Multiple Endocrine Neoplasia Type 1 (MEN1)

Sometimes referred to as Wermer syndrome, multiple endocrine neoplasia type 1 (MEN1) is an inherited health condition that involves the growth of tumors in the endocrine glands. It is a rare condition that affects approximately 1 in 30,000 people.

The majority of tumors associated with MEN1 are benign. Despite this, they can still lead to significant symptoms for patients due to overproduction of hormones in the affected endocrine glands. Additionally, up to a third of some types of growths, such as those of the islet cells in the pancreas, are malignant and may spread to other areas of the body.

Characteristics of Type 1

There are three types of multiple endocrine neoplasias: MEN1, MEN2A, and MEN2B. The defining characteristic of multiple endocrine neoplasia type 1 is a mutation in the MEN1 gene, which causes a tumor or excessive growth in at least two of the following:

• parathyroid gland
• islet cells of the pituitary gland
• thyroid gland
• adrenal glands
• pancreas

Adrenal cortical tumors, carcinoid tumors, pheochromocytomas, and tumors of the digestive tract may also affect patients. Some patients may also develop tumors in areas outside the endocrine system. This may include facial angiofibromas, collagenomas, lipomas, leiomyomas, meningiomas, and ependymomas.

Symptoms

There is a wide range of symptoms that may affect a patient with MEN1, depending on the endocrine that is affected and the changes in the production of hormones. Increases in the following hormones may cause these symptoms:

• Prolactin: increased production of milk by the breast, amenorrhea in women, reduced testosterone levels in men
• Growth hormone: increased growth of the jaw and other tissues
• Adrenocorticotropic hormone: increased production of cortisol
• Gastrin: increased risk of stomach ulcers
• Glucagon: increased risk of diabetes mellitus
• Parathyroid hormone: increased risk of hypercalcemia and kidney stones
• Vasoactive intestinal peptide: severe diarrhea

Cause

Multiple endocrine neoplasia type 1 (MEN1) is an inherited condition caused by a mutation in the MEN1 gene. People who have inherited the altered mutation from their parents have a significantly increased of developing tumors associated with the endocrine glands. Approximately 9 in 10 individuals with the gene will develop symptoms of MEN1.

It has been suggested that the gene mutationin MEN1 changes the regulation of cell growth and division due to abnormal function of the cyclin-dependent kinase inhibitor (CDKI) proteins. However, more research is required to investigate the etiology of the condition.

MEN1 is inherited in an autosomal dominant inheritance pattern. This means that an individual only needs to inherit one copy (out of two; one from each parent) in order to be affected by the condition. As a result, if one parent is affected, each child has a 50% chance of inheriting the gene mutation and carrying an increased risk of developing a tumor of the endocrine glands. Approximately 10% of patients with MEN1 do not have a family history of the condition and have a spontaneous or de novo gene mutation.

Diagnosis

MEN1 should be investigated for patients who have at least 2 tumors in the commonly affected glands: parathyroid, pancreatic islet cell, and pituitary gland.

Genetic testing is available for individuals with a family history of multiple endocrine neoplasia type 1. This should be recommended for any patient with a known family history who has developed at least one tumor of the commonly affected pituitary glands.

Diagnostic tests that may be required include:

• Blood tests to measure levels of calcium and hormones (e.g. prolactin, insulin-like growth factor (IGF-1), glucose and insulin)
• Magnetic resonance imaging (MRI) of the brain to detect changes
• MRI or computed tomography (CT) scan of the chest and abdomen to detect changes

Treatment

The treatment for the tumors associated with MEN1 will depend on which endocrine gland is affected and the nature of the tumor. Close surveillance is needed to detect the growth of tumors and take the appropriate action.

Surgical removal of the tumor is the most common treatment, particularly for parathyroid tumors, which are usually benign. Medicines to suppress the growth of the tumor can also sometimes be indicated.

Tumors of the pancreatic islet cells are the most difficult to treat due to the role of the pancreas in digestion and the regulation of blood glucose. Removal of the pancreas will result in the inability to produce insulin and diabetes mellitus. Therefore, treatment decisions are made on a case-by-case basis to reduce the risk of cancer spreading and diabetes mellitus.

References

• http://www.cancer.net/cancer-types/multiple-endocrine-neoplasia-type-1
• https://www.niddk.nih.gov/health-information/health-topics/endocrine/multiple-endocrine-neoplasia-type-1/Pages/fact-sheet.aspx
• https://medlineplus.gov/ency/article/000398.htm
• http://patient.info/doctor/multiple-endocrine-neoplasia-type-1-men1
• http://emedicine.medscape.com/article/1093723-overview