Pediatric VIPoma 

  • Author: Robert J Ferry Jr, MD; Chief Editor: Stephen Kemp, MD, PhD   more...
 
Updated: Aug 11, 2010
 

Background

In 1958, Verner and Morrison described a syndrome of watery diarrhea, hypokalemia, and achlorhydria (WDHA).[1] Said and Nutt extracted the responsible hormone in 1970 from animal gut. In 1975, Swift et al was the first to report a child who had watery diarrhea and a ganglioneuroma with secretion of vasoactive intestinal peptide (VIP).[2]

VIPomas originate in amine precursor uptake and decarboxylation (APUD) cells of the gastroenteropancreatic endocrine system and in adrenal or extra-adrenal neurogenic sites. Neural crest cells are precursors of APUDoma and neurogenic cells.

VIPomas in adults commonly originate in the pancreas but extremely rarely originate in the pancreas of affected children. Instead, WDHA syndrome is usually associated with VIP-secreting neurogenic tumors involving the retroperitoneum and mediastinum in children. Pancreatic non–beta-cell hyperplasia is rare, but has been reported in children. Clinical experience is based mainly on case reports (about 85 cases prior to 2005).

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Pathophysiology

VIPomas in adults are usually neuroendocrine islet cell tumors of the pancreas that produce high amounts of VIP. Other secreted hormones may include secreted gastrin and pancreatic polypeptide.

In children and adolescents, VIP is produced mainly by ganglioneuromas, ganglioneuroblastomas, neurofibromas, or other tumors in the adrenal area (most common location). Only a small fraction of neuroblastomas and ganglioneuroblastomas produce VIP, but VIP production indicates a more favorable prognosis.

Ganglioneuromatosis that affects the entire colon and rectum has been reported in a 7-year-old boy.[3] In contrast to individuals with VIP-secreting pancreatic tumors, patients with neurogenic lesions generally have normal serum levels of pancreatic polypeptide, gastrin, insulin, and somatostatin.

VIP, a 28-aminoacid neuropeptide, is expressed in neurons of the GI, respiratory, and urogenital tracts, as well as in the CNS (ie, hypothalamus, hippocampus, cortex).

Physiological actions of VIP include relaxation of vascular and nonvascular smooth muscles and escalation of gut secretions.

VIP is a potent stimulator of adenosine 3',5'-cyclic phosphate (cAMP) production by the gut. Thus, overproduction leads to massive secretion of water and electrolytes, mainly potassium.

Other important VIP effects include stimulation of alkaline pancreatic juice secretion and lipolysis and glycogenolysis, and inhibition of histamine release and pentagastrin-stimulated acid secretion.

VIPomas can be part of multiple endocrine neoplasia (MEN) type 1 syndrome. This relationship has not been observed with extrapancreatic VIP-secreting tumors of childhood.

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Epidemiology

Frequency

United States

No data are available for incidence in children. Annually, 0.05-0.2 new cases per million adults have been reported. VIPomas are the third most common neuroendocrine tumor of the pancreas (15%), after insulinomas (50%) and gastrinomas (30%).

Mortality/Morbidity

Death may result from renal failure or cardiac arrest caused by volume depletion and acidosis.

Sex

Male-to-female ratio in children is approximately 1:1, compared with 1:3 in adults.

Age

In a series of 19 childhood cases, the mean age of onset was 2.5 years.[4] In another series of 10 cases, the mean age of onset was 4 years. The earliest age of onset ever reported is 2 weeks.

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Contributor Information and Disclosures
Author

Robert J Ferry Jr, MD  Professor and Chief, Division of Pediatric Endocrinology and Metabolism, Department of Pediatrics, University of Tennessee Health Science Center; Brigade Surgeon, 36th Sustainment Brigade, US Army; Adjunct Professor, Pediatric Surgery Department, King Saud University, Saudi Arabia

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: Nutropin Speakers Bureau Honoraria Speaking and teaching; Genotropin Speakers Bureau Honoraria Speaking and teaching; Eli Lilly & Co. Grant/research funds Investigator; MacroGenics, Inc. Grant/research funds Investigator; Ipsen, S.A. (formerly Tercica, Inc.) Grant/research funds Investigator; NovoNordisk SA Grant/research funds Investigator; Diamyd Investigator

Coauthor(s)

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.

Specialty Editor Board

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, Endocrine Society, Florida Pediatric Society, Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

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.

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, Endocrine Society, Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Pfizer Grant/research funds P.I.; Tercica Grant/research funds Other; Eli Lily Grant/research funds PI; NovoNordisk Grant/research funds PI

Merrily P M Poth, MD  Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences

Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

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, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

References

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