Adverse Events Associated with Methimazole Therapy of Graves' Disease in Children

Graves' disease is the most common cause of hyperthyroidism in the pediatric population [1, 2]. Treatment options for Graves' disease include antithyroid medications, radioactive iodine, and surgery [1, 2]. Antithyroid medications used in children and adults include propylthiouracil (PTU) and methimazole (MMI), and carbimazole, which is metabolized to MMI, and is available in Europe but not the United States [3].Recently, a significant safety concern related to hepatotoxicity risk associated with PTU use in children was brought to attention [4, 5]. It is thus now recommended that PTU not be used in children, except in special circumstances [4, 5], and MMI should be used for antithyroid drug therapy in children.To date, the majority of publications related to medical therapy for Graves' disease have focused on children treated with PTU [6–14]. The use of MMI in children has been described in far fewer reports [15]. The description of the nature of adverse events that are associated with methimazole use in the pediatric population is modest, as well.At our center, we have routinely used MMI for Graves' disease therapy for many years. To provide insights into adverse events that can be associated with MMI use, we reviewed the adverse events associated with MMI use in our last one hundred consecutive pediatric patients treated with this medication.This review of treatment practice outcomes was conducted with the approval of the Yale University Human Investigation Committee. All adverse events were reported to the United States Food and Drug Administration via the MedWatch program. Patients with the diagnosis of Graves' disease were identified from ICD-9 coding (242.0 or 242.9).The diagnosis of Graves' disease was made if there were elevated total and/or free thyroxine [T4] and/or triiodothyronine [T3] concentrations, subnormal thyrotropin levels, and evidence of thyroid autoimmunity not thought to be consistent with Hashitoxicosis. The presence of goiter and ophthalmopa