Multiple endocrine neoplasia (MEN) is an inherited condition that causes growths (tumours) in endocrine glands. There are endocrine glands throughout the body. They make chemicals called hormones. These control many functions in the body and help keep it in balance.

There are two types of MEN: MEN1 and MEN2. Although their names are similar, they are completely separate conditions. This information is about MEN2.

Tumours caused by MEN2 can be non-cancerous (benign) or cancerous (malignant). Cancerous tumours can spread to other parts of the body, but non-cancerous tumours don’t spread. Some tumours make the gland they are growing in produce large amounts of hormones.

The endocrine glands that are most likely to be affected in MEN2 are:

• the thyroid gland, in the front of the neck
• the adrenal glands, on top of the kidneys
• the parathyroid glands, in the front of the neck.

There are three types of MEN2:

• MEN2A
• MEN2B
• familial medullary thyroid cancer (FMTC).

All types of MEN2 cause a thyroid cancer called medullary thyroid carcinoma.

People with MEN2A may also develop:

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

People with MEN2B may also develop:

• tumours of the adrenal gland called phaeochromocytoma
• non-cancerous tumours (neuromas) on the lips, tongue and lining of the mouth and bowel.

MEN2 is caused by a change (mutation) in a gene, called the RET gene. The faulty gene is usually inherited from a parent. But some people who have the gene change don’t have any family history of MEN2.

The most common symptoms are:

• a lump at the front of the neck
• sweating, irregular heart rate and headaches caused by a tumour in the adrenal gland(s).

MEN2 is diagnosed when someone has:

• one or more tumours linked to MEN2 and a MEN2 gene mutation
• one tumour linked to MEN2 and a member of their family has MEN2
• a MEN2 gene change found after gene testing.

If you have a tumour that could be caused by MEN2, your doctors will examine you and arrange tests to check for other tumours linked to MEN2. They will also ask you about any illnesses your close relatives have had. This is to check whether other family members may have had MEN2 tumours.

You will have a blood sample taken for genetic testing. This will look for the MEN2 gene. If you have the MEN2 gene, other close family members will be offered genetic testing too. Close family members are parents, brothers, sisters and children.

Problems caused by MEN2 can often be recognised at an early stage and successfully treated or controlled. The earlier someone knows they have a MEN2 gene change, the sooner they can have treatment and monitoring to help prevent problems.

Gene testing for MEN2

MEN2 is due to a change in a gene (mutation). We inherit two copies of every gene – one from our mother and one from our father.

People with MEN2 have one normal MEN2 gene and one MEN2 gene with a change (mutation). They can pass on either copy to their children, so there is a 1 in 2 (50%) chance that a child of someone with MEN2 will inherit the condition. The chance is the same for each child whether they are a boy or girl.

Before genetic testing is carried out, counselling is arranged to help people understand how the test results may affect them individually and as a family.

If a gene change is found, family members can then be tested to see whether they have inherited the same gene change. Family members who don’t have the MEN2 gene change won't need further tests or investigations. Family members who have inherited MEN2 will have regular tests to check for signs of tumours. This is called screening. When appropriate, they will be offered surgery to reduce the risk of medullary thyroid cancer developing.

Tests for MEN2

Tests can be used to find the cause for particular symptoms. They can also be used to check for MEN2 tumours before they cause any symptoms. This is called monitoring or screening. It’s done so that tumours can be detected and treated at an early stage before they begin to cause problems.

You can usually have any tests done as an outpatient.

You may have the following tests:

Blood tests

These are used to check the levels of different hormones and chemicals in your body.

24-hour urine collection

This test may be done to check for adrenal gland tumours. It measures the level of hormones called catecholamines, which are made by the adrenal glands. People with adrenal gland tumours (phaeochromocytoma) often produce too much of these hormones.

Biopsy

This is used to look at tissue in part of the body. It shows whether the tissue is normal or abnormal and cancerous or non-cancerous. A doctor takes a sample of cells or tissue from a part of the body. The sample is then examined under a microscope to look for changes in the cells.

Ultrasound scan

An ultrasound scan uses soundwaves to build up a picture of the organs inside the body. The person doing the ultrasound spreads a gel over the part of your body to be scanned. Then they rub a small device over the area. The device produces soundwaves, which are converted into a picture by a computer.

CT (computerised tomography) scan

A CT scan takes a series of x-rays that build up a three-dimensional picture of the inside of the body. The scan is painless and takes about 10–30 minutes. CT scans use a small amount of radiation, which is very unlikely to harm you. They don’t make you radioactive.

