What is multiple endocrine neoplasia type 2?

Multiple endocrine neoplasia type 2 (MEN2) is a hereditary condition associated with medullary thyroid carcinoma, a specific type of thyroid cancer. MEN2 is divided 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 (tumor of the adrenal glands)
  • Parathyroid adenomas (benign [noncancerous] tumors) or hyperplasia (increased size) of the parathyroid gland
  
  
  
• MEN2B, which affects 5% of MEN2 families
  • Medullary thyroid carcinoma
  • Pheochromocytoma
  • Mucosal neuromas (benign tumors of nerve tissue on the tongue and lips)
  • Digestive problems
  • Muscle, joint, and spinal problems
  • Typical facial features

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.

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?

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, including swollen lips and thick eyelids. Medullary thyroid cancer can occur very early in childhood.

FMTC is suspected in families with at least four cases of medullary thyroid cancer and no evidence of parathyroid or adrenal gland problems.

Genetic testing for mutations in the RET gene is available and is recommended for people with a family history of MEN2A, MEN2B, and FMTC, and anyone diagnosed with medullary thyroid cancer. Mutations in the RET gene are found in approximately 95% of families with MEN2A or MEN2B, and in more than 85% of families with FMTC. 

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.

Additional screening recommendations include:

• Yearly blood tests for calcium-stimulated calcitonin levels, beginning as early as possible (MEN2A, MEN2B, FMTC)
  
  
• Yearly blood tests for ionized calcium and parathyroid hormone levels, beginning in childhood (MEN2A)
  
  
• Yearly blood and urine tests for catecholamines and catecholamine metabolites, beginning in childhood (MEN2A, MEN2B, FMTC)
  
  
• Magnetic resonance imaging (MRI) or computerized tomography (CT or CAT) scan of the abdomen, 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.

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 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

Cancer.Net Guide to Thyroid Cancer

The Genetics of Thyroid Cancer

What to Expect When You Meet With a Genetic Counselor

National Cancer Institute (NCI)
www.nci.nih.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