A Report of Three Girls with Antithyroid Drug-Induced Agranulocytosis; Retrospective Analysis of 18 Cases Aged 15 Years or Younger Reported between 1995 and 2009

Agranulocytosis is an extremely serious, although rare, adverse effect of antithyroid drugs (ATDs), including methimazole (MMI) and propylthiouracil (PTU), in children and adolescents. There are few reports about the characteristics of ATD-induced agranulocytosis in Japanese children and adolescents. This report presents the cases of three girls with ATD-induced agranulocytosis and a retrospective analysis of 18 patients with ATD-induced agranulocytosis, whose cases had been referred to the drug manufacturer, Chugai Pharmaceutical Co., Ltd. Our 3 patients, ranging in age from 12 to 14 yr, developed ATD-induced agranulocytosis between the 15th and 57th day of ATD treatment for hyperthyroidism. Fever and sore throat were the earliest symptoms of agranulocytosis. The patients were rescued by ceasing ATD therapy and administering antibiotics, potassium iodide, glucocorticoid, immunoglobulin and granulocyte colony-stimulating factor (G-CSF). We retrospectively analyzed 18 cases of ATD-induced agranulocytosis treated with MMI in 16 cases and PTU in 2 cases. Twelve patients were treated with 20–45 mg/d MMI. Agranulocytosis developed between the 15th and 1,344th day of therapy. In conclusion, considering the risk of ATD-induced agranulocytosis, we recommend low-dose MMI therapy for treatment of Graves’ disease.