Efficacy and adverse events related to the initial dose of methimazole in children and adolescents with graves’ disease

Abstract

Purpose: The first-line antithyroid drug for children and adolescents with Graves’ disease (GD) is methimazole (MMI). This study evaluated the relationship between the initial MMI dose and the clinical course of GD after treatment. Methods: We studied the efficacy of the initial MMI dose and the relationship between the initial MMI dose and adverse events (AEs). We retrospectively enrolled 22 males and 77 females and divided those subjects into 3 groups according to the initial dose of MMI: <0.4 mg/kg/day (group A; n=32); 0.4–0.7 mg/kg/day (group B; n=39); and >0.7 mg/kg/day (group C; n=28). Results: The mean time to the normalization of free thyroxine (fT4) levels upon initial treatment was 5.64, 8.61, and 7.98 weeks in groups A, B, and C, respectively (P=0.116). The incidence of liver dysfunction, neutropenia, and skin rash was 12.5%, 20.5%, and 42.9% in groups A, B, and C, respectively (P=0.018). Neutropenia, as a severe AE, was absent in group A, but its prevalence was 7.7% in group B and 21.4% in group C (P=0.015). When comparing only groups B and C, the incidences of liver dysfunction and neutropenia were higher in group C (P=0.04 and P=0.021, respectively). Conclusion: The mean time to the normalization of fT4 levels did not differ among the 3 groups, but the incidence of AEs was higher in the groups that received high MMI doses. High doses of MMI (>0.7 mg/kg/day) should be reconsidered as an initial treatment for children and adolescents with GD.