Zollinger-Ellison 

Syndrome 

National Digestive Diseases Information Clearinghouse 

U.S. Department 

of Health and 

Human Services 

NATIONAL 

INSTITUTES 

OF HEALTH 

What is Zollinger-Ellison 

syndrome (ZES)? 

ZES is a rare disorder characterized by one 

or more tumors in the pancreas, duodenum, 

or both. The tumors cause the stomach to 

make too much acid, leading to peptic ulcers 

in the duodenum. The tumors are sometimes cancerous and spread to other areas of 

the body. 

What are the stomach, 

duodenum, and pancreas? 

The stomach, duodenum, and pancreas are 

digestive organs. The stomach produces 

gastric acid and other digestive juices that 

break down food. Partially digested food 

moves into the duodenum and is further broken down. The duodenum is the first part of 

the small intestine—the tube-shaped organ 

between the stomach and the large intestine. 

The pancreas is a large gland that produces 

digestive juices that flow into the duodenum. 

The pancreas also makes hormones that are 

released into the bloodstream. Hormones 

are powerful chemicals produced by glands 

that control the function of cells and organs. 

Stomach 

Duodenum 

Pancreas 

Tumors called gastrinomas that grow in the pancreas 

and duodenum cause Zollinger-Ellison syndrome. 
 

What causes ZES? 

ZES is caused by tumors called gastrinomas, 

which release the hormone gastrin. 

Normally, cells in the stomach produce and 

control gastrin so only the right amount is 

released. Gastrin travels through the bloodstream to signal other cells in the stomach to 

release gastric acid to help break down food. 

Gastrinomas release abnormal amounts of 

gastrin, resulting in excess gastric acid in the 

stomach and duodenum. The excess acid 

eventually causes sores called peptic ulcers to 

form in the lining of the duodenum. 

Scientists are unsure what causes the majority of gastrinomas, which appear sporadically. About 25 percent of gastrinoma cases 

are caused by an inherited genetic disorder 

called multiple endocrine neoplasia type 1 

(MEN1).1 MEN1 can cause a variety of 

hormone-releasing tumors such as prolactinomas and insulinomas. Prolactinomas form 

in the pituitary gland in the brain and cause 

excess prolactin—a hormone that influences 

milk production, fertility, and bone strength. 

Insulinomas form in the pancreas and cause 

excess insulin—a hormone that helps control 

blood glucose, also called blood sugar. Signs 

and symptoms of MEN1 include increased 

hormone levels in the blood, kidney stones, 

diabetes, muscle weakness, and weakened 

bones and fractures. 

1Norton JA, Fraker DL, Alexander HR, et al. Surgery 

to cure the Zollinger-Ellison syndrome. New England 

Journal of Medicine. 1999;341(9):635–644. 

2 Zollinger-Ellison Syndrome 

Who gets ZES? 

Anyone can get ZES, but the disease is more 

common among men 30 to 50 years old. 

People with MEN1 have a 20 to 61 percent 

chance of developing ZES.2 Children who 

have a parent with MEN1 have a 50 percent 

chance of inheriting the MEN1 gene and are, 

therefore, also at increased risk of ZES. 

What are the symptoms 

of ZES? 

ZES symptoms are similar to those of peptic 

ulcers and include 

•	 burning abdominal pain 

•	 nausea and vomiting 

•	 weight loss 

•	 diarrhea 

•	 severe gastroesophageal reflux—a 

condition where gastric acid and food 

from the stomach backs up into the 

esophagus 

How is ZES diagnosed? 

A doctor diagnoses ZES by 

•	 assessing symptoms 

•	 measuring stomach acid and the amount 

of gastrin circulating in the blood 

•	 conducting imaging tests to look for 


gastrinomas
 

A doctor may suspect ZES if diarrhea 

accompanies peptic ulcer symptoms or if 

treatment for peptic ulcers fails. Most peptic 

2Jensen RT. Management of the Zollinger-Ellison 

syndrome in patients with multiple endocrine 

neoplasia type 1. Journal of Internal Medicine. 

