histopathological effects. Additionally, the effect of PTI on thyroid peroxidase activity, a key step in thyroid hormone synthesis, was evaluated in vitro using microswine thyroid microsomes. PTI was shown to inhibit thyroid peroxidase, with an IC50 of 0.02 M. These data suggest that PTI enhances the excretion of T4 via induction of glucuronyltransferase and inhibits thyroid hormone synthesis via a direct affect on thyroid peroxidase. Both of these effects contribute to the disruption of the hypothalamic-pituitary-thyroid axis and result in sustained elevation of TSH and the corresponding thyroid hypertrophy and hyperplasia.

Topics: Animals; Body Weight; Cell Division; Eating; Female; Glucuronosyltransferase; In Vitro Techniques; Intubation, Gastrointestinal; Iodide Peroxidase; Liver; Male; Methimazole; Organ Size; Rats; Swine; Swine, Miniature; Thyroid Diseases; Thyroid Gland; Thyroid Hormones

The well documented ability of immunoglobulins G (IgGs) from Graves' patients to stimulate cAMP production is believed to be involved in the pathophysiology of this disease. It is still under discussion whether other intracellular messengers known to regulate thyroid function might play a similar role. This study shows that phospholipase-A2, a signal pathway unrelated to cAMP, is activated by Graves' IgGs. The IgGs from 67 patients with active Graves' disease, 8 patients with Graves' disease in remission, 5 patients with idiopathic myxedema, 2 patients with Hashimoto's thyroiditis, 57 patients with nonautoimmune thyroid disease, and 65 normal subjects were tested for their ability to stimulate phospholipase-A2 activity, as measured by arachidonic acid release from FRTL5 thyroid cells. The IgGs from patients with active Graves' disease caused a significant increase in arachidonic acid release compared to those from normal subjects, patients with nonautoimmune thyroid diseases, and patients with Graves' disease in remission (P less than 0.0001). The IgGs from active Graves' patients were also able to increase cAMP accumulation in FRTL5 cells. This effect did not correlate with the ability of the same IgGs to induce arachidonic acid release, suggesting that Graves' IgGs stimulate these two pathways by separate mechanisms. Moreover, a subgroup of IgGs that stimulated phospholipase-A2 did not increase the cAMP levels in FRTL5 cells. Our data suggest a novel mechanism of action of Graves' IgGs, the activation of phospholipase-A2, well distinguishable from the known effect on cAMP accumulation. The assay we describe could be helpful in improving the diagnosis and therapy of Graves' disease and in distinguishing it from nonautoimmune thyroid diseases. It also supplies the basis for a prospective subclassification of the Graves' patients, which might become useful to clarify the pathophysiology of this disease.

Topics: Adolescent; Adult; Aged; Animals; Arachidonic Acids; Cell Line; Cyclic AMP; Female; Graves Disease; Humans; Immunoglobulin G; Male; Methimazole; Middle Aged; Phospholipases A; Phospholipases A2; Propylthiouracil; Rats; Reference Values; Thyroid Diseases; Thyroid Gland; Thyroid Hormones; Thyrotropin

Radiofluorescent analysis (RFA) with the help of various devices and a new method of investigation was employed for a combined in vivo study of 1) the concentration (in micrograms/l g); and 2) the total amount (in mg) of stable iodine in the thyroid; 3) a scan of the distribution of halogen in the organ; 4) organ mass (in g) in the control groups, in 15 patients with toxic goiter before and after mercasolil therapy, and in 6 patients with endemic goiter after iodine prophylaxis. The importance of some of the indices in the diagnosis and therapy of patients with toxic goiter was shown.

