The portal for rare diseases and orphan drugs

The incidence of VIPoma in the general population is of less than 1/10,000,000 individuals per year. There is a slight female predominance.

The median age of diagnosis is the fifth decade of life but VIPoma can occur at any age. The most common presentation includes chronic watery diarrhea (described as >3L/day, odorless, blood and mucus free and unaffected by fasting), hypokalemia (manifesting with muscle weakness, abdominal muscle cramps, or respiratory depression), and various dietary deficiencies (iron and B12 deficiency) caused by achlorhydia/hypochlorhydia. Other less common manifestations include nausea, vomiting, weight loss, bloating, indigestion, skin rash and facial flushing, backache and lethargy. In 60-80% of cases, metastasis has occurred at the time of diagnosis as symptoms usually only occur once a tumor has reached a certain size. The most common site of metastasis is liver but lung, lymph node and kidney involvement have also been reported. If untreated, prolonged dehydration can lead to renal failure and cardiac arrest. In rare cases, VIPomas are non-functional.

Most cases are sporadic but VIPomas can also occur in association with multiple endocrine neoplasia type 1 (MEN1; see this term). VIPomas are, in 90% of cases, located in the pancreas (mainly in the body and tail) and are usually solitary with a diameter ranging from 1-7cm. The remainder (10%) originate from non-pancreatic tissue such as the colon, liver and neural crest-derived tissues (mainly pediatric cases). These tumors secrete VIP, which stimulates cyclic adenosine monophosphate (cAMP) production in the intestine, causing increased water and electrolyte secretion into the lumen. VIP also has an inhibitory effect on gastric mucosa parietal cells leading to decreased gastric acid production.

Diagnosis is based on clinical, laboratory and imaging findings. Typical blood laboratory findings include elevated VIP levels (>200pg/mL is diagnostic), hypokalemia, hypochlorhydia or achlorhydia, hyperglycemia, hypercalcemia and non-anion gap metabolic acidosis. Computed tomography (CT) and octreotide scans, magnetic resonance imaging (MRI) and endoscopic ultrasound can be used to localize neoplasms, confirming diagnosis. Immunohistochemically, VIPomas stain positively for VIP, synaptophysin, chromagranin A, somatostatin, neuron specific enolase and cytokeratin.

Differential diagnoses include all other causes of chronic diarrhea such as malabsorption syndrome, Crohn disease, ulcerative colitis, microscopic colitis (see these terms), and gastrointestinal infections.

Initial treatment focuses on replacing the massive loss of fluids, restoring electrolyte levels and reversing acidosis. Some patients may require intravenous fluid and potassium replacement in a hospital setting. Octreotide (a somatostatin analogue) is successful in controlling diarrhea and reducing VIP hormone levels. Loperamide may also be used. Surgical resection is the standard treatment in those with primary or metastatic VIPoma. Unresectable metastatic disease has been treated with chemotherapy (docorubicin/streptozocin regimen) in some cases.

Prognosis is highly variable and is dependent on many factors. In those with benign, surgically resectable tumors, the reported 5-year survival rate is almost 95%.