Antithyroid drugs agranulocytosis

Agranulocytosis is one of the most serious adverse effects of antithyroid drug therapy. 

Patients who receive antithyroid drugs must be monitored for adverse drug events such as agranulocytosis. 

Carbimazole is an antithyroid drug indicated in hyperthyroidism. It is usually administered as 15 mg daily in the morning. Carbimazole tends to cause agranulocytosis and therefore patients are advised to report immediately any signs of infections, such as sore throat. 

Reactions to antithyroid drugs have been described above. A minor rash can often be controlled by antihistamine therapy. Because the more severe reaction of agranulocytosis is often heralded by sore throat or high fever, patients receiving antithyroid drugs must be instructed to discontinue the drug and seek immediate medical attention if these symptoms develop. White cell and differential counts and a throat culture are indicated in such cases, followed by appropriate antibiotic therapy. 

Neutropenia, agranulocytosis, aplastic anemia, and thrombocytopenia are the most important adverse effects of antithyroid drugs. 

There are two different types of neutropenia due to antithyroid drugs a mild dose-related reduction in leukocyte count and a true allergic agranulocytosis (SEDA-10, 368 18). 

Outcomes have been reported in a consecutive series of 91 patients hospitalized with non-chemotherapy drug-induced agranulocytosis from 1985-2000 (34). All but two survived. Antithyroid drugs were the cause of agranulocytosis in 20% of cases. Univariate and multivariate analyses failed to reveal a specific effect of antithyroid drugs on the time to neutrophil recovery. In contrast, hemopoietic growth factor treatment was associated with speedier hematological recovery. 

Aplastic anemia due to antithyroid drugs is very rare and has been said to occur as an adverse effect of thionamide therapy with about one-tenth of the frequency of agranulocytosis. 

Antithyroid drug-induced agranulocytosis. The usefulness of routine white blood cell count monitoring. Arch Intern... 

Retsagi G, Kelly JP, Kaufman DW. Risk of agranulocytosis and aplastic anaemia in relation to use of antithyroid drugs. International Agranulocytosis and Aplastic Anaemia Study. BMJ 1988 297(6643) 262-5. 

Cooper DS, Goldminz D, Levin AA, Ladenson PW, Daniels GH, Molitch ME, Ridgway EC. Agranulocytosis associated with antithyroid drugs. Effects of patient age and drug dose. Ann Intern Med 1983 98(l) 26-9. 

Tajiri J, Noguchi S. Antithyroid drug-induced agranulocytosis special reference to normal white blood cell count agranulocytosis. Thyroid 2004 14(6) 459-62. 

Hirsch D, Luboshitz J, Blum I. Treatment of antithyroid drug-induced agranulocytosis by granulocyte colony-stimulating factor a case of primum non nocere. Thyroid 1999 9(10) 1033-5. 

Fukata S, Kuma K, Sugawara M. Granulocyte colony-stimulating factor (G-CSF) does not improve recovery from antithyroid drug-induced agranulocytosis a prospective study. Thyroid 1999 9(1) 29-31. 

Andres E, Maloisel F, Ruellan A. Use of colony-stimulating factors for the treatment of antithyroid drug-induced agranulocytosis a retrospective study in twelve patients. Thyroid 2000 10(1) 103. 

Andres E, Kurtz JE, Perrin AE, Dufour P, Schlienger JL, Maloisel F. Haematopoietic growth factor in antithyroid-drug-induced agranulocytosis. QJM 2001 94(8) 423-8. 

Antithyroid drugs for long-term therapy (C). Thiourea-derivatives (thioamides) inhibit peroxidase and, hence, hormone synthesis. To restore a euthyroid state, two therapeutic principles can be applied in Graves disease (a) monotherapy with a thioamide, with gradual dose reduction as the disease abates (b) administration of high doses of a thioamide, with concurrent administration of thyroxine to offset diminished hormone synthesis. Adverse effects of thioamides are rare, but the possibility of agranulocytosis has to be kept in mind. 

Patients should therefore be warned to seek immediate medical help if a fever or sore throat develops during antithyroid drug treatment. If the drug is withdrawn immediately recovery is the rule, but fatal cases have also been reported (20,21). In one case agranulocytosis unusually occurred after a second exposure to the drug, in this case propylthiouracil (22). 

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