propylthiouracil and Drug-Hypersensitivity

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

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

Propylthiouracil and methimazole are frequently used in the management of hyperthyroidism. Two patients in whom adverse immunologic effects other than isolated agranulocytosis developed during treatment with propylthiouracil are described. A review of the literature revealed 53 similar cases over a 35-year period. Rash, fever, arthralgias and granulocytopenia were the most common manifestations. Vasculitis, particularly with cutaneous manifestations, occurs and may be fatal. The clinical evidence suggests that an immunologic mechanism is involved. A number of different autoantibodies were reported, but antinuclear antibodies were infrequent, and none of the cases met the criteria for a diagnosis of systemic lupus erythematosus. Thus, the reactions do not represent a true drug-induced lupus syndrome. Current hypotheses and experimental data regarding the cause of the reactions are reviewed. No specific clinical subgroup at high risk can be identified, and manifestations may occur at any dosage and at any time during therapy. Cross-reactivity between the two antithyroid drugs can be expected. Except for minor symptoms (e.g., mild arthralgias or transient rash), such reactions are an indication for withdrawal of the drug and the use of alternative methods to control the hyperthyroidism. In rare cases of severe vasculitis a short course of high-dose glucocorticoid therapy may be helpful.

Topics: Adult; Agranulocytosis; Antibody Formation; Cross Reactions; Drug Hypersensitivity; Female; Graves Disease; Humans; Hyperthyroidism; Immunity, Cellular; Methimazole; Middle Aged; Propylthiouracil

Topics: Adrenal Cortex Hormones; Adrenergic beta-Antagonists; Adult; Anti-Inflammatory Agents; Antithyroid Agents; Drug Hypersensitivity; Eosinophilia; Exanthema; Female; Humans; Patch Tests; Postpartum Thyroiditis; Propranolol; Propylthiouracil; Syndrome

Topics: Anti-Bacterial Agents; Antidotes; Antithyroid Agents; Child; Costs and Cost Analysis; Drug Costs; Drug Eruptions; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Economics, Pharmaceutical; Female; Humans; Iatrogenic Disease; Kanamycin; Male; Middle Aged; Propylthiouracil

Topics: Adult; Asthma; Drug Hypersensitivity; Female; Humans; Hyperthyroidism; Propylthiouracil

Severe adverse reactions to propylthiouracil occur in 1-5% of patients. Three major side effects, namely agranulocytosis, hepatotoxicity and drug-induced hypersensitivity, have been described though these syndromes are not distinct entities and there can be overlaps in the clinical manifestations. The drug-induced hypersensitivity may be an immune-mediated reaction with multiorgan involvement in which a combination of polyarthritis, cutaneous vasculitis and fever is common. We report a patient with propylthiouracil-induced hypersensitivity with an unusual combination of high spiking fever, migratory polyarthritis, reversible sensorineural deafness, normochromic normocytic anaemia, leucocytosis and hepatotoxicity associated with polyclonal activation of multiple autoantibodies. This case illustrates the highly variable clinical manifestations of the syndrome. The prompt recovery upon withdrawal of the drug indicates the importance of early diagnosis.

Topics: Adult; Arthritis; Carbimazole; Drug Hypersensitivity; Female; Graves Disease; Hearing Loss, Sensorineural; Humans; Propranolol; Propylthiouracil; Thyroxine

The pregnancy of a women with diabetes mellitus was complicated by Graves' disease and maternal allergies to propylthiouracil and methimazole. Preparations for surgical removal of the thyroid gland were being made until pregnancy intervened. Several well-documented mechanisms of hyperthyroidism, including increased intestinal absorption of glucose, decreased insulin responsiveness, and increased glucose production may exacerbate glucose intolerance; the daily insulin requirement of this patient rose 80% from her pregestational dosage. When large doses of propranolol failed to control her thyrotoxic symptoms and led to severe, recurrent hypoglycemic episodes, subtotal thyroidectomy was performed. A 42% decrease in insulin requirements was observed postoperatively, with return to the euthyroid state. A propensity for symptomatic postoperative hypoglycemia should be anticipated in diabetic patients undergoing thyroidectomy.

Topics: Adult; Drug Hypersensitivity; Female; Graves Disease; Humans; Insulin Coma; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics; Propranolol; Propylthiouracil; Thyroidectomy

Cutaneous vasculitis is an uncommon complication of propylthiouracil therapy. Its pathogenesis has been related to the presence of circulating immune complexes. The lesions may be purpuric or bullous hemorrhagic, possibly evolving into necrotic ulcerations. Usually, lesions develop on the extremities and earlobe. The vasculitis has been related to the duration of the treatment and disappears with the withdrawal of the drug, although a fatal case has been reported. Corticosteroid therapy is often prescribed, but its efficacy has not been demonstrated. We describe a patient in whom treatment with propylthiouracil for a year was associated with vasculitic lesions on the lower extremities and earlobe. Discontinuation of the drug was correlated with disappearance of the lesions.

Topics: Adult; Drug Hypersensitivity; Ear, External; Extremities; Female; Humans; Hyperthyroidism; Propylthiouracil; Vasculitis, Leukocytoclastic, Cutaneous

Topics: Agranulocytosis; Drug Hypersensitivity; Female; Humans; Middle Aged; Plasmapheresis; Propylthiouracil; Vasculitis

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

Topics: Adult; Drug Hypersensitivity; Female; Humans; Propylthiouracil; Purpura

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

Topics: Adolescent; Agranulocytosis; Child; Child, Preschool; Drug Hypersensitivity; Female; Fever; Humans; Hyperthyroidism; Kidney Glomerulus; Leukocyte Count; Leukopenia; Lupus Erythematosus, Systemic; Male; Propylthiouracil; Urticaria

Topics: Adolescent; Antithyroid Agents; Black People; Drug Hypersensitivity; Humans; Hyperthyroidism; Lupus Erythematosus, Systemic; Prednisolone; Propylthiouracil; Radiography, Thoracic; Thyroid Function Tests; Toxicology

Topics: Autoimmune Diseases; Drug Hypersensitivity; Humans; Hypersensitivity; Hyperthyroidism; Leukopenia; Propylthiouracil