Multiple Endocrine Neoplasia 2 (MEN2)

The MEN types

MEN stands for multiple endocrine neoplasia. It is a rare condition that is caused by a faulty gene; this can be passed on, within families, from one generation to another (inherited). There are two types: MEN1 and MEN2. Because they have similar names, MEN1 and MEN2 are often confused. In fact, they are completely separate conditions with different genetic causes. MEN1 cannot turn into MEN2, nor can MEN2 turn into MEN1.

In multiple endocrine neoplasia, a number of different tumours develop in the endocrine system. The endocrine system is a network of glands in the body. The word neoplasia means 'new growth' or 'tumour'.

MEN2 tumours can be non-cancerous (benign) or cancerous (malignant). Malignant tumours can spread to other parts of the body, but benign tumours do not spread.

MEN2 is diagnosed when a person has more than two endocrine tumours in the body, and is found to have a faulty gene (genetic mutation). A person can also be diagnosed as having MEN2 if they have one endocrine tumour and one or more members of their family have been diagnosed with MEN2.

The endocrine system

The endocrine system is made up of endocrine glands. Endocrine glands produce hormones; these chemicals control many of the body's functions. Normally, the hormones released by endocrine glands are carefully balanced to meet the body's needs.

The endocrine glands include the thyroid gland (in the front of the neck), the parathyroid glands (that lie just behind the thyroid gland), and the adrenal glands (which sit on top of the kidneys in the abdomen).

Who MEN2 affects

MEN2 is a very rare condition, which can affect men or women at any age. Although MEN2 tends to be an inherited condition, known as familial MEN2, it can occasionally occur in people who do not have any family members diagnosed with it and it is then known as sporadic MEN2.

If a person has MEN2, they are known as an MEN2 carrier. There is a 1 in 2 chance that they will pass the genetic mutation on to their children.

Causes

MEN2 occurs because of an inherited genetic change (mutation). We all inherit many genes from our parents. Genes affect the way your body grows, works, and looks. In people with MEN2 there is a mutation, or mistake, in one gene of every cell. This mutation causes tumours to develop in the endocrine system. It is not known exactly what causes this genetic change, and research is ongoing to try to find out.

MEN2

Many people with MEN2 develop a type of thyroid gland tumour called a medullary cell carcinoma. This is a malignant tumour.

Some people who have MEN2 will develop a type of tumour of their adrenal gland called a phaeochromocytoma (see the section Tumours of the adrenal gland).

Some people who have MEN2 will develop a type of tumour of their adrenal gland called a phaeochromocytoma.

MEN2 is further divided into three subtypes:

• MEN 2A
• MEN 2B
• familial medullary thyroid cancer (familial MTC).

People with MEN 2A people commonly develop hyperplasia (overactivity and enlargement) of the parathyroid glands.

People with MEN 2B develop tumours that appear as swellings on their tongue, lips, eyelids, or lining of their mouths. These are called neuromas and are benign. Tumours of the parathyroid glands do not occur in MEN 2B.

In familial MTC, people tend to get medullary thyroid cancer only.

Signs and symptoms

The symptoms for people with MEN2 can vary according to whether or not tumours develop and where these tumours are. Symptoms often occur because a tumour is making too many hormones. The particular symptoms depend on:

• the type of MEN2
• the type of tumour
• the type of endocrine glands involved
• the particular hormones that are being overproduced.

The main endocrine tumours that occur with MEN2 are listed below. It is important to remember that these tumours can affect people in different ways, and that the symptoms can be similar to those of many other non-cancerous conditions.

Hyperplasia of the parathyroid glands Possible symptoms include high levels of calcium in the blood (hypercalcaemia); a possible lump or swelling in the neck; muscle weakness; pain in the bones; vomiting; loss of appetite; weight loss; constipation; difficulty sleeping; lethargy; nervousness; and stomach ulcers.

Cancer of the thyroid gland You may notice a painless lump in the neck, and possible difficulty in breathing or swallowing due to the tumour pressing on the gullet or windpipe.

Tumours of the adrenal gland Some people with MEN2 may develop a type of tumour of their adrenal gland called a phaeochromocytoma. These tumours are almost always benign but may occur in both adrenal glands. Symptoms include: sudden attacks of panic and anxiety; headaches; pallor or flushing (looking red); sweating; a racing heartbeat (palpitations); high blood pressure (hypertension); weight loss; irritability; and mood changes.

Screening and genetic testing

MEN2 is due to a change in a gene (mutation). We all have many thousands of genes, and we have two copies of every gene, one inherited from our mother and the other inherited from our father. People with MEN2 have a change in one of the copies in their MEN2 gene, and one normal copy of the gene. They can pass on either copy to their children, so there is half a chance that a child of someone with MEN2 will inherit the condition. The chance is the same for each child, regardless of the sex of the child.

It is possible to identify the gene change in an affected person by doing a genetic test. This involves analysis of the DNA (genetic code) from a blood sample. This can be a time-consuming process which often takes a number of months. Before genetic testing is carried out, counselling is arranged to help people to understand how the test results may affect them individually and as a family.

If a gene change is found, other family members can then be tested to see if they have inherited the same gene change. If they have not inherited the gene change, then they do not need any monitoring. However, if they have inherited it, then they will need to be closely monitored to detect any possible complications at an early stage. Preventative surgery to remove the thyroid gland, before it becomes cancerous, may also be recommended.

Treatment

The treatment for MEN2 depends on which tumours have developed, and can involve surgery to remove the tumours, or medicines to help control the symptoms. Unfortunately, there is no way of changing the genetic mutation. However, problems caused by MEN2 can often be recognised and controlled, or treated, at an early stage. Careful monitoring enables your doctor to adjust your treatment as needed, and to check for any new problems that MEN2 may cause.

Clinical trials

Research into treatments for MEN2 tumours is ongoing and advances are being made. 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 asked to take part in a clinical trial. Your doctor must 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 then receive the best standard treatment available.

Your feelings

The need for practical and emotional support is, of course, different for each person. Some people with MEN2 may find that their life is largely unaffected, but for others the condition may be a source of great fear and distress.

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 and its treatment. You don't have to cope with these feelings on your own; people are available to help you. Some hospitals have their own emotional support services with specially trained staff and some of the nurses will have received training in counselling. Cancerbackup can also put you in contact with counselling services in your area.

References

This section has been compiled using information from a number of reliable sources including;

• Oxford Textbook of Oncology (2nd edition). Eds Souhami et al. Oxford University Press, 2002.
• Gastrointestinal Oncology: Principles and Practice. Eds Kelsen et al. Lippincott, Williams and Wilkins, Philadelphia, 2002.
• The Textbook of Uncommon Cancers (3rd edition). Eds Raghavan et al. Wiley, 2006.
• Endocrine Tumours. Eds Clark et al. Ontario, B.C.Decker Inc. 2003

For further references, please see the general bibliography.

Via: http://www.cancerbackup.org.uk