Highlights & Basics
- VIPomas are rare functional neuroendocrine tumors typically originating within the pancreas.
- VIPoma is characterized by profuse watery diarrhea, hypokalemia, metabolic acidosis, and hypochlorhydria or achlorhydria, in the presence of elevated serum vasoactive intestinal peptide (VIP).
- The clinical syndrome associated with VIPomas is sometimes referred to as WDHA syndrome (watery diarrhea, hypokalemia, and achlorhydria), Verner-Morrison syndrome, or pancreatic cholera.
- VIPomas are highly malignant. Patients usually present with regional lymph node or liver involvement at diagnosis.
- Surgical resection is the standard treatment.
Quick Reference
History & Exam
Key Factors
Other Factors
Diagnostics Tests
Treatment Options
Definition
Epidemiology
Etiology
Pathophysiology
Images
Citations
National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: neuroendocrine and adrenal tumors [internet publication].[Full Text]
Hofland J, Falconi M, Christ E, et al. European Neuroendocrine Tumor Society 2023 guidance paper for functioning pancreatic neuroendocrine tumour syndromes. J Neuroendocrinol. 2023 Aug;35(8):e13318.[Abstract][Full Text]
Pavel M, Öberg K, Falconi M, et al. Gastroenteropancreatic neuroendocrine neoplasms: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020 Jul;31(7):844-60.[Full Text]
Del Rivero J, Perez K, Kennedy EB, et al. Systemic therapy for tumor control in metastatic well-differentiated gastroenteropancreatic neuroendocrine tumors: ASCO guideline. J Clin Oncol. 2023 Nov 10;41(32):5049-67.[Abstract][Full Text]
1. Soga J, Yakuwa Y. Vipoma/diarrheogenic syndrome: a statistical evaluation of 241 reported cases. J Exp Clin Cancer Res. 1998 Dec;17(4):389-400.[Abstract]
2. World Health Organization. WHO classification of tumours online: endocrine and neuroendocrine tumors (5th edition, 2022). 2022 [internet publication].
3. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: neuroendocrine and adrenal tumors [internet publication].[Full Text]
4. Helderman NC, Suerink M, Kilinç G, et al. Relation between WHO classification and location- and functionality-based classifications of neuroendocrine neoplasms of the digestive tract. Neuroendocrinology. 2024;114(2):120-33.[Abstract][Full Text]
5. American College of Surgeons. American Joint Committee on Cancer: cancer programs. Sep 2023 [internet publication].
6. Camera L, Severino R, Faggiano A, et al. Contrast enhanced multi-detector CT and MR findings of a well-differentiated pancreatic vipoma. World J Radiol. 2014 Oct 28;6(10):840-5.[Abstract][Full Text]
7. Sonbol MB, Mazza GL, Mi L, et al. Survival and incidence patterns of pancreatic neuroendocrine tumors over the last 2 decades: a SEER database analysis. Oncologist. 2022 Jul 5;27(7):573-8.[Abstract][Full Text]
8. Dasari A, Shen C, Halperin D, et al. Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol. 2017 Oct 1;3(10):1335-42.[Abstract][Full Text]
9. Ghaferi AA, Chojnacki KA, Long WD, et al. Pancreatic VIPomas: subject review and one institutional experience. J Gastointest Surg. 2008 Feb;12(2):382-93.[Abstract]
10. Thakker RV, Newey PJ, Walls GV, et al. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012 Sep;97(9):2990-3011.[Abstract][Full Text]
11. Holst JJ, Fahrenkrug J, Knuhtsen S, et al. Vasoactive intestinal polypeptide (VIP) in the pig pancreas: role of VIPergic nerves in the control of fluid and bicarbonate secretion. Regul Pept. 1984 Apr;8(3):245-59.[Abstract]
12. Robberecht P, Conlon TP, Gardner JD. Interaction of porcine vasoactive intestinal peptide with dispersed pancreatic acinar cells from the guinea pig: structural requirements for effects of vasoactive intestinal peptide and secretin on cellular adenosine 3':5'-monophosphate. J Biol Chem. 1976 Aug 10;251(15):4635-9.[Abstract]
