Methimazole-Induced Concomitant Agranulocytosis and Cholestasis in a Young Female

ABSTRACT Objective: To report a case of methimazole (MMI)-induced agranulocytosis and cholestasis in a patient with Graves disease. Methods: Case-based review of thionamide-induced concomitant agranulocytosis and hepatotoxicity. We performed a PubMed search using the search terms methimazole, carbimazole (CBZ), thionamides, agranulocytosis, hepatotoxicity, and cholestasis. Results: A 31-year-old female with newly di agnosed hyperthyroidism presented to our hospital with fever, odynophagia, and jaundice 8 weeks after she was started on MMI. Physical examination was significant for scleral icterus, tremors, and generalized hyperreflexia. Laboratory tests revealed marked neutropenia; her absolute neutrophil count (ANC) was 24, total bilirubin 3.1 (0.2–1.2 mg/dL), direct bilirubin 1.4 (0–0.2 mg/dL), and free thyroxine had trended down from 3.6 (0.58–1.64 ng/dL) at diagnosis 2 months earlier to 2.27 on admission. MMI was discontinued, and antibiotics and granulocyte colony-stimulating factor (G-CSF) were started. A bone marrow (BM) biopsy revealed hypercellularity and trilineage hematopoiesis with left-shifted myeloid maturity. Total serum bilirubin decreased 24 hours after stopping MMI and normalized by day 7 of admission. ANC started rising on day 6 and normalized on day 9. Diagnostic radioactive iodine (RAI) uptake was high (64%), and she received therapeutic RAI treatment the following week with improvement in her clinical condition. Conclusion: Concomitant agranulocytosis and cholestasis is a rare complication of antithyroid drugs (ATDs). To date, only 3 other such cases have been reported in the literature; 2 with use of CBZ and 1 with MMI. This case underscores the importance of remaining vigilant for adverse effects of ATD treatment. Abbreviations: ANC = absolute neutrophil count ATD = antithyroid drugs BM = bone marrow CBZ = carbimazole G-CSF = granulocyte colony-stimulating factor MMI = metimazole PTU = propylthiouracil