Multiple endocrine neoplasia type 1 (MEN1) is an inherited disorder that affects the endocrine glands. It is sometimes called multiple endocrine adenomatosis or Wermer's syndrome, after one of the first doctors to recognise it. MEN1 is quite rare, occurring in about 3 to 20 persons out of 100,000. It affects both sexes equally and shows no geographical, racial, or ethnic preferences.
Endocrine glands are different from other organs in the body because they release hormones into the bloodstream. Hormones are powerful chemicals that travel through the blood, controlling and instructing the functions of various organs. Normally, the hormones released by endocrine glands are carefully balanced to meet the body's needs.
In patients with MEN1, sometimes multiple endocrine glands, such as the parathyroid, the pancreas, and the pituitary become overactive at the same time. Most people who develop overactivity of only one endocrine gland do not have MEN1.
How does MEN1 affect the endocrine glands?
The Parathyroid Glands
The parathyroids are the endocrine glands earliest and most often affected by MEN1. The human body normally has four parathyroid glands, which are located close to the thyroid gland in the front of the neck. The parathyroids release into the bloodstream a chemical called parathyroid hormone, which helps maintain a normal supply of calcium in the blood, bones, and urine.
In MEN1, all four parathyroid glands tend to be overactive. They release too much parathyroid hormone, leading to excess calcium in the blood. High blood calcium, known as hypercalcemia, can exist for many years before it is found by accident or by family screening. Unrecognised hypercalcemia can cause excess calcium to spill into the urine, leading to kidney stones or kidney damage.
Nearly everyone who inherits a susceptibility to MEN1 (a "cancer") will develop overactive parathyroid glands (hyperparathyroidism) by age 50, but the disorder can often be detected before age 20. Hyperparathyroidism may cause no problems for many years or it may cause problems such as tiredness, weakness, muscle or bone pain, constipation, indigestion, kidney stones, or thinning of bones.
Treatment of Hyperparathyroidism.
The Pancreas Gland
The pancreas gland, located behind the stomach, releases digestive juices into the intestines and releases key hormones into the bloodstream. Some hormones produced in the islet cells of the pancreas and their effects are:
About one in three patients with MEN1 has gastrin-releasing tumours, called gastrinomas. (The illness associated with these tumours is sometimes called Zollinger-Ellison syndrome.) The ulcers caused by gastrinomas are much more dangerous than typical stomach or intestinal ulcers; left untreated, they can cause rupture of the stomach or intestine and even death.
Treatment of Gastrinomas.
The Pituitary Gland
The pituitary is a small gland inside the head, behind the bridge of the nose. Though small, it produces many important hormones that regulate basic body functions. The major pituitary hormones and their effects are:
The pituitary gland becomes overactive in about one of four persons with MEN1. This overactivity can usually be traced to a very small, benign tumour in the gland that releases too much prolactin, called a prolactinoma. High prolactin can cause excessive production of breast milk or it can interfere with fertility in women or with sex drive and fertility in men.
Treatment of Prolactinomas.
Some prolactinomas are small, and treatment may not be needed. If treatment is needed, a very effective type of medicine known as a dopamine agonist can lower the production of prolactin and shrink the prolactinoma. Occasionally, prolactinomas do not respond well to this medication. In such cases, surgery, radiation, or both may be needed.
Rare complications of MEN1
Occasionally, a person who has MEN1 develops an islet tumour of the pancreas which secretes high levels of pancreatic hormones other than gastrin. Insulinomas, for example, produce too much insulin, causing serious low blood sugar, or hypoglycaemia. Pancreatic tumours that secrete too much glucagon or somatostatin can cause diabetes, and too much vasoactive intestinal peptide can cause watery diarrhoea.
Other rare complications arise from pituitary tumours that release high amounts of ACTH, which in turn stimulates the adrenal glands to produce excess cortisol. Pituitary tumours that produce growth hormone cause excessive bone growth or disfigurement.
