Zollinger-Ellison syndrome (ZES) is a disease consisting of a clinical triad of gastric acid hypersecretion, severe PUD, and gastrin-producing neuroendocrine tumors (NETs; gastrinomas). It derives its name from the the American surgeons, Robert Zollinger and Edwin Ellison, who first described it in 1955.


  • Gastrinoma
    • Islet cell tumor
    • Functional neuroendocrine tumor
  • Multiple endocrine neoplasia (MEN) type 1


  • Abdominal pain (most common)
  • Peptic ulcer disease
  • GERD
  • Diarrhea
  • ± Weight loss
  • ± Steatorrhea
  • ± Esophagitis


  • Elevated fasting gastrin levels  (> 200 pg/mL)
  • Secretin-stimulated gastrin level
    • Generally not required to establish diagnosis because fasting gastrin levels are high
    • Most sensitive diagnostic test
    • +: increase in serum gastrin level > 200 pg/mL above basal levels


  • Endoscopy
    • Findings: prominent rugal folds


  • High-dose PPI
  • Localization and staging of the tumor
    • Triple-phase abdominal CT 
    • Abdominal MRI
    • If initial imaging is undiagnosed, localization can sometime be achieved using somatostatin receptor scintigraphy or endoscopic US (EUS)
    • If all above options to not localize tumor, surgical exploration can be considered
  • Localized gastrinoma → tumor resected with at least 10 LNs

Relevant Information

  • Most ZES gastrinomas are located in the duodenum or pancreas within the “gastrinoma triangle” → cystic-common bile duct junction, pancreas body-neck junction, junction between second and third portions of the duodenum


  • Bleeding
  • Perforation 

Differential Diagnoses

  • Vagotomy
  • Peptic ulcer disease secondary to H. pylori infection or NSAID use
  • Gastric outlet obstruction
  • Renal insufficiency
  • Short bowel syndrome
  • Autoimmune gastritis