1998;243(6):477–488. 
 

ulcers are caused by bacteria called Helicobacter pylori (H. pylori) or the use of nonsteroidal anti-inflammatory drugs (NSAIDs) 

such as aspirin and ibuprofen. Peptic ulcers 

in the absence of H. pylori infection or 

NSAIDs usage or severe peptic ulcers that 

bleed or cause perforation of the duodenum 

are possible indicators of ZES. A MEN1 

diagnosis in the patient or the patient’s 

family or the presence of MEN1 signs and 

symptoms strongly suggests ZES. 

Multiple ulcers in the duodenum—seen during upper gastrointestinal (GI) endoscopy— 

may cause a doctor to suspect ZES. Upper 

GI endoscopy is used to see inside the 

upper GI tract. During the procedure, an 

endoscope—a thin, flexible, lighted tube 

with a small camera on the tip—is inserted 

through the mouth, esophagus, and stomach 

and into the duodenum. The endoscope 

sends images taken inside the upper GI tract 

to a video monitor where they can be viewed. 

Upper GI endoscopy, however, rarely reveals 

gastrinomas, which grow in tissue layers 

beneath the visible surface. 

A procedure called somatostatin receptor 

scintigraphy (SRS)—sometimes called 

OctreoScan—is used to find gastrinomas 

in the duodenum, pancreas, and other 

parts of the body. SRS uses a radioactive 

compound called a radiotracer that, when 

injected into the bloodstream, selectively 

labels tumor cells. The labeled cells light up 

when scanned with a device called a gamma 

camera. 

Other imaging procedures used to find gastrinomas include the following: 

•	 Angiography is sometimes used to find 

tumors in the pancreas. A special tube 

called a catheter is guided through the 

bloodstream to blood vessels in the 

pancreas. Contrast material is injected 

through the catheter. On x ray, the contrast material highlights blood vessels, 

which are more dense inside tumors. 

•	 Endoscopic ultrasonography is sometimes used to look for tumors in the 

pancreas. A special endoscope called 

an endoechoscope is used to perform 

ultrasound inside the duodenum. Ultrasound uses sound waves to look beyond 

the surface of tissues. 

•	 A computerized tomography (CT) scan 

takes hundreds of cross-sectional x-ray 

images in a few seconds. A computer 

assembles the images to produce 

three-dimensional views of internal 

organs and tissues. While not good 

at finding tumors in the pancreas or 

duodenum, this technique is more 

useful in finding gastrinomas that have 

spread to the liver. 

How is ZES treated? 

ZES is treated with medications to relieve 

ulcer symptoms and surgery, if appropriate, 

to remove tumors. Chemotherapy is sometimes used when tumors are too widespread 

to remove with surgery. 

A class of drugs called proton pump inhibitors effectively reduces gastric acid secretion 

in the stomach and includes 

•	 esomeprazole (Nexium) 

•	 lansoprazole (Prevacid) 

•	 pantoprazole (Protonix) 

•	 omeprazole (Prilosec) 

3 Zollinger-Ellison Syndrome 
 

Reducing stomach acid allows peptic ulcers 

to heal and relieves ZES symptoms. 

Surgical removal of gastrinomas is the only 

cure for ZES. Some gastrinomas behave 

like cancers and spread to other parts of the 

body, especially the liver and bones. Finding 

and removing all gastrinomas is often 

challenging. 

Gastrinomas that cannot be surgically 

removed are sometimes treated with chemotherapy drugs, including 

•	 streptozotocin (Zanosar) 

•	 5-fluorouracil (Adrucil) 

•	 doxorubicin (Doxil) 

What is the likely outcome 

for people with ZES? 

The outcome for people with ZES largely 

depends on the nature and extent of the 

gastrinomas. About 25 percent of gastrinoma cases are considered cancerous, with 

an estimated 10-year survival rate of around 

30 percent.3 The remaining cases are considered slow-growing, with an estimated 10-year 

survival rate of around 95 percent.3 If peptic 

ulcer symptoms are well controlled, however, 

most patients—even those with tumors that 

spread—will feel well until the late stages of 

the disease. 

Points to Remember 

•	 Zollinger-Ellison syndrome (ZES) 

is a rare disorder characterized by 

tumors called gastrinomas in the 

pancreas, duodenum, or both. 

