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VIPomas Workup

  • Author: Sai-Ching Jim Yeung, MD, PhD, FACP; Chief Editor: George T Griffing, MD  more...
 
Updated: Jun 02, 2014
 

Approach Considerations

Plasma vasoactive intestinal peptide (VIP) levels are determined by radioimmunoassay. In cases of VIPoma, VIP levels are usually 2-10 times the normal range (20-30 pmol/L). VIP levels must be determined when the patient is symptomatic because VIP release from the tumor fluctuates.

Imaging studies focus primarily on the pancreas, where 90% of VIPomas are located. Tumor localization normally is not difficult, because at the time of diagnosis, these tumors are generally larger than 3 cm in their longest dimension. Computed tomography (CT), magnetic resonance imaging (MRI), and somatostatin receptor scintigraphy are imaging modalities that can be used in the diagnosis of VIPoma. Reports have demonstrated successful VIPoma localization with99m Tc sestamibi.[15]

No formal staging criteria for VIPoma have been generally accepted. Metastasis most often occurs to the liver or regional lymph nodes. Rarely, metastasis to skin has been reported.

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Laboratory Studies

A diagnosis of VIPoma is made when watery diarrhea, hypokalemia, and achlorhydria are present in the setting of elevated serum VIP concentrations. Stool volumes of less than 700 mL/day virtually exclude the diagnosis; typical stool volumes in the presence of a VIPoma exceed 3 L/day.

A normal plasma VIP level is 20-30 pmol/L or less, as determined by radioimmunoassay. VIP levels in patients with VIPoma often reach 160-250 pmol/L or higher. VIP levels should be drawn after fasting.[16] Because VIP is degraded rapidly, a protease inhibitor, such as aprotinin, is added to the blood sample, which must be kept frozen at −70°C until processed. Because VIP secretion from the tumor may be episodic, serum VIP levels should be collected during bouts of severe diarrhea.

Hypokalemia and non–anion gap acidosis are the main diagnostic features of VIPomas. Hypokalemia may necessitate aggressive potassium replacement.

Hypercalcemia may occur in the absence of multiple endocrine neoplasia (MEN) type 1 syndrome or elevated parathyroid hormone levels. The mechanism of action is not clear but is believed to involve increased bone resorption. The dehydration from severe diarrhea certainly may exacerbate the hypercalcemia.

Hyperglycemia may be caused by the direct glycogenolytic effect of VIP on the liver and by the inhibitory effect of hypokalemia on pancreatic islet cell insulin release.

Hypochlorhydria or achlorhydria is seen in at least 75% of patients with VIPoma because VIP inhibits histamine- and pentagastrin-stimulated gastric acid secretion. This abnormality can be evaluated by measuring gastric pH or basal gastric acid output.

Renal function should be assessed by measuring blood urea nitrogen (BUN) and serum creatinine levels. Other electrolytes, including magnesium, should be checked and replaced. Stool weight with potassium measurements verifies high gastrointestinal (GI) potassium losses.

VIPomas may cosecrete other hormones, including pancreatic polypeptide, calcitonin, and neurotensin.

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Computed Tomography

CT is indicated to search for neck, mediastinal, or retroperitoneal masses. No calcifications or bony infiltrations should be found. CT will successfully identify the primary tumor in most cases; it also assists in including or excluding liver metastasis.

In a series of 31 patients from China, Peng et al reported that CT successfully identified all VIPomas in the pancreatic body and tail but only 71% of VIPomas in the pancreatic head.[14]

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Magnetic Resonance Imaging

MRI may be used if CT is contraindicated (eg, if the patient is allergic to iodine contrast dyes or is in a state of renal failure). VIPomas are best observed on T1-weighted, fat-suppressed images as low-signal-intensity masses. Liver metastases may demonstrate intensive peripheral ring enhancement on immediate postgadolinium spoiled gradient-echo images.[17]

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Somatostatin Receptor Scintigraphy

Somatostatin receptor scintigraphy using radionuclide-labeled octreotide (111 In-pentetreotide (ie, DTPA-D-Phe-1-octreotide),111 In-DOTA-DPhe1 -Tyr3 -octreotide), or lanreotide (111 In -DOTA-lanreotide) may be useful for characterizing an abnormality found on a CT scan or for identifying occult or distant metastatic disease. It may also be used if postoperative changes diminish the clarity of a CT scan. Sensitivity for localization of all pancreatic endocrine tumors has been reported at 80-90%, with 92% sensitivity for tumors larger than 1 cm.