Topics: Adult; Female; Goiter, Endemic; Graves Disease; Humans; Iodine Isotopes; Methimazole; Middle Aged; Spectrometry, X-Ray Emission; Thyroid Diseases; Thyroid Gland

We have recently reported that, in patients with hyperthyroidism, the red blood cell (RBC) carbonic anhydrase I (CAI) and zinc (Zn) concentrations both reflect the patient's integrated thyroid hormone level over the preceding few months. In this study, we evaluated the clinical usefulness of determining the RBC CAI and Zn concentrations in patients with various types of thyroid disease. Six patients with painless thyroiditis (PT) had normal RBC CAI concentrations and the two patients tested had normal RBC Zn levels. In four patients with syndromes of inappropriate thyrotropin (TSH) secretion (SITSH) two euthyroid patients had normal RBC CAI and two hyperthyroid patients had subnormal RBC CAI and Zn. In a patient with Graves' disease whose plasma thyroxine (T4) and triiodothyronine (T3) concentrations changed remarkably because of poor compliance with the regimen, the change in plasma thyroid hormone levels preceded the change in the RBC CAI and Zn concentrations by 2 to 3 months. These observations suggest that the measurement of RBC CAI and Zn concentrations may be useful clinically as follows: (1) in differentiating hyperthyroid Graves' disease from transient hyperthyroidism due to destructive thyroiditis; and (2) in obtaining an accurate estimate of the extent of elevated thyroid hormone levels in hyperthyroid patients over time.

Topics: Adult; Carbonic Anhydrases; Erythrocytes; Graves Disease; Humans; Methimazole; Middle Aged; Osmolar Concentration; Thyroid Diseases; Thyroid Function Tests; Thyroid Hormones; Thyroiditis; Zinc

Topics: Biological Assay; Female; Humans; Immunoenzyme Techniques; Infant, Newborn; Male; Methimazole; Pituitary Function Tests; Pregnancy; Radioimmunoassay; Radioligand Assay; Reference Values; Thyroid Diseases; Thyrotropin; Thyrotropin-Releasing Hormone

It is a well-known fact that a thyroid stimulation blocking antibody (TSBAb) may play an important role in primary hypothyroidism. However, it has rarely been reported that TSBAb appears in only a few cases of Graves' disease which became hypothyroidism in their clinical courses. We examined TSBAb in 120 sera from 79 cases with Graves' disease before or while under methimazole (MMI)-treatment. TSBAb value was expressed as the percentage inhibition of TSH-stimulated cAMP response of porcine thyroid cells by the patient's IgG. TSBAb was positive in 9 cases (11.4%) of 79 cases of Graves' disease. In 6 of the 9 cases, TSBAb was detected at the untreated period. In the other 2 of the 9 cases, it was detected during the exacerbation related with their pregnancy. It was difficult to control Graves' disease in all 9 cases. These results suggest that TSBAb appears not only in primary hypothyroidism but also even in the hyperthyroid state of Graves' disease, and that the combination of TSAb and TSBAb may regulate the pathogenesis of Graves' disease.

Topics: Adult; Aged; Autoantibodies; Autoimmune Diseases; Binding, Competitive; Female; Graves Disease; Humans; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Receptors, Thyrotropin; Thyroid Diseases; Thyroiditis, Autoimmune

A 52-year-old woman developed a toxic, solitary, autonomously functioning thyroid nodule four years after antithyroid drug treatment for Graves' disease. When she was initially seen, a thyroid scan showed the homogeneous enlargement of both lobes with increased uptake. Graves' disease was diagnosed and the patient was treated with methimazole. Thyroid function was well-controlled with medication for 18 months, after which the patient stopped taking the drug for three years. Four years after Graves' disease was diagnosed, the patient again showed symptoms of hyperthyroidism. The etiology was a toxic, autonomously functioning nodule.

