Primary Pancreatic Secretinoma: Further Evidence Supporting Secretin as a Diarrheogenic Hormone

Ann Surg. 2017 Aug;266(2):346-352. doi: 10.1097/SLA.0000000000001938.


Objectives: To document the existence of primary pancreatic secretinoma in patients with watery diarrhea syndrome (WDS) and achlorhydria and establish secretin as a diarrheogenic hormone.

Background: Vasoactive intestinal peptide (VIP) has been widely accepted as the main mediator of WDS. However, in 1968, Zollinger et al reported 2 female patients with pancreatic neuroendocrine tumors, WDS, and achlorhydria. During surgery on the first, a 24-year-old patient, they noticed distended duodenum filled with fluid and a dilated gallbladder containing dilute bile with high bicarbonate concentration. After excision of the tumor, WDS ceased and gastric acid secretion returned. The second, a 47-year-old, patient's metastatic tumor extract given intravenously in dogs, produced significantly increased pancreatic and biliary fluid rich in bicarbonate. They suggested a secretin-like hormone of islet cell origin explains WDS and achlorhydria. These observations, however, predated radioimmunoassay, immunohistochemical staining, and other molecular studies.

Methods: The first patient's tumor tissue was investigated for secretin and VIP. Using both immunohistochemistry and laser microdissection and pressure catapulting technique for RNA isolation and subsequent reverse transcription polymerase chain reaction, the expression levels of secretin, and VIP were measured.

Results: Immunoreactive secretin and its mRNA were predominantly found in the tumor tissue whereas VIP and its mRNA were scarce.

Conclusions: The findings strongly support that the WDS and achlorhydria in this patient may have been caused by secretin as originally proposed in 1968 and that secretin may act as a diarrheogenic hormone.

MeSH terms

  • Adult
  • Bicarbonates / metabolism
  • Body Water / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Intestinal Mucosa / metabolism
  • Intestine, Small / metabolism
  • Laser Capture Microdissection
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / metabolism*
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Secretin / analysis
  • Secretin / metabolism*
  • Vipoma / metabolism*


  • Bicarbonates
  • RNA, Messenger
  • Secretin