Methimazole-Associated Neutropenia and Agranulocytosis in Pediatric Patients with Graves' Disease: A Chinese Cohort Study.

Abstract

Background: Graves' disease (GD) is rare in children, and methimazole (MMI) is recommended as the first-line therapy. However, data on MMI-associated neutropenia and agranulocytosis in pediatric patients remain limited. In this study, we aimed to characterize the clinical features of these adverse events and to identify their associated risk factors.

Methods: A cohort study was conducted involving 432 pediatric patients with GD treated with MMI. Clinical and biochemical data were collected retrospectively and prospectively, with follow-up 0.5, 1, 2, 3, 4, 5, 6, 7-9, and 10-12 months after treatment initiation. Multivariable logistic regression analysis was performed to identify risk factors for MMI-associated neutropenia.

Results: During the 12-month follow-up period, 104 (24.1%) patients developed neutropenia, with 84.6% developing neutropenia within the first 3 months, 72.1% within 1 month, and 59.6% within 2 weeks. Among the affected patients, 83.7%, 13.5%, and 2.8% had mild, moderate, and severe neutropenia (agranulocytosis), respectively. All patients with moderate or severe neutropenia were asymptomatic and were identified through routine monitoring within the first month. Multivariable analysis revealed that a thyroid peroxidase antibody (TPOAb)-negative status (odds ratio [OR], 2.020; confidence interval [CI], 1.113-3.666) was associated with a higher prevalence of MMI-associated neutropenia, whereas older age (OR, 0.916; CI, 0.848-0.989) and higher baseline absolute neutrophil count (ANC; OR, 0.775; CI, 0.665-0.903) were protective factors.

Conclusions: ANC monitoring is recommended every 1 to 2 weeks during the first month and monthly for the first 3 months after MMI initiation. Pediatric patients with GD younger than 3 years with TPOAb-negative status or a baseline ANC < 3 × 10⁹/L may have a higher prevalence of MMI-associated neutropenia.