eMedicine Specialties > Endocrinology > Multiple Endocrine Disease and Miscellaneous Endocrine Disease

VIPomas: Treatment & Medication

Author: Daniel S Tung, MD, Fellow in Endocrinology, Department of Internal Medicine, Baylor College of Medicine
Coauthor(s): Sai-Ching Jim Yeung, MD, PhD, FACP, Deputy Section Chief of Emergency Care, Assistant Professor, Department of General Internal Medicine, Ambulatory Treatment and Emergency Care, University of Texas MD Anderson Cancer Center; Klaus Radebold, MD, PhD, Research Associate, Department of Surgery, Yale University School of Medicine
Contributor Information and Disclosures

Updated: Dec 18, 2008

Treatment

Medical Care

  • Initial treatment for VIPoma is aimed at correcting any volume, electrolyte, and acid-base abnormalities with intravenous normal saline, potassium chloride, and, if acidosis is severe, sodium bicarbonate. In many cases, these abnormalities are severe, requiring hospital admission.
  • Somatostatin is highly effective in reducing serum vasoactive intestinal polypeptide levels and promptly controlling diarrhea in more than 90% of patients.7 To circumvent the short serum half-life of somatostatin, the derivative octreotide is used. Octreotide is delivered subcutaneously at an initial dose of 50-100 mcg, 3 times a day, which may be titrated up for symptom control to a maximum of 500 mcg, 3 times a day. An available long-acting formulation of octreotide called Sandostatin LAR allows for once monthly intragluteal administration. The starting dose of Sandostatin LAR is 10-20 mg per month. The dose can subsequently be titrated up to a maximum of 40 mg monthly. Diarrhea recurs when Sandostatin treatment is discontinued. It is currently debated whether somatostatin analogues also diminish tumor size.   
  • Long-term octreotide treatment frequently results in gradual resistance to this therapy. When maximum tolerable doses of octreotide are unable to control symptoms, interferon alpha may be added to control diarrhea, with a possible modest reduction in tumor size. 
  • Glucocorticoids are less effective but less expensive, reducing symptoms in approximately 50% of patients.
  • Preoperative treatment with a proton pump inhibitor is advisable to prevent rebound gastric acid hypersecretion after surgical tumor removal. 
  • Systemic chemotherapy may be needed in cases of unresectable or progressive disease. Streptozocin, doxorubicin, or fluorouracil, or a combination of these, appears to be beneficial, although the number of treated cases has been limited.
  • The use of radiolabeled octreotide to target radiation treatment to VIPoma is based on the affinity of octreotide to the somatostatin receptors on the VIPoma cells. In one trial, half of the patients achieved stabilization of previously progressive tumors, with minimal bone marrow toxicity. This therapeutic approach is still considered experimental.

Surgical Care

  • After appropriate fluid and electrolyte replacement, all operable patients with apparently resectable disease should receive abdominal exploration with careful staging. Intraoperative ultrasonography of the pancreas may aid in locating an otherwise unidentified tumor. For patients without nodal or distant metastasis, complete surgical resection offers the only chance for a cure.
    • Local tumor resection is the treatment of choice.7,12,13,14
    • Pancreatoduodenectomy is indicated when the tumor is in the pancreatic head or processus uncinatus.
  • If no tumor is found at surgery, a blind pancreatic tail resection may be performed. A total pancreatectomy no longer is recommended.
  • In most cases, metastatic disease is found at the time of diagnosis. For these patients, tumor debulking may reduce clinical symptoms,7,14 but surgical plans ought to include resection of more than 90% of tumor volume for substantial clinical benefit.
    • Postoperative octreotide therapy will usually be needed indefinitely to control symptoms of vasoactive intestinal polypeptide (VIP) hypersecretion from residual tumor.13
    • Unresectable liver metastases may be treated with bland hepatic artery embolization or transcatheter chemoembolization with doxorubicin or cisplatin.15
    • When embolization is unsuccessful or not feasible for liver metastases, percutaneous or intraoperative radiofrequency tumor ablation may be attempted, although this is not ideal for large metastatic tumors. 
  • All patients having surgery should undergo a cholecystectomy to alleviate concerns of gallstones with somatostatin analogue therapy in case such therapy may be needed in the future. 
  • Orthotopic liver transplantation has been performed in a small number of select patients with pancreatic endocrine tumors; the 5-year survival rate has been approximately 50%.16

Consultations

  • Consultation with an endocrinologist is indicated, particularly in MEN 1 or other polyhormonal secretion states or if long-term hormonal suppression is required.
  • Consultation with a gastroenterologist may be indicated for evaluation of long-term diarrhea or for colonoscopy evaluation for villous adenoma.
  • Consultation with a surgeon who is experienced in pancreatic surgery may be indicated if the evaluation suggests a resectable or debulkable tumor or if exploratory surgery is contemplated.

