People with Multiple Endocrine Neoplasia Type 2 have an increased risk of developing medullary thyroid cancer (MTC) and pheochromocytomas, which are tumors of the adrenal gland. People with this condition may also develop other types of abnormal growths in endocrine tissues or glands.
There are three subtypes of Multiple Endocrine Neoplasia Type 2:
- MEN2A: People with this subtype have an increased risk for medullary thyroid cancer and pheochromocytomas. They also have an increased risk for primary hyperparathyroidism, a condition in which the parathyroid glands produce too much parathyroid hormone. This usually happens because non-cancerous tumors (adenomas) develop in the parathyroid glands, or because the parathyroid gland tissue grows more than normal (hyperplasia). Signs and symptoms of Multiple Endocrine Neoplasia Type 2A usually begin in early adulthood.
- Familial medullary thyroid cancer (FMTC): People with this subtype have an increased risk of developing medullary thyroid cancer in early or middle adulthood. However, they do not appear to be at risk of having pheochromocytomas or hyperparathyroidism. This subtype is considered a variant of type 2A.
- MEN2B: People with this subtype have an increased risk for medullary thyroid cancer and pheochromocytomas. They also have a higher likelihood of developing ganglioneuromas in the digestive tract. Ganglioneuromas are tumors made of nerve cells and ganglion cells, which are special cells that normally support the nerve cells in the body. People with Multiple Endocrine Neoplasia Type 2B may also develop non-cancerous growths of the lips and tongue (mucosal neuromas), and they often have a tall, slender body type. Signs and symptoms of Multiple Endocrine Neoplasia Type 2B usually begin in infancy or early childhood.
Multiple Endocrine Neoplasia Type 2 is caused by changes in a gene known as RET. Genes carry information telling cells in the body how to work. The RET gene helps to control how and when cells grow and divide.
People without Multiple Endocrine Neoplasia Type 2 carry two working copies of the RET gene in their cells. One copy of RET is inherited from each parent. Cells from people with Multiple Endocrine Neoplasia Type 2 carry one working copy of RET and one copy that is changed. This change causes RET to work more than it should. It is called a RET gain-of-function variant.
Nearly all children with Multiple Endocrine Neoplasia Type 2A and about half of children with Multiple Endocrine Neoplasia Type 2B inherit the RET gene variant from a parent who also has the syndrome. Those who do not inherit the RET variant have developed a new RET variant that did not come from a parent. These children have no history of the syndrome in their family. In these cases, the change either happened in an egg or sperm cell when the child was formed or in one of the child’s cells during pregnancy. These children are the first in their families to have Multiple Endocrine Neoplasia Type 2.
No matter how they acquired the RET variant, people with Multiple Endocrine Neoplasia Type 2 have a 50% (or 1 in 2) chance of passing it on to their children.
Since people with Multiple Endocrine Neoplasia Type 2 have one copy of RET that causes it to work more than it should, those cells are at risk for growing and dividing uncontrollably, which can cause a tumor. This happens most often in certain cells of the endocrine system, especially thyroid cells. Researchers believe that this is why people with Multiple Endocrine Neoplasia Type 2 have a higher risk of developing tumors than people who do not have this condition.
A doctor may suspect this diagnosis based on physical exam, and/or after looking at a person’s medical or family history. In most cases, a doctor or genetic counselor will ask questions about the person’s health and the health of other family members. Read more about genetic counseling and genetic testing.
Diagnosing this syndrome is usually done by sequencing the RET gene to find variants (gene changes).
Genetic testing does not always find a variant in the RET gene for all people with Multiple Endocrine Neoplasia Type 2 and a family history of the condition. There may be other types of variants causing this condition that health care providers do not yet know about. Therefore, a person can still have Multiple Endocrine Neoplasia Type 2, even if no RET variant is found.
The diagnosis may also be made based on the following clinical information alone:
Multiple Endocrine Neoplasia Type 2A is diagnosed when two or more of the following are seen in a person or among close relatives:
- Medullary thyroid cancer
- Pheochromocytomas
- Parathyroid adenoma/hyperplasia
Multiple Endocrine Neoplasia Type 2B is suspected when a person has medullary thyroid cancer as well as the presence of some of the following:
- Mucosal neuromas of the lips and tongue
- Distinctive facial features, including an elongated face and protruding lips
- A tall and slender body type
- Medullated corneal nerve fibers (abnormal nerves in the clear covering of the eyeball, which an ophthalmologist can see during an eye exam)
Familial medullary thyroid cancer is diagnosed in families where 4 or more family members have medullary thyroid cancer but do not have pheochromocytomas, parathyroid adenoma, or parathyroid hyperplasia.
Nearly all people with Multiple Endocrine Neoplasia Type 2 develop some type of endocrine cancer at some point in their lives.
In people with MEN2A, the lifetime risks of medullary thyroid carcinoma, pheochromocytoma, and parathyroid disease are 95%, 50%, and 20-30%, respectively.
Nearly all people with familial medullary thyroid cancer will develop medullary thyroid carcinoma but will probably not develop pheochromocytoma or parathyroid disease.
In people with MEN2B, the lifetime risk of medullary thyroid carcinoma and pheochromocytoma are 100% and 50%, respectively, while parathyroid disease is uncommon.
Cancer screening involves tests to check for cancer before symptoms occur. The goal is to find cancer at the earliest and most treatable stage. Guidelines for cancer screening are available online. Recommended screenings may change over time as doctors learn more about this syndrome, so these screening tests should be discussed with a health care provider who knows this syndrome well.
For people with Multiple Endocrine Neoplasia Type 2, there is the option of preventing cancer by removing the thyroid gland. For children with MEN2B, this surgery should take place as soon as possible after the child’s birth. For people with MEN2A, this surgery can be delayed until later in life, depending on several factors.
Other ideas to reduce the risk of cancer includes:
- Eat a healthful diet with lots of fruits and vegetables
- Get regular exercise
- Avoid smoking or using tobacco products
- Avoid secondhand smoke
- Avoid excess sun exposure and always wear sunscreen, hat, and protective clothing when out in the sun
- Get medical attention for unusual or ongoing symptoms
People with Multiple Endocrine Neoplasia Type 2 should avoid certain kinds of medicines. These include:
- Dopamine D2 receptor antagonists (for example, metoclopramide and veralipride)
- Beta blockers
- Monoamine oxidase inhibitors
- Sympathomimetics (e.g., ephedrine)
- Certain peptide and corticosteroid hormones
It is important to check with a health care provider who is experienced in managing patients with Multiple Endocrine Neoplasia Type 2 about the safety of any medicines.
Because of the medical concerns related to this syndrome, specialists in the following areas may need to assess a child with Multiple Endocrine Neoplasia Type 2:
- Endocrinology
- Gastroenterology
- Otolaryngology (Ear, nose, and throat specialist)
Resources about Multiple Endocrine Neoplasia Type 2:
- Genetics Home Reference (ghr.nlm.nih.gov/condition/multiple-endocrine-neoplasia)
- American Multiple Endocrine Neoplasia Support (www.amensupport.org)
- National Organization for Rare Disorders (rarediseases.org/rare-diseases/multiple-endocrine-neoplasia-type)
Other resources:
- Making Sense of Your Genes: A Guide to Genetic Counseling (www.ncbi.nlm.nih.gov/books/NBK115508/)
Adapted from educational materials developed by the St. Jude Children’s Research Hospital Cancer Predisposition Program