SAT-625 Dose-Dependent, Methimazole-Induced Agranulocytosis in a Pregnant Hispanic Woman with Grave's Disease

Introduction Agranulocytosis is a known but very rare complication of Methimazole (MTZ). The exact incidence of Methimazole induced agranulocytosis (MIA) in pregnant patients is unknown but thought to be extremely rare. We present a rare and unique case of MIA during the second trimester of pregnancy. Case Presentation A 31-year-old woman with a history of Grave’s disease (GD) previously treated with MTZ was referred to the Endocrinology clinic for evaluation of fatigue, palpitations and heat intolerance. She was 20 weeks of gestational age. Physical examination was significant for exophthalmos, thyromegaly, and tachycardia. Laboratory investigation revealed low TSH- 0.00uIU/mL (N: 0.45-5.33uIU/mL) and elevated free T4- 1.98ng/dl (N: 0.6-1.32ng/dl), free T3- 9.1pg/ml (N: 2.5-3.9pg/ml), TRAB-74 % (N: ≤16%) and TSI- 344 % (N: <140%) levels. Patient was commenced on 10mg of MTZ daily. On the next scheduled visit, WBC was 3000/mm³ (N: 4.8-10.9/mm³), free T4- 1.92ng/dl and free T3- 6.9pg/ml. Her values were deemed to not be at target and her MTZ dose was increased to 20mg daily. Two weeks later, she presented to the ER because of fever and throat pain. Laboratory evaluation revealed WBC of 0.3/mm³ and ANC of 6 cells/μL (N: >1500/μL). Myeloperoxidase and Proteinase 3 Antibodies were negative. MTZ was immediately discontinued and a multidisciplinary management team was constituted. She was placed on neutropenic precautions and commenced on propranolol, potassium iodide, betamethasone, antibiotics and G-CSF. In view of potential maternal-fetal risks associated with uncontrolled GD, the patient had a total thyroidectomy when her WBC improved. Following the total thyroidectomy, she continued with pregnancy delivering at term a healthy boy. Conclusions MIA occurs in about 0.2-0.5% in the general population, more common in females, 5(th) decade of life, first time users and with higher doses. (1) It is even much rarer in pregnancy. The exact mechanisms of MTZ are still unclear. Vicente et al suggest a possible direct drug toxicity effect through myeloperoxidase antibodies versus an immune mediated toxicity effect due to ANCA antibodies. (2) Similarly, Cheung et al found that HLA-B*380201 was strongly associated with MTZ induced agranulocytosis but not with Propylthiouracil induced agranulocytosis (2). There is a need for continued research in this area. To the best of our knowledge, this index case is the only report of MIA occurring in the second trimester in the United States, possibly triggered by a dose increase and occurring in the setting of prior use of MTZ. References 1. Nakamura H. et al. Analysis of 754 cases of antithyroid drug-induced agranulocytosis over 30 years in Japan. Clin Endo Met. 2013;98(12):4776-4783 2. Vicente N. et al. Antithyroid Drug-Induced Agranulocytosis: State of the Art on Diagnosis and Management. Drugs R D. 2017;17(1):91-96.