Stauffer Syndrome: A Comprehensive Review of the Icteric Variant of the Syndrome

Abstract

Stauffer syndrome is a rare paraneoplastic syndrome classically associated with renal cell carcinoma (RCC). This association gave it the historical name of nonmetastatic nephrogenic hepatic dysfunction syndrome without jaundice. It is a syndrome of unclear pathophysiology characterized by a reversible anicteric elevation of liver enzymes, alkaline phosphatase, erythrocyte sedimentation rate (ESR), thrombocytosis, prolongation of prothrombin time, and hepatosplenomegaly in the absence of direct hepatobiliary obstruction or jaundice. A rare atypical variant of this syndrome with jaundice has been recently described in the literature. Thus, it is important to consider both these variants of Stauffer syndrome in the differential diagnosis of unexplained cholestasis in the absence of hepatic metastasis. This may allow early recognition and treatment of an occult malignancy. Herein, we present a comprehensive review of the literature available on the icteric variant of the Stauffer syndrome, outlining its association with various malignancies and the diagnostic challenges it poses. The objective of this review is to help clinicians in its early diagnosis and management.

Stauffer syndrome, clinical implications and knowledge gaps, does size matter? Case report

“…Stauffer syndrome can be divided into a classic presentation and jaundice variant. The latter is characterized by high alkaline phosphatase, thrombocytosis, elevated erythrocyte sedimentation rate, hyperbilirubinemia, hepatosplenomegaly, in some cases, abnormal coagulation profile and hypoalbuminemia, jaundice, choluria, pruritus are clinical features of this syndrome [3,5,8]. Our case corresponds to the aforementioned jaundice variant.…”

“…Stauffer syndrome is an uncommon paraneoplastic syndrome [4,5]. It is usually associated with RCC, but it can present along with other types of malignancies such as soft-tissue sarcomas, prostate cancer and malignant lymphoproliferative diseases [3,5]. Stauffer syndrome can be divided into a classic presentation and jaundice variant.…”

A Rare Presentation of Stauffer’s Syndrome Associated with Renal Cell Carcinoma

“…Most RCC patients present with a paraneoplastic manifestation of the disease [11]. A recent review looking at all reported cases of Stauffer's syndrome yielded >100 cases, most of which described the association with RCC; the incidence rate was 3-6% among these patients [6].…”

“…Multiple theories have been proposed to try and explain the pathophysiology of Stauffer's syndrome behind this paraneoplastic manifestation. One hypothesis relates it to the high lysosomal enzyme activity which was found in the liver cells of RCC patients suggesting that the tumor is releasing these substances which have a direct effect on the liver [6]. Other hypotheses suggested hepatic amyloid deposition, generalized hepatic hypervascularity, nonspecific focal periportal inflammation, or an autoimmune phenomenon which cross-reacts with the liver protein [6].…”

“…The most common laboratory finding is elevated alkaline phosphatase, seen in 90% of all cases. While elevated hyperbilirubinemia and transaminase have been found in 15 and 21% of all cases, respectively, other laboratory abnormalities are a prolongation of prothrombin time, an elevation of gamma-glutamyltransferase, erythrocyte sedimentation rate, alpha-2-globulin, and thrombocytosis [6].…”