SUN-324 - A Case of Methimazole-Induced Agranulocytosis Complicated by Neutropenic Enterocolitis and Gastrointestinal Perforation

Background
Methimazole is an antithyroid medication used to manage hyperthyroidism. Although highly effective, it carries a rare but significant risk of agranulocytosis. This care report describes a patient who developed methimazole-induced agranulocytosis that progressed to neutropenic enterocolitis (typhilis), resulting in life-threatening gastrointestinal perforation.

Case presentation
A 20-year-old woman with hyperthyroidism on methimazole 10mg twice daily for two months presented with a five-day history of right lower-quadrant abdominal pain, sore throat, dysphagia, and vomiting. Initial laboratory studies revealed profound leukopenia (white blood cell count 0.3 x 10⁹/L) and significant electrolyte disturbances. Abdominal CT revealed marked terminal ileal and cecal wall thickening. She was diagnosed with methimazole-induced agranulocytosis complicated by peritonsillar abscess and typhilitis, and was started on broad-spectrum intravenous antibiotics and granulocyte colony-stimulating factor (G-CSF). Her course progressed to septic shock requiring intensive care management. Persistent abdominal pain, fever, and rising leukocytosis prompted repeat CT imaging, which demonstrated cecal perforation with bowel necrosis. She underwent emergent right hemicolectomy with small-bowel resection. Postoperatively, she recovered without further complication, her leukocyte count normalized, and she was discharged with Endocrinology follow-up for definitive management of her hyperthyroidism.

Discussion
Methimazole-induced agranulocytosis is an uncommon but serious adverse effect thought to arise from both direct toxicity to myeloid precursors and immune-mediated destruction of granulocytes, although the exact pathophysiology remains unclear. The condition affects roughly 0.2- 0.5% of patients receiving methimazole, with evidence suggesting a dose-dependent risk, as higher methimazole doses are linked with increased incidence. Most cases develop within the first 90 days of therapy, typically between 4 and 8 weeks after initiation, often with abrupt onset. Leukocyte counts recover upon discontinuation of medication, especially with adjunctive G-CSF administration. Although monitoring of cell count is recommended, the current endocrine guidelines do not recommend routine blood count monitoring in patients starting methimazole for hyperthyroidism.

Conclusions
This patient required an extended hospitalization of over 10 days for septic shock necessitating vasopressor support, further complicated by severe gastrointestinal perforation likely secondary to typhlitis in the setting of methimazole-induced agranulocytosis. This case highlights the potential for serious, life-threatening toxicity associated with methimazole and reinforces the need for early hematologic surveillance at treatment initiation.

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