Multiple Endocrine Neoplasia Type 1

Disorders of the Parathyroid, Pituitary, and Pancreas

Multiple Endocrine Neoplasia Type 1 Overview
Multiple endocrine neoplasia type 1 (MEN 1) is a relatively uncommon inherited disease. Individuals who inherit the gene for MEN 1 have an increased chance of developing over-activity and enlargement of certain endocrine glands. The endocrine glands most commonly affected by MEN 1 are the parathyroid glands, the pancreas, and the pituitary glands.

Almost everyone who inherits MEN 1 develops over-activity of the parathyroid glands (hyperparathyroidism) at some stage in their life. The other endocrine glands become over-active less frequently; however, people who inherit MEN 1 will usually develop over-activity in more than one endocrine gland. Over-activity in different endocrine glands may occur simultaneously or at separate times during a person's life.

How Common is MEN 1?
MEN 1 is a rare condition. It occurs in about 1 person in every 30,000 people.1 MEN 1 is passed down in families from one generation to the next.  MEN 1 can be inherited by a child if one of their parents has MEN 1.

The Effect of MEN 1 on the Endocrine Glands
MEN 1 can lead to over-activity and enlargement of 3 endocrine glands:  the parathyroid glands, the pancreas, and the pituitary gland. 

To understand fully what this over-activity means, here's a review of the endocrine system and what it does:  Endocrine glands each produce different and specific hormones. Hormones are chemicals that regulate the function of various tissues throughout the body (see our article on the endocrine system). The endocrine glands release a controlled amount of their hormone directly into the blood stream. Once in the blood stream, hormones circulate throughout the body. Only small quantities of hormones are needed to produce the required effect throughout the body. Under normal circumstances, the level of endocrine gland activity is carefully regulated by the body.

People who inherit the gene for MEN 1 are pre-disposed to developing an over-activity in hormone production from the parathyroid glands, pituitary gland, and pancreas. Increased hormone production is usually associated with enlargement of these glands. Endocrine gland enlargement and hormone overproduction does not usually occur in all areas of an endocrine gland at the same point in time. Some parts of overactive endocrine glands grow more rapidly than others, and produce more hormone than other parts of the same gland. The parts of an endocrine gland which grow most rapidly become "lumpy." These lumps are usually benign tumors. Benign tumors in endocrine glands are known as adenomas.


What Age Does MEN 1 Usually Present Itself?
Different endocrine glands become over-active at different times in life. Similarly, different areas within one endocrine gland will become overactive (or develop adenoma) at different times during life.  Additionally, the effect of MEN 1 varies from person to person; there is no "standard" with MEN 1.

In general, the likelihood of endocrine gland over-activity and the development of adenoma increases with age. By age 30, most people who inherit MEN 1 will have some type of endocrine gland over-activity. Over-activity from the adenoma can usually be detected by special blood tests (measurement of ionized calcium and parathyroid hormone in the blood) before people reach age 30. Symptoms, however, do not develop in many people with MEN 1 until they are older than 30. For this reason it is important for all people at risk to be tested for MEN 1, even though they may feel quite well.


Parathyroid Glands The Endocrine Glands Usually Affected by MEN 1
The parathyroid glands, pituitary gland, and pancreas are most commonly affected. The parathyroid glands are affected in almost everyone who inherits MEN 1. They are often the first endocrine glands to show signs of overactivity. Parathyroid gland overactivity (known as hyperparathyroidism) often develops during the teenage years. However, over 95% of people with MEN 1 will have parathyroid gland overactivity by age 30 years. Many people with hyperparathyroidism related to MEN 1 do not develop obvious symptoms until they are over 30 years of age.Pancreas

The pancreas is the next most commonly affected gland in MEN 1. Many people who inherit MEN 1 develop small pancreatic adenoma which can be detected by measuring pancreatic hormones in the blood.  If suspected, a CT scan or ultrasound scan is usually done to examine the pancreas more closely. These adenomas do not usually produce symptoms and are mostly less than 3cm in diameter. Occasionally cancerous (malignant) pancreatic tumors develop. For this reason, it is recommended people with MEN 1 have regular blood screens of the pancreatic hormones, and even scans of the pancreas to detect the minority of pancreatic lumps which are at risk for developing malignancy. Malignancy of the pancreas is rare prior to 30 years of age.

Over-production of pancreatic hormones is common in MEN 1. Many different types of pancreatic hormones can be over-produced (see our page on pancreatic hormones). Some hormones are frequently over-produced without causing symptoms (such as pancreatic polypeptide), while other hormones such as gastrin (which can cause severe stomach ulcers and diarrhea) and insulin (which can produce a low blood sugar) may cause important symptoms and ill-health. Insulin over-production is most common in people under 30 years of age, whereas gastrin over-production is is most common after 30 years of age. 

Should Everyone with an Endocrine Gland Problem Be Tested for MEN 1?
Only a very small proportion of people with endocrine disorders have MEN 1. Most endocrine problems have nothing to do with MEN 1. The endocrine disorders which may be related to MEN 1 are those in which the parathyroid gland, pancreas, and pituitary gland become overactive. Less than 1% of all people with parathyroid over-activity (hyperparathyroidism) or pituitary tumors have MEN 1. Certain types of pancreatic endocrine tumors (gastrinoma {Zollinger-Ellison syndrome} and insulinoma) are more likely to be related to MEN 1. People who have overactivity of 2 or more of the above endocrine glands should be examined for MEN 1.


