Introduction
Stauffer syndrome is frequently attributed to patients suffering from renal cell carcinoma (RCC). However, it is paraneoplastic in origin, showing systemic signs and symptoms that are not directly associated with the malignancy. The RCC patients have shown several signs of hepatic dysfunction, such as hepatosplenomegaly (enlargement of the liver and spleen), elevated liver enzymes, abnormal liver function tests, and histologic changes that are non-specific hepatitis type. All these symptoms have been reported majorly in the early stages of renal cancer. It is important to note that no signs of jaundice or any other hepatic metastasis are observed in these patients. The symptoms are only limited to carcinoma and diminish upon successful tumor removal. This article briefly overviews the Stauffer syndrome, its clinical presentation, and its management.
What Is the Pathophysiology of the Stauffer Syndrome?
Stauffer syndrome is a cholestatic hepatic biliary dysfunction syndrome. This implies that it is characterized by an obstruction in the bile flow or reduced bile secretion. The underlying cause of this particular syndrome is yet to be established. However, many proposed mechanisms provide the reasoning for such hepatic dysfunction without hepatic metastasis.
-
Interleukin-6 Overexpression (IL-6): The primary culprit for such hepatic disruptions is the overexpression of interleukin-6 by the tumor cells. Renal cancer releases IL-6, which results in elevated levels of C-reactive protein and haptoglobin. In return, a reduction in the hepatobiliary transporter gene expression is observed. The pro-inflammatory activity of IL-6 tops the other consequences, such as cholestasis and hepatic dysfunction. All these changes lead to an impaired biliary outflow.
-
Colony-Stimulating Factor (CSF): This theory states that the administration of CSF inhibitors in Stauffer syndrome patients resulted in the reversal of the hepatic afflictions in these patients. The hypothesis was established by administering renal carcinoma cells from Stauffer syndrome patients into mice. The mice showed a hepatic function decline upon completion of the transfer. However, administering polysulfones naphthyl urea suramin, a known CSF inhibitor, improved these mice's conditions.
-
Autoimmunity: This theory is the least favored of all the other theories proposed to explain hepatobiliary dysfunction in renal cancer patients. The theory states that an underlying autoimmune response generated in these patients leads to abnormal hepatic function.
How Is Stauffer Syndrome Clinically Presented?
There are two distinct types of Stauffer syndromes observed in patients with renal cell carcinoma.
-
Type 1: The classical variant.
-
Type 2: The jaundice variant.
The classical variant of the Stauffer syndrome is characterized by pain in the groin area, bleeding during urination (hematuria), accompanied by abnormal liver function tests observing elevated levels of alkaline phosphatase, increased erythrocyte sedimentation rate (ESR), prolonged prothrombin time (PTT), markedly increased levels of alpha-2 globulin and gamma-glutamyl transferase, decreased albumin levels, thrombocytosis, and hepatosplenomegaly—all of these manifests without any signs of hepatobiliary obstruction or jaundice.
The jaundice variant is a relatively rare type, complemented by hyperbilirubinemia (excess bilirubin levels in the blood), hepatosplenomegaly, disrupted coagulation profile, choluria (bile in urine), jaundice, pruritus (itching).
The imaging modalities reveal a moderate to large-sized mass on the kidney; however, no abnormalities were found in the liver. Dark urine and stool discoloration are the typical findings in all patients with Stauffer syndrome.
How Is Stauffer Syndrome Diagnosed?
The diagnosis of Stauffer syndrome poses a significant challenge to clinicians to date. The extreme rarity of the disorder is held accountable for the same. However, there are several procedures one can perform to confirm the diagnosis of this highly uncommon syndrome.
-
Liver Function Tests: These can be carried out, especially to check the levels of bilirubin, alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT). An abnormal rise in the liver function tests indicates that the bile flow is obstructed or defective. Alanine transaminase (ALT) levels may also be elevated in later stages of the cholestasis.
-
Prothrombin Time: The disrupted biliary flow results in an abnormal coagulation profile. The prothrombin time is prolonged in this instance.
-
Imaging Studies: The imaging modalities should be utilized to confirm hepatic metastasis or rule out hepatosplenomegaly. The lack of hepatic metastasis or any other liver damage indicates Stauffer syndrome.
Additional clinical research is recommended to fully understand this uncommon and unrecognized illness to ensure appropriate diagnosis and treatment that prevents its deadly outcomes. When a patient has increased liver enzymes and presents in either a cholestatic or non-cholestatic pattern, it should alert the doctor to move on to the next phase, a more thorough review of the patient's medical history to look for an underlying reason.
How Is Stauffer Syndrome Managed?
The management of this disease primarily involves resection of the underlying renal tumor. In most cases, the hepatotoxic symptoms are reversed upon tumor removal. Often, the hepatic dysfunctions make it difficult to tackle the renal malignancy. In such cases, symptomatic treatment of the hepatic derangement should be made. The information regarding abnormally dark-colored urine and discolored stools must be well-explained to the patient to avoid any undesirable concerns. The restricted bile flow results in malabsorption of fat-soluble vitamins (A, D, E, K). Therefore, multi-vitamin supplementation is advised for patients with Stauffer syndrome. A multidisciplinary team is required to keep the patient’s overall well-being in check.
Conclusion
Stauffer's syndrome is an uncommon paraneoplastic consequence of renal cell carcinoma that results in cholestatic liver enzyme disruption and hepatosplenomegaly. The most widely recognized idea about pathophysiology is the tumor upregulation of cytokines. Nephrectomy is the ultimate treatment, and it is recommended to control cholestasis symptomatically before surgery with the assistance of gastroenterologists.
When the diagnosis of the primary tumor is delayed until the time of the diagnosis of the associated paraneoplastic syndrome, the development of Stauffer's syndrome in a patient with renal cell carcinoma has been linked to a poor prognosis because of hepatic function decline or because of the advanced stage of the tumor.
When a patient exhibits cholestatic jaundice without a discernible cause, it is advisable to conduct additional testing to rule out the possibility of an underlying cancer, such as renal cell carcinoma. This is one of the many presenting forms of "the internist's tumor," and early detection and better treatment outcomes could result from recognizing it.
