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Disease Profile

Zollinger-Ellison syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Adult

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ICD-10

E16.4

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

ZES; Gastrinoma; Pancreatic ulcerogenic tumor syndrome;

Categories

Digestive Diseases; Endocrine Diseases; Rare Cancers

Summary

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]

Symptoms

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.

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

Cause

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]

Diagnosis

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.

Treatment

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)

Organizations

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

    Learn more

    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.

        References

        1. David C. Dugdale, III and George F. Longstreth. Zollinger-Ellison syndrome. MedlinePlus. November 11, 2010; https://www.nlm.nih.gov/medlineplus/ency/article/000325.htm. Accessed 1/14/2014.
        2. Elliot M. Livstone. Pancreatic Endocrine Tumors. Merck Manuals. October, 2012; https://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; https://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; https://digestive.niddk.nih.gov/ddiseases/pubs/zollinger/. Accessed 10/28/2012.
        5. Zollinger Ellison syndrome. NORD. January 20, 2012; https://www.rarediseases.org/rare-disease-information/rare-diseases/byID/360/viewAbstract. Accessed 1/14/2014.
        6. Multiple endocrine neoplasia. Genetics Home Reference. August, 2013; https://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; https://www.ncbi.nlm.nih.gov/books/NBK1538/. Accessed 4/5/2014.

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