Topics: Female; Graves Disease; Humans; Methimazole; Middle Aged; Sodium Pertechnetate Tc 99m; Thyroid Diseases; Time Factors; Ultrasonography

The placenta contains iodothyronine 5-deiodinase activity (P5-Dase) that probably acts on iodothyronines in the fetal circulation to convert T4 to rT3 and T3 to 3,3'-T2. Since thyroid status and fasting have profound effects on iodothyronine deiodinases in other tissues, the present studies were performed to determine if these perturbations affected P5-Dase. Control and treated rats were mated and killed near term on the 20th day of gestation. P5-Dase was determined in placenta homogenates enriched with dithiothreitol by measuring the conversion of T4 to rT3. In four of five studies, P5-Dase was similar in dams that underwent thyroidectomy (Tx) on day 7 of gestation and sham Tx dams. P5-Dase was not altered in dams that were treated with methimazole (MMI) to induce maternal and fetal hypothyroidism. Treatment of dams with supraphysiological doses of T4, beginning on the seventh day of gestation, did not significantly affect P5-Dase. In three of four studies, P5-Dase was similar in fed dams to values in dams fasted for the last 5 days of pregnancy. Placenta iodothyronine 5'-deiodinase activity (P5'-Dase) was also measured in some studies. P5'-Dase was not decreased in Tx rats and was modestly decreased in MMI-treated rats. However, the effect of MMI was not reversed by the administration of supraphysiological doses of T4, Tx, MMI treatment, and fasting all decreased hepatic T4 5'-deiodinase activity in pregnant rats. These results strongly suggest that thyroid status and fasting do not alter P5-Dase activity.

Topics: Animals; Fasting; Female; Hypothyroidism; Iodide Peroxidase; Liver; Male; Methimazole; Placenta; Pregnancy; Rats; Rats, Inbred Strains; Thyroid Diseases; Thyroidectomy; Thyrotoxicosis; Thyroxine

Topics: Autoimmune Diseases; Graves Disease; Humans; Methimazole; T-Lymphocytes; Thyroid Diseases

Evidence has been accumulated that the anti-thyroid drugs used in the treatment of Graves' disease may have immunosuppressive properties but the exact mechanism of action is still unclear. In the present study, we have investigated the in vitro effect of carbimazole (CBZ) on the expression of lymphocyte differentiation antigens and on suppressor cell activity. The incorporation of radiolabelled methimazole (35S-MMI, the active metabolite of CBZ) by resting and mitogen stimulated lymphocytes was also investigated. CBZ at concentrations of 60 microM significantly inhibited the expression of the receptor for interleukin-2 (as defined by the anti-TAC monoclonal antibody [MoAb]) by lymphocytes stimulated with phytohaemagglutinin. The expression of an early activation antigen (as characterized by the 4F2 MoAb) was not affected. Twenty-four hour pre-incubation of cells with different concentrations of CBZ or medium alone did not change the lymphocyte response to mitogenic stimulation, thus suggesting no effect of the compound on suppressor cell function. Finally, there were no significant differences in the uptake of 35S-MMI between resting and stimulated lymphocytes. These data suggest that the immunosuppressive effect of CBZ may be due to its effect of reducing the expression of the receptor for interleukin-2 on lymphocytes undergoing full activation. This property of CBZ could be of relevance in the therapy of autoimmune thyroid diseases (not only Graves' disease) which are characterised by the presence of activated T cells in the thyroid and in circulation.

Topics: Adult; Antigens, Differentiation, T-Lymphocyte; Antigens, Surface; Autoimmune Diseases; Carbimazole; Female; Humans; Lymphocyte Activation; Male; Methimazole; Receptors, Antigen, T-Cell; Receptors, Immunologic; Receptors, Interleukin-2; T-Lymphocytes; T-Lymphocytes, Regulatory; Thyroid Diseases

Plasma fibronectin concentrations up to 85 mg/100 ml were found in hyperthyroid patients. There was a significant correlation between free thyroxine index and plasma fibronectin values. Hypothyroid patients had low to normal fibronectin concentrations. Parallel decreases of thyroid hormones and plasma fibronectin concentrations were noted during treatment with thiamazole. A direct effect of thyroid hormones on fibronectin synthesis seems probable.

