{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T21:19:53Z","timestamp":1783977593980,"version":"3.55.0"},"reference-count":45,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T00:00:00Z","timestamp":1695772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>VIPomas are a type of neuroendocrine tumor that independently produces vasoactive intestinal peptide (VIP). VIPomas causing watery diarrhea, hypokalemia, and achlorhydria (WDHA) syndrome are not frequently observed in adult patients without pancreatic ailments. However, in children, the occurrence of a VIPoma originating in the pancreas is exceedingly uncommon. Instead, WDHA syndrome is more commonly associated with neurogenic tumors that secrete VIP, often located in the retroperitoneum or mediastinum. Among infants, chronic diarrhea is a prevalent issue that often necessitates the attention of pediatric gastroenterologists. The underlying causes are diverse, and delays in arriving at a definitive diagnosis can give rise to complications affecting the overall well-being of the child. The authors present the case of an infant with chronic watery diarrhea, subocclusion manifestations, mild hypokalemia, and metabolic hyperchloremic acidosis secondary to a VIPoma in the retroperitoneum that was diagnosed via abdominal ultrasound and tomography. The laboratory results revealed lowered potassium levels and an excessive secretion of VIP. Following the surgical removal of the tumor, the diarrhea resolved, and both electrolyte levels and the imbalanced hormone levels returned to normal. Immunohistochemical examination confirmed the diagnosis of ganglioneuroblastoma, with N-MYC negative on molecular biology tests. We present the clinical and histo-genetic aspects of this rare clinical entity, with a literature review.<\/jats:p>","DOI":"10.3390\/life13101974","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T01:42:12Z","timestamp":1695865332000},"page":"1974","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Chronic Diarrhea Caused by Vasoactive Intestinal Peptide-Secreting Tumor"],"prefix":"10.3390","volume":"13","author":[{"given":"Oana","family":"Belei","sequence":"first","affiliation":[{"name":"First Pediatric Clinic, Disturbances of Growth and Development on Children Research Center, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"},{"name":"Third Pediatric Clinic, \u201cLouis \u021aurcanu\u201d Emergency Hospital for Children, 300011 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4599-0912","authenticated-orcid":false,"given":"Diana-Georgiana","family":"Basaca","sequence":"additional","affiliation":[{"name":"First Pediatric Clinic, Disturbances of Growth and Development on Children Research Center, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"},{"name":"Third Pediatric Clinic, \u201cLouis \u021aurcanu\u201d Emergency Hospital for Children, 300011 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena Rodica","family":"Heredea","sequence":"additional","affiliation":[{"name":"Department of Pathology, \u201cLouis \u0162urcanu\u201d Emergency Hospital for Children, 300011 Timi\u0219oara, Romania"},{"name":"Department of Clinical Practical Skills, \u201cVictor Babe\u015f\u201d University of Medicine and Pharmacy, 300041 Timi\u015foara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5863-6613","authenticated-orcid":false,"given":"Emil Radu","family":"Iacob","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Olariu","sequence":"additional","affiliation":[{"name":"Third Pediatric Clinic, \u201cLouis \u021aurcanu\u201d Emergency Hospital for Children, 300011 Timi\u0219oara, Romania"},{"name":"First Pediatric Clinic, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana","family":"Folescu","sequence":"additional","affiliation":[{"name":"Department of Balneology, Medical Recovery, and Rheumatology, Family Medicine Discipline, Center for Preventive Medicine, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7090-7677","authenticated-orcid":false,"given":"Andrei Gheorghe Marius","family":"Motoc","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Embryology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anda-Maria","family":"Nanu","sequence":"additional","affiliation":[{"name":"Third Pediatric Clinic, \u201cLouis \u021aurcanu\u201d Emergency Hospital for Children, 300011 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otilia","family":"M\u0103rginean","sequence":"additional","affiliation":[{"name":"First Pediatric Clinic, Disturbances of Growth and Development on Children Research Center, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"},{"name":"Third Pediatric Clinic, \u201cLouis \u021aurcanu\u201d Emergency Hospital for Children, 300011 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/0002-9343(58)90075-5","article-title":"Islet Cell Tumor and a Syndrome of Refractory Watery Diarrhea and Hypokalemia","volume":"25","author":"Verner","year":"1958","journal-title":"Am. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.beem.2015.10.004","article-title":"A Short History of Neuroendocrine Tumours and Their Peptide Hormones","volume":"30","author":"Rehfeld","year":"2016","journal-title":"Best. Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1097\/MPA.0b013e31828e34a4","article-title":"Consensus Guidelines for the Management and Treatment of Neuroendocrine Tumors","volume":"42","author":"Kunz","year":"2013","journal-title":"Pancreas"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"561019","DOI":"10.3389\/fped.2020.00430","article-title":"Rare Cases of Pediatric Vasoactive Intestinal Peptide Secreting Tumor with Literature Review: A Challenging Etiology of Chronic Diarrhea","volume":"8","author":"Yeh","year":"2020","journal-title":"Front. Pediatr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3564","DOI":"10.1210\/jc.2016-2051","article-title":"Pancreatic Neuroendocrine Tumor Secreting Vasoactive Intestinal Peptide and Dopamine with Pulmonary Emboli: A Case Report","volume":"101","author":"Nilubol","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1080\/21548331.2016.1210474","article-title":"Pancreatic Neuroendocrine Tumors: Contemporary Diagnosis and Management","volume":"44","author":"Parbhu","year":"2016","journal-title":"Hosp. Pract."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.soc.2015.12.003","article-title":"Clinical Presentation and Diagnosis of Pancreatic Neuroendocrine Tumors","volume":"25","author":"Anderson","year":"2016","journal-title":"Surg. Oncol. Clin. N. Am."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"R423","DOI":"10.1530\/ERC-16-0200","article-title":"Medical Management of Secretory Syndromes Related to Gastroenteropancreatic Neuroendocrine Tumours","volume":"23","author":"Dimitriadis","year":"2016","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_9","first-page":"938325","article-title":"Vasoactive Intestinal Peptide Tumor","volume":"2009","author":"Natanzi","year":"2009","journal-title":"Sch. Res. Exch."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"158","DOI":"10.5152\/TJAR.2017.22220","article-title":"Paediatric VIPoma: A Jamboree of Electrolytes","volume":"46","author":"Rastogi","year":"2018","journal-title":"Turk. J. Anaesthesiol. Reanim."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e11","DOI":"10.1097\/MPG.0b013e318253d3c7","article-title":"Intractable Diarrhea and a Paravertebral Mass","volume":"57","author":"Kargl","year":"2013","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1055\/s-2004-44901","article-title":"Der VIP-Produzierende Tumor in Der P\u00e4diatrie Als Differenzialdiagnose Der Protrahierten Diarrh\u00f6","volume":"216","author":"Reindl","year":"2004","journal-title":"Klin. Padiatr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1097\/MPA.0000000000001347","article-title":"Diagnostic and Management Challenges in Vasoactive Intestinal Peptide Secreting Tumors: A Series of 15 Patients","volume":"48","author":"Angelousi","year":"2019","journal-title":"Pancreas"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1542\/pir.26-1-5","article-title":"Chronic Diarrhea","volume":"26","author":"Keating","year":"2005","journal-title":"Pediatr. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"195","DOI":"10.14740\/jmc3535","article-title":"Pancreatic VIPoma as a Differential Diagnosis in Chronic Pediatric Diarrhea: A Case Report and Review of the Literature","volume":"12","author":"Gonzalez","year":"2021","journal-title":"J. Med. Cases"},{"key":"ref_16","first-page":"229","article-title":"VIPoma: Mechanisms, Clinical Presentation, Diagnosis and Treatment (Review)","volume":"1","author":"Abdullayeva","year":"2019","journal-title":"World Acad. Sci. J."},{"key":"ref_17","first-page":"415","article-title":"Clinicopathological Data and Treatment Modalities for Pan-Creatic Vipomas: A Systematic Review","volume":"24","author":"Moris","year":"2019","journal-title":"JBUON"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"69","DOI":"10.9734\/jpri\/2021\/v33i56B33930","article-title":"Etiology, Assessment and Management of WDHA (Watery Diarrhea, Hypokalemia, and Achlorhydria) and VIPoma","volume":"33","author":"Hussein","year":"2021","journal-title":"J. Pharm. Res. Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1097\/MPA.0000000000001402","article-title":"Vasoactive Intestinal Peptide-Secreting Tumors: A Review","volume":"48","author":"Siddappa","year":"2019","journal-title":"Pancreas"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1440-1754.1988.tb01334.x","article-title":"Vasoactive Intestinal Peptide Secreting Tumours in Children: A Case Report with Literature Review","volume":"24","author":"Quak","year":"1988","journal-title":"J. Paediatr. Child. Health"},{"key":"ref_21","unstructured":"Sandhu, S., and Jialal, I. (2021). ViPoma, StatPearls Publishing."},{"key":"ref_22","unstructured":"(2023, August 29). VIPoma: Clinical Manifestations, Diagnosis, and Management\u2014UpToDate. Available online: https:\/\/www.uptodate.com\/contents\/vipoma-clinical-manifestations-diagnosis-and-management."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1016\/j.pan.2021.08.001","article-title":"Efficacy of Treatments for VIPoma: A GTE Multicentric Series","volume":"21","author":"Brugel","year":"2021","journal-title":"Pancreatology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"860","DOI":"10.36347\/sjmcr.2022.v10i09.002","article-title":"Vipoma or Pancreatic Cholera: About a Case and Literature Review","volume":"10","author":"Abdellah","year":"2022","journal-title":"Sch. J. Med. Case Rep."},{"key":"ref_25","first-page":"234","article-title":"VIP-Secreting Ganglioneuroblastoma as an Unusual Cause of Watery Diarrhoea in Childhood","volume":"4","author":"Huysentruyt","year":"2013","journal-title":"J. Med. Cases"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1136\/adc.55.12.929","article-title":"Watery Diarrhoea with a Vasoactive Intestinal Peptide-Producing Ganglioneuroblastoma","volume":"55","author":"Iida","year":"1980","journal-title":"Arch. Dis. Child."