Multiple endocrine neoplasia 2 (MEN2)

There are 2 types of multiple endocrine neoplasia. They are MEN1 and MEN2. Although their names are similar, they are separate conditions. This information is about MEN2.

Your body is made up of tiny building blocks called cells. Inside every cell is a set of genes. These are the instructions the cell needs to work normally. Sometimes the structure of a gene is permanently changed. The change is called a gene variant or alteration. Doctors sometimes use the term gene mutation. It means the gene no longer gives the correct instructions.

People with MEN2 have a RET gene variant. If you have this variant, you are more likely to develop certain types of tumour.

There are 2 types of MEN2:

• MEN2A is the most common type. 95 in 100 (95%) are this type.
• MEN2B is sometimes called MEN3. Only 5 in 100 (5%) are this type.

MEN2A can be divided further into 4 subtypes:

• classical MEN2A
• MEN2A with a skin condition called cutaneous lichen amyloidosis – this is very rare
• MEN2A with a bowel condition called Hirschsprung disease – this is very rare
• familial medullary thyroid cancer (FMTC) but no history of phaeochromocytoma or hyperparathyroidism.

MEN2A and MEN2B both cause a higher risk of a specific type of thyroid cancer called medullary thyroid carcinoma (MTC).

People with MEN2A may also develop:

• a tumour of the adrenal gland called phaeochromocytoma
• overactive and enlarged parathyroid glands.

People with MEN2B may also develop:

• a tumour of the adrenal gland called phaeochromocytoma
• benign tumours (neuromas) on the lips, tongue and lining of the mouth, and in the bowel.

You may have some of the tests below to find the cause of particular symptoms.

The tests can also be used to check for MEN2 tumours before you have any symptoms. This is called screening or monitoring. Screening helps your doctor find and treat tumours at an early stage, usually before symptoms begin to cause problems. The earlier someone knows they have MEN2, the sooner they can have treatment and monitoring to help prevent problems.

You usually have these tests at the hospital and go home on the same day (an outpatient appointment).

MTC is a cancer of the thyroid gland. It is the most common tumour caused by MEN2. Most people with MEN2 will develop MTC unless they have an operation to remove the thyroid at an early age.

The thyroid is a small gland in the front of the neck, just below the voicebox (larynx). It is made up of 2 parts called lobes. The thyroid produces the following hormones:

• thyroxine (T4)
• triiodothyronine (T3)
• calcitonin.

Thyroxine and triiodothyronine keep the body functioning at its normal rate. Calcitonin helps control the amount of calcium in the blood.

The thyroid

The signs and symptoms of MTC include:

• a painless lump in the neck
• difficulty breathing or swallowing – this is due to the tumour pressing on the windpipe (trachea) or gullet (oesophagus)
• feeling hot and having a red face (flushing)
• loose poo (stools) or diarrhoea.

You will have an ultrasound scan of your neck to check the thyroid gland. Your doctor will also check the lymph nodes in your neck to see whether any are abnormal. This is because thyroid cancer can sometimes spread to the lymph nodes. Lymph nodes drain fluid from the tissues and help the body fight infections.

The doctor will take a biopsy from any abnormal areas that show on the scan. They gently pass a small needle into the area and withdraw some cells into a syringe. This is called a fine needle aspiration cytology (FNAC).

You will have a blood test to check the level of calcitonin in your blood. You will also usually have a 24-hour urine test.

The main treatment for MTC is surgery to remove the thyroid gland. This is called a thyroidectomy. The surgeon will usually also remove nearby lymph nodes.

Some people may not be able to have an operation – for example, if the MTC has spread. In this case, they may have treatment with radiotherapy. Radiotherapy uses high-energy rays called radiation to treat cancer. It destroys cancer cells in the area where the radiotherapy is given.

Some people may also have the targeted drugs vandetanib or cabozantinib. Targeted drugs work by blocking signals in the thyroid cancer cells that make them grow and divide. These treatments cannot cure MTC, but they may help control it.

Almost everyone with MEN2 will develop MTC. Because of this, children and young adults with the RET gene variant will usually have surgery to remove the thyroid gland before a cancer develops. Children with MEN2A may have surgery before they are 5 years old. Babies with MEN2B may have surgery before they are 1 year old.

After the thyroid gland is removed, you will need to take thyroid hormone tablets (levothyroxine) every day for the rest of your life. These replace the thyroid hormones your body needs to function. You will have regular blood tests to check your thyroid hormones are at the right level.

You will also have blood tests to check the levels of calcitonin and a protein called CEA. These blood tests are used to look for any signs of the MTC coming back after surgery.

There are 4 parathyroid glands. They are just behind the thyroid gland or sometimes inside it. This is in the front of the neck.

If you have MEN2A, the parathyroid glands may become large and overactive. This is most likely to happen between the ages of 20 to 40.

The thyroid and parathyroid glands

Parathyroid glands make a hormone called parathyroid hormone (PTH). PTH helps control calcium levels in the body. People with overactive parathyroid glands may make too much PTH. This can cause your bones to release calcium from the bones into the blood. A high level of calcium in the blood is called hypercalcaemia.

High levels of calcium in the blood can make you:

• feel sick (nauseous)
• thirsty
• drowsy
• confused
• unwell
• constipated
• need to pee (pass urine) often.

If hypercalcaemia is not treated, the bones get thinner due to loss of calcium. This can lead to osteoporosis. This can cause bone pain, and your bones can break more easily.

High levels of calcium in the blood may also affect the kidneys. Some people develop kidney stones or their kidneys may become damaged. Most people are treated early, so this is not usually a problem.

You will have a blood test every year to check your calcium and PTH levels. It is important to tell your doctor if you have any symptoms that may be caused by high levels of calcium in between screening tests.

The main treatment for overactive parathyroid glands is an operation to remove some or all of the parathyroid glands.

If the surgeon needs to remove all of your parathyroid glands, you will need to take tablets for the rest of your life. This is to control calcium levels.

If the surgeon only removes some of the parathyroid glands, the remaining glands can sometimes become overactive after surgery. If this happens, you may need another operation to remove the affected parathyroid glands.

Your surgeon will explain the different treatments for overactive parathyroid glands. You can then decide together what is right for you.

Your doctor may give you drugs called calcimimetic agents to reduce symptoms of overactive parathyroid tissue. They reduce the amount of parathyroid hormone made by the glands.

Neuromas are benign growths. In people with MEN2B, they may develop on the:

• eyelids
• lips
• lining of the mouth
• bowel.

Neuromas are painless and do not usually need treatment. They often look like little bumps. They may be pale or the same colour as surrounding tissue. They can make the lips look larger and fuller. Neuromas in the bowel can cause constipation or diarrhoea. Your doctor or specialist nurse can give you information and advice about managing this.

You may have many different emotions including anger, resentment, guilt, anxiety and fear. These are all normal reactions. They are part of the process many people go through as they try to come to terms with their condition.

Everyone has their own way of dealing with illness and the different emotions they experience. There is no right or wrong way to cope, but help is there if you need it. You may find it helpful to talk things over with family and friends or your specialist doctor or nurse.

Macmillan is also here to support you. If you would like to talk, you can:

• call the Macmillan Support Line on 0808 808 00 00
• chat to our specialists online
• share your thoughts with members of our Online Community.

You may also find it helpful to contact AMEND for more information and support.