Topics: Adult; Aged; Female; Fibronectins; Humans; Hyperthyroidism; Hypothyroidism; Methimazole; Middle Aged; Prealbumin; Thyroid Diseases; Thyroid Function Tests; Thyroxine

Serum ferritin measurements were evaluated as a marker of thyroid hormone action on peripheral tissues. Mean serum ferritin concentrations were not significantly different in euthyroid, thyrotoxic, and hypothyroid subjects due to a wide spread in ferritin levels among individuals. Intraindividual changes in serum ferritin, however, occurred with changing thyroid function. All 18 patients with thyrotoxic Graves' disease had a decrease in serum ferritin levels when they became euthyroid during antithyroid drug therapy. Furthermore, a significant intraindividual correlation between serum levels of ferritin and T4 or T3 was found in 2 patients with thyrotoxic Graves' disease in whom levels were measured serially throughout the course of therapy. Similarly, serum ferritin levels increased in all 12 hypothyroid patients with Hashimoto's disease when euthyroidism was achieved with L-T4 therapy. Administration of 75 micrograms T3 daily for 1 week to 11 euthyroid subjects resulted in a 23-243% (mean +/- SD, 117 +/- 70%) increase in serum ferritin above basal values. In contrast, in 3 patients with thyroid hormone resistance, the same treatment produced rises in serum ferritin concentrations of only 2%, 5%, and 15%. Our data suggest that alterations in thyroid status in a given individual produce changes in serum ferritin levels. Measurement of this protein before and after T3 therapy may prove useful in the diagnosis of thyroid hormone resistance.

Topics: Adult; Child; Drug Resistance; Female; Ferritins; Humans; Male; Methimazole; Thyroid Diseases; Thyroid Function Tests; Thyroid Hormones; Triiodothyronine

Untreated rats, and rats treated with methimazole (0.05% w/v in drinking water) or thyroxine (1 mg/kg, s.c., three times weekly) for 4-6 weeks to induce hypo- and hyperthyroidism respectively, were used to study the influence of thyroid hormone upon negative chronotropic and inotropic responses mediated by cardiac muscarinic receptors, and upon the affinity of these receptors for atropine. Negative chronotropic effects of methacholine were investigated by establishing partial concentration-response curves for isolated preparations of right atria. Methacholine was least potent in tissues from thyroxine-treated rats. Isolated left atria paced at 3 Hz, and spontaneously beating right atria, were used in studies of the negative inotropic effects of methacholine. This agonist was least potent in atria from the thyroxine-treated rats in which it also produced the smallest maximal responses. The negative inotropic effects of carbachol were examined on left atria paced at 3, 5 and 5.8 Hz to approximate the basal contraction rates of isolated right atria from methimazole-treated, untreated control and thyroxine-treated rats, respectively. At each of these frequencies, carbachol was most potent in atria from methimazole-treated rats, and least potent in atria from thyroxine-treated rats. Maximal responses were smallest in the latter group. pA2 values for atropine with methacholine as the agonist were obtained by the method of Arunlakshana & Schild (1959) for spontaneously beating right atria (negative chronotropic and inotropic effects) and left atria paced at 3 Hz (negative inotropic effects). Slopes of Schild plots did not differ from minus one in tissues from each of the experimental groups; pA2 values were similar, indicating that thyroid status is without effect upon the affinity of this antagonist for muscarinic receptors mediating both negative inotropic and chronotropic effects. 6 The results are discussed in the light of reports that hypothyroidism increases, and hyperthyroidism decreases the numbers of high affinity muscarinic receptor binding sites in the rat myocardium.

Topics: Animals; Atropine; Carbachol; Heart; Heart Rate; In Vitro Techniques; Male; Methacholine Compounds; Methimazole; Myocardial Contraction; Rats; Receptors, Muscarinic; Thyroid Diseases; Thyroxine

Topics: Antithyroid Agents; Carbimazole; Female; Fetus; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Infant, Newborn, Diseases; Methimazole; Pregnancy; Pregnancy Complications; Propranolol; Propylthiouracil; Thyroid Diseases; Thyroid Gland

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

This paper deals with the activity of glucose-6-phosphate dehydrogenase in patients with hyper- and hypothyroidism as well as in hyperthyroxinaemic rats. The activity of glucose-6-phosphate dehydrogenase is enhanced in red blood cells of hyperthyreotic patients and hyperthyroxinaemic animals. The activity will be decreased to normal range in patients by administration of antithyreotic drugs, such as thiamazole. Patients with hypothyroidism exhibit decreased enzymatic activity. It is suggested that thyroid hormones stimulate the HMP-shunt in red blood cells as a defence mechanism against additional oxidative stress.