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1002\/pbc.21912","article-title":"VIP Hypersecretion as Primary or Secondary Syndrome in Neuroblastoma: A Retrospective Study by the Soci\u00e9t\u00e9 Fran\u00e7aise Des Cancers de l\u2019Enfant (SFCE)","volume":"52","author":"Bourdeaut","year":"2009","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1136\/bmj.320.7248.1524","article-title":"Lesson of the Week: Persistent Diarrhoea and Occult Vipomas in Children","volume":"320","author":"Murphy","year":"2000","journal-title":"BMJ"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1136\/adc.50.11.896","article-title":"Watery Diarrhoea and Ganglioneuroma with Secretion of Vasoactive Intestinal Peptide","volume":"50","author":"Swift","year":"1975","journal-title":"Arch. Dis. Child."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1056\/NEJMcpc0910932","article-title":"Case 13-2010\u2014An 18.5-Month-Old Girl with Watery Diarrhea and Poor Weight Gain","volume":"362","author":"LeLeiko","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jus.2011.04.006","article-title":"Ganglioneuroblastoma: Case Report and Review of the Literature","volume":"14","author":"Alessi","year":"2011","journal-title":"J. Ultrasound"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Decarolis, B., Simon, T., Krug, B., Leuschner, I., Vokuhl, C., Kaatsch, P., von Schweinitz, D., Klingebiel, T., Mueller, I., and Schweigerer, L. (2016). Treatment and Outcome of Ganglioneuroma and Ganglioneuroblastoma Intermixed. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2513-9"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/BF01949097","article-title":"Das Ganglioneuroblastom, Ein Besonderer Typus Im System Der Neurome","volume":"220","author":"Robertson","year":"1915","journal-title":"Virchows Arch. Pathol. Anat. Physiol. Klin. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1002\/(SICI)1097-0142(19990715)86:2<349::AID-CNCR20>3.0.CO;2-Y","article-title":"Terminology and Morphologic Criteria of Neuroblastic Tumors: Recommendations by the International Neuroblastoma Pathology Committee","volume":"86","author":"Shimada","year":"1999","journal-title":"Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1002\/pbc.22106","article-title":"Clinicopathological Characteristics of Ganglioneuroma and Ganglioneuroblastoma: A Report from the CCG and COG","volume":"53","author":"Okamatsu","year":"2009","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1210\/jcem-22-2-126","article-title":"Studies of Catecholamine Excretion by Children with Neural Tumors","volume":"22","author":"Voorhess","year":"1962","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/S0140-6736(73)91947-8","article-title":"Vasoactive Intestinal Peptide and Watery-Diarrhoea Syndrome","volume":"302","author":"Bloom","year":"1973","journal-title":"Lancet"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1080\/01616412.2016.1250458","article-title":"The Effects of Vasoactive Intestinal Peptide in Neurodegenerative Disorders","volume":"39","author":"Deng","year":"2017","journal-title":"Neurol. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3621","DOI":"10.1210\/en.2016-1399","article-title":"Vasoactive Intestinal Peptide Excites Gnrh Neurons in Male and Female Mice","volume":"157","author":"Piet","year":"2016","journal-title":"Endocrinology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1002\/pbc.25385","article-title":"Pediatric Reference Intervals for Plasma Free and Total Metanephrines Established with a Parametric Approach: Relevance to the Diagnosis of Neuroblastoma","volume":"62","author":"Franscini","year":"2015","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.clinbiochem.2014.04.015","article-title":"Urinary Homovanillic and Vanillylmandelic Acid in the Diagnosis of Neuroblastoma: Report from the Italian Cooperative Group for Neuroblastoma","volume":"47","author":"Barco","year":"2014","journal-title":"Clin. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"37005","DOI":"10.5812\/atr.37005","article-title":"The Serum Changes of Neuron-Specific Enolase and Intercellular Adhesion Molecule-1 in Patients with Diffuse Axonal Injury Following Progesterone Administration: A Randomized Clinical Trial","volume":"5","author":"Shahrokhi","year":"2016","journal-title":"Arch. Trauma. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1002\/jcla.21984","article-title":"Biological Variation and Reference Change Value Data for Serum Neuron-Specific Enolase in a Turkish Population","volume":"30","author":"Matyar","year":"2016","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1200\/JCO.2008.16.6785","article-title":"The International Neuroblastoma Risk Group (INRG) Classification System: An INRG Task Force Report","volume":"27","author":"Cohn","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_45","first-page":"371","article-title":"Verner-Morrison Syndrome. Literature Review","volume":"58","author":"Belei","year":"2017","journal-title":"Rom. J. Morphol. Embryol."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/10\/1974\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:00:00Z","timestamp":1760130000000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/10\/1974"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,27]]},"references-count":45,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["life13101974"],"URL":"https:\/\/doi.org\/10.3390\/life13101974","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,27]]}}}