National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Zollinger-Ellison syndrome


Other Names:
ZES; Gastrinoma; Pancreatic ulcerogenic tumor syndrome; ZES; Gastrinoma; Pancreatic ulcerogenic tumor syndrome; Z E syndrome See More
Categories:
Zollinger-Ellison syndrome (ZES) is a condition in which tumors called gastrinomas in the pancreas and duodenum (part of the small intestine) cause high levels of the hormone gastrin in the blood. High levels of gastrin then cause production of too much stomach acid. Signs and symptoms may include abdominal pain, peptic ulcers, vomiting blood, and diarrhea.[1][2] The tumors are sometimes cancerous and may spread to other areas of the body.[3] In most cases, the cause of ZES is unknown. However, about 25-30% of gastrinomas are caused by an inherited condition called multiple endocrine neoplasia type 1 (MEN1). Treatment for ZES may include medication to reduce the production of stomach acid, and surgery for peptic ulcers or to remove tumors.[4]
Last updated: 1/14/2014

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
100% of people have these symptoms
Zollinger-Ellison syndrome 0002044
80%-99% of people have these symptoms
Duodenal ulcer 0002588
Episodic abdominal pain 0002574
Esophagitis
Inflammation of the esophagus
0100633
Nausea 0002018
Peptic ulcer
Sore in the lining of gastrointestinal tract
0004398
30%-79% of people have these symptoms
Weight loss 0001824
5%-29% of people have these symptoms
Adrenocortical adenoma 0008256
Elevated circulating parathyroid hormone level 0003165
Erythema 0010783
Extrahepatic cholestasis 0012334
Glucagonoma 0030404
Growth hormone excess 0000845
Hematochezia
Rectal bleeding
0002573
Hypercalcemia
High blood calcium levels
Increased calcium in blood
[ more ] 		0003072
Hyperparathyroidism
Elevated blood parathyroid hormone level
0000843
Increased circulating cortisol level 0003118
Increased glucagon level 0030688
Increased urinary cortisol level
High urine cortisol level
0012030
Intestinal obstruction
Bowel obstruction
Intestinal blockage
[ more ] 		0005214
Jaundice
Yellow skin
Yellowing of the skin
[ more ] 		0000952
Lipoma
Fatty lump
Noncancerous fatty lump
[ more ] 		0012032
Multiple lipomas
Multiple fatty lumps
0001012
Parathyroid hyperplasia
Enlarged parathyroid glands
0008208
Pituitary corticotropic cell adenoma 0008291
Pituitary growth hormone cell adenoma 0011760
Pituitary null cell adenoma 0011761
Pituitary prolactin cell adenoma 0006767
Thyroid adenoma 0000854
1%-4% of people have these symptoms
Adrenocortical carcinoma 0006744
Percent of people who have these symptoms is not available through HPO
Abnormality of the thyroid gland
Thyroid abnormality
0000820
Adenoma sebaceum 0009720
Autosomal dominant inheritance 0000006
Cafe-au-lait spot 0000957
Carcinoid tumor 0100570
Confetti-like hypopigmented macules 0007449
Diarrhea
Watery stool
0002014
Hypoglycemia
Low blood sugar
0001943
Increased circulating prolactin concentration 0000870
Insulinoma 0012197
Pancreatic islet cell adenoma 0008261
Parathyroid adenoma 0002897
Pituitary adenoma
Noncancerous tumor in pituitary gland
0002893
Prolactinoma 0040278
Subcutaneous lipoma 0001031
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Last updated: 7/1/2020
In most people with Zollinger-Ellison syndrome (ZES), the cause is not known. However, in about 25-30% of cases, it occurs with an inherited condition called multiple endocrine neoplasia type 1 (MEN1). This condition is caused by changes (mutations) in the MEN1 gene and is inherited in an autosomal dominant manner. Most, but not all, individuals with an MEN1 gene mutation will develop symptoms of multiple endocrine neoplasia type 1.[3][5]

The MEN1 gene normally regulates the body's production of a protein thought to play a role in preventing the development of tumors (a tumor suppressor gene). Mutations that affect the function of this gene therefore affect the body's ability to prevent the growth of tumors, thus leading the the signs and symptoms of multiple endocrine neoplasia type 1.[5]
Last updated: 1/14/2014
Zollinger-Ellison syndrome (ZES) usually occurs sporadically, for unknown reasons in a person with no history of the condition in the family. In about 25-30% of people with ZES, it is associated with an inherited condition called multiple endocrine neoplasia type 1 (MEN1).[3]

MEN1 is inherited in an autosomal dominant manner and is caused by mutations in the MEN1 gene. Most affected people inherit the mutated gene from a parent, and a few cases result from a new mutation that was not inherited. Unlike most autosomal dominant conditions, both copies of the MEN1 gene must have a mutation to cause symptoms of the condition. The mutation in the second copy of the gene occurs during a person's lifetime. Because of this, most, but not all, people born with an MEN1 gene mutation will develop signs and symptoms of the condition.[6] This phenomenon is known as reduced penetrance. A person with an MEN1 gene mutation has a 50% (1 in 2) risk to pass on the mutated gene to each child.
Last updated: 1/14/2014
There is not a genetic test specifically for Zollinger-Ellison syndrome (ZES), which usually occurs sporadically as a result of a tumor that secretes gastrin (a gastrinoma). However, genetic testing is available for multiple endocrine neoplasia type 1 (MEN1), which is a genetic condition present in about 25-30% of people with ZES.

People who have a single MEN1-related tumor (such as one gastrinoma) and no family history of multiple endocrine neoplasia type 1 are rarely born with MEN1 gene mutations. Generally, the chance of detecting a MEN1 gene mutation increases in people with more main tumors (parathyroid, pancreatic, and pituitary).[7]

Genetic testing is most informative for asymptomatic family members when the affected family member has genetic testing first. The person with symptoms of MEN1 typically first has sequencing analysis of the gene to look for changes; if no mutation is found, they may have duplication/deletion analysis (a test that detects extra or missing parts of the gene).[7]

Predictive testing for at-risk, asymptomatic, adult family members requires first finding the disease-causing mutation in the affected family member. It is important to note that in people with a MEN1 gene mutation, the chance to develop symptoms by age 20 is over 50%. The chance to develop symptoms by age 40 is 95%.[7] Therefore, as a person ages and does not have signs or symptoms, the chance to have a MEN1 gene mutation decreases significantly.

The Genetic Testing Registry (GTR) provides information about the genetic tests for multiple endocrine neoplasia type 1. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Last updated: 1/14/2014

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

  • Synthetic human secretin (Brand name: ChiRhoStim) - Manufactured by ChiRhoClin, Inc.
    FDA-approved indication: For use in the diagnosis of gastrinoma associated with Zollinger-Ellison syndrome.
    National Library of Medicine Drug Information Portal
  • Synthetic porcine secretin (Brand name: Synthetic porcine secretin) - Manufactured by ChiRhoClin, Inc.
    FDA-approved indication: For use in secretin stimulation testing for: Stimulation of pancreatic secretions to facilitate the identification of the ampulla of Vater and accessory papilla during endoscopic retrograde cholangio-pancreatography (ERCP)

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include other causes of increased acid output and elevated FSG levels: Helicobacter pylori infections, retained gastric antrum, gastric outlet obstruction, renal failure, antral G cell syndromes, idiopathic gastroesophageal reflux or peptic ulcer disease, and physiological causes of hypergastrinemia (atrophic gastritis, pernicious anemia, or use of potent antisecretory drugs).
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Zollinger-Ellison syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

In-Depth Information

  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Zollinger-Ellison syndrome. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • My dad had ZE syndrome and passed away at age 31. Are there genetic tests that could be done to see if my brother and I carry this gene? I have a gastro specialist and he tests my gastric levels every year for this reason. I have mixed feelings about knowing if I have the gene or not. See answer


  1. David C. Dugdale, III and George F. Longstreth. Zollinger-Ellison syndrome. MedlinePlus. November 11, 2010; http://www.nlm.nih.gov/medlineplus/ency/article/000325.htm. Accessed 1/14/2014.
  2. Elliot M. Livstone. Pancreatic Endocrine Tumors. Merck Manuals. October, 2012; http://www.merckmanuals.com/professional/gastrointestinal_disorders/tumors_of_the_gi_tract/pancreatic_endocrine_tumors.html?qt=&sc=&alt=. Accessed 1/14/2014.
  3. Zollinger-Ellison Syndrome. National Digestive Diseases Information Clearinghouse (NDDIC). December 24, 2013; http://www.digestive.niddk.nih.gov/ddiseases/pubs/zollinger/. Accessed 1/14/2014.
  4. Zollinger-Ellison Syndrome. National Digestive Diseases Information Clearinghouse (NDDIC). May 10, 2012; http://digestive.niddk.nih.gov/ddiseases/pubs/zollinger/. Accessed 10/28/2012.
  5. Zollinger Ellison syndrome. NORD. January 20, 2012; http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/360/viewAbstract. Accessed 1/14/2014.
  6. Multiple endocrine neoplasia. Genetics Home Reference. August, 2013; http://ghr.nlm.nih.gov/condition/multiple-endocrine-neoplasia. Accessed 1/14/2014.
  7. Francesca Giusti, Francesca Marini, and Maria Luisa Brandi. Multiple Endocrine Neoplasia Type 1. GeneReviews. February 2015; http://www.ncbi.nlm.nih.gov/books/NBK1538/. Accessed 4/5/2014.