Topics: Animals; Erythrocytes; Female; Glucosephosphate Dehydrogenase; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Rats; Thyroid Diseases; Thyroxine

A survey is given on the therapy of hyperthyroidism, hypothyroidism and the bland struma including the thyrogenic crises. Indications and contraindications of the therapeutic measures available are described. During the therapy of hyperthyroidism the suppression test for the control of the course is recommended. Furthermore it is shown that the thyroxine is more favourable for the long-term treatment than triiodine thyronine or the combination preparations offered at present. But the rules described for the treatment of diseases of the thyroid gland must always be adapted to the individual case.

Topics: Female; Humans; Methimazole; Prednisolone; Pregnancy; Preoperative Care; Thyroid Diseases; Thyroxine; Triiodothyronine

In normal, nonmedicated volunteers and in patients with thyroid disorders the plasma half-lives of antipyrine, propylthiouracil, and methimazole were determined after single oral doses. The plasma half-liver plus or minus S.D. of antipyrine, propylthiouracil, and methimazole were 11.9 plus or minus 1.4 hr, 6.7 plus or minus 1.0 hr, and 9.3 plus or minus 1.4 hr, respectively, in normal volunteers, but were shortened to 7.7 plus or minus 1.2 hr, 4.3 plus or minus 0.7 hr, and 6.9 plus or minus 0.6 hr, respectively, in hyperthyroid patients. In hypothyroid patients the plasma half-lives of these drugs were prolonged to 26.4 plus or minus 4.0 hr, 24.7 plus or minus 34.5 hr, and 13.6 plus or minus 4.8 hr, respectively. Return to the euthyroid state restored plasma half-lives to or toward normal. Alterations in plasma drug half-lives during thyroid dysfunction appear to result mainly from accelerated hepatic microsomal drug metabolism in hyperthyroidism and retarded drug biotransformation during hypothyroidism.

Topics: Adult; Aged; Antipyrine; Biotransformation; Female; Half-Life; Humans; Hyperthyroidism; Hypothyroidism; Kinetics; Male; Methimazole; Middle Aged; Propylthiouracil; Spectrophotometry; Thyroid Diseases; Thyroid Function Tests

Over a 7-yr period from January 1967 to January 1974, 141 patients underwent thyroid surgery for various pathology at the Bexar County Hospital - University of Texas Medical School at San Antonio. Of these, 113 patients underwent subtotal thyroidectomy for benign diseases, including 28 of thyrotoxic patients who underwent subtotal thyroidectomy as definitive treatment. In this group of patients special interest and emphasis was placed in the preoperative and intraoperative management of the difficult and complicated hyperthyroid patient. Preoperative treatment was accomplished by the utilization of multiple drug combinations - including antithyroid drugs, adrenergic blocking agents, and iodine - which resulted in significant decrease in preparation time for surgery. Furthermore, this short intensive preoperative management of complicated hyperthyroid patients allowed satisfactory correction of their problems with little or no morbidity which otherwise would have been extremely difficult if not impossible to resolve. At operation, 28 patients were diagnosed to have malignant disease; 23 underwent total thyroidectomy and the other 5 had subtotal thyroidectomy. In addition to total or subtotal thyroidectomy, 23 patients had either classical or modified radical neck dissection including 9 patients who had bilateral neck dissection. The various surgical techniques utilized, the rationale for rapid preoperative preparation of complicated hyperthyroid patients, morbidity, and long-term follow-up are discussed.