MRI (magnetic resonance imaging) scan

This test uses magnetism to build up a detailed picture of areas of your body. Before the scan, you may be asked to complete and sign a checklist. This is to make sure that it’s safe for you to have an MRI scan.

During the test, you lie very still on a couch inside a long cylinder (tube) for about 30 minutes. It is painless but some people feel a bit claustrophobic during the scan. It’s also noisy, but you’ll be given earplugs or headphones.

I-123-MIBG scan

People who have phaeochromcytoma may be offered this test. It involves having an injection of I-123-MIBG. This is mildly radioactive iodine, which is absorbed by adrenal cells. The body is then scanned to check for areas that have absorbed the iodine.

The dose of radiation from the scan is very low – about the same amount you get from an x-ray. Almost all the radiation leaves your body within a week. If you are planning to travel abroad within three months of the scan, let the doctor in the scanning department know. They can give you a letter to show to customs officials. This is because ports and airports have very sensitive radiation detectors that may pick up tiny amounts of radioactivity.

Your care will be organised by a team of specialists with experience in managing endocrine tumours. This multidisciplinary team (MDT) will often include:

• an endocrinologist – a doctor who specialises treating disorders of the endocrine system
• an endocrine surgeon – a surgeon who specialises in operating on endocrine glands
• a cancer doctor (oncologist) who specialises in treating endocrine tumours
• a clinical geneticist – a doctor with specialist experience in genetics
• a radiologist – a doctor with specialist experience in interpreting ultrasound scans, CT scans and MRI scans
• a pathologist – a doctor with expertise in examining changes in tissues and cells to diagnose tumours
• a specialist endocrine nurse, who can give you support and information about living with MEN2.

Treatment for MEN2 depends on the type of tumour and where it is. Treatment can involve surgery to remove the tumour(s) and medicines to control symptoms.

You will be monitored regularly with tests and scans. This helps your doctor to adjust your treatment as needed, and to check for any problems that MEN2 may cause.

Research into treatment for MEN2 is ongoing. Doctors use clinical trials to assess new treatments. Before any trial is allowed to take place, an ethics committee must have approved it and agreed that the trial is in the interest of the patients.

You may be invited to take part in a clinical trial. Your doctor will discuss the treatment with you so that you have a full understanding of the trial and what it involves. You may decide not to take part, or to withdraw from a trial at any stage. You will still receive the best standard treatment available.

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 gland at a young age, before the cancer starts to grow.

The thyroid is a small gland in the front of the neck, just below the voicebox (larynx). It is made up of two parts (lobes). The thyroid produces two hormones – thyroxine (T4) and triiodothyronine (T3). These hormones keep the body functioning at its normal rate. The part of the thyroid where MTC can develop also makes a hormone called calcitonin.

Signs and symptoms of MTC

The signs and symptoms of MTC can include:

• a painless lump in the neck
• changes in breathing or swallowing due to the tumour pressing on the windpipe (trachea) or gullet (oesophagus)
• flushing
• loose stools or diarrhoea.

Diagnosing MTC

You will have a scan of your neck to check the thyroid gland and the lymph nodes. Lymph nodes drain fluid from the tissues and help the body fight infections. There are groups of pea-sized lymph nodes on either side of the neck. If cancer spreads from the thyroid, the first place it usually spreads to is nearby lymph nodes.

The doctor will arrange to take a biopsy from any abnormal areas that show up on the scan. The doctor puts a needle into the area and withdraws some cells into a syringe. This is called fine needle aspiration cytology (FNAC).

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

Treating MTC

The main treatment for MTC is surgery to remove the thyroid gland (thyroidectomy) and nearby lymph nodes.

If MTC is causing symptoms but has spread beyond the thyroid gland and can’t be removed by surgery, it may be treated with radiotherapy or the targeted treatments vandetanib (Caprelsa®) or cabozantanib. Radiotherapy uses radiation to destroy cells. Targeted drug treatments work by blocking (inhibiting) signals in the thyroid cancer cells that make them grow and pide. These treatments can’t cure MTC but they may help to control it.

Preventing MTC

Almost everyone with the MEN2 gene change will develop MTC. Because of this, children and young adults with the MEN2 gene usually have an operation to remove the thyroid gland to prevent cancer developing. The earlier the operation is done, the better chance it has of preventing MTC. In children with MEN2A, this operation is often done before they are five years old. People with MEN2B can develop MTC at a very early age. Babies born with the MEN2B gene change have an operation to remove their thyroid gland before they are a year old.

