Background

Zollinger-Ellison syndrome (ZES) is caused by a non–beta islet cell, gastrin-secreting tumor of the pancreas that stimulates the acid-secreting cells of the stomach to maximal activity, with consequent gastrointestinal mucosal ulceration.^{[1, 2, 3]}ZES may occur sporadically or as part of an autosomal dominant familial syndrome, multiple endocrine neoplasia type 1 (MEN 1). The primary tumor is usually located in the duodenum, the pancreas, and abdominal lymph nodes, but ectopic locations have also been described (eg, heart, ovary, gall bladder, liver, kidney).

Pathophysiology

The symptoms of Zollinger-Ellison syndrome (ZES) are secondary to hypergastrinemia, which causes hypertrophy of the gastric mucosa, leading to increased numbers of parietal cells and increased maximal acid output. Gastrin by itself also stimulates acid secretion, resulting in increased basal acid secretion. The large quantity of acid produced leads to gastrointestinal mucosal ulceration. It also leads to diarrhea and malabsorption.

Malabsorption in ZES usually is multifactorial, being caused by direct mucosal damage by acid, inactivation of pancreatic enzymes, and precipitation of bile salts. ZES is sporadic in 75% of patients, whereas in the other 25% it is associated with MEN 1, an autosomal dominant condition characterized by hyperparathyroidism, pancreatic endocrine tumors, and pituitary tumors.

Etiology

ZES may occur sporadically or as part of multiple endocrine neoplasia-type 1 (MEN 1).

Frequency

United States statistics

Zollinger-Ellison syndrome (ZES) occurs in approximately 0.1-1% of all patients with duodenal ulcers. Its frequency of occurrence is reported to be approximately the same as insulinoma, the most common functioning pancreatic endocrine tumor.

Race-, sex-, and age-related demographics

All races can be affected.

A slight male predominance exists, with a male-to-female ratio of 1.3:1.

The mean age of onset of ZES is 43 years; however, patients with multiple endocrine neoplasia-type 1 and ZES (MEN 1/ZES) present a decade earlier. Generally, a 5- to 7-year delay in diagnosis occurs. In a prospective study, fewer than 3% of patients were younger than 20 years, whereas 7% were older than 60 years at the time of disease onset.

International statistics

Incidence is 1-3 cases per million patients per year in Sweden, 0.5 cases per million patients per year in Ireland, and 0.1-0.2 cases per million patients per year in Denmark.

Prognosis

Prognosis is excellent in patients with Zollinger-Ellison syndrome (ZES) without metastatic disease. Early recognition generally results in more than 80% survival at 15 years.^[1]

Morbidity/mortality

In general, the morbidity and mortality of ZES is low because of improved medical and surgical management of the disease. Fewer than 5% of patients develop a complication, such as abdominal perforation, gastric outlet obstruction, or esophageal stricture.

Complications

The following complications may arise in patients with ZES:

Abdominal perforation secondary to ulceration (The duodenum and jejunum are the most common sites.)
Esophageal stricture, with reflux
Bowel obstruction
Gastrointestinal bleeding
Gastric carcinoids (especially in patients with multiple endocrine neoplasia-type 1 [MEN 1])

Clinical Presentation

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Author

Praveen K Roy, MD, MSc Clinical Assistant Professor of Medicine, University of New Mexico School of Medicine

Praveen K Roy, MD, MSc is a member of the following medical societies: Alaska State Medical Association, American Gastroenterological Association

Disclosure: Nothing to disclose.

Coauthor(s)

Sarah D Komanapalli, MBBS Resident Physician in Internal Medicine, Marshfield Clinic

Sarah D Komanapalli, MBBS is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Homayoun Shojamanesh, MD Former Fellow, Digestive Diseases Branch, National Institutes of Health

Homayoun Shojamanesh, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Showkat Bashir, MD Assistant Professor, Department of Medicine, Division of Gastroenterology, George Washington University, Washington, DC

Showkat Bashir, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Chief Editor

Philip O Katz, MD, FACP, FACG Chairman, Division of Gastroenterology, Albert Einstein Medical Center; Clinical Professor of Medicine, Jefferson Medical College of Thomas Jefferson University

Philip O Katz, MD, FACP, FACG is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Medtronic<br/>Received income in an amount equal to or greater than $250 from: Torax medical: pfizer consumer, .

Additional Contributors

Anil Minocha, MD, FACP, FACG, AGAF, CPNSS Professor of Medicine, Director of Digestive Diseases, Medical Director of Nutrition Support, Medical Director of Gastrointestinal Endoscopy, Internal Medicine Department, University of Mississippi Medical Center; Clinical Professor, University of Mississippi School of Pharmacy

Anil Minocha, MD, FACP, FACG, AGAF, CPNSS is a member of the following medical societies: American Academy of Clinical Toxicology, American Society for Gastrointestinal Endoscopy, American Federation for Clinical Research, American Association for the Study of Liver Diseases, American College of Forensic Examiners Institute, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association

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Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous coauthor, Jehad Barakat, MD, to the development and writing of this article.