VIPomas 

VIPomas are neuroendocrine tumors that secrete vasoactive intestinal polypeptide (VIP) autonomously.^{[1, 2, 3]} VIPomas arise from the pancreas in 90% of cases, but they may also be found in periganglionic tissue or at other sites, including the colon, bronchus, adrenal glands, and liver, especially in children (see the image below). (See Workup.)^[4]

VIPomas are almost always solitary, with less than 5% of cases being multicentric. The tumors are usually greater than 3cm at the time of diagnosis and are found primarily in the body and tail of the pancreas. (See Workup.)

Approximately 60-80% of VIPomas are malignant and have metastasized at the time of diagnosis. Metastasis occurs most frequently in the liver, but it may also occur in the lymph nodes, lungs, or kidneys.^[5] Approximately 5% of VIPomas are associated with multiple endocrine neoplasia type 1 (MEN 1) syndrome. Conversely, 17% of patients with MEN 1 develop VIPomas at some stage of their disease. Approximately 10% of neuroendocrine tumors of the gastrointestinal tract (except carcinoids) are VIPomas. (See Prognosis, Presentation, and Workup.)

The symptoms of VIPoma were described in 1958, when Verner and Morrison reported on 2 patients with a syndrome of watery diarrhea, hypokalemia, and achlorhydria (WDHA).^[6] These patients eventually succumbed to the condition as a result of dehydration and renal failure, despite attempted intravenous hydration. (See Presentation and Workup.)

In 1970, Said and Mutt extracted the putative hormone causing WDHA from pig gut tissue.^[7] In 1973, Bloom causally linked this hormone to WDHA, in a report on 6 patients with watery diarrhea resulting from pancreatic tumors associated with raised plasma levels of the hormone. The extirpated tumors from these cases were found to contain large amounts of the polypeptide now known as VIP.

VIP physiology

VIP has a molecular weight of 3381, consists of 28 amino acids, and belongs to the secretin-glucagon family. The VIP gene is located on chromosome 6. VIP is normally expressed in the central nervous system and in the neurons of the gastrointestinal, respiratory, and urogenital tracts, where it functions as a neurotransmitter.

VIP regulates the synthesis, secretion, and action of other neuroendocrine hormones; it also regulates cytokines and chemokines. Deficiency of VIP leads to developmental and behavioral abnormalities, including impaired circadian rhythms, in animal models.^[8] Overexpression of VIP causes diarrhea and cancer, and overexpression of VIP receptors promotes cancerous growth. In the gastrointestinal tract, VIP is largely responsible for the relaxation of vascular and nonvascular smooth muscle and for water and electrolyte secretion. VIP is released in response to gut distension by food.

VIP is a potent stimulator of gut cyclic adenosine monophosphate (cAMP) production, which leads to massive secretion of water and electrolytes (mainly potassium). VIP resembles secretin, which stimulates the secretion of alkaline pancreatic juices. In the stomach, VIP inhibits histamine- and pentagastrin-stimulated acid secretion. Like glucagon, VIP stimulates lipolysis and glycogenolysis and has an inotropic effect on the myocardium. It also has anti-inflammatory properties and modulates the immune system.

Etiology

Point mutations of the MEN1 gene on chromosome 11 have been identified in cases in which VIPomas are part of MEN 1 syndrome and, to a lesser extent, in sporadic tumors.

Epidemiology

The incidence of new cases of VIPoma is 0.05-0.5 per million people annually. The male-to-female ratio for VIPoma is approximately 1:1. Peak incidence occurs in the fifth decade of life, but VIPomas may occur in any age group, including in young children and elderly persons.

Approximately 50% of surgical patients with VIPoma are cured after tumor resection. In a series of 241 patients, the 5-year survival rate was 68.5% for patients with pancreatic VIPomas.^[9] The 5-year survival rate for patients without metastatic disease was reported to be about 95%. For patients with metastases, the 5-year survival rate was approximately 60%.

Morbidity from untreated WDHA syndrome is associated with long-standing dehydration and with electrolyte and acid-base disturbances, which may cause chronic renal failure.^[10] Death results from renal failure or cardiac arrest caused by volume depletion, hypokalemia, and severe acid-base disturbances.