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Multiple Endocrine Neoplasia Type 2

Disorders of the Parathyroid, Adrenal, and Thyroid Cancer

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 (which is different from multiple endocrine neoplasia type 1—also called MEN 1) develops medullary thyroid cancer at some stage in their life.

In this Article

The other endocrine glands also become overactive, including overproduction of adrenaline by a tumor in the medulla of the adrenal gland (see our articles on the adrenal glands and pheochromocytomas). Overactivity in different endocrine glands may occur simultaneously or at separate times during your life.

How Common Is MEN 2?
MEN 2 is a rare condition. On average, fewer than 1 person in every 20,000 people 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 that are produced by endocrine glands to regulate the function of various tissues throughout the body (see our in-depth article about the endocrine system).

The endocrine glands are relatively small, and they release a controlled amount of their hormone directly into the bloodstream. Once in the bloodstream, 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.

MEN 2 Diagnosis
Although a person is born with the gene for MEN 2, endocrine gland overactivity is rare before 10 years old. 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.

As with 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 years old. 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). 

This cancer tends to begin early in life in MEN 2 patients, and it grows quickly.  For this reason, patients identified with the MEN 2 gene should have their thyroid surgically removed completely while they are still young.

Should Everyone With an Endocrine Gland Problem Be Tested for MEN 2?
No! Only a very small portion 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 that are caused by different 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, medications will be developed to prevent MEN 2-related endocrine gland overactivity. However, in the foreseeable future the treatment of people with MEN 2 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 before it becomes cancerous. This has been shown to prevent the formation of medullary thyroid cancer in these individuals and increase life expectancy.

Testing for MEN 2

There are 2 main types of MEN 2 tests: those that test for inheritance of the MEN 2 gene and those that screen 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) require tests to determine if they have inherited the 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 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 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, but if you would like more information on the criteria for genetic testing, talk to your doctor.

What Tests Are Needed If a Person Inherits MEN 2?

If a person has inherited MEN 2, they should have regular screening for endocrine gland overactivity. 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 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, a hormone over-produced by the adrenal gland
  • Calcitonin, 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.

Multiple Endocrine Neoplasia Type 2 Conclusion

If multiple endocrine neoplasia type 2 runs in your family, have a conversation with your doctor. He or she may want to run some tests, and if you're diagnosed with multiple endocrine neoplasia type 2, your doctor will create a treatment plan for you.