Multiple Endocrine Neoplasia 1 (MEN1)

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 and MEN2 cannot 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.

MEN1 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.

MEN1 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 MEN1 if they have one endocrine tumour and one or more members of their family have been diagnosed with MEN1.

The endocrine system

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

The endocrine glands include the pituitary gland (which lies immediately underneath the brain), 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 MEN1 affects

MEN1 is a very rare condition that can affect men or women at any age. Although it tends to be an inherited condition, known as familial MEN1, it can sometimes occur in people who do not have any family members diagnosed with it and it is then known as sporadic MEN1.

If a person has MEN1, they are known as a MEN1 carrier. There is a 1 in 2 chance that they will pass the genetic mutation on to their children.

Causes

MEN1 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 MEN1 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.

MEN1

Almost all people with MEN1 will develop overactivity of the parathyroid glands, known as hyperparathyroidism, at some stage in their life. This is often shown by an abnormally high level of calcium in the blood (hypercalcaemia). There may be tumours in the parathyroid glands, which are usually benign.

Tumours can also develop in the digestive system (gastrointestinal tract or GI tract), usually the stomach, intestines and/or pancreas. These tumours can be benign or malignant. Other tumours can develop in the pituitary gland or the adrenal glands, these are usually benign.

Rarely, people may develop a particular type of tumour (known as a carcinoid tumour) in the chest, thymus gland (behind the breast bone), or the gastrointestinal tract.

Signs and symptoms

The symptoms for people with MEN1 can vary according to whether or not tumours develop and where these tumours are. Symptoms often occur because a tumour is causing too many hormones to be produced. The particular symptoms depend on:

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

The main endocrine tumours, and some of the most common symptoms they cause, 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.

Tumours of the parathyroid gland 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.

Tumours of the pituitary gland Symptoms can include headaches and sight problems. Infertility may occur. Some people have a condition called acromegaly which affects growth, leading to an enlargement of the hands and feet, and can lead to high blood pressure and diabetes. Women may notice that their periods stop, and they may produce small amounts of breast milk. Men may be unable to have an erection (impotence).

GEP tumours

There are several different types of GEP tumours (gastroenteropancreatic tumours). They tend to develop in the organs of the digestive system, such as the stomach (gastro), intestines (entero) and the pancreas.

Insulinomas Symptoms include: headaches, confusion, trembling, palpitations, anxiety, visual disturbances and possible fits (seizures).

Gastrinomas Possible symptoms include: bleeding in the stomach, black tar-like stools, or pale, greasy and offensive-smelling stools (steatorrhoea) or diarrhoea, possible narrowing of the bowel, which may cause general abdominal pain, and inflammation of the gullet lining (oesophagitis).

Somatostatinomas Symptoms can include pale, greasy and offensive-smelling stools (steatorrhoea), weight loss, anaemia, pain, diarrhoea, and possible diabetes.

Glucagonomas Symptoms such as anaemia, weight loss, diabetes, rash, or formation of blood clots can occur.

VIPomas Excessive watery diarrhoea, low levels of potassium (as a result of excessive diarrhoea), weakness, sickness (nausea), and vomiting are possible symptoms.

Tumours of the adrenal gland These tend to be 'non-functioning' which means there is not an excess production of hormones and there are no obvious symptoms.

Screening and genetic testing

MEN1 is due to an alteration in a gene (also called a 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 MEN1 have an alteration in one of the copies in their MEN1 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 MEN1 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. In some cases, the gene change cannot be found although the person is affected with MEN1. This is probably due to technical limitations of the test. 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.

Treatment

The treatment for MEN1 depends on which tumours have developed, and can involve surgery to remove the tumours or medicines to help control the symptoms. Although there is no way of changing the genetic mutation, problems caused by MEN1 can often be recognised at an early stage and successfully controlled or treated. Careful monitoring enables your doctor to adjust your treatment as needed and to check for any new problems that the MEN1 may cause.

Clinical trials

Research into treatment for MEN1 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 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 MEN1 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