Multiple Endocrine Neoplasia Type 2

General DescriptionMultiple Endocrine Neoplasia type 2 (MEN 2) is a VERY uncommon inherited disease. Individuals who inherit the gene for MEN 2 will develop overactivity and enlargement of certain endocrine glands. The endocrine glands most commonly affec

General Description
Multiple Endocrine Neoplasia type 2 (MEN 2) is a VERY uncommon inherited disease. Individuals who inherit the gene for MEN 2 will develop overactivity and enlargement of certain endocrine glands. The endocrine glands most commonly affected by MEN 2 are the parathyroid, adrenal, and thyroid glands. Almost everyone who inherits MEN 2 develops medullary thyroid cancer at some stage in their life (separate page on medullary thyroid cancer). The other endocrine glands also become overactive including overproduction of adrenaline by a tumor in the medulla of the adrenal (see our pages on adrenal glands and pheochromocytomas) Overactivity in different endocrine glands may occur simultaneously or at separate times during a persons life.

How common is MEN 2 ?
MEN 2 is a VERY rare condition. On average, fewer than 1 person in every 20,000 will carry the gene for MEN 2. MEN 2 is passed down in families from one generation to the next.  MEN 2 can be inherited by a child if one of their parents has MEN 2. Males and females are equally likely to inherit the MEN 2 gene from an affected parent. MEN 2 is known to occur in all major racial groups.

The Effect of MEN 2 on the Endocrine Glands
MEN 2 can lead to overactivity and enlargement of the three endocrine glands listed above. The different endocrine glands in the body each produce different and specific hormones. Hormones are chemicals which are produced by endocrine glands to regulate the function of various tissues throughout the body (see our page which introduces the Endocrine System). The endocrine glands are relatively small in size and 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 (a little bit goes a long way!). Under normal circumstances, the level of endocrine gland activity is carefully regulated.

People who inherit the gene for MEN 2 are predisposed to developing an overactivity in hormone production from the parathyroid glands, the central portion of the adrenal gland (the adrenal medulla) and a very certain type of thyroid cancer (that's why physicians will measure hormones in the blood to check for overproduction of each specific hormone). Increased hormone production is usually associated with enlargement of these glands.

What Age Does MEN 2 Usually Present Itself ?
Although a person is born with the gene for MEN 2, endocrine gland overactivity is rare prior to 10 years of age. Different endocrine glands become overactive at different times in life. Similarly, different areas within one endocrine gland will become overactive (or develop adenoma) at different times during life. In general, the likelihood of endocrine gland overactivity and the development of adenoma increases with age. It is rare for overactivity (or adenoma) to be present before 10 years of age. Like those affected by the MEN 1 gene, by age 30, most people who inherit MEN 2 will have some type of endocrine gland overactivity. Overactivity 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 2 until they are older than 30. For this reason it is important for all people at risk to be tested for MEN 2, even though they may feel quite well.

The Endocrine Glands Usually Affected by MEN 2
MEN 2 is different from MEN 1 in one very important way...those with MEN 2 will almost certainly develop thyroid cancer.  The type of thyroid cancer these people get is considerably more aggressive than when thyroid cancer develops in non-MEN patients (normal individuals).  First of all, the type of cancer which develops is a more aggressive type, and secondly, this cancer begins early in life in MEN 2 patients and grows quickly.   For this reason, patients identified with the MEN 2 gene should have their thyroid surgically removed completely while they are still young...certainly before they are in their mid-teenage years.

Should Everyone With an Endocrine Gland Problem be Tested for MEN 2?
No! Only a very small proportion of people with endocrine disorders have MEN 2. Most endocrine problems have nothing to do with MEN 2.

Is MEN 1 the Same as MEN 2 ?
MEN 1 and MEN 2 are completely different conditions due to quite separate genes.

Does MEN 2 Cause Cancer ?
Most of the endocrine problems related to MEN 1 are not cancerous (malignant).  As noted above, however, MEN 2 is very different in this regard with the development of thyroid cancer in all affected individuals.

Can MEN 2 be Prevented or Cured?
The health problems caused by inheriting MEN 2 can usually be controlled with the right treatment. Because MEN 2 is caused by a malfunctioning gene, which is present in every cell of the body, it is not possible to cure MEN 2. Curing MEN 2 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 2 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 overactive adenomas).  The exception to this rule, however, is the complete removal of the thyroid in patients with MEN 2 PRIOR to it becoming cancerous.  This has been shown to prevent the formation of medullary thyroid cancer in these individuals and increase life expectancy.

Testing For MEN 2

Tests Needed for MEN 2
There are two main types of MEN 2 tests. These are [1] those to test for inheritance of the MEN 2 gene and [2] those for screening people for endocrine gland overactivity.  Tests to determine if the MEN 2 gene has been inherited are therefore the most important tests to do first if a family member has the gene.

Who Needs to be Tested for Inheritance of the MEN 2 Gene?
People with a family history of MEN 2 as well as those individuals in whom illness may be related to MEN 2 (even if there is no obvious family history because sometimes the gene will become bad in an individual for the first time in that family...but this is even more rare), require tests to determine if they have inherited the MEN 1 gene.   This may include patients who develop hyperparathyroidism or pheochromocytomas at an early age.

How is inheritance of the MEN 2 gene diagnosed?
The most reliable way to determine if MEN 2 gene has been inherited is to do agenetic 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 2 gene. People with an abnormal MEN 1 gene are said to have a positive result. This test can detect MEN 2 even when all other tests are normal. A negative genetic test result means that a person does not have MEN 2, nor can they pass MEN 2 to their children. Those individuals with a positive genetic test result should have regular tests for endocrine gland overactivity. Genetic testing is not usually part of routine MEN 2 blood testing. If you would like more information on the criteria for genetic testing please discuss the issue with your doctor. Genetic testing is now available for everybody in the U.S..

What Tests are Needed if a Person has Inherited MEN 2?
If a person has inherited MEN 2 they should have regular screening for endocrine gland overactivity. This involves periodic blood tests (about two per year) and occasional scans. These blood tests and scans are done in order to detect endocrine gland overactivity and adenoma at an early stage. Early detection of endocrine gland overactivity 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 2).
• Epinephrine is a hormone over-produced by the adrenal gland.
• Calcitonin  is the hormone produced by the cells of the thyroid which eventually become malignant in the form of medullary thyroid cancer.  Everybody with medullary thyroid cancer will have elevated levels of calcitonin in their blood.

MEN Syndromes  |  MEN-1  |  MEN-2  |  Hyperparathyroidism  |  Pheochromocytoma   |  Medullary Thyroid Cancer