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| Familial multiple endocrine
neoplasia type 1 (FMEN1) is an inherited disorder that affects
the endocrine glands. It is sometimes called familial multiple
endocrine adenomatosis or Wermer's syndrome, after one of the
first doctors to recognize it. FMEN1 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 FMEN1, sometimes more than one group of 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 FMEN1.
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How Does FMEN1 Affect the Endocrine Glands? |
The Parathyroid Glands The parathyroids are the endocrine glands earliest and most often affected by FMEN1. 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 a chemical called parathyroid hormone, which helps maintain a normal supply of calcium in the blood, bones, and urine.
Nearly everyone who inherits a susceptibility to FMEN1 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, 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 FMEN1 has gastrin-releasing tumors, called gastrinomas. (The illness associated with these tumors 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 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:
Treatment of Prolactinomas.
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Rare Complications of FMEN1 |
Occasionally, a person who has
FMEN1 develops islet tumors of the pancreas that secrete high
levels of pancreatic hormones other than gastrin. Insulinomas,
for example, produce too much insulin, causing serious low blood
sugar, or hypoglycemia. Pancreatic tumors that secrete too much
glucagon or somatostatin can cause diabetes, and too much
vasoactive intestinal peptide can cause watery diarrhea. Other rare complications arise from pituitary tumors that release high amounts of ACTH, which in turn stimulates the adrenal glands to produce excess cortisol. Pituitary tumors that produce growth hormone cause excessive bone growth or disfigurement. Another rare complication is an endocrine tumor inside the chest or in the stomach, known as a carcinoid. In general, surgery is the mainstay of treatment for all of these rare types of tumors, except for gastric carcinoids which usually require no treatment.
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Are the Tumors Associated With FMEN1 Cancerous? |
The overactive endocrine glands
associated with FMEN1 may contain benign tumors, but usually
they do not have any signs of cancer. Benign tumors can
disrupt normal function by releasing hormones or by crowding
nearby tissue. For example, a prolactinoma may become quite
large in someone with FMEN1. As it grows, the tumor 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 tumor in FMEN1. Another type of benign tumor often seen in people with FMEN1 is a plum-sized, fatty tumor called a lipoma, which grows under the skin. Lipomas cause no health problems and can be removed by simple cosmetic surgery if desired. These tumors are also fairly common in the general population. Benign tumors do not spread to or invade other parts of the body. Cancer cells, by contrast, break away from the primary tumor and spread, or metastasize, to other parts of the body through the bloodstream or lymphatic system. The pancreatic islet cell tumors associated with FMEN1 tend to be numerous and small, but most are benign and do not release active hormones into the blood. A proportion of pancreatic islet cell tumors in FMEN1 are cancerous