SUN-378 A Case Of Rapid Onset Agranulocytosis Secondary To Methimazole Use

Abstract Disclosure: A. Abualnil: None. A. Al-Thunaibat: None. L.L. Ponce Rosas: None. J.S. Martins Torrontegui: None. C. Penaherrera: None. P.S. Sidhu,MD: ; None. Introduction: Methimazole is widely used in treating hyperthyroidism, especially Graves’ disease. Though generally well-tolerated, it can cause rare but severe adverse effects, including agranulocytosis. This life-threatening condition, defined by an absolute neutrophil count (ANC) below 500/μL, requires rapid recognition and urgent management. It often develops within the first three months of therapy but may occur earlier. Case Presentation: We present a 71-year-old female who was sent to the ER after being found tachycardic before laser eye surgery. She was diagnosed with new-onset atrial fibrillation and overt thyrotoxicosis (TSH suppressed, T4 at 5.38 ng/dL, total T3 at 3.2 ng/mL). Elevated thyrotropin receptor antibodies (25.9 IU/L) confirmed Graves’ disease. The patient began methimazole at 15 mg twice daily, but self-discontinued propranolol due to respiratory issues. After one month, she developed pharyngitis and laboratory tests revealed leukopenia (WBC count of 1.2 ×10^3/μL). Thyroid function tests showed decreased free T4 (3.69 ng/dL) and total T3 (2.8 ng/mL), with suppressed TSH. Suspecting methimazole-induced agranulocytosis, she was referred to the ED. Laboratory results confirmed severe neutropenia (ANC of 12/μL) and lactic acidosis (lactate: 2.4 mmol/L). Methimazole was discontinued, and Filgrastim (Neupogen) was administered for neutrophil stimulation, along with intravenous hydrocortisone for thyrotoxicosis. After two doses of Neupogen, her WBC count rose to 5.0×10^3/μL. Endocrinology advised against further antithyroid drugs due to the risk of recurrent agranulocytosis. Given her hyperthyroid state and atrial fibrillation, a total thyroidectomy was deemed urgent. Discussion: The exact mechanism remains unclear, but it may involve direct toxic effects on granulopoiesis or immune-mediated neutrophil death. Genetic factors, particularly certain HLA alleles, may increase susceptibility, with a dose-dependent risk. Other risk factors include older age, female gender. Granulocyte colony-stimulating factor (G-CSF) can aid in neutrophil recovery, especially in severe cases, as seen in this patient. Conclusion: This case underscores the importance of careful monitoring in older patients beginning antithyroid treatment. While methimazole is effective for Graves' disease, its potential to cause severe neutropenia necessitates prompt recognition and discontinuation to prevent serious infections. Thyroidectomy remains a viable option when antithyroid medications pose risks. Presentation: Sunday, July 13, 2025