13. Barbezat GO, Grossman MI. Intestinal secretion: stimulation by peptides. Science. 1971 Oct 22;174(4007):422-4.[Abstract]
14. Fahrenkrug J. Transmitter role of vasoactive intestinal peptide. Pharmacol Toxicol. 1993 Jun;72(6):354-63.[Abstract]
15. Biancani P, Walsh JH, Behar J. Vasoactive intestinal polypeptide: a neurotransmitter for lower esophageal sphincter relaxation. J Clin Invest. 1984 Apr;73(4):963-7.[Abstract][Full Text]
16. Usdin TB, Bonner TI, Mezey E. Two receptors for vasoactive intestinal polypeptide with similar specificity and complementary distributions. Endocrinology. 1994 Dec;135(6):2662-80.[Abstract]
17. Hofland J, Falconi M, Christ E, et al. European Neuroendocrine Tumor Society 2023 guidance paper for functioning pancreatic neuroendocrine tumour syndromes. J Neuroendocrinol. 2023 Aug;35(8):e13318.[Abstract][Full Text]
18. Vinik AI, Woltering EA, Warner RR, et al; North American Neuroendocrine Tumor Society (NANETS). NANETS consensus guidelines for the diagnosis of neuroendocrine tumor. Pancreas. 2010 Aug;39(6):713-34.[Abstract][Full Text]
19. Kulke MH, Anthony LB, Bushnell DL,et al; North American Neuroendocrine Tumor Society (NANETS). NANETS treatment guidelines: well-differentiated neuroendocrine tumors of the stomach and pancreas. Pancreas. 2010 Aug;39(6):735-52.[Abstract][Full Text]
20. Una Cidon E. Vasoactive intestinal peptide secreting tumour: an overview. World J Gastrointest Oncol. 2022 Apr 15;14(4):808-19.[Abstract]
21. de Herder WW, Hofland J. Vasoactive intestinal peptide-secreting tumor (VIPoma). 2023 Apr 5. In: Feingold KR, Anawalt B, Blackman MR, et al. eds. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000.[Abstract][Full Text]
22. Scottish Neuroendocrine Tumour Group. Consensus guidelines for the management of patients with neuroendocrine tumours. July 2015 [internet publication].[Full Text]
23. O'Toole D, Kianmanesh R, Caplin M. ENETS 2016 consensus guidelines for the management of patients with digestive neuroendocrine tumors: an update. Neuroendocrinology. 2016;103(2):117-8.[Abstract][Full Text]
24. Pavel M, Öberg K, Falconi M, et al. Gastroenteropancreatic neuroendocrine neoplasms: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020 Jul;31(7):844-60.[Full Text]
25. Kunz PL, Reidy-Lagunes D, Anthony LB, et al; North American Neuroendocrine Tumor Society. Consensus guidelines for the management and treatment of neuroendocrine tumors. Pancreas. 2013 May;42(4):557-77.[Abstract][Full Text]
26. Sundin A, Arnold R, Baudin E, et al. ENETS consensus guidelines for the standards of care in neuroendocrine tumors: radiological, nuclear medicine & hybrid imaging. Neuroendocrinology. 2017;105(3):212-44.[Abstract]
27. Hope TA, Bergsland EK, Bozkurt MF, et al. Appropriate use criteria for somatostatin receptor PET imaging in neuroendocrine tumors. J Nucl Med. 2018 Jan;59(1):66-74.[Abstract][Full Text]
28. Gabriel M, Decristoforo C, Kendler D, et al. 68Ga-DOTA-Tyr3-octreotide PET in neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT. J Nucl Med. 2007 Apr;48(4):508-18.[Abstract][Full Text]
29. Barrio M, Czernin J, Fanti S, et al. The impact of somatostatin receptor-directed PET/CT on the management of patients with neuroendocrine tumor: a systematic review and meta-analysis. J Nucl Med. 2017 May;58(5):756-61.[Abstract][Full Text]
30. Metz DC, Jensen RT. Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors. Gastroenterology. 2008 Nov;135(5):1469-92.[Abstract][Full Text]
