eMedicine Specialties > Endocrinology > Multiple Endocrine Disease and Miscellaneous Endocrine Disease
VIPomas
Updated: Dec 18, 2008
Introduction
Background
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).1 These patients eventually succumbed to the condition as a result of dehydration and renal failure, despite attempted intravenous hydration. In 1970, Said and Mutt extracted the putative hormone causing WDHA from pig gut tissue.2 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 this hormone. The extirpated tumors from these cases were found to contain large amounts of what is now known as vasoactive intestinal polypeptide (VIP).
Related eMedicine topics:
Neoplasms of the Endocrine Pancreas
Pancreas, Islet Cell Tumors
VIPoma
WDHA Syndrome
Pathophysiology
Found mainly in the pancreas, VIPomas are neuroendocrine tumors that secrete vasoactive intestinal polypeptide (VIP) autonomously.
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.3 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.
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.4 These tumors are almost always solitary, with less than 5% of cases being multicentric. VIPomas are usually greater than 3 cm at the time of diagnosis and are found primarily in the body and tail of the pancreas.
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, lung, 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.
Related eMedicine topics:
Multiple Endocrine Neoplasia
Multiple Endocrine Neoplasia Type 1
Wermer Syndrome (MEN Type 1)
Frequency
International
The incidence of new cases of VIPoma is 0.05-0.5 per million people per year.
Mortality/Morbidity
- Morbidity from untreated WDHA syndrome is associated with long-standing dehydration and with electrolyte and acid-base disturbances, which may cause chronic renal failure.6
- Death results from renal failure or cardiac arrest caused by volume depletion, hypokalemia, and severe acid-base disturbances.
Sex
- The male-to-female ratio for VIPoma is approximately 1:1.
Age
- Peak incidence occurs in the fifth decade of life, but VIPomas may occur in any age group, including in young children and elderly persons.
Clinical
History
- The onset of VIPoma is insidious.
- The dominant symptom is profuse diarrhea despite fasting; this symptom may persist for years before the diagnosis is established. Diarrhea may be episodic initially, but it becomes continuous as the tumor progresses. Stool volumes are typically profound, with volumes greater than 3 L per day in 70% of cases. The stool is typically odorless and tea-colored, without blood or mucus.
- The loss of water, sodium, and chloride may lead to volume depletion, dehydration, and exhaustion among patients who are unable to replace fluid and electrolyte losses. Weight loss and even renal failure have been reported in some patients.
- Excretion of large amounts of potassium and bicarbonate in the stool causes hypokalemia and non–anion gap acidosis. Hypokalemia may present as muscle cramps and/or weakness.
- Abdominal discomfort or bloating has been reported.
- Facial flushing involved one third of patients from a 31-case series in China.7 Other studies have also reported facial flushing, but without a reported frequency.
- One reported case in China involved periodic backache and a rash involving the chest, back, and upper limb. These 2 symptoms occurred before or after the diarrhea, worsened over 6 years, and resolved after surgical resection.
Physical
- Volume depletion may lead to tachycardia, decreased skin turgor, and documented weight loss.
- Because of marked fecal loss of potassium, patients may have muscle weakness on examination.
- Patients may present with a mildly distended abdomen.
- Hepatomegaly may be detected if liver metastasis has occurred.
- Facial flushing may be seen because of the vasodilatory effects of vasoactive intestinal polypeptide.
- An electrocardiogram may reveal QRS widening and T-wave flattening if hypokalemia is severe.
Causes
Point mutations on chromosome 11 of the MEN1 gene have been identified in cases where VIPomas are part of MEN 1 syndrome and, to a lesser extent, in sporadic tumors.
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Overview: VIPomas |
| Differential Diagnoses & Workup: VIPomas |
| Treatment & Medication: VIPomas |
| Follow-up: VIPomas |
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References
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Further Reading
Keywords
VIPoma, pancreatic cancer, cancer pancreas, pancreatic cancer symptoms, neuroendocrine tumor, neuroendocrine carcinoma, pancreatic tumor, pancreas tumor, multiple endocrine neoplasia, pancreas tumors, pancreatic tumors, Verner-Morrison syndrome, pancreatic cholera, watery diarrhea-hypokalemia-achlorhydria syndrome, WDHA syndrome, vasoactive intestinal polypeptide, VIP, pancreatic endocrine tumor, multiple endocrine neoplasia type 1 syndrome, MEN 1
Overview: VIPomas