•	 Gastrinomas result in excess gastric 

acid, which can lead to ulcers in the 

duodenum. 

•	 Anyone can get ZES, but the disease is more common among men 

30 to 50 years old or in people who 

have an inherited condition called 

multiple endocrine neoplasia type 1 

(MEN1). 

•	 ZES symptoms are similar to those 

of peptic ulcers. 

•	 A doctor diagnoses ZES by assessing symptoms, measuring stomach 

acid and the amount of gastrin 

circulating in the blood, and conducting imaging tests to look for 

gastrinomas. 

•	 ZES is treated with medications 

to relieve ulcer symptoms and 

surgery, if appropriate, to remove 

tumors. ZES is sometimes treated 

with chemotherapy. 

•	 The outcome for people with ZES 

largely depends on the nature and 

extent of the gastrinomas. About 

25 percent of gastrinomas are 

considered cancerous. If peptic 

ulcer symptoms are well controlled, 

however, most patients—even 

those with tumors that spread—will 

feel well until the late stages of the 

disease. 

3Del Valle J, Scheiman JM. Zollinger-Ellison 

syndrome. In: Yamada T, ed. Textbook of 

Gastroenterology. Vol. 1. Philadelphia: Lippincott 

Williams & Wilkins; 2003: 1377–1394. 

4 Zollinger-Ellison Syndrome 
 

Hope through Research 

The National Institute of Diabetes and 

Digestive and Kidney Diseases (NIDDK) 

conducts and supports basic and clinical 

research into many digestive disorders, 

including ZES. The NIDDK is working on 

better approaches to the diagnosis and management of ZES, including better ways of 

diagnosing MEN1 and finding gastrinomas. 

Participants in clinical trials can play a more 

active role in their own health care, gain 

access to new research treatments before 

they are widely available, and help others 

by contributing to medical research. For 

information about current studies, visit 

www.ClinicalTrials.gov. 

For More Information 

A fact sheet about MEN1 is available from 

the National Endocrine and Metabolic 

Diseases Information Service (NEMDIS), 

part of the NIDDK. The fact sheet is available online at www.endocrine.niddk.nih.gov/ 

pubs/men1/men1.htm or by contacting the 

NEMDIS at 1–888–828–0904. 

National Endocrine and Metabolic Diseases 

Information Service 

6 Information Way 

Bethesda, MD 20892–3569 

Phone: 1–888–828–0904 

TTY: 1–866–569–1162 

Fax: 703–738–4929 

Email: endoandmeta@info.niddk.nih.gov 

Internet: www.endocrine.niddk.nih.gov 

National Organization for Rare Disorders 

55 Kenosia Avenue 

P.O. Box 1968 

Danbury, CT 06813–1968 

Phone: 1–800–999–6673 or 203–744–0100 

Fax: 203–798–2291 

Email: orphan@rarediseases.org 

Internet: www.rarediseases.org 

Acknowledgments 

Publications produced by the Clearinghouse 

are carefully reviewed by both NIDDK scientists and outside experts. This publication 

was reviewed by Paul N. Maton, M.D., University of Oklahoma College of Medicine. 

5 Zollinger-Ellison Syndrome 
You may also find additional information about this 

topic by visiting MedlinePlus at www.medlineplus.gov.

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medications. When prepared, this publication 

included the most current information available. 

For updates or for questions about any medications, 

contact the U.S. Food and Drug Administration 

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National Digestive Diseases 

Information Clearinghouse

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TTY: 1–866–569–1162

Fax: 703–738–4929

Email: nddic@info.niddk.nih.gov

Internet: www.digestive.niddk.nih.gov

The National Digestive Diseases Information 

Clearinghouse (NDDIC) is a service of the 

National Institute of Diabetes and Digestive 

and Kidney Diseases (NIDDK). The 

NIDDK is part of the National Institutes of 

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the Clearinghouse provides information 

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U.S. DEPARTMENT OF HEALTH 

AND HUMAN SERVICES

National Institutes of Health

NIH Publication No. 09–4692

May 2009