31. Perren A, Couvelard A, Scoazec JY, et al. ENETS consensus guidelines for the standards of care in neuroendocrine tumors: pathology: diagnosis and prognostic stratification. Neuroendocrinology. 2017;105(3):196-200.[Abstract][Full Text]
32. Garcia-Carbonero R, Sorbye H, Baudin E, et al. ENETS consensus guidelines for high-grade gastroenteropancreatic neuroendocrine tumors and neuroendocrine carcinomas. Neuroendocrinology. 2016;103(2):186-94.[Abstract][Full Text]
33. Pavel M, O'Toole D, Costa F, et al; Vienna Consensus Conference participants. ENETS consensus guidelines update for the management of distant metastatic disease of intestinal, pancreatic, bronchial neuroendocrine neoplasms (NEN) and NEN of unknown primary site. Neuroendocrinology. 2016;103(2):172-85.[Abstract]
34. Del Rivero J, Perez K, Kennedy EB, et al. Systemic therapy for tumor control in metastatic well-differentiated gastroenteropancreatic neuroendocrine tumors: ASCO guideline. J Clin Oncol. 2023 Nov 10;41(32):5049-67.[Abstract][Full Text]
35. Modlin IM, Pavel M, Kidd M, et al. Review article: somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine (carcinoid) tumours. Aliment Pharmacol Ther. 2010 Jan 15;31(2):169-88.[Abstract][Full Text]
36. Perez K, Del Rivero J, Kennedy EB, et al. Symptom management for well-differentiated gastroenteropancreatic neuroendocrine tumors: ASCO guideline. JCO Oncol Pract. 2025 May 9:OP2500133.[Abstract][Full Text]
37. Oberg K. Chemotherapy and biotherapy in the treatment of neuroendocrine tumours. Ann Oncol. 2001;12 Suppl 2:S111-4.[Abstract]
38. Maton PN, Gardner JD, Jensen RT. Use of long-acting somatostatin analog SMS 201-995 in patients with pancreatic islet cell tumors. Dig Dis Sci. 1989;34(3 suppl):28-39S.[Abstract]
39. Brighi N, Panzuto F, Modica R, et al. Biliary stone disease in patients with neuroendocrine tumors treated with somatostatin analogs: a multicenter study. Oncologist. 2020 Mar;25(3):259-65.[Abstract][Full Text]
40. Halfdanarson TR, Strosberg JR, Tang L, et al. The North American Neuroendocrine Tumor Society consensus guidelines for surveillance and medical management of pancreatic neuroendocrine tumors. Pancreas. 2020 Aug;49(7):863-81.[Abstract]
41. Howe JR, Merchant NB, Conrad C, et al. The North American Neuroendocrine Tumor Society consensus paper on the surgical management of pancreatic neuroendocrine tumors. Pancreas. 2020 Jan;49(1):1-33.[Abstract]
42. Tanaka M, Heckler M, Mihaljevic AL, et al. Systematic review and metaanalysis of lymph node metastases of resected pancreatic neuroendocrine tumors. Ann Surg Oncol. 2021 Mar;28(3):1614-24.[Abstract]
43. Perry RR, Vinik AI. Clinical review 72: diagnosis and management of functioning islet cell tumors. J Clin Endocrinol Metab. 1995 Aug;80(8):2273-8.[Abstract]
44. Ho AS, Picus J, Darcy MD, et al. Long-term outcome after chemoembolization and embolization of hepatic metastatic lesions from neuroendocrine tumors. AJR Am J Roentgenol. 2007 May;188(5):1201-7.[Abstract][Full Text]
45. King J, Quinn R, Glenn DM, et al. Radioembolization with selective internal radiation microspheres for neuroendocrine liver metastases. Cancer. 2008 Sep 1;113(5):921-9.[Abstract]
46. Johnston PC, Ardill JE, Johnston BT, et al. Vasoactive intestinal polypeptide secreting pancreatic tumour with hepatic metastases: long term survival after orthotopic liver transplantation. Ir J Med Sci. 2010 Sep;179(3):439-41.[Abstract]
47. Máthé Z, Tagkalos E, Paul A, et al. Liver transplantation for hepatic metastases of neuroendocrine pancreatic tumors: a survival-based analysis. Transplantation. 2011 Mar 15;91(5):575-82.[Abstract]
48. Merola E, Panzuto F, Delle Fave G. Antiproliferative effect of somatostatin analogs in advanced gastro-entero-pancreatic neuroendocrine tumors: a systematic review and meta-analysis. Oncotarget. 2017 Jul 11;8(28):46624-34.[Abstract][Full Text]
49. Rinke A, Müller HH, Schade-Brittinger C, et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol. 2009 Oct 1;27(28):4656-63.[Abstract][Full Text]
50. Caplin ME, Pavel M, Ćwikła JB, et al. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med. 2014 Jul 17;371(3):224-33.[Abstract][Full Text]
51. Raymond E, Dahan L, Raoul JL, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med. 2011 Feb 10;364(6):501-13.[Abstract]
52. National Institute for Health and Care Excellence. Everolimus and sunitinib for treating unresectable or metastatic neuroendocrine tumours in people with progressive disease. June 2017 [internet publication].[Full Text]
53. Yao JC, Shah MH, Ito T, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011 Feb 10;364(6):514-23.[Abstract][Full Text]
54. Capdevila J, Teulé A, Barriuso J, et al. Phase II study of everolimus and octreotide LAR in patients with nonfunctioning gastrointestinal neuroendocrine tumors: the GETNE1003_EVERLAR study. Oncologist. 2019 Jan;24(1):38-46.[Abstract][Full Text]
55. Bajetta E, Catena L, Pusceddu S, et al. Everolimus in combination with octreotide long-acting repeatable in a first-line setting for patients with neuroendocrine tumors: a 5-year update. Neuroendocrinology. 2018;106(4):307-11.[Abstract]
56. Moertel CG, Lefkopoulo M, Lipsitz S, et al. Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med. 1992 Feb 20;326(8):519-23.[Abstract][Full Text]
57. Dilz LM, Denecke T, Steffen IG, et al. Streptozocin/5-fluorouracil chemotherapy is associated with durable response in patients with advanced pancreatic neuroendocrine tumours. Eur J Cancer. 2015 Jul;51(10):1253-62.[Abstract]
58. Kouvaraki MA, Ajani JA, Hoff P, et al. Fluorouracil, doxorubicin, and streptozocin in the treatment of patients with locally advanced and metastatic pancreatic endocrine carcinomas. J Clin Oncol. 2004 Dec 1;22(23):4762-71.[Abstract][Full Text]
59. Strosberg JR, Fine RL, Choi J, et al. First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas. Cancer. 2011 Jan 15;117(2):268-75.[Abstract][Full Text]
60. Hope TA, Bodei L, Chan JA, et al. NANETS/SNMMI consensus statement on patient selection and appropriate use of (177)Lu-DOTATATE peptide receptor radionuclide therapy. J Nucl Med. 2020 Feb;61(2):222-7.[Abstract][Full Text]
61. Strosberg J, El-Haddad G, Wolin E, et al. Phase 3 Trial of (177)Lu-Dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017 Jan 12;376(2):125-35.[Abstract][Full Text]
62. Strosberg JR, Caplin ME, Kunz PL, et al. (177)Lu-Dotatate plus long-acting octreotide versus high‑dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2021 Dec;22(12):1752-63.[Abstract]
63. Nguyen HN, Backes B, Lammert F, et al. Long-term survival after diagnosis of hepatic metastatic VIPoma: report of two cases with disparate courses and review of therapeutic options. Dig Dis Sci. 1999 Jun;44(6):1148-55.[Abstract]
64. Xu J, Shen L, Zhou Z, et al. Surufatinib in advanced extrapancreatic neuroendocrine tumours (SANET-ep): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Nov;21(11):1500-12.[Abstract]
65. Chan JA, Geyer S, Zemla T, et al. Phase 3 trial of cabozantinib to treat advanced neuroendocrine tumors. N Engl J Med. 2024 Sep 16.[Abstract]
66. Roland CL, Bian A, Mansour JC, et al. Survival impact of malignant pancreatic neuroendocrine and islet cell neoplasm phenotypes. J Surg Oncol. 2012 May;105(6):595-600.[Abstract]
67. van der Zwan JM, Trama A, Otter R, et al. Rare neuroendocrine tumours: results of the surveillance of rare cancers in Europe project. Eur J Cancer. 2013 Jul;49(11):2565-78.[Abstract]