Is MEN 1 the Same as MEN 2?
MEN 1 and MEN 2 are completely different conditions due to quite separate genes. The behavior and type of endocrine over-activity is different. MEN 1 is also known as MEA 1 (Multiple Endocrine Adenomatosis Type 1) and Wermer's Syndrome (after Dr. Wermer).


Does MEN 1 Cause Cancer?
Most of the endocrine problems related to MEN 1 are not cancerous (malignant). However, malignancy can occur and is one reason why people who inherit the MEN 1 gene need regular tests. If malignancy develops, it is most likely to occur in relation to the pancreas and thymus (the thymus is in the chest). Malignancy in MEN 1 is rare before 30 years of age, and most people with MEN 1 never develop a malignancy due to MEN 1. It is believed that regular tests will lead to early diagnosis of malignancy. It is hoped early diagnosis of such tumors will reduce the likelihood of serious complications.


Will a Person with MEN 1 Always Know that MEN 1 Runs in Their Family?
A person will not always know that MEN 1 runs in their family. In some families, relatives are unaware that there is a history MEN 1. The symptoms of MEN 1 are extremely variable; some people live to old age with few health problems. Also, many of the health problems associated with MEN 1 occur frequently in the general population. Conditions such as stomach ulcers, kidney stones, and tiredness are all very common among people without MEN 1. For these reasons, MEN 1 may go unrecognized in a family.


Does MEN 1 Affect Life Expectancy?
The majority of people with MEN 1 live beyond 65 years of age. With regular tests and appropriate treatment (when necessary), most people with MEN 1 can expect to live a long and productive life. Regular medical follow-up is, however, essential.


Can MEN 1 Be Prevented or Cured?
The health problems caused by inheriting MEN 1 can usually be controlled with the right treatment.

Because MEN 1 is caused by a malfunctioning gene, which is present in every cell of the body, it is not possible to cure MEN 1. Curing MEN 1 would require replacing the malfunctioning gene in billions of the body's cells. It is possible that in the future drugs will be developed to prevent MEN 1 related endocrine gland overactivity. However, in the foreseeable future the treatment of people with MEN 1 will continue to be based on regular tests, early diagnosis of problems, and appropriate treatment (almost always surgical removal of the over-active adenomas). 

Testing for MEN 1


Tests Needed for MEN 1
There are 2 main types of MEN 1 tests. These are:

  • those to test for inheritance of the MEN 1 gene
  • those for screening people for endocrine gland over-activity. Only people who have inherited the MEN 1 gene are at an increased risk of developing the MEN 1 syndrome.

Tests to determine if the MEN 1 gene has been inherited are the most important tests to do if a family member has the gene.


Who Needs to Be Tested for Inheritance of the MEN 1 Gene?
People with a family history of MEN 1 as well as those individuals in whom illness may be related to MEN 1 require tests to determine if they have inherited the MEN 1 gene.


How Is Inheritance of the MEN 1 Gene Diagnosed?
The most reliable way to determine if MEN 1 gene has been inherited is to do a genetic test (predictive genetic testing). Recent advances have made it possible to perform predictive genetic testing at any age. This requires only a single blood sample.

The DNA in the blood sample is analyzed for the presence of an abnormal MEN 1 gene. People with an abnormal MEN 1 gene are said to have a positive result. This test can detect MEN 1 even when all other tests are normal. A negative genetic test result means that a person does not have MEN 1, nor can they pass MEN 1 to their children.

Those individuals with a positive genetic test result should have regular tests for endocrine gland over-activity. Genetic testing is not usually part of routine MEN 1 blood testing. If you would like more information on the criteria for genetic testing, please discuss the issue with your doctor. Some people may live in places where MEN 1 genetic testing is not be available. Under this circumstance, regular screening for endocrine gland overactivity is usually offered to all individuals with a strong family history of MEN 1.


What Tests Are Needed if a Person Has Inherited MEN 1?
If a person has inherited MEN 1, they should have regular screening for endocrine gland over-activity. This involves periodic blood tests (about 2 per year) and occasional scans. These blood tests and scans are done in order to detect endocrine gland over-activity and adenoma at an early stage. Early detection of endocrine gland over-activity and adenoma allows any necessary treatment to be started before complications develop.

The blood tests measure the level of:

  • Parathyroid hormone and calcium (and ionized calcium) to detect hyperparathyroidism (often the first sign of MEN 1).
  • Prolactin is a hormone commonly over-produced by the pituitary gland.
  • Gastrin causes stomach ulcers and is produced by overactivity in the region of the pancreas.  Gastrinomas are the most common neuroendocrine tumor of the pancreas which occurs with MEN 1.  Although the pancreas can have endocrine tumors of insulin secreting cells or other hormones, gastrin is the most common.
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Reference

  1. Multiple Endocrine Neoplasia Type 1 page. National Endocrine and Metabolic Diseases Information Service Web site. Available at: http://endocrine.niddk.nih.gov/pubs/men1/men1.htm. November 2009. Accessed May 20, 2010.

Source

  • Multiple endocrine neoplasia page.  Genetics Home Reference Web site.  Available at:  http://ghr.nlm.nih.gov/condition/multiple-endocrine-neoplasia.  April 2006.  Accessed May 20, 2010.