Another rare complication is an endocrine tumour inside the chest or in the stomach, known as a carcinoid. In a person with MEN1 a carcinoid tumour rarely secretes a hormone. In general, surgery is the mainstay of treatment for all of these rare types of tumours, except for gastric carcinoids which usually require no treatment.
Are the tumours associated with MEN1 cancerous?
The overactive endocrine glands associated with MEN1 may contain benign tumours, but usually they do not have any signs of cancer. Benign tumours can disrupt normal function by releasing hormones or by crowding nearby tissue. For example, a prolactinoma may become quite large in someone with MEN1. As it grows, the tumour can press against and damage the normal part of the pituitary gland or the nerves that carry vision from the eyes. Sometimes impaired vision is the first sign of a pituitary tumour in MEN1.
Another type of benign tumour often seen in people with MEN1 is a plum-sized, fatty tumour called a lipoma, which grows under the skin. Lipomas cause no health problems and can be removed by simple cosmetic surgery if desired. These tumours are also fairly common in the general population.
Benign tumours do not spread to or invade other parts of the body. Cancer cells, by contrast, break away from the primary tumour and spread, or metastasize, to other parts of the body through the bloodstream or lymphatic system.
The pancreatic islet cell tumours associated with MEN1 tend to be numerous and small, but most are benign and do not release active hormones into the blood.
Eventually, about half of MEN1 cases will develop a cancerous pancreatic tumour or a cancerous carcinoid tumour.
Treatment of Pancreatic Endocrine Cancer in MEN1.
One approach is to "watch and wait," using medical, or nonsurgical treatments. According to this school of thought, pancreatic surgery has serious complications, so it should not be attempted unless it will cure a tumour that is secreting too much hormone.
Another school advocates early surgery, perhaps when a tumour grows to a certain size, to prevent or remove pancreatic endocrine cancer in MEN1 (even if it does not over secrete a hormone) before it spreads and becomes dangerous. There is no clear evidence, however, that aggressive surgery to prevent pancreatic endocrine cancer from spreading actually leads to longer survival for patients with MEN1. This is partly because these complex operations can have their own side effects.
Doctors agree that excessive release of certain hormones (such as gastrin) from pancreatic endocrine cancer in MEN1 needs to be treated, and medications are often effective in blocking the effects of these hormones. Some tumours, such as insulin-producing tumours of the pancreas, are usually benign and single and are curable by pancreatic surgery. Such surgery needs to be considered carefully in each patient's case.
Is MEN1 the same in everyone?
Although MEN1 tends to follow certain patterns, it can affect a person's health in many different ways. Not only do the features of MEN1 vary among members of the same family, but some families with MEN1 tend to have a higher rate of prolactin-secreting pituitary tumours and a much lower frequency of gastrin-secreting tumours.
In addition, the age at which MEN1 can begin to cause endocrine gland overfunction can differ strikingly from one family member to another. One person may have only mild hyperparathyroidism beginning at age 50, while a relative may develop complications from tumours of the parathyroid, pancreas, and pituitary by age 20.
Sometimes a patient with MEN1 knows of no other case of MEN1 among relatives. The commonest explanation is that knowledge about the family is incomplete; less often, the patient carries a new MEN1 gene mutation.
Can MEN1 be cured?
There is no cure for MEN1 itself, but most of the health problems caused by MEN1 can be recognised at an early stage and controlled or treated before they become serious problems.
If you have been diagnosed with MENl, it is important to get periodic checkups because MEN1 can affect different glands, and even after treatment, residual tissue can grow back. Careful monitoring enables your doctor to adjust your treatment as needed and to check for any new disturbances caused by MEN1. Most MEN1 cases will have a long and productive life.
How is MEN1 detected?
Each of us has millions of genes in each of our cells, which determine how our cells and bodies function. In people with MEN1, there is a mutation, or mistake, in one gene of every cell. A carrier is a person who has the MEN1 gene mutation. The MEN1 gene mutation is transmitted directly to a child from a parent carrying the gene mutation.
