methimazole and Drug-Hypersensitivity

Topics: Acute Disease; Antithyroid Agents; Carbimazole; Drug Hypersensitivity; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Pancreatitis

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: Antithyroid Agents; Drug Hypersensitivity; Humans; Methimazole

Topics: Adolescent; Anaphylaxis; Antithyroid Agents; Drug Hypersensitivity; Female; Graves Disease; Humans; Hypersensitivity, Delayed; Methimazole; Skin Tests

Antithyroid drugs are usually considered first-line therapy for management of pediatric Graves' disease because they avoid permanent hypothyroidism, provide a chance for remission, and are less invasive than the alternatives of thyroidectomy or radioactive iodine. Methimazole (MMI) is the only antithyroid drug recommended in pediatrics due to the risk of propylthiouracil-induced liver toxicity. Allergic reactions with MMI occur in up to 10% of patients and, when mild, can be managed with concurrent antihistamine therapy. Guidelines recommend discontinuation of MMI with serious allergic reactions. We present the case of an adolescent girl with Graves' disease and a serious allergic reaction after starting MMI whose family refused radioactive iodine and was reluctant to proceed to surgery. Antihistamine therapy was successfully used to allow continued treatment with MMI. This case demonstrates extension of management guidelines for minor cutaneous allergic reactions to MMI, through the use of antihistamines for a serious allergic reaction, allowing us to continue MMI and provide treatment consistent with the family's preferences and values.

Topics: Adolescent; Antithyroid Agents; Diphenhydramine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Hypersensitivity; Female; Graves Disease; Histamine H1 Antagonists; Humans; Methimazole; Treatment Outcome

Severe cardiovascular events, such as coronary vasospasm or acute myocardial infarction can occur during anaphylactic reactions. Although rare, this cause of ischaemic heart disease is known. We present the case of a patient who suffered an angina episode after an anaphylactic reaction due tot administering metamizole, with no significant lesions observed in the coronary catheterisation.

Topics: Aged, 80 and over; Anaphylaxis; Atrioventricular Block; Coronary Angiography; Coronary Vasospasm; Drug Hypersensitivity; Humans; Hypotension; Male; Methimazole; Postoperative Complications; Prostatic Hyperplasia; Recovery Room; Syndrome; Transurethral Resection of Prostate

Topics: Antithyroid Agents; Diabetes Mellitus, Type 1; Drug Hypersensitivity; Graves Disease; Humans; Male; Methimazole; Middle Aged

Drug-induced hypersensitivity syndrome is one of the most severe forms of drug eruption and is characterized by high fever and multiorgan involvement. Reactivation of human herpesvirus-6 (HHV-6) or cytomegalovirus (CMV) has been suggested to be involved in this syndrome, although the exact role of these viruses remains elusive. We report the case of a 50-year-old Japanese male with Graves' disease who developed hypersensitivity syndrome caused by the antithyroid drug methimazole (MMI). After treatment with MMI 30 mg three times daily for 1(1/2) months, the patient developed generalized exfoliative erythematous eruption and high fever. Cessation of treatment with the drug improved his condition. Readministration of MMI worsened his clinical features. Treatment with high-dose methylprednisolone for 6 days and subsequent administration of prednisolone 20 mg twice daily improved his clinical manifestations. Elevated titers of anti-HHV-6 immunoglobulin G (IgG) and anti-CMV IgG antibodies were observed, and these gradually decreased during the clinical course, indicating reactivation of HHV-6 and CMV. Drug-induced lymphocyte stimulation test for MMI was negative. This is the first reported case of MMI-induced hypersensitivity syndrome associated with the reactivation of HHV-6 and CMV.

Topics: Antibodies, Viral; Antithyroid Agents; Cytomegalovirus; Drug Hypersensitivity; Graves Disease; Herpesvirus 6, Human; Humans; Immunoglobulin M; Male; Methimazole; Middle Aged; Virus Activation

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

Topics: Adult; Aged; Anthracenes; Anthralin; Benzimidazoles; Drug Hypersensitivity; Female; Humans; Male; Methimazole; Middle Aged

Antineutrophil antibody capable of opsonising normal neutrophils was detected in the sera of 16 neutropenic patients receiving various drugs. A single drug was involved in 10 cases, multiple medication in 6. 4 patients received semisynthetic penicillins, 8 some form of antimicrobial, and 2 antithyroid agents. Neutrophil counts rose, and antineutrophil antibody activity declined or disappeared, after drug therapy was stopped. Opsonisation related to the semisynthetic penicillins was independent of complement but dependent on drug concentration. Complement-dependent opsonic activity was demonstrated in 2 patients (1 receiving methimazole and 1 receiving multiple medication) and in the patient receiving methimazole this activity was shown to reside in the IgM serum-fraction. In another patient receiving multiple drugs, a complement-independent IgG antibody was demonstrated.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Chlorothiazide; Chlorpromazine; Complement C3; Drug Hypersensitivity; Drug Therapy, Combination; Female; Humans; Immunoglobulin G; Immunoglobulin M; Male; Methimazole; Middle Aged; Neutropenia; Neutrophils; Opsonin Proteins; Penicillins; Quinidine

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

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