Resident Physician Saint Louis University Hospital Saint Louis, Missouri, United States
Introduction : Graves’ disease is an autoimmune disorder that induces excessive thyroid hormone production. Thionamides are typically used for treatment but in rare circumstances can result in agranulocytosis. We present the case of a patient who was initiated on methimazole for treatment of Graves’ disease, resulting in agranulocytosis, with subsequent Serratia marcescens bacteremia and septic shock.
Case(s) Description : A 36-year-old female with history of Graves’ disease initially presented with fever and anal pain. Of note, she had been started on methimazole two months prior. On admission, she had a white blood cell (WBC) of 0.3, with an absolute neutrophil count (ANC) of 10. WBC baseline before starting methimazole was 3.6. Exam was concerning for right axillary and sacral abscesses, which was confirmed on imaging. Blood cultures ultimately grew Serratia marcescens. Patient was admitted to the ICU for management of septic shock and ultimately required intubation for worsening encephalopathy. Bone marrow biopsy demonstrated marked hypocellularity. Patient was initiated on filgastrim, with appropriate uptrend in WBC count and ANC over the following weeks. Patient ultimately recovered from sepsis and was discharged to skilled nursing facility after a two-month hospital stay.
Discussion : Agranulocytosis is an uncommon but potentially life-threatening complication of thalinomides, and is believed to occur in about 0.2-0.5% of patients. The mechanism is either direct toxicity to neutrophils or immune toxicity via ANCA reacting against neutrophils. It commonly develops within the first three months of therapy but can be seen as early as 5 days into treatment. It most typically presents as fever and sore throat, although patients can also be asymptomatic. Currently the American Thyroid Association does not recommend monitoring complete blood counts (CBC) due to rarity of this complication. While no guidelines have been produced in the US, Japan monitors CBCs every two weeks for the first two months of therapy. Treatment with granulocyte colony-stimulating factor has been shown to decrease the time of recovery from agranulocytosis, the rate of complications from infection, and the mortality rate, even in patients with asymptomatic agranulocytosis. In the absence of CBC monitoring, educating patients about the prodromes of thalinomide-induced agranulocytosis (fever, sore throat, and cervical lymphadenopathy) could help with early recognition of agranulocytosis and prevent life-threatening complications.
