methimazole and Leukopenia

Thyroid hormone preparations, especially thyroxine, are widely used either at replacement doses to correct hypothyroidism or at suppressive doses to abolish thyrotropin (thyroid-stimulating hormone) secretion in patients with differentiated thyroid carcinoma after total thyroidectomy or with diffuse/ nodular nontoxic goitre. In order to suppress thyrotropin secretion, it is necessary to administer slightly supraphysiological doses of thyroxine. Possible adverse effects of this therapy include cardiovascular changes (shortening of systolic time intervals, increased frequency of atrial premature beats and, possibly, left ventricular hypertrophy) and bone changes (reduced bone density and bone mass), but the risk of these adverse effects can be minimised by carefully monitoring serum free thyroxine and free liothyronine (triiodothyronine) measurements and adjusting the dosage accordingly. Thionamides [thiamazole (methimazole), carbimazole, propylthiouracil] are the most widely used antithyroid drugs. They are given for long periods of time and cause adverse effects in 3 to 5% of patients. In most cases, adverse effects are minor and transient (e.g. skin rash, itching, mild leucopenia). The most dangerous effect is agranulocytosis, which occurs in 0.1 to 0.5% of patients. This life-threatening condition can now be effectively treated by granulocyte colony-stimulating factor administration. Other major adverse effects (aplastic anaemia, thrombocytopenia, lupus erythematosus-like syndrome, vasculitis) are exceedingly rare.

Topics: Adult; Agranulocytosis; Antithyroid Agents; Bone and Bones; Carbimazole; Cardiovascular System; Child; Collagen Diseases; Humans; Leukopenia; Liver; Methimazole; Propylthiouracil; Skin; Thyroid Hormones; Thyroxine

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

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

Male, 23.. Thyroid storm.. Delirium • diarrhea • fever • hypertension • hyperventilation • tachycardia • weight loss.. -.. Endocrinology and Metabolic.. Unusual clinical course.. The clinical presentation of thyroid storm includes fever, tachycardia, hypertension, and neurological abnormalities. It is a serious condition with a high mortality rate. Furthermore, some other complications affect the clinical course of thyroid storm. Although it is reported that prognosis is poor when thyroid storm is complicated by disseminated intravascular coagulation syndrome (DIC) and leukopenia, reports of such cases are rare.. A 23-year-old man presented with delirium, high pyrexia, diarrhea, and weight loss of 18 kg over 2 months. According to the criteria of Burch and Wartofsky, he was diagnosed with thyroid storm on the basis of his symptom-complex and laboratory data that confirmed the presence of hyperthyroidism. Investigations also found leukopenia, thrombocytopenia, and disseminated intravascular coagulation, all of which are very rare complications of thyroid storm. We successfully treated him with combined therapy including anti-thyroid medication, despite leukopenia.. Early diagnosis and treatment are essential in ensuring a good outcome for patients with this rare combination of medical problems.

Topics: Adrenergic beta-Antagonists; Antithyroid Agents; Disseminated Intravascular Coagulation; Drug Therapy, Combination; Humans; Iodates; Leukocyte Count; Leukopenia; Male; Methimazole; Potassium Compounds; Propranolol; Thyroid Crisis; Young Adult

The present study investigated risk factors and subjective symptoms associated with drug-induced leucopenia. We selected 248 patients with drug-induced leucopenia from the Case Reports of Adverse Drug Reactions and Poisoning Information System (CARPIS) database of over 47000 case reports of adverse drug reactions and assigned them to a case group. We also randomly selected 743 cases of adverse drug reactions not associated with leucopenia as a control group. A comparison of patient characteristic data between the two groups using logistic-regression analysis revealed that female sex, autoimmune disease and renal damage were background risk factors for drug-induced leucopenia. In addition, thiamazole, ritodrine, propylthiouracil, ticlopidine, allopurinol, minocycline and captopril administration significantly increased the risk of drug-induced leucopenia. A significant association was also found for fever, chills and pharyngeal abnormalities. Based on these findings, we developed two estimated regression equations to help prevent drug-induced leucopenia in the community pharmacy setting.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Autoimmune Diseases; Case-Control Studies; Child; Databases, Factual; Female; Humans; Kidney Diseases; Leukopenia; Logistic Models; Male; Methimazole; Methotrexate; Middle Aged; Risk Factors; Ritodrine; Sex Factors; Ticlopidine; Young Adult

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

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

A method has previously been described which detected xenogeneic and allogeneic antibodies to human granulocytes by their inhibition of the normal phagocytosis-associated hexose monophosphate shunt (HMS) activity. This method was used to study three patients with acute agranulocytosis secondary to antithyroid drug administration. Two patients with methimazole and one patient with propylthiouracil induced agranulocytosis were studied. Serum samples from each of these three patients taken during the acute phase of agranulocytosis had inhibitory effects on phagocytosis-associated HMS activity in leukocytes from both normal donors and the patients after their full recovery from agranulocytosis. IgM but not IgG prepared from acute sera in two patients was also inhibitory. Disruption of IgM disulfide bonds by dithiothreitol destroyed its inhibitory activity. The possibility of drug-dependent immune destruction of leukocytes in these patients is discussed.

Topics: Adult; Agranulocytosis; Antithyroid Agents; Drug Hypersensitivity; Female; Granulocytes; Graves Disease; Humans; Immunoglobulin M; Leukopenia; Methimazole; Phagocytosis; Propylthiouracil; Remission, Spontaneous