Topics: Adolescent; Adult; Aged; Child; Dexamethasone; Female; Follow-Up Studies; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Neck Dissection; Potassium Iodide; Propylthiouracil; Reserpine; Thyroid Diseases; Thyroid Neoplasms; Thyroidectomy

In homogenate supernatants of kidneys of male rats the extent of deiodination of L-diiodotyrosine (L-DJT) and L-thyroxine (L-T4) was investigated in dependence on the thyroid function (hypo- and hyperthyroidized) and also in dependence on age. In rats hypothyroidized by loading with Methylthiouracil (MTU) or Methimazol (MMI) the deiodination for L-DJT and L-T4 was significantly reduced, in rats loaded with 40 mug T4 sc. for 10 days, the deiodination was significantly enhanced compared with untreated control animals. With advancing age (6 weeks, 3 or 12 month) the deiodination activity is highly significantly reduced. The results underline relations between thyroid gland function and deiodination activity in kidney.

Topics: Age Factors; Animals; Diiodotyrosine; Hyperthyroidism; Hypothyroidism; Iodine; Kidney; Male; Methimazole; Methylthiouracil; Monoiodotyrosine; Rats; Thyroid Diseases; Thyroid Hormones; Thyroxine; Triiodothyronine

Topics: Animals; Exophthalmos; Goldfish; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Methimazole; Muscles; Orbit; Sulfates; Sulfur Radioisotopes; Thyroid Diseases; Thyrotropin

Topics: Animals; Hypothyroidism; Lactates; Male; Methimazole; Methylthiouracil; Pyruvates; Rats; Thyroid Diseases; Thyroxine

Topics: Carbimazole; Humans; Methimazole; Perchlorates; Propylthiouracil; Radionuclide Imaging; Thyroid Diseases; Thyroid Function Tests; Thyroid Hormones; Thyrotropin-Releasing Hormone; Tissue Extracts

Topics: Adolescent; Antibodies, Antinuclear; Child; Collagen Diseases; Drug Hypersensitivity; Female; Humans; Methimazole; Propylthiouracil; Thyroid Diseases

Topics: Female; Fetal Diseases; Humans; Maternal-Fetal Exchange; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Diseases; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones

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

Topics: Antipyrine; Carbimazole; Humans; Hyperthyroidism; Methimazole; Thyroid Diseases; Triiodothyronine

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; Aged; Antithyroid Agents; Diet; Female; Graves Disease; Humans; Hyperthyroidism; Imidazoles; Iodine; Iodine Isotopes; Male; Methimazole; Middle Aged; Thyroid Diseases; Thyroid Gland; Time Factors

Topics: Achilles Tendon; Adolescent; Diagnosis, Differential; Female; Humans; Hyperthyroidism; Hypophysectomy; Hypothyroidism; Male; Methimazole; Methods; Middle Aged; Obesity; Reflex, Stretch; Statistics as Topic; Thyroid Diseases; Thyroid Function Tests; Triiodothyronine

Topics: Antithyroid Agents; Hypophysectomy; Imidazoles; Iodine Radioisotopes; Methimazole; Thyroid Diseases; Thyroid Gland; Thyrotropin

Topics: Adolescent; Child; Child, Preschool; Diagnosis, Differential; Germany, East; Humans; Hyperthyroidism; Hypothyroidism; Infant; Infant, Newborn; Methimazole; Methylthiouracil; Thyroid Diseases; Thyroid Hormones; Thyroidectomy

Topics: Adult; Eye Manifestations; Female; Graves Disease; Humans; Hyperthyroidism; Iodine Radioisotopes; Long-Acting Thyroid Stimulator; Methimazole; Propylthiouracil; Skin Manifestations; Thyroid Diseases

Topics: Adult; Aged; Antibodies; Chronic Disease; Female; Humans; Hyperthyroidism; Hypothyroidism; Iodine Isotopes; Male; Methimazole; Middle Aged; Myxedema; Propranolol; Propylthiouracil; Pulse; Thiocyanates; Thyroid Diseases; Thyroid Function Tests; Thyroiditis; Time Factors; Triiodothyronine