Evaluation and Treatment of VIPoma

What is a VIPoma?

A VIPoma is a neuroendocrine tumor which secretes vasoactive intestinal peptide (VIP). They were first characterized by Verner and Morrison in 1958. Classically, these tumors present with secretory diarrhea, achlorhydria with metabolic acidosis and hypokalemia; the so called watery diarrhea syndrome; pancreatic, or endocrine cholera.

These rare tumors occur with a frequency of 1 per 10,000,000 per year. Adults typically present between ages 30 and 50 years. Children can present with these tumors between 2 and 4 years of age. VIPomas are typically solitary and greater than 3 centimeters in diameter with 75% located in the tail of the pancreas. Sixty to eighty percent are metastatic at the time of diagnosis.

While they originate in the pancreas in 90% of cases, they have also been described in the colon, bronchus, adrenals, liver, and sympathetic ganglia; as this polypeptide acts as a neurotransmitter in enteric neurons, central nervous system, lungs and other endocrine organs. VIP stimulates the secretion and inhibits the absorption of sodium, chloride, potassium and water within the small intestine, increasing bowel motility. These actions lead to secretory diarrhea, hypokalemia, and dehydration. Stool volumes of greater than three liters per day occur in 70% of these patients. Volumes less than 700 ml/day without treatment excludes the diagnosis. The diarrhea persists despite fasting, is odorless and tea-colored. Chemical evaluation of the stool demonstrates a high sodium load and a low stool osmolal gap. Hypokalemia has been reported in most patients with VIPoma and can be accompanied by lethargy, nausea, and muscular discomfort. In patients with secretory diarrhea and hypokalemia suspected of having VIPoma, a fasting plasma VIP measurement is mandatory (normal < 60 pmol/l). At the time of diagnosis, most tumors are greater than 3 cm in size, allowing for a complete visualization and evaluation using CT or MRI.

What is the treatment of VIPoma?

The first course of action once VIPoma has been diagnosed is to aggressively correct the dehydration and metabolic derangements which are often associated with the tumor. Octreotide can stop the diarrhea and allow for the correction of hypokalemia and other metabolic abnormalities in the majority of these patients. Once the fluid and electrolyte status has been normalized, surgical exploration is warranted for nearly all patients.

For those patients with no evidence of nodal or hepatic metastases, complete resection is the only chance for complete cure. Even for those patients with preoperative or intraoperative evidence of metastasis, surgical debulking can assist with postoperative medical management of locally invasive or residual disease. Postoperatively, octreotide can minimize symptoms of VIP hypersecretion in most patients in this scenario, although resistance to the drug, even in high dosages, has been described.