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 gland. Other endocrine tumors seen in MEN1 include adrenal cortical tumors, neuroendocrine tumors (previously called carcinoid tumors), and rare pheochromocytomas, as well as tumors in other parts of the digestive tract.
Non-endocrine tumors are also seen in MEN1. These tumors can include:
facial angiofibroma, which is a tumor of blood vessels and fibrous tissue
collagenoma, which is a flesh-colored tumor on the skin
lipoma, which is a fatty tumor
leiomyoma, which is a smooth muscle tumor
meningioma, which is a tumor from nervous system tissue; uncommon
ependymoma, which is a tumor from nervous system tissue; uncommon
The majority of tumors in people with MEN1 are benign (noncancerous). However, approximately 1 out of 3 pancreatic neuroendocrine tumors and mediastinal neuroendocrine tumors are cancerous, meaning the tumor can spread to other parts of the body. These tumors can also cause problems by producing high amounts of hormones. There is a wide variety of symptoms that can occur due to this increased hormone production by this type of tumor. These include increased production of:
Prolactin, which causes abnormal milk production by the breast, lack of menstruation in women, and lowered testosterone production in men
growth hormone, which causes excessive growth of the jaw and other soft tissues
adrenocorticotropic hormone, which causes excessive cortisol production by the adrenal glands
gastrin, which causes stomach ulcers
glucagon, which causes diabetes mellitus and skin rash
vasoactive intestinal peptide, produced by a pancreatic neuroendocrine tumor, causing intense watery diarrhea
parathyroid hormone, produced by parathyroid tumors, causing high blood calcium (hypercalcemia) and kidney stones
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 1 or more symptoms of MEN1. A small percentage of people without MEN1 genetic 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 through inheritance) 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 2 copies of each gene: 1 inherited from the mother and 1 from the father. MEN1 follows an autosomal dominant inheritance pattern, in which a mutation happens in only 1 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 genetic mutation has a 50% chance of inheriting that mutation. However, if the parents test negative for the mutation, the risk to the siblings significantly decreases but their risk may still be higher than an average risk.
Options exist for people interested in having a child when a prospective parent carries a gene mutation that increases the risk for this hereditary cancer syndrome. For more information, talk with an assisted reproduction specialist at a fertility clinic.
How common is MEN1?
It is estimated that about 1 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 2 of the most common tumors listed below:
Pancreatic neuroendocrine tumor
Pituitary gland tumor
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 2 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 1 out of 3 pancreatic neuroendocrine tumors are cancerous. If the cancer has spread beyond where it started, the most common site of spread is the liver. A small percentage of mediastinal neuroendocrine tumors are cancerous and spread to local (nearby) lymph nodes or to the liver, lung, or other locations.
What are the screening options for MEN1?
Current suggested screening for people who are known or suspected to have MEN1 includes:
Genetic testing is available. It should be considered for children or young adults who are members of a family diagnosed with MEN1 and an identified mutation of the MEN1 gene to determine which children and young adults should have the screening studies described below. In a family with an identified mutation of the MEN1 gene, children with a genetic test showing no mutation (expected to be 50% of children born to an individual affected with MEN1) may not need the screening tests described below.
Regular blood tests every 1 to 3 years for prolactin, insulin-like growth factor 1 (IGF-1), fasting glucose, insulin, and proinsulin, beginning at age 5 to 10 years.
A yearly ionized or albumin-corrected calcium level test, beginning at age 8
Regular blood tests for fasting gastrin and fasting and meal stimulated pancreatic polypeptide (PP), fasting VIP, and glucagon, beginning at age 20.
Magnetic resonance imaging (MRI) scan of the brain, every 3 to 5 years, beginning between ages 5 to 10, or at any time the results of the tests for serum prolactin or insulin-like growth factor is abnormal.
MRI or computed tomography (CT) scan of the chest and abdomen, every 2 to 4 years, beginning at age 20 or when the serum gastrin, PP, or VIP is noted to be abnormal.
Screening guidelines may change over time as new technologies are developed and more is learned about MEN1. It is important to talk with your doctor about appropriate screening tests.
What are the treatment options for the endocrine tumors?
Most of these tumors are treated with surgery or by taking a medicine that suppresses growth or function of the tumor. Parathyroid tumors, which are almost always benign, should be surgically removed when the albumin-corrected serum calcium level is greater than 12 mg/dl, there is significant bone loss, or kidney damage or stones. There are challenging treatment issues related to removing pancreatic neuroendocrine tumors. In addition to its role in normal digestion, the pancreas regulates the level of blood glucose through insulin production. Removal of the pancreas will cause diabetes mellitus, a condition that can lead to significant health problems and it will be necessary to take pancreatic enzyme supplements to promote digestion. Doctors must balance the benefits of pancreatic removal in a person with MEN1, such as the prevention of development of cancer spread, against the risks of diabetes mellitus. Patients with a pancreatic neuroendocrine tumor that has spread to the liver may be treated with a somatostatin analogue or a drug that regulates signaling in the pancreatic islet cell, everolimus. Other neuroendocrine tumors are typically removed by surgery and other treatments may be recommended.
Pituitary tumors producing the hormone prolactin are most commonly managed with dopamine agonists, which are drugs that imitate the action of dopamine, a naturally occurring substance produced in the brain. Tumors that produce growth hormone or adrenocorticoptropin hormone or non-functioning tumors are most commonly treated with surgery. There are 2 hormonal therapies, a somatostatin analogue and a growth hormone antagonist, that have been successfully used to treat too much growth hormone in patients who are not cured by surgery. Learn more about pituitary tumor treatment.
Learn more about what to expect when having common tests, procedures, and scans.
Questions to ask the health care team
If you are concerned about your risk of an endocrine tumor, talk with your health care team. It can be helpful to bring someone along to your appointments to take notes. Consider asking your health care team the following questions:
What is my risk of developing a neuroendocrine tumor?
What can I do to reduce my risk of other types of tumors?
What are my options for screening?
If you are concerned about your family history and think you or other family members may have MEN1, consider asking the following questions:
Does my family history increase my risk of developing cancer?
Does it suggest the need for a cancer risk assessment?
Will you refer me to a genetic counselor or other genetics specialist?
Should I consider genetic testing?
American Multiple Endocrine Neoplasia Support
Association for Multiple Endocrine Neoplasia Disorders (AMEND)
National Cancer Institute
To find a genetic counselor in your area, ask your doctor or visit these websites:
National Society of Genetic Counselors
National Cancer Institute