S5495 Paraneoplastic Hepatic Dysfunction in the Absence of Metastases: A Case of Stauffer Syndrome

Introduction: Stauffer syndrome is a rare paraneoplastic hepatic dysfunction characterized by elevated liver enzymes and intrahepatic cholestasis in the absence of hepatic metastasis. Most commonly linked to renal cell carcinoma (RCC), it is reported in only 3%–15% of RCC cases. Early recognition is critical in patients with unexplained liver function abnormalities or cholestatic injury in the setting of known or suspected malignancy, as hepatic dysfunction typically resolves with treatment of the primary tumor. Case Description/Methods: An 85-year-old man with a history of RCC, hypertension, and dysphagia presented with acute metabolic encephalopathy. Laboratory studies revealed elevated liver enzymes, and the R factor indicated cholestatic liver injury. Imaging showed a normal common bile duct (4.4 mm) on ultrasound and no obstruction on magnetic resonance cholangiopancreatography. Drug-induced liver injury was excluded by negative urine drug screening; autoimmune and infectious workup (antinuclear antibody, antimitochondrial antibodies, anti-smooth muscle antibodies, LKM, herpes simplex virus, varicella zoster virus, Epstein-Barr virus, cytomegalovirus) was negative. Erythrocyte sedimentation rate was elevated. Alpha-1 and Alpha-2 globulin were elevated on serum protein electrophoresis, raising suspicion for paraneoplastic liver dysfunction. While a liver biopsy was considered, the patient’s encephalopathy worsened, and patient's family made the decision to transition to comfort-focused care. Discussion: Although classically seen in RCC, Stauffer syndrome has also been reported in association with other malignancies. It is characterized by reversible, non-metastatic hepatic dysfunction, often presenting with elevated alkaline phosphatase, gamma-glutamyl transferase, and erythrocyte sedimentation rate; aminotransferases are typically normal or only mildly elevated. Elevated alpha-2 globulin is a frequently reported laboratory finding in RCC-associated cases. The underlying pathogenesis likely involves immune-mediated cytokine release, particularly interleukin-6 (IL-6). Clinical symptoms are often nonspecific, including fatigue, malaise, weight loss, fever, and occasional right upper quadrant pain, with hepatosplenomegaly and jaundice in some cases. Treatment focuses on managing the underlying malignancy, with some early evidence suggesting potential benefit of anti–IL-6 monoclonal antibodies. Unfortunately, in this case, the patient died before oncologic management could be pursued. Raising awareness for Stauffer syndrome may lead to earlier recognition, allowing timely targeted interventions to treat this rare but potentially reversible paraneoplastic syndrome.