Vipom D37.70

Verner and Morrison, 1958

Very rarely, vasoactive intestinal polypetide (VIP)-producing benign (adenoma) or malignant (adenocarcinoma: 50-75% of VIPomas), pancreatic, (90%), non-β islet tumor belonging to the family of neuroendocrine tumors, leading to a hypersecretion syndrome with aqueous diarrhea, hypokalemia and achlorohydrism (WDHA syndrome).

Sporadic VIPome (>90% of all VIPome)

Syndromal VIPomas (as a partial symptom of the syndrome of multiple endocrine neoplasia- MEN)

Incidence: 0.05-0.2 /100,000 persons. VIPomas form about 2% of all neuroendocrine tumors of the gastroentero-pancreatic system (Lehnert H 2015).

Children and adults; peak age: 50 years.

90% of all VIPomas are localized in the pancreas (75% in the pancreatic body and tail, 25% in the pancreatic head), 10% in the adrenal medulla, lung, esophagus, retroperitoneal space and jejunum.

Prolonged, massive and aqueous (secretory) diarrhoea (fasting stool volume from > 750-1000 ml/day and non fasting volume up to > 3000 ml/day); symptoms of hypokalemia, acidosis and dehydration In about 50% of the patients the diarrhoea is constant; in the others the severity of diarrhoea changes in the course of time. In about 1/3 of patients diarrhoea precedes the diagnosis < 1 year.

25% of patients suffer from diarrhoea several years before the diagnosis is made. Other clinical symptoms: lethargy, muscle weakness, nausea, vomiting and cramping abdominal pain.

Elevated VIP in serum. Note: Markedly elevated levels assure diagnosis, but mild elevations may also occur in short bowel syndrome and inflammatory diseases.

Determination of electrolytes and blood count.

Hyperglycemia and glucose intolerance occur in ≤ 50% of patients.

Hypercalcemia occurs in 50% of patients.

Clinic with secretory diarrhoea (Note: stool osmolality is close to plasma osmolality and twice the sum of Na and K is equal to the total measured stool osmolality). Increased VIP serum level.

Imaging procedures: CT and endosonography, possibly PET

Fluid and electrolytesmust be replaced initially. Bicarbonate must be given to replace stool-induced loss to prevent acidosis.

Octreotide (somatostatin analog) usually controls diarrhea, but high doses may be required. Responding patients may benefit from monthly administration of 20-30 mg i.m. of a long-acting octreotide preparation. Patients on octreotide medication often require supplemental pancreatic enzymes because octreotide inhibits secretion of pancreatic enzymes.

Chemotherapy for metastatic VIPoma: mostly temozolomide-based regimens. The success of chemotherapy is questionable.

Alternative: everolimus or sunitinib.

Therapeutic guidelines according to AWMF Guideline 2018:

All NF-pNET >2cm without diffuse distant metastasis should be resected unless significant comorbidity argues against surgery.

In case of suspected malignancy of the VIPoma (50-75% of VIPomas are suspected to be malignant) large tumors and/or V.a. nodular infestation) without evidence of distant metastases the complete resection with formal pancreas resection and lymphadenectomy should be performed.

In cases of malignant VIPoma with resectable distant metastases, the complete removal of the primary tumor and metastases should be attempted. If liver metastases are present, hepatic (chemo)embolization with the controlled, available procedures should be performed.

In the case of malignant VIPom with surgically incurable distant metastases, removal of the primary tumor and debulking of the distant metastases to improve the hyperglycemia symptoms should be considered.

In patients with elevated VIP levels, tumor localization examinations such as endosonography, PET and octreotide scintigraphy or angiography should be initiated to localize metastases

1. Lehnert H (2015) Rational diagnostics and therapy in endocrinology, diabetology and metabolism. Georg Thieme Publishing House, Stuttgart-New York S. 236
2. Perren A et al (2010): Classification and pathology of gastroenteropancreatic neuroendocrine tumors. Visceralmed 26: 234-240
3. Rinke A et al (2018) S2k guideline neuroendocrine tumors. Z Gastroenterol 56: 583-681
4. Ruszniewski P et al (2006) Well-differentiated gastric tumors/carcinomas. Neuroendocrinology 84:158-164
5. Scherübl H et al (2003) Neuroendocrine gastrointestinal tumors. Diagnosis and therapy. Dtsch Med Weekly 128: 81-83
6. Scherübl H et al (2011) Management of early gastrointestinal neuroendocrine neoplasms. World J Gastrointestinal test Endosc 3: 133-139
7. Verner JV, Morrison AB(1958) Islet cell tumor and a syndrome of refractory watery diarrhea and hypokalemia. At J Med 25: 374.