Multiple Endocrine Neoplasia Type 2

Multiple endocrine neoplasia type 2 (MEN2) is a rare genetic disorder that is passed down from parents to their children (inherited). People with MEN2 have a high risk of developing cancer in glands of the endocrine system. The endocrine system includes the:

• Thyroid gland
• Adrenal gland
• Pancreas
• Testes
• Ovaries

These glands make hormones. The hormones send chemical messages that control the activities of cells and organs.

Types of multiple endocrine neoplasia type 2

There are 3 types of MEN2 :

• Type 2A: People with this type have a greater risk for medullary thyroid cancer and pheochromocytomas. They also have an increased risk for primary hyperparathyroidism, where their parathyroid glands make too much parathyroid hormone. Non-cancerous tumors (adenomas) develop in the parathyroid glands, or the parathyroid gland tissue grows more than normal (hyperplasia). Signs and symptoms of MEN2A 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. But they do not have a risk for pheochromocytomas or hyperparathyroidism. This type is similar to type 2A.
• Type 2B — People with this type have a higher risk for medullary thyroid cancer and pheochromocytomas. They also have a higher risk of ganglioneuromas in the digestive tract. Ganglioneuromas are tumors made of nerve cells and ganglion cells that support nerves.

People with MEN2B are often tall and slender. They may also develop non-cancerous growths of the lips and tongue (mucosal neuromas). Signs and symptoms of multiple endocrine neoplasia type 2B usually begin in infancy or early childhood.

Cancer risk with multiple endocrine neoplasia type 2

Nearly all people with MEN2 develop some type of endocrine cancer at some point in their lives. Those with MEN2 have an increased risk of developing medullary thyroid cancer (MTC) and pheochromocytomas, which are tumors of the adrenal gland. People with MEN2 may also develop other types of abnormal growths in their endocrine tissues or glands.

The lifetime risks of developing cancer for the subtypes of MEN2 are:

Symptoms of multiple endocrine neoplasia type 2

MEN2 can affect many areas of the body, so people with this condition may have a variety of symptoms. Their symptoms will vary, depending on where their cancerous tumors are located and the amount of hormones the tumors make.

People with MEN2 may have some of these symptoms, many of them, or none.

Causes of Multiple endocrine neoplasia type 2

MEN2 is caused by changes in a gene known as RET. This gene carries important information that controls cell growth and function. A change that causes the gene to not work correctly is called a mutation.

How multiple endocrine neoplasia type 2 is inherited

Everyone has 2 copies of the RET gene. Children without this disorder carry 2 normal copies of the RET gene in their cells. One copy of RET is inherited from the child’s mother, and the other comes from the child’s father.

Children who have MEN2 inherit 1 normal copy of the RET gene and 1 copy that is changed (mutated). This change makes the gene not work correctly. It is called a RET mutation.

Nearly all children with MEN2A and about 50% (1 in 2) of children with MEN2B inherit the RET gene mutation from a parent who also has the syndrome. Those who did not inherit the RET mutation have developed a new RET mutation 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 ovum (egg) or sperm that formed the child
• 1 of the child’s cells before they were born

These children are the first in their families to have MEN2.

No matter how they acquired the RET mutation, people with MEN2 have a 50% (1 in 2) chance of passing it on to their children.

Because people with MEN2 have only 1 normal copy of RET in their cells, those cells are harder to control. They tend to grow and divide more than usual, which can cause a tumor. This happens most often in certain cells of the endocrine system, especially thyroid cells. This may be why people with MEN2 have a higher risk of developing tumors than people who do not have this condition.

Multiple endocrine neoplasia type 2 diagnosis

Health history

A health care provider may suspect that your child has MEN2 after studying their medical and family cancer history.

This information helps the health care provider and the genetic counselor know if:

• There are more cancers than normal in your family
• These cancers happened at a younger age than expected
• The types of tumors match up with what might be seen in those with MEN2
• There are family members who have clinical signs of MEN2

Your provider or genetics counselor may recommend genetic testing if they suspect MEN2.

Learn more about types of genetic tests. 

Genetic testing for MEN2

A blood sample is sent to a genetic testing lab. The lab runs genetic tests that look for changes in the RET gene.

If your child has a RET mutation, a genetic counselor will work with your family to:

• Work with your family to see if other family members should be tested
• Help your family understand their increased cancer risk
• Give you information to help you with decisions about prenatal genetic testing

Even if genetic testing does not find a mutation in the RET gene, a person can still have this condition. There may be other types of mutations that cause MEN2 that doctors do not yet know about.

Genetic testing before or during pregnancy

Parents may undergo prenatal testing to find out if the pregnancy is affected by a known RET mutation in the family. Testing may take place either before or during pregnancy.

You should work with a genetic counselor to review the pros and cons of the test. The genetic counselor can also help you prepare for the test results.

Testing before pregnancy is called preimplantation genetic testing (PGT). This special type of genetic testing is done along with in vitro fertilization (IVF). PGT tests embryos for a known RET mutation before a doctor places the embryo into the uterus.

Testing during pregnancy can help doctors see if a pregnancy has a known RET mutation. A doctor gathers cells from the pregnancy in 1 of 2 ways:

• Chorionic villus sampling (CVS) is done during the first 3 months of pregnancy (1st trimester).
• Amniocentesis is done after the first 3 months of pregnancy (2nd trimester or later).

After tissue collection, the lab checks the sample for a mutation in RET. Both tests carry minor risks. Discuss these risks with an experienced health care provider or a genetic counselor.

Special concerns for genetic testing

Take time to think carefully about the benefits and risks of genetic testing. Speak with a genetic counselor before testing. If you decide to get tested, talk with your health care provider or a genetic counselor about your results so you can understand what they mean.