The MEN1 gene was recently identified. As of 2001, a small number of centers around the world began to offer MEN1 gene testing on a research or commercial basis. The likelihood of finding a mutation in an MEN1 family has varied from 60 percent to 95 percent depending on methods. When a mutation is found, further testing in other relatives can become much easier. Many relatives can be tested once and be found without the known MEN1 mutation in their family, and then they can be freed from uncertainty and from any further testing ever for MEN1. When a mutation is not found in a family or isolated case, it does not prove that no MEN1 mutation is present. Depending on the clinical and laboratory information, it may still be very likely that a mutation is present but undetected.
When the MEN1 mutation test is normal in an effected relative or when the test is not available, screening of close relatives of persons with MEN1, who are at high risk, generally involves testing for hyperparathyroidism, the most common and usually the earliest sign of MEN1.
What is the role for genetic counselling with MEN1 gene testing?
Genetic counselling, which should accompany the gene testing, can assist family member(s) address how the test results affect them individually and as a family. In genetic counselling, there can be a review and discussion of issues about the psychosocial benefits and risks of the genetic testing results. Genetic testing results can affect self-image, self-esteem, and individual and family identity. In genetic counselling, issues related to how and with whom genetic test results will be shared and their possible effect on important matters such as health and life insurance coverage can be reviewed and discussed. The times for these discussions can be when a family member is deciding whether or not to go ahead with the gene testing and again later when the gene testing results are available. The person, who provides the genetic counselling to the family member(s), may be a professional from the disciplines of genetics, nursing, or medicine.
Who should consider MEN1 screening by gene testing?
Screening may be offered to persons with MEN1 or with features resembling them. Affected relatives of persons with MEN1 can be tested. Asymptomatic offspring, brothers, or sisters of a person with MEN1 were born with a 50 percent chance of having inherited the gene; they too can be offered gene testing. While gene testing for any genetic disease can be definitive at any age, it is usually not offered to children below age 18 unless the test outcome would have an important effect on their medical treatment. Since treatable tumours occasionally begin by age 5 in MEN1, gene testing and tumour surveillance can begin at age 5.
Who should consider MEN1 screening by laboratory tests?
MEN1 screening by gene testing will be the most definitive test, when it is available. However, it is not yet widely available, and, when no gene mutation is found in a MEN1 family, then it may be necessary to rely upon laboratory tests for diagnosis. Hyperparathyroidism, most often the first sign of MEN1, can usually be detected by blood tests between the ages of 5 and 50. Periodic tumour testing should begin between ages 5 to 10 and be repeated every year. There is no age at which periodic testing should stop, since (lacking a specific DNA test) doctors cannot rule out the chance that a person has inherited the MEN1 gene mutation. However, a person with normal tumour testing beyond age 50 is very unlikely to have inherited the MEN1 gene mutation.
Why screen for MEN1 tumours?
MEN1 is not an infectious or contagious disease, nor is it caused by environmental factors. Because MEN1 is a genetic disorder inherited from one parent, and its transmission pattern is well understood, family members at 50–50 risk for the disorder can be easily identified.
Streamlined tumour testing can be used to identify an MEN1 carrier. After a carrier is identified, more detailed tumour surveys are generally recommended. Tumour testing can detect the problems caused by MEN1 tumours many years before their later complications develop. Finding these tumours early enables your doctor to begin preventive treatment, reducing the chances that MEN1 will cause problems later.
Should a person who has MEN1 avoid having children?
A person who has MEN1 or who has a MEN1 gene mutation may have a hard time deciding whether to have a child. No one can make this decision for anyone else, but some of the important facts can be summarized as follows:
Genetic counselling can help individuals and couples through the decision-making process with family planning. Genetic counsellors and other professionals will provide information to help with the decision-making process, but they will not tell individuals or couples what decision to make or how to make it.