Other previously employed techniques include technetium-99m scintigraphy, 123-iodine-VIP receptor scintigraphy, and single-photon emission CT (SPECT). Investigations have suggested that in the future, the use of SPECT scanning may improve the value of somatostatin receptor scintigraphy for the localization of neuroendocrine tumors, including VIPomas.[18]

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Other Studies

18 F-deoxyglucose (FDG)-PET scan has also been used to diagnose neuroendocrine tumors. However, it may not be as sensitive as somatostatin receptor scintigraphy.[19]

Chest radiography may reveal a paravertebral mass. Endoscopic retrograde cholangiopancreatography may demonstrate occlusion of the major pancreatic duct. It may also reveal calcifications in the body of the pancreas. Transabdominal ultrasonography may be used for early screening to exclude liver metastases, which may be present as hepatic calcifications.

Electrocardiography may reveal QRS widening and T-wave flattening if hypokalemia is severe. Colonoscopy may be useful as a means of evaluating for a villous adenoma as an alternative cause of potassium-losing diarrhea.

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Histology

VIPomas, like other pancreatic endocrine tumors, are thought to arise from the pluripotent cells in ductal epithelium. Histologic examination usually reveals, as is typical for neuroendocrine tumors, sheets of nested, uniform-appearing cells with round nuclei and a low mitotic rate.

Immunohistochemical staining is positive for chromogranin A and VIP. Under electron microscopy, neurosecretory granules may be seen clustering around Golgi complexes and the endoplasmic reticulum. Classifying a tumor as malignant or benign on the basis of microscopic appearance alone is difficult.

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Contributor Information and Disclosures
Author

Sai-Ching Jim Yeung, MD, PhD, FACP Professor of Medicine, Department of Emergency Medicine, Department of Endocrine Neoplasia and Hormonal Disorders, The 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, Endocrine Society

Disclosure: Nothing to disclose.

Coauthor(s)

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, American Medical Association

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD Professor Emeritus 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, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Acknowledgements

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 Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Informatics Association, American Society for Bone and Mineral Research, Endocrine Society, and International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

Alicia Diaz-Thomas, MD, MPH Assistant Professor of Pediatrics, University of Tennessee Health Science Center

Alicia Diaz-Thomas, MD, MPH is a member of the following medical societies: American Academy of Clinical Endocrinology, Tennessee Medical Association, and The Endocrine Society

Disclosure: Nothing to disclose.

Robert J Ferry Jr, MD Le Bonheur Chair of Excellence in Endocrinology, Professor and Chief, Division of Pediatric Endocrinology and Metabolism, Department of Pediatrics, University of Tennessee Health Science Center

Robert J Ferry Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, American Medical Association, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research, and Texas Pediatric Society

Disclosure: Eli Lilly & Co Grant/research funds Investigator; MacroGenics, Inc Grant/research funds Investigator; Ipsen, SA (formerly Tercica, Inc) Grant/research funds Investigator; NovoNordisk SA Grant/research funds Investigator; Diamyd Grant/research funds Investigator; Bristol-Myers-Squibb Grant/research funds Other; Amylin Other; Pfizer Grant/research funds Other; Takeda Grant/research funds Other

Stephen Kemp, MD, PhD Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas for Medical Sciences College of Medicine, Arkansas Children's Hospital

Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Phi Beta Kappa, Southern Medical Association, Southern Society for Pediatric Research, and The Endocrine Society

Disclosure: Nothing to disclose.

Lynne Lipton Levitsky, MD Chief, Pediatric Endocrine Unit, Massachusetts General Hospital; Associate Professor of Pediatrics, Harvard Medical School

Lynne Lipton Levitsky, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Diabetes Association, American Pediatric Society, Pediatric Endocrine Society, Society for Pediatric Research, and The Endocrine Society

Disclosure: Pfizer Grant/research funds P.I.; Tercica Grant/research funds Other; Eli Lily Grant/research funds PI; NovoNordisk Grant/research funds PI; NovoNordisk Consulting fee Consulting; Onyx Heart Valve Consulting fee Consulting

Klaus Radebold, MD, PhD Former Research Associate, Department of Surgery, Yale University School of Medicine

Disclosure: Nothing to disclose.

Arlan L Rosenbloom, MD Adjunct Distinguished Service Professor Emeritus of Pediatrics, University of Florida College of Medicine; Fellow of the American Academy of Pediatrics; Fellow of the American College of Epidemiology

Arlan L Rosenbloom, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Epidemiology, American Pediatric Society, Florida Pediatric Society, Pediatric Endocrine Society, Society for Pediatric Research, and The Endocrine Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Frederick H Ziel, MD Associate Professor of Medicine, University of California, Los Angeles, David Geffen School of Medicine; 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 InternationalSociety for Clinical Densitometry

Disclosure: Nothing to disclose.

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Patient with a large VIPoma. (A) Arteriogram showing vascularity of a large VIPoma preoperatively. (B) Large mass seen intraoperatively. (C) Gross pathologic specimen. Patient subsequently developed liver metastases; he was treated with chemoembolization of liver masses multiple times and finally succumbed to disease 20 years after initial surgical treatment.
 
 
 
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