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Somatostatin analogs

These agents may control diarrheal symptoms in as many as 80% of patients with unresectable or metastatic tumors. High-dose treatment may lead to additional, antiproliferative effects. However, the long-term application of somatostatin may down-regulate receptor expression levels, resulting in decreased efficiency despite increasing doses. Short-acting and long-acting depot preparations are available.


Octreotide acetate (Sandostatin)

Acts similarly to the natural hormone somatostatin and has the ability to suppress the secretion of gastroenteropancreatic peptides, including VIP. Start with small doses in patients with VIPomas.

Adult

150-300 mcg/24 h SC divided bid/qid (range 150-750 mcg) during initial 2 wk; adjust dose to individual; doses >450 mcg usually not required; LAR long-acting preparation can be used intragluteally once/mo with initial dose of 10-20 mg to maximum of 40 mg monthly; long-acting preparation not for IV/SC administration

Pediatric

Not established

Associated with alterations in nutrient absorption; carefully consider effect on any PO drug

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Dosage adjustments may be required to control symptoms; patients may develop hypoglycemia or hyperglycemia due to alterations in balance between counter regulatory hormones; baseline and periodic thyroid function tests advised; gallstones may develop; half-life may be increased in patients with renal failure

Glucocorticoids

Glucocorticoids, which elicit anti-inflammatory properties and cause profound and varied metabolic effects, modify the body's immune response to diverse stimuli. These agents are less effective but are also less expensive; they reduce symptoms in approximately 50% of patients.


Prednisone (Deltasone, Meticorten, Orasone)

Immunosuppressant for the treatment of autoimmune disorders. Prednisone may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. It stabilizes lysosomal membranes and also suppresses lymphocytes and antibody production.

Adult

30-50 mg/d PO qd; gradually taper dose following resolution of symptoms

Pediatric

Disease rarely occurs in children

Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, and fungal or tubercular skin infections; GI disease

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

More on VIPomas

Overview: VIPomas
Differential Diagnoses & Workup: VIPomas
Treatment & Medication: VIPomas
Follow-up: VIPomas
Multimedia: VIPomas
References
Further Reading
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References

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  2. Said SI, Mutt V. Polypeptide with broad biological activity: isolation from small intestine. Science. Sep 18 1970;169(951):1217-8. [Medline].

  3. Aton SJ, Colwell CS, Harmar AJ, et al. Vasoactive intestinal polypeptide mediates circadian rhythmicity and synchrony in mammalian clock neurons. Nat Neurosci. Apr 2005;8(4):476-83. [Medline]. [Full Text].

  4. Doherty GM. Rare endocrine tumours of the GI tract. Best Pract Res Clin Gastroenterol. Oct 2005;19(5):807-17. [Medline].

  5. Ayub A, Zafar M, Abdulkareem A, et al. Primary hepatic vipoma. Am J Gastroenterol. Jun 1993;88(6):958-61. [Medline].

  6. Grier JF. WDHA (watery diarrhea, hypokalemia, achlorhydria) syndrome: clinical features, diagnosis, and treatment. South Med J. Jan 1995;88(1):22-4. [Medline].

  7. Peng SY, Li JT, Liu YB, et al. Diagnosis and treatment of VIPoma in China: (case report and 31 cases review) diagnosis and treatment of VIPoma. Pancreas. Jan 2004;28(1):93-7. [Medline].

  8. de Herder WW. Biochemistry of neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab. Mar 2007;21(1):33-41. [Medline].

  9. Sofka CM, Semelka RC, Marcos HB, et al. MR imaging of metastatic pancreatic VIPoma. Magn Reson Imaging. 1997;15(10):1205-8. [Medline].

  10. Schillaci O, Corleto VD, Annibale B, et al. Single photon emission computed tomography procedure improves accuracy of somatostatin receptor scintigraphy in gastro-entero pancreatic tumours. Ital J Gastroenterol Hepatol. Oct 1999;31 Suppl 2:S186-9. [Medline].

  11. Cesani F, Ernst R, Walser E, et al. Tc-99m sestamibi imaging of a pancreatic VIPoma and parathyroid adenoma in a patient with multiple type I endocrine neoplasia. Clin Nucl Med. Jun 1994;19(6):532-4. [Medline].

  12. Ruiz-Tovar J, Priego P, Martínez-Molina E, et al. Pancreatic neuroendocrine tumours. Clin Transl Oncol. Aug 2008;10(8):493-7. [Medline].

  13. Ghaferi AA, Chojnacki KA, Long WD, et al. Pancreatic VIPomas: subject review and one institutional experience. J Gastrointest Surg. Feb 2008;12(2):382-93. [Medline].

  14. Akerstrom G, Hellman P. Surgery on neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab. Mar 2007;21(1):87-109. [Medline].

  15. King J, Quinn R, Glenn DM, et al. Radioembolization with selective internal radiation microspheres for neuroendocrine liver metastases. Cancer. Sep 1 2008;113(5):921-9. [Medline].

  16. Bramley PN, Lodge JP, Losowsky MS, et al. Treatment of metastatic Vipoma by liver transplantation. Clin Transplant. Oct 1990;4(5 part 1):276-8; discussion 279. [Medline].

