Zollinger-Ellison syndrome

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Last reviewed: 7 Apr 2025

Last updated: 25 Jul 2024

Zollinger-Ellison syndrome (ZES) is a condition caused by gastrin-producing neuroendocrine tumor that causes gastric acid hypersecretion and peptic ulcer disease.

Can be sporadic or associated with multiple endocrine neoplasia syndrome type 1.

Common presentation includes refractory peptic ulcer disease, abdominal pain, diarrhea, and gastroesophageal disease.

The main goal of treatment is control of gastric hypersecretion with proton-pump inhibitors.

The most common cause of morbidity and mortality is metastatic gastrinoma.

Definition

Zollinger-Ellison syndrome is a condition caused by a gastrin-secreting tumor that causes hypersecretion of gastric acid leading to ulcer disease. It most commonly presents with abdominal pain (70% to 100% of patients), diarrhea (37% to 73% of patients), and gastroesophageal reflux disease (44% of patients). Less common presentations include weight loss, gastrointestinal bleeding, nausea, and vomiting.[1][2]

History and exam

Key diagnostic factors

refractory or recurrent peptic ulcer disease
diarrhea

Full details

Other diagnostic factors

epigastric abdominal pain
gastroesophageal reflux disease
steatorrhea
gastrointestinal bleed
bone pain

Full details

Risk factors

multiple endocrine neoplasia type 1 (MEN1)

Full details

Diagnostic tests

1st tests to order

fasting serum gastrin
gastric pH

Full details

Tests to consider

secretin stimulation test
calcium infusion test
glucagon test
abdominal CT scan
abdominal MRI scan
somatostatin receptor scintigraphy (SRS)
gallium(Ga)-68 DOTATATE PET
endoscopic ultrasound (EUS)
esophagogastroduodenoscopy (EGD)
chest CT
genetic testing for multiple endocrine neoplasia type 1 (MEN1)

Full details

Treatment algorithm

ACUTE

localized disease: sporadic

localized disease: MEN1

metastatic disease: predominantly hepatic

metastatic disease: extrahepatic

Contributors

Authors

Joseph R. Pisegna, MD

Professor of Medicine

Chief

Division of Gastroenterology, Hepatology, and Parenteral Nutrition

David Geffen School of Medicine at University of California

VA Greater Los Angeles Healthcare System

Department of Veterans Affairs

Los Angeles

Disclosures

JRP is an author of a number of references cited in this topic. JRP is a Speaker for Phathom Pharmaceuticals.

Acknowledgements

Dr Joseph R. Pisegna would like to gratefully acknowledge Dr Deepinder Goyal, Dr Jihane Benhammou, Dr David Oh, and Dr Hank Wang, previous contributors to this topic.

Disclosures

DG, JB, DO, and HW declare that they have no competing interests.

Peer reviewers

Peter Draganov, MD

Associate Professor of Medicine Division

Gastroenterology, Hepatology and Nutrition

University of Florida

Gainesville

Disclosures

PD declares that he has no competing interests.

Petros Perros, BSc, MBBS, MD, FRCP

Consultant Endocrinologist

Freeman Hospital

Newcastle-Upon-Tyne Hospitals Trust

Disclosures

PP declares that he has no competing interests.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

Falconi M, Eriksson B, Kaltsas G, et al. ENETS consensus guidelines update for the management of patients with functional pancreatic neuroendocrine tumors and non-functional pancreatic neuroendocrine tumors. Neuroendocrinology. 2016;103(2):153-71.Full text Abstract

National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: neuroendocrine and adrenal tumors [internet publication].Full text

Kunz PL, Reidy-Lagunes D, Anthony LB, et al. Consensus guidelines for the management and treatment of neuroendocrine tumors. Pancreas. 2013 May;42(4):557-77.Full text Abstract

Pavel M, Öberg K, Falconi M, et al. Gastroenteropancreatic neuroendocrine neoplasms: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020 Jul;31(7):844-60.Full text Abstract

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials
- Atrophic gastritis
- Peptic ulcer disease from Helicobacter pylori infection
- Idiopathic gastric hypersecretion
More Differentials
Guidelines
- NCCN clinical practice guidelines in oncology: neuroendocrine and adrenal tumors
- Clinical practice update on management of subepithelial lesions encountered during routine endoscopy: expert review
More Guidelines
Patient information
Pancreatic cancer
Peptic ulcers
More Patient information
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Zollinger-Ellison syndrome

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic tests

1st tests to order

Tests to consider

Treatment algorithm

localized disease: sporadic

localized disease: MEN1

metastatic disease: predominantly hepatic

metastatic disease: extrahepatic

Contributors

Authors

Joseph R. Pisegna, MD

Disclosures

Acknowledgements

Disclosures

Peer reviewers

Peter Draganov, MD

Disclosures

Petros Perros, BSc, MBBS, MD, FRCP

Disclosures

References

Key articles

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials

Guidelines

Patient information

Log in or subscribe to access all of BMJ Best Practice

Log in or subscribe to access all of BMJ Best Practice

Log in to access all of BMJ Best Practice