Higher dose of methimazole causes frequent adverse effects in the management of Graves' disease in children and adolescents

Objective: Methimazole (MMI) is used as a first-line antithyroid drug in children and adolescents with Graves' disease (GD). The aim of this study was to evaluate the correlation between the initial dose of MMI and the clinical course of GD after treatment. Design: Retrospective and collaborative study. Setting: Nine facilities in Chiba prefecture, Japan. Patients: Sixty-four children and adolescents with GD were analyzed. The subjects were divided into three groups by the initial daily dose of MMI: group A, 0.4 +/- 0.1 mg/kg (mean +/- SD, n=11); group B, 0.7 +/- 0.2 (n=37); group C, 0.9 +/- 0.2 (n=16). Main outcome measures: The duration of time required for normalization of serum free T4 on initial treatment and the incidence of adverse effects for 1 year after the start of MMI were compared. Outcomes were compared among patients who were followed more than 3 years (group A, n=7; group B, n=24; group C, n=12). Results: Mean duration of times for normalization of T4 was 1.9 +/- 1.5 months in group A, 1.6 +/- 0.9 in group B and 1.9 +/- 1.5 in group C (NS). No major adverse reactions were observed. Minor adverse effects occurred in 9.1% of cases in group A, 13.5% in group B and 62.0% in group C (p<0.01). Remission rates did not differ among the three groups. Conclusions: Higher doses of MMI are harmful for initial use in children and adolescents with GD.