7245 A case of refractory methimazole-induced agranulocytosis treated with high-dose G-CSF
Authors: Shah Shivesh , Mathur Diya , Bao Ginny , Shah Soham , Antoniucci Diana Mirella 
Published: October 2024

Abstract
Disclosure: S. Shah: None. D. Mathur: None. G. Bao: None. S. Shah: None. D.M. Antoniucci: None.
Case Presentation: Despite their efficacy in treating hyperthyroidism, antithyroid drugs (ATDs) carry a rare risk of life-threatening agranulocytosis (ANC &lt;500/μL), with incidence varying from 0.1 to 0.4%. Patients with agranulocytosis may benefit from granulocyte-colony stimulating factor (G-CSF) to shorten recovery and reduce hospitalization costs. We present the case of a 37-year-old woman with Graves disease, who developed methimazole (MMZ)-induced agranulocytosis and was treated with high-dose G-CSF. At diagnosis, MMZ 10 mg BID was started and later reduced to 5 mg BID. After 2 months, she presented to the ED with a dental infection, an arm abscess after a cat scratch, and fevers. Blood-work showed WBC of 1500/μL, ANC of 0/μL, and rare granulocytes on manual differential. Flow cytometry did not show clonal lymphoid or blast populations. MMZ was stopped and antibiotics were started. Her hyperthyroidism was managed with propranolol and iodine solution in anticipation of definitive thyroidectomy. On day 4 of admission, tbo-filgrastim 450 mcg daily injections were started for persistent neutropenia. Despite 3 doses of G-CSF, ANC remained at 0/μL, prompting a bone marrow biopsy that showed no dysplastic or aplastic phenotype. After 9 doses of G-CSF up to 600 mcg daily, ANC fully recovered on day 14. She underwent thyroidectomy, and 2 months later her ANC and thyroid hormone levels were within normal. Discussion: This report illustrates a case of severe, refractory ATD-induced agranulocytosis and highlights the utility of G-CSF in treating high risk patients. Classically, ATD-induced agranulocytosis occurs in those aged &gt;65 years, follows high dose therapy, and occurs within 60 days of treatment initiation. G-CSF is often used in clinical practice, although its efficacy is not well established. A recent meta-analysis demonstrated that G-CSF can hasten recovery by 3 days. Other studies report no difference or prolonged agranulocytosis up to 14 days despite G-CSF, especially in patients with ANC &lt;100/μL. Whether this is a lack of true benefit or inadequate dosing is unclear. This case reviews the use of high dose G-CSF in a patient with profound neutropenia. Prompt ANC recovery was crucial given neutropenic fevers and need for thyroidectomy. Even with escalating doses of G-CSF, her ANC required 14 days to recover - twice the typical length of recovery. Whether G-CSF impacted the time course of her recovery is difficult to discern. Identifying the mechanisms underlying ATD induced agranulocytosis may explain delayed responses to G-CSF. Notably, the 2016 ATA guidelines do not incorporate G-CSF into ATD-induced agranulocytosis management. This conservative approach reflects a paucity of evidence supporting G-CSF use. Further research must investigate underlying mechanisms and clarify indications for G-CSF use to improve outcomes and reduce costs of care.
Presentation: 6/1/2024