Late-Onset and Recurrent Agranulocytosis During Low-Dose Methimazole Therapy in an Adolescent with Graves' Disease.

Abstract

Graves' disease (GD) is the most common cause of thyrotoxicosis in the pediatric population. Methimazole (MMI) is the first-line therapy; however, it may rarely cause agranulocytosis, a potentially life-threatening adverse effect. Recurrent or delayed-onset agranulocytosis presents diagnostic and therapeutic challenges due to the scarcity of reported cases. This report aims to describe a pediatric case with recurrent MMI-induced agranulocytosis and to discuss potential mechanisms and management strategies. We describe a 16-year-old female with GD who developed recurrent MMI-induced agranulocytosis. The initial episode was identified during routine monitoring at the 16th month of treatment, in the absence of clinical signs of infection. MMI was promptly discontinued, and infection precautions were implemented. Treatment with granulocyte colony-stimulating factor (G-CSF) led to rapid neutrophil recovery. However, intermittent neutropenia recurred, requiring repeated G-CSF administration. Despite persistent thyroid-stimulating immunoglobulin (TSI) positivity, the patient remained euthyroid and did not require further antithyroid therapy during 20 months of follow-up. Autoimmune serology revealed positive antinuclear antibody (ANA) and anti-centromere protein B (anti-CENP-B) antibodies, while bone marrow and genetic analyses were unremarkable. This case illustrates the complex and variable course of methimazole-induced agranulocytosis in pediatric GD. Recurrent neutropenia may occur even after initial resolution, emphasizing the need for individualized management. Persistent TSI positivity alone may not necessarily reflect ongoing disease activity or justify continued antithyroid therapy.