PSAT344 Zeroing In: Methimazole Induced Agranulocytosis in Amiodarone Induced Thyrotoxicosis

Abstract

Background Agranulocytosis, defined as absolute neutrophil count (ANC) < 500/µL due to antithyroid drugs (ATDs), methimazole, carbimazole, and propylthiouracil (PTU), is a rare but serious complication with an occurrence of 0.1- 0.5%. ATDs induced agranulocytosis occurs abruptly, usually in the first three months of treatment but can occur any time after initiation of treatment, and although it is more common with a higher dose of methimazole > 30 mg/day, it can also occur with lower dosages. We present a rare case of agranulocytosis in a patient with Amiodarone-induced Thyrotoxicosis (AIT) with an ANC of 0/µL. Clinical Case A 68-year-old male with atrial fibrillation and heart failure was diagnosed with AIT when he presented to ED with thyrotoxicosis. Amiodarone was discontinued. Methimazole 40 mg daily with prednisone 20 mg daily was initiated. The ANC was 4360/µL. After nine weeks on methimazole, he presented with fever and tremors. The laboratory tests during this admission revealed WBC 1310/µL (4000-11000/µL) with granulocytes 0% (35%-80%), ANC 0/µL (1820-7420/µL), TSH < 0.01 (0.45-5.3mIU/mL), free T4 5.5 (0.58-1.64 ng/dL), free T3 4.4 (2.8-4.4 pg/dL). Methimazole was discontinued and antibiotics started. He received six doses of Granulocyte colony-stimulating factor (G-CSF) Filgrastim 480 mcg with an improvement of WBC to 6370/µL with a granulocyte count of 60% on the 6th day of admission. He eventually underwent thyroidectomy for treatment of the thyrotoxicosis. Discussion The proposed mechanism of agranulocytosis with ATDs is twofold. First, there is a direct toxic effect on mature circulating neutrophils and stem cells. The second is complement-mediated antibodies against granulocytes. Furthermore, AIT is associated with a higher risk for ATD induced agranulocytosis, although the mechanism remains elusive. The most common manifestations are fever and sore throat. The management includes discontinuation of ATD and starting antibiotics. G-CSF is used to treat agranulocytosis as it decreases the recovery time, the rate of infectious complications, and the mortality rate. Patients with ANC < 100/µL have a greater risk of infectious and fatal complications than patients with ANC > 100/µL. After resolution of agranulocytosis, methimazole or any other thionamides are generally not recommended due to concern for recurrence due to cross-reactivity among thionamides. Thyroidectomy or radioiodine therapy should be considered for definitive treatment of the hyperthyroidism in this circumstance. Conclusion Due to the low incidence and abruptness of agranulocytosis from ATDs, controversy exists over the value of routine monitoring of WBC count. This case emphasizes routine WBC monitoring could be considered in patients on higher doses of methimazole, especially in the first three months, due to the increased risk of agranulocytosis. Patient education on the life-threatening complication of ATD induced agranulocytosis is vital. It helps patients recognize early symptoms and seek medical care promptly, which aids in early intervention and reduces morbidity and mortality. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.