7876 Complex Complications of Thionamide Therapy in One Patient: Methimazole-Induced Agranulocytosis and PTU-Induced ANCA-Vasculitis

Abstract

Abstract Disclosure: E. Zweibach: None. A. Chang: None. Introduction: Thionamides, including methimazole and propylthiouracil (PTU), are essential for treating Graves' disease but can cause serious side effects such as agranulocytosis and ANCA-vasculitis. Although agranulocytosis itself is quite uncommon, the incidence of ANCA vasculitis is even more infrequent, making combination of conditions particularly exceptional. We present a unique case of a Graves' disease patient who suffered both complications: agranulocytosis due to methimazole and ANCA vasculitis from PTU, with successful resolution of both the clinical signs and laboratory findings following drug discontinuation. Case: 61-year-old female with a history of Graves' disease previously managed with methimazole but discontinued due to agranulocytosis, presented with lower extremity swelling, atrial fibrillation with RVR, and high output cardiac failure. Laboratory tests showed hyperthyroidism (TSH 0.008, Free T4 3.07), leading to a diagnosis of thyroid storm. Patient was started on PTU inpatient and discharged with this medication to home. Eight months later, the patient developed alarming signs including gross hematuria, oral ulcers, widespread muscle pain, found to have AKI with Cr of 2.79 and hospitalized for further eval. While hospitalized, the patient was found to have a range of complications including leukopenia with normal granulocyte count, anemia, AKI, proteinuria, and microscopic hematuria. Rheumatological evaluation showed +ANA and a high ANCA titer >1:1280, along with elevated levels of MPO and PR-3, and reduced complement levels. These symptoms and laboratory findings led to a diagnosis of ANCA vasculitis induced by PTU, resulting in the cessation of this medication. Following the discontinuation of PTU there was a notable improvement with normalization of serum Cr and resolution of proteinuria within 1.5 months. Concurrently, MPO and PR-3 levels began to decrease, and her hematological abnormalities resolved. During this period, her Free T4 levels gradually increased, leading to the administration of radioactive iodine for the treatment of her Graves' disease. Discussion: This case underscores the complexities in treating a patient with Graves' disease highlighting the unpredictable and severe side effects of antithyroid drugs like agranulocytosis and ANCA vasculitis. We report the first documented case of sequential thionamide-induced complications: agranulocytosis with methimazole, followed by ANCA vasculitis with propylthiouracil. Although both can arise from immune responses to these medications, they are distinct in their pathophysiology and are not associated with one another. The unpredictable nature of these side effects complicates prevention. Educating patients to promptly report any unusual symptoms and immediate medical intervention with drug discontinuation are key to managing these adverse reactions effectively. Presentation: 6/1/2024