What is Stauffer Syndrome?
Stauffer syndrome is a paraneoplastic syndrome characterized by signs of cholestasis (elevated liver enzymes, particularly alkaline phosphatase) unrelated to tumor infiltration of the liver or intrinsic liver disease, which typically resolves after resection of the underlying kidney tumor. 1
Classic Clinical Features
The syndrome presents with the following laboratory and clinical abnormalities in the absence of hepatic metastases:
- Elevated alkaline phosphatase (most characteristic finding) 2, 3
- Elevated aminotransferases (transaminitis) 2, 4
- Prolonged prothrombin time 1, 2
- Elevated erythrocyte sedimentation rate (ESR) 2
- Thrombocytosis 2
- Hepatosplenomegaly (may be present) 1, 2
- Hypoalbuminemia and elevated alpha-2-globulin 3
The Icteric Variant
While Stauffer syndrome was classically described as an anicteric (without jaundice) condition, a rare icteric variant with jaundice has been increasingly recognized in recent literature. 2, 4 This variant can occur even with small renal masses (as small as 2.5 cm), demonstrating that tumor size does not predict syndrome development. 4
Primary Association and Other Malignancies
Stauffer syndrome is most commonly associated with renal cell carcinoma (RCC), earning it the historical designation of "nonmetastatic nephrogenic hepatic dysfunction syndrome." 1, 2 However, emerging evidence shows it can occur with other solid malignancies, including prostate cancer and liposarcoma. 5, 6
Diagnostic Significance
The syndrome is clinically important because:
- It may be the presenting feature of an otherwise occult renal cell carcinoma 1, 3
- The hepatic dysfunction is reversible upon treatment (typically nephrectomy) of the primary tumor 1, 4
- Liver function tests can predict postoperative course and monitor for recurrence 3
Critical Diagnostic Pitfall
Do not dismiss unexplained cholestasis as primary hepatobiliary disease without excluding underlying malignancy, particularly RCC. 2, 4 The absence of hepatic metastases on imaging does not rule out paraneoplastic hepatic dysfunction. When encountering a patient with liver dysfunction and cholestasis (with or without jaundice) and no mechanical biliary obstruction, maintain high suspicion for occult renal or other solid organ malignancy. 5
Pathophysiology
The exact mechanism remains poorly understood, but the syndrome represents indirect paraneoplastic effects rather than direct tumor infiltration. 6 The complete reversibility after tumor resection supports a humoral or cytokine-mediated mechanism, though this has not been definitively established. 2, 4