SAT-387 Propylthiouracil-Induced Cholestatic Jaundice: A Case Report

Abstract Disclosure: A. Malipeddi: None. L. Jabbar: None. W. Pan: None. Introduction: Propylthiouracil (PTU) is a second-line treatment for hyperthyroidism due to its hepatotoxic potential. Most PTU-induced liver injuries exhibit a hepatocellular pattern with elevated transaminases AST/ALT, while cholestatic jaundice with alkaline phosphatase (ALP) and bilirubin (TB) elevation is rarer. We describe a case of rapid onset cholestatic liver injury after PTU initiation. Case: A 62-year-old female with Graves' disease and heart failure with preserved ejection fraction presented with shortness of breath and pedal edema. Examination revealed icterus and exophthalmos. Labs showed TSH <0.02 mIU/L, FT4 >6.99 ng/dL, AST 35 U/L (13- 40 U/L), ALT 16 U/L (5- 35 U/L), ALP 194 U/L (34-122 U/L), TB 12.4 mg/dL (0.1- 1.1 mg/dL). She was discharged 6 days earlier after stopping methimazole due to reported palpitations and was started on PTU to enhance adherence. Discharge labs showed AST 39 U/L, ALT 16 U/L, TB 3.5 mg/dL, ALP 265 U/L. PTU was continued given that there was no lab evidence of hepatocellular injury- R factor 0.3. Gastroenterology evaluation, including ultrasound, MRCP, and hepatitis panel, was unremarkable. Autoimmune markers (IgG, ANA, ASMA, AMA) were elevated, but minimal AST/ALT elevation and no response to steroid therapy made autoimmune hepatitis unlikely. TB peaked at 14.3 mg/dL. After discussion, PTU was discontinued and methimazole was restarted. This intervention resulted in a rapid decrease in TB to 6.2 mg/dL and ALP to 144 U/L, in 5 days implicating PTU as the likely cause of her cholestatic jaundice. TFTs, TB and ALP normalized at the 8-week mark followed by a rapid rise in TB after restarting PTU at another hospital. Discussion: PTU- induced hepatotoxicity is usually hepatocellular, but rare cholestatic cases exist. A study by HJ et al. reported symptomatic hepatic injury in 1.2% of PTU-treated patients, with cholestasis observed in a small subset. This case highlights the need to recognize atypical cholestatic injury. Elevated autoimmune markers and hyperthyroidism may complicate the diagnosis, but minimal ALT/AST elevation and rapid improvement post-PTU withdrawal support a drug-induced etiology. The suspected mechanism involves oxidative stress and immune-mediated impairment of bile acid transporters. Monitoring liver function and considering alternative antithyroid therapies are crucial when PTU-induced cholestatic injury is suspected. Presentation: Saturday, July 12, 2025