Follow-up

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 at its normal rate. 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.

Phaeochromocytoma (phaeo) is a tumour of the adrenal gland. It is usually non-cancerous.

People with MEN2A or MEN2B can develop phaeochromocytoma. One or both of the adrenal glands can be affected. Phaeochromocytoma can cause the adrenal gland to make large amounts of hormones called catecholamines. One of these hormones is adrenaline (epinephrine), which regulates the heart rate and blood pressure. Having too much adrenaline can cause symptoms such as:

• severe headaches
• a fast heart rate (palpitations)
• excessive sweating
• feeling anxious
• increased appetite
• feeling sick
• trembling hands
• pain in the chest or tummy area (abdomen).

Diagnosing phaeochromocytoma

Tests used to investigate and diagnose phaeochromcytoma include:

• a blood test or 24-hour urine test to check the levels of catecholamines in the body
• a CT or MRI scan of the tummy area (abdomen) to check the kidneys and adrenal glands
• an I-123_MIBG scan, although this is less common than a CT or MRI scan.

Treating phaeochromocytoma

The main treatment for phaeochromocytoma is an operation to remove the affected adrenal gland. If you are diagnosed with phaeochromocytoma, you will start taking a drug called an alpha blocker (phoxybenzamine or doxazosin). This stops problems in your body caused by too much adrenaline. Before your operation, you will be asked to increase the dose of the drug. This causes temporary side effects, including a stuffy feeling in the nose and dizziness when standing (postural hypotension). You will be encouraged to drink plenty of fluids during this time.

The operation is usually done using keyhole (laparoscopic) surgery. The surgeon uses a tube with a camera on its end (laparoscope) and specially designed surgical tools. They operate through 3–4 small cuts (incisions) made in the side of your tummy (abdomen) or back. Operations to remove larger tumours may be done through one larger incision in the abdomen.

If just one adrenal gland is removed, the other gland will soon take over the work of two adrenal glands, making the hormones your body needs. You will have yearly blood or urine tests to check the adrenal gland is healthy.

If both adrenal glands are removed, you will need to take tablets daily to keep the body in balance and prevent problems.

If you have MEN2A, the parathyroid glands may become enlarged and overactive. This is most likely to happen when you're 20–40 years old.

Parathyroid glands make a hormone called PTH, which helps control calcium levels in the blood. Most of the calcium in the body is stored in the bones. If calcium levels in the blood are low, the parathyroid glands make more PTH. This causes the bones to release calcium into the blood. When calcium levels in the blood are too high, the parathyroid glands make less PTH and the calcium levels drop. But people with overactive parathyroid glands may make too much PTH, so too much calcium is released from the bones. This can lead to calcium levels becoming too high. This is called hypercalcaemia.

Common symptoms of hypercalcaemia include:

• thirst
• tiredness
• changes in mood – feeling low, depressed, irritable or nervous
• aches and pains
• indigestion
• loss of appetite
• constipation
• muscle weakness.

If hypercalcaemia is left untreated, eventually the bones get thinner due to loss of calcium. This is called osteoporosis. It can cause back pain and bones that break easily.

The kidneys can also be affected by high calcium levels in the blood. Some people develop kidney stones, or their kidneys may become damaged and not work as well. Most people are treated early, so this is not usually a problem.

You will have a yearly blood test to check your calcium and PTH levels as part of your screening tests. But it’s still important to tell your doctor if you have any symptoms that may be caused by high levels of calcium in between screening tests.

Treating overactive parathyroid glands

The main treatment for overactive parathyroid glands is an operation to remove the enlarged glands. If the surgeon needs to remove all of your parathyroid glands, you’ll need to take tablets to keep your calcium levels in balance.

Sometimes the remaining parathyroid glands can become overactive after surgery. If this happens, you may need another operation to remove the affected parathyroid glands or tissue.

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

Medicines called calcimimetic agents are also sometimes used to reduce symptoms of overactive parathyroid tissue. They reduce the amount of parathyroid hormone made by the glands.

Neuromas are non-cancerous growths that may develop on the eyelids, lips and lining of the mouth and bowel in people with the MEN2B gene change. Neuromas are painless and don’t usually need treatment. They often look like little bumps and 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 on managing this.

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

Everyone has their own way of coping with difficult situations. Some people find it helpful to talk to family or friends, while others prefer to seek help from people outside their situation. Some people prefer to keep their feelings to themselves. There is no right or wrong way to cope, but help is there if you need it. Our cancer support specialists can give you information about counselling in your area.