Antithyroid drug — induced agranulocytosis: Clinical experience with ten patients treated at one institution and review of the literature

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Abstract
The frequency, predisposing factors and course of agranulocytosis (granulocytes Methimazole dose in patients with agranulocytosis was almost twice as in other patients (63.3±19.7 vs 34.3±29.7 mg daily) suggesting that this complication was related to dose. The interval between start of antithyroid drug treatment and first symptoms of agranulocytosis was 33 days (median; range, 23–55 days); hence, prolonged treatment beyond this period would appear relatively safe. Withdrawal of the causative agent and treatment of infection led to recovery of leukocyte counts within 15 days (median; range, 5–31 days). Two fatal outcomes were seen in referred patients. In one severely hyperthyroid patient with methimazole-induced agranulocytosis, recombinant human granulocyte/macrophage colony stimulating factor induced clinical and hematologic recovery within a few days of administration. In conclusion, agranulocytosis is the most severe side effect of antithyroid drugs. According to our results and a literature review, it occurs almost exclusively during the first ten weeks of treatment and is probably related to the drug dose. Physicians should be aware of this potentially serious complication particularly during this period. A reduction of traditionally prescribed thionamide doses seems quite possible and might lead to considerable reduction of adverse reactions. In severe cases, a trial of recombinant human granulocyte/macrophage colony stimulating factor should be considered.