  17. Soga J, Yakuwa Y. Vipoma/diarrheogenic syndrome: a statistical evaluation of 241 reported cases. J Exp Clin Cancer Res. Dec 1998;17(4):389-400. [Medline].

  18. Cellier C, Yaghi C, Cuillerier E, et al. Metastatic jejunal VIPoma: beneficial effect of combination therapy with interferon-alpha and 5-fluorouracil. Am J Gastroenterol. Jan 2000;95(1):289-93. [Medline].

  19. Jensen RT. Pancreatic endocrine tumors: recent advances. Ann Oncol. 1999;10 Suppl 4:170-6. [Medline].

  20. Mansour JC, Chen H. Pancreatic endocrine tumors. J Surg Res. Jul 2004;120(1):139-61. [Medline].

  21. Marks IN, Bank S, Louw JH. Islet cell tumor of the pancreas with reversible watery diarrhea and achlorhydria. Gastroenterology. Apr 1967;52(4):695-708. [Medline].

  22. Remme CA, de Groot GH, Schrijver G. Diagnosis and treatment of VIPoma in a female patient. Eur J Gastroenterol Hepatol. Jan 2006;18(1):93-9. [Medline].

  23. Robichon A, Marie JC. Selective photolabeling of high and low affinity binding sites for vasoactive intestinal peptide (VIP): evidence for two classes of covalent VIP-receptor complexes in intestinal cell membranes. Endocrinology. Mar 1987;120(3):978-85. [Medline].

  24. Shan L, Nakamura Y, Nakamura M, et al. Somatic mutations of multiple endocrine neoplasia type 1 gene in the sporadic endocrine tumors. Lab Invest. Apr 1998;78(4):471-5. [Medline].

  25. Swift PG, Bloom SR, Harris F. Watery diarrhoea and ganglioneuroma with secretion of vasoactive intestinal peptide. Arch Dis Child. Nov 1975;50(11):896-9. [Medline]. [Full Text].

  26. Tennvall J, Ljungberg O, Ahren B, et al. Radiotherapy for unresectable endocrine pancreatic carcinomas. Eur J Surg Oncol. Feb 1992;18(1):73-6. [Medline].

  27. Verner JV, Morrison AB. Endocrine pancreatic islet disease with diarrhea. Report of a case due to diffuse hyperplasia of nonbeta islet tissue with a review of 54 additional cases. Arch Intern Med. Mar 1974;133(3):492-9. [Medline].

  28. Virgolini I, Kurtaran A, Leimer M, et al. Location of a VIPoma by iodine-123-vasoactive intestinal peptide scintigraphy. J Nucl Med. Sep 1998;39(9):1575-9. [Medline]. [Full Text].

  29. Warner RR. Enteroendocrine tumors other than carcinoid: a review of clinically significant advances. Gastroenterology. May 2005;128(6):1668-84. [Medline].

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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

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Contributor Information and Disclosures

Author

Daniel S Tung, MD, Fellow in Endocrinology, Department of Internal Medicine, Baylor College of Medicine
Daniel S Tung, MD is a member of the following medical societies: American Association of Clinical Endocrinologists and American Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Sai-Ching Jim Yeung, MD, PhD, FACP, Deputy Section Chief of Emergency Care, Assistant Professor, Department of General Internal Medicine, Ambulatory Treatment and Emergency Care, University of Texas MD Anderson Cancer Center
Sai-Ching Jim Yeung, MD, PhD, FACP is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Medical Association, American Thyroid Association, and Endocrine Society
Disclosure: Nothing to disclose.

Klaus Radebold, MD, PhD, Research Associate, Department of Surgery, Yale University School of Medicine
Klaus Radebold, MD, PhD is a member of the following medical societies: American Gastroenterological Association and New York Academy of Sciences
Disclosure: Nothing to disclose.

Medical Editor

Frederick H Ziel, MD, Associate Professor of Medicine, David Geffen School of Medicine at UCLA; Physician-In-Charge, Endocrinology/Diabetes Center, Director of Medical Education, Kaiser Permanente Woodland Hills; Chair of Endocrinology, Co-Chair of Diabetes Complete Care Program, Southern California Permanente Medical Group
Frederick H Ziel, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Federation for Medical Research, American Medical Association, American Society for Bone and Mineral Research, California Medical Association, Endocrine Society, and International Society for Clinical Densitometry
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS, Professor of Medicine (Endocrinology, Adj), Johns Hopkins School of Medicine; Affiliate Research Professor, Bioinformatics and Computational Biology Program, School of Computational Sciences, George Mason University; Principal, C/A Informatics, LLC
Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Nutrition, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Informatics Association, American Society for Bone and Mineral Research, American Society of Law Medicine and Ethics, Endocrine Society, and International Society for Clinical Densitometry
Disclosure: Nothing to disclose.

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor of Medicine, St Louis University School of Medicine
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
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