What is multiple endocrine neoplasia type 2?
Multiple endocrine neoplasia type 2 (MEN2) is a hereditary condition associated primarily with medullary thyroid carcinoma, a specific type of thyroid cancer. MEN2 is classified into three subtypes based on symptoms.
- Familial medullary thyroid carcinoma (FMTC), which affects 5% to 35% of MEN2 families
- Medullary thyroid carcinoma only
- MEN2A, which affects 60% to 90% of MEN2 families
- Medullary thyroid carcinoma
- Pheochromocytoma (a typically [benign] noncancerous tumor of the adrenal glands)
- Parathyroid adenoma (benign tumor) or hyperplasia (increased size) of the parathyroid gland
- MEN2B, which affects 5% of MEN2 families
- Medullary thyroid carcinoma
- Pheochromocytoma
- Mucosal neuroma (benign tumor of nerve tissue on the tongue and lips)
- Digestive problems
- Muscle, joint, and spinal problems
- Typical facial features, including swollen lips and thick eyelids
What causes MEN2?
MEN2 is a genetic condition. This means that the cancer risk and other features of MEN2 can be passed from generation to generation in a family. The gene associated with MEN2 is called RET. A mutation (alteration) in the RET gene gives a person an increased risk of developing medullary thyroid cancer and other symptoms of MEN2. Research is ongoing to learn more about MEN2.
How is MEN2 inherited?
Normally, every cell has two copies of each gene: one inherited from the mother and one inherited from the father. MEN2 follows an autosomal dominant inheritance pattern, in which a mutation happens in only one 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, a child who has a parent with a mutation has a 50% chance of inheriting that mutation. A brother, sister, or parent of a person who has a mutation also has a 50% chance of having the same mutation. If a child inherits the mutant RET gene from an affected parent, there is almost a 100% chance of developing medullary thyroid carcinoma and other symptoms of this syndrome during his or her lifetime.
How common is MEN2?
It is estimated that about one in 30,000 people has MEN2. About 50% of people with MEN2B do not have any family history of the condition. They have a de novo (new) mutation in the RET gene. Less than 5% of people with MEN2A are thought to have a de novo mutation in the RET gene.
How is MEN2 diagnosed?
FMTC is suspected in families with two or more cases of medullary thyroid cancer and no evidence of parathyroid or adrenal gland problems.
MEN2A is suspected when there are at least two of the three common tumors (medullary thyroid cancer, pheochromocytoma, or parathyroid adenoma) in one person or close relatives. Close relatives are generally considered to be parents, siblings, and children.
MEN2B is suspected in children with mucosal neuromas and typical facial features of a person with MEN2B. Medullary thyroid cancer can occur very early in childhood.
Genetic testing for mutations in the RET gene is available. It is recommended for people with a family history of FMTC, MEN2A, and MEN2B, and anyone diagnosed with medullary thyroid cancer. Mutations in the RET gene are found in more than 95% of families with MEN2A or MEN2B, and in more than 85% of families with FMTC. Certified genetic testing laboratories for this condition can be found at www.genetests.org.
What are the estimated cancer risks associated with MEN2?
The risk of medullary thyroid cancer in people with MEN2 is nearly 100% for all subtypes.
What are the screening options for MEN2?
Due to the high risk of medullary thyroid cancer, RET gene testing is recommended for children at risk for any of the MEN2 subtypes. If a mutation is found, the thyroid gland should be surgically removed to prevent cancer from developing. This surgery is recommended by age 3 in children with MEN2B and by age 6 in children with MEN2A or FMTC. The procedure should be performed by a surgeon with experience in both thyroid surgery in children and with the management of medullary thyroid carcinoma.
Additional screening recommendations may include:
- Yearly blood tests for ionized calcium and parathyroid hormone levels, beginning in childhood (MEN2A)
- Yearly blood tests for catecholamines and catecholamine metabolites (metanephrine and normetanephrine), beginning in childhood (FMTC, MEN2A, MEN2B)
- Magnetic resonance imaging (MRI) or computerized tomography (CT or CAT) scan of the abdomen to detect pheochromocytomas, as needed
Screening guidelines may change over time as new technologies are developed and more is learned about MEN2. It is important to talk with your doctor about appropriate screening tests.
Learn more about what to expect when having common tests, procedures, and scans.
Find out more about common terms used during a diagnosis of cancer.
What is the treatment for medullary thyroid cancer that has spread to the lymph nodes of the neck or beyond?
Surgical resection (removal) of lymph nodes in the neck and upper chest (performed by a surgeon experienced with this technique) can result in cure in 10% to 20% of cases where there is spread to neck lymph nodes.
Recent studies of drugs that target the RET gene have shown promise for the treatment of medullary thyroid carcinoma that has spread to liver or other sites. While these studies are promising, these medications are only available through participation in a clinical trial (research study). For more information on treatment options, read the guide to thyroid cancer.
What are the risks associated with pheochromocytoma?
Pheochromocytoma associated with MEN2 is almost always a benign tumor. However, such tumors commonly produce abnormally high levels of adrenalin and noradrenalin and may cause high blood pressure, a rapid or irregular heart rate, or cardiac arrest. Medical treatments to prevent these symptoms are highly effective and should be started at the time of diagnosis and before the surgical removal of the tumor. Learn more in the guide to adrenal gland tumors.
What is the typical treatment for a parathyroid tumor?
Increased production of parathyroid hormone by a benign parathyroid tumor can cause hypercalcemia (high blood calcium), kidney stones, and osteoporosis (loss of bone mass). Surgical removal of the parathyroid tumor often cures the problem. More information can be found in the guide to parathyroid tumors.
Questions to ask the doctor
If you are concerned about your risk of thyroid cancer, talk with your doctor. Consider asking the following questions of your doctor:
- What is my risk of developing thyroid cancer?
- What is my risk of developing other types of tumors?
- What can I do to reduce my risk of cancer?
- What are my options for cancer screening?
If you are concerned about your family history and think you or other family members may have MEN2, consider asking the following questions:
- Does my family history increase my risk of developing thyroid cancer?
- Should I meet with a genetic counselor?
- Should I consider genetic testing?
Additional resources
Guide to Thyroid Cancer
The Genetics of Thyroid Cancer
What to Expect When You Meet With a Genetic Counselor
National Cancer Institute
www.cancer.gov
American Cancer Society
www.cancer.org
CancerCare
www.cancercare.org
To find a genetic counselor in your area, ask your doctor or visit these websites:
National Society of Genetic Counselors
www.nsgc.org
National Cancer Institute
www.cancer.gov/search/geneticsservices
