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Multiple Endocrine Neoplasia Type 1

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What is multiple endocrine neoplasia type 1?

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary condition associated with tumors of the endocrine (hormone producing) glands. MEN1 was originally known as Wermer syndrome. The most common tumors seen in MEN1 involve the parathyroid gland, islet cells of the pancreas, and pituitary glands. Other endocrine tumors seen in MEN1 include adrenal cortical tumors and carcinoid tumors, as well as tumors in other parts of the digestive tract.

Non-endocrine tumors are also seen in MEN1. These tumors can include:

facial angiofibromas (tumors of blood vessels and fibrous tissue)

collagenomas (flesh-colored tumors on the skin)

lipomas (fatty tumors)

leiomyomas (smooth muscle tumors).

meningiomas (tumors from nervous system tissue; uncommon)

ependymomas (tumors from nervous system tissue; uncommon)

The majority of tumors in people with MEN1 are benign (noncancerous), however, approximately one-third of islet cell tumors and mediastinal carcinoid tumors are malignant (cancerous, meaning it can spread to other parts of the body).

In addition, there is a broad spectrum of clinical syndromes associated with increased hormone production by these tumors. These include increased production of:

prolactin (abnormal milk production by the breast and lack of menstruation in women)

growth hormone (excessive growth of the jaw and other soft tissues)

adrenocorticotropic hormone (excessive cortisol production) by pituitary tumors

gastrin (causing stomach ulcers)

glucagon (causing diabetes mellitus and skin rash)

vasoactive intestinal peptide (VIPoma; causing intense watery diarrhea) by islet cell tumors of the pancreas

parathyroid hormone (causing high blood calcium and kidney stones) by parathyroid tumors

What causes MEN1?

MEN1 is a genetic condition. This means that the cancer risk and other features of MEN1 can be passed from generation to generation in a family. The gene associated with MEN1 is also called MEN1. A mutation (alteration) in the MEN1 gene gives a person an increased risk of developing endocrine tumors and other symptoms of MEN1. More than 90% of individuals who inherit the MEN1 mutation will develop one or more symptoms of MEN1. A small percentage without MEN1 alterations have been found to have germline mutations (alterations in the body’s egg or sperm cells that become incorporated into the DNA of every cell in the body of the offspring) in a class of proteins called cyclin-dependent kinase inhibitors (CDKIs) that regulate cell growth and division. Research is ongoing to learn more about MEN1.

How is MEN1 inherited?

Normally, every cell has two copies of each gene: one inherited from the mother and one inherited from the father. MEN1 follows an autosomal dominant inheritance pattern, in which a mutation happens in only one copy of the gene. This means that a parent with a gene mutation may pass along a copy of their normal gene or a copy of the gene with the mutation. Therefore, any child from a parent with a mutation has a 50% chance of inheriting that mutation. A tumor develops in the affected individual when the normal copy of the gene (inherited from the unaffected parent) is lost or mutated (damaged) in a specific cell type during normal cell division.

How common is MEN1?

It is estimated that about one in 30,000 people has MEN1. About 10% of people with MEN1 do not have a family history of the condition; they have a de novo (new) mutation in the MEN1 gene.

How is MEN1 diagnosed?

MEN1 is suspected when a person has at least two of the most common tumors listed.




If a person has a family history of MEN1, he or she is suspected of also having MEN1 if diagnosed with a parathyroid, pancreatic, or pituitary tumor. Genetic testing for mutations in the MEN1 gene is available for people suspected to have MEN1. A mutation in the MEN1 gene is found in about 80% to 90% of families diagnosed with MEN1. Approximately 65% of people with two or more tumors associated with MEN1, but no family history, will have a mutation in the MEN1 gene. 

What are the estimated cancer risks associated with MEN1?

Approximately one-third of islet cell tumors of the pancreas are cancerous. If the cancer has spread, the most common site of spread is the liver. A small percentage of mediastinal carcinoid tumors are malignant and spread to local (nearby) lymph nodes or to the liver, lung, or other locations.

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