ODP496 Methimazole Induced Agranulocytosis Despite Minimal Intermittent Therapy

INTRODUCTION: Anti-thyroid drugs, such as methimazole (MMI), are standard therapies for the medical management of Graves Disease. Agranulocytosis is a rare but lethal adverse effect of anti-thyroid medications. Here we discuss a case that highlights the importance of monitoring not only in the early stages of therapy, but also low dosing of therapy, intermittent therapy and even missing doses/discontinuation of therapy. CASE HISTORY: A 65 year-old male with past medical history of end-stage renal disease on peritoneal dialysis who presented to the hospital with syncope, ventricular tachycardia, tremulousness, weight loss of 22 pounds over 2 weeks was subsequently diagnosed with pericardial effusion with tamponade as well as hyperthyroidism. Suppressed TSH of < 0. 005 µIU/mL, Free T4 = 4.5 ng/dL, FT3 8.4 pg/ml, Negative TSI and TPO antibodies. He was started on methimazole 30 mg daily which he received 2 doses prior to discharge as well as beta-blocker therapy. He was re-admitted 1 week later for hypotension, nausea, vomiting and reportedly not taking any medications due to the vomiting right after last discharge supported by his hyperthyroidism being unchanged with a TSH of <0. 005 µIU/mL, free T4 4.21, Free T3 5.8 pg/ml. He was restarted on methimazole 3 days into admission. He received 4 days total of 30 mg daily and was discharged on methimazole 20 mg bid. He was re-admitted 8 days later, during which time again he had nausea and vomiting resulting in not taking methimazole for 1 week prior to admission, maximally 1 day of therapy. At this 3rd admission he was found to have evidence of agranulocytosis with a WBC count of 0.97×10^9 and absolute granulocyte count of 0. 06×10^9. Methimazole was held, he was started on propranolol 60 q6 and cholestyramine 4g bid. Hematology Oncology consultation indicated there would be little benefit from granulocyte colony stimulating factor therapy in medication induced agranulocytosis. He was monitored inpatient for recovery of he neutrophil count. He began to improve after 3 days of monitoring and was discharged. Repeat blood counts 3 months later showed full normalization. Further work-up revealed the etiology of his hyperthyroidism as likely a sub-acute/viral thyroiditis with thyroid I-123 uptake scan at 0.8% at 4, 6, and 24 hours. His hyperthyroidism also resolved over a total of 3 months and his beta-blocker and cholestyramine were discontinued. DISCUSSION: This case demonstrates that agranulocytosis is not a dose dependent side effect and can occur with as little as 7 days of therapy that are not even sequentially given. It also may support what very few case reports have demonstrated that even discontinuation of therapy may incite agranulocytosis as a side effect. It helps prescribers inform frequency of surveillance and selection of therapy in hyperthyroidism management. Presentation: No date and time listed