Sometimes, children or adults with MEN2 experience sadness, anxiety, or anger after getting their test results. Parents may feel guilty if they passed on a mutation of RET to 1 or more of their children. People with these mutations may also have trouble getting disability or life insurance.

Read more about genetic discrimination. 

Diagnosis of MEN2 without genetic testing

Patients have a clinical diagnosis of MEN2A when they or their close relatives have 2 or more of these conditions:

• Medullary thyroid cancer
• Pheochromocytomas
• Parathyroid adenoma/ hyperplasia

A person may be diagnosed with type MEN2B if they have medullary thyroid cancer and some of these conditions:

• Mucosal neuromas of the lips and tongue
• Unusual features, such as a long face and lips that stick outward
• A tall and slender body type
• Abnormal nerves in the clear covering of the eyeball (medullated corneal nerve fibers)

The diagnosis of familial medullary thyroid cancer is given if:

• A family has 4 or more family members with medullary thyroid cancer
• None of the family members have pheochromocytomas, parathyroid adenoma, or parathyroid hyperplasia

Monitoring and follow-up care for multiple endocrine neoplasia type 2

Monitoring and follow-up care for MEN2 depends on how severe the disease is, the location of any tumors that may arise, and a person’s overall health. Care may involve managing symptoms with medications or hormones. Patients may also have surgical removal of their tumors if the tumor presses on nearby organs or produces very high levels of hormones in their bodies. They may require other types of cancer-related treatments depending on the type of cancer they have and where it is located.

Because MEN1 is a complex condition, parents should discuss screening options for their child with an experienced doctor who knows this condition well. The goal of screening is to find and treat tumors early. Doing so allows the best outcome for patients. There are clinics throughout the country that specialize in taking care of people with MEN.

It is also important to work with a genetic counselor to find experienced doctors for your child. To find a genetics counselor in your area, visit Personalized Care for Your Genetic Health.

Preventive care for MEN2

It is recommended that children with MEN2 have surgery to remove their thyroid.

Children with subtype 2A or the familial medullary thyroid cancer subtype: This surgery depends on several factors, including RET gene mutation, serum calcitonin levels, and what the family wants.

Children with subtype 2B: This surgery should take place as soon as possible after the child’s birth, often within the first month of life. Health care providers have found this type of thyroid cancer in very young infants.

Cancer screenings for MEN2

Recommended screenings for people with MEN2 include:

• Yearly physical exams by a health care provider who is familiar with MEN2
• Yearly neck ultrasound and serum calcitonin (blood test) starting in the first few months of life to ages 3–5 years, depending on the RET mutation
• Yearly free plasma metanephrines and normetanephrines blood work starting at 8 years old, with follow-up imaging through CT or MRI if results are abnormal
• Yearly calcium and vitamin D blood work starting at 11 or 16 years old, depending on the type of RET mutation

People with MEN2 should avoid certain kinds of medicines. These include:

• Dopamine D2 receptor antagonists (such as metoclopramide and veralipride)
• Beta blockers
• Monoamine oxidase inhibitors
• Sympathomimetics (e.g., ephedrine)
• Certain peptide and corticosteroid hormones

Check with a health care provider who is experienced in managing patients with MEN2 about the safety of any medicines.

Living with multiple endocrine neoplasia type 2

People of any age with MEN2 have a higher risk of cancer. They should monitor their health and adopt healthy habits throughout life. It is important to continue to have regular physical checkups and screenings. That way, any cancer can be found early and at the most treatable stage.

Problems to watch for

People with MEN2 should watch closely for general signs or symptoms that could signal a cancer, including:

• Unexplained weight loss
• Loss of appetite
• Pain in the abdomen
• Blood in the stool or changes in bowel habits
• Aches, pains, lumps, or swelling that cannot be explained
• Headaches or changes in vision or nerve function that do not go away

It is important to seek medical help if anything unusual appears.

Maintain a healthy lifestyle

Habits that will help you maintain a healthy lifestyle include:

• Eat a healthy diet with lots of fruit and vegetables.
• Get regular exercise.
• Avoid excess sun exposure. Always wear a hat, protective clothing, and sunscreen (at least SPF 30 or higher) when out in the sun.
• Avoid unnecessary radiation exposure.
• Avoid smoking or the use of tobacco products.
• Avoid being around secondhand smoke.
• Avoid excessive alcohol use.

Multiple endocrine neoplasia type 2 care at         St. Jude

The St. Jude Cancer Predisposition Program is dedicated to diagnosing and screening children with a genetic predisposition for cancer. Our program offers the best clinical care possible. We engage in cutting-edge research to gain more information about genetic disorders and cancer, and to improve the care and treatment for patients who are affected by these conditions. Learn more about the Division of Cancer Predisposition at St. Jude.

Our genetic counselors, clinicians, genetics nurse practitioners, and research assistants work together to provide patients with:

• A complete health history
• A record of cancer that happened over the past 3 generations (family tree or pedigree) to see how diseases were passed down
• Physical exams to check for genetic disease
• Confidential genetic counseling and testing
• Cancer screenings for those with genetic disease to detect and treat cancer as soon as it occurs
• Recommended cancer treatments and ways to reduce cancer risk
• Genetic testing for immediate (1st degree) relatives

MEN2 increases your child’s risk for cancer.

Related clinical trials 

St. Jude offers clinical trials and cancer research studies for children, teens, and young adults who have cancers associated with MEN2. Learn more about clinical research at St. Jude. 

If you have questions about the Genetic Predisposition Clinic and care for MEN2, email our team at GPTeam@stjude.org.

Resources outside St. Jude