FRI505 A Rare Case Of Methimazole Induced Grave Agranulocytosis

Abstract

Abstract Disclosure: N. Barua: None. S. Idriss: None. R. Panta: None. I. Jamal: None. J. Hodge: None. Introduction: Agranulocytosis is a rare side effect of methimazole that usually occurs in a dose-dependent fashion within the first 3 to 6 months of initiation. It occurs in 0.2 - 0.5% of patients with Graves' disease who receive treatment with antithyroid drugs (ATD). We describe a rare case of agranulocytosis in a 36-year-old female treated with methimazole for hyperthyroidism. Case: A 36-year-old female, who was diagnosed with Graves' disease 2 months prior, presented to the Emergency Department for evaluation of worsening sore throat, odynophagia, dysphagia, and fever for 12 days after failed outpatient treatment with amoxicillin. Pre-admission labs showed free T4 > 7.77ng/dl, TSH <0.01 mIU/L, thyrotropin receptor antibody elevated at 28.30. She was initially treated with methimazole 10mg TID then reduced to BID few weeks prior to hospitalization. On arrival, her temperature was 102.8 F, heart rate 120 bpm, and blood pressure 116/65 mmHg. On physical exam, she had thyromegaly and discomfort on palpation of the neck. Labs showed WBC of 0.6k/mm3, absolute neutrophil count (ANC) of 0, Hgb 11.1 g/dl, TSH <0.01 mIU/L, Free T4 3.11 ng/dL and free T3 6.7 pg/ml. CT neck with contrast revealed tonsillitis and epiglottitis with associated tonsillar and peritonsillar abscess. She was started on Vancomycin, Cefepime and Acyclovir for 7 days; and Fluconazole 14 days for epiglottitis, tonsillitis, HSV, and oral candidiasis. Methimazole was discontinued, and she was started on cholestyramine 4 gm 6 hourly, dexamethasone 2 mg IV 8 hourly and propranolol 20 mg 8 hourly with improvement of her free T4 from 3.11-2.93. Her free T3 worsened from 8.1 to 11.1, potassium iodide 50 mg 6 hourly was added to the regimen. After 10 days of treatment, her thyroid blood tests and ANC improved, and she was discharged. She underwent total thyroidectomy 2 weeks after discharge and was placed on levothyroxine 75 mcg daily. Conclusion: Agranulocytosis from ATDs has a remarkably high mortality rate of about 21.5%. The mechanism behind is both immune-mediated toxicity and direct toxicity from oxidative process mediated by myeloperoxidase and cytochrome P450 enzymes. Agranulocytosis caused by ATD is usually dose dependent and mostly present with significant hyperthyroid state. Alternative ways of treatment should be promptly initiated as cross-reaction between methimazole and propylthiouracil occurs in about 15.2% of cases. Patient education about this dreadful side effect and awareness about seeking immediate medical attention at symptom onset is key in successful remediation of this condition. Presentation: Friday, June 16, 2023