Abstract #1411962: Methimazole Induced Agranulocytosis: A Treatment Dilemma

Abstract

Agranulocytosis is a phrase often used to indicate severe neutropenia. It is a rare, but serious adverse effect of anti-thyroid medications with prevalence of less than one percent. Diagnosis warrants immediate termination of the offending agent, in addition to prompt evaluation for definitive treatment options. Due to low prevalence, the presentation can pose a diagnostic and treatment challenge. We present a case of a 21-year-old female with Graves’ disease who was initiated on methimazole, and was subsequently hospitalized for methimazole induced agranulocytosis. Patient was a 21-year-old female without any significant prior medical history who initially presented to the hospital with symptoms of weight loss and heart palpitations. She was diagnosed with Graves’ disease on the basis of laboratory and imaging data. She was initiated on high doses of methimazole thirty milligrams twice daily. Her baseline white blood cell count at the time of treatment initiation was normal. She was on treatment therapy for four weeks, before she presented back to the hospital at the request of her outpatient endocrinologist with symptoms of fever, sore throat, vomiting, and diarrhea. Based on laboratory data and clinical presentation, she was diagnosed with neutropenic fever and was initiated on prophylactic antibiotics. The methimazole treatment was terminated on admission due to concern for drug induced agranulocytosis. Subsequently, her infectious work up was negative and antibiotics were stopped. The patient received granulocyte stimulating colony factor with normalization of her neutrophil counts and resolution of her fever. Unfortunately, her thyroid hormones began to rise once methimazole was stopped. Therefore, the patient promptly underwent a total thyroidectomy for definitive treatment of Graves’ disease during the admission. She was successfully discharged home on levothyroxine therapy with appropriate follow up. Anti-thyroid drugs are the cornerstone of management of hyperthyroidism. Treatment with these agents carries a less than one percent risk of developing agranulocytosis. This adverse effect is thought to be related to direct toxicity and immune mediated process. The use of high doses of anti-thyroid medications is a risk factor for development of agranulocytosis. The clinical presentation varies, but the most common symptoms include fever and sore throat. The use of granulocyte stimulating colony factor may shorten the length of hospital stay and improve the neutrophil recovery time, but it has not been linked to improved mortality rates. Ultimately, both surgery and radioactive iodine therapy are effective alternative treatments when medical therapy is terminated. Clinical suspicion and patient education regarding potential adverse effects of anti-thyroid medications are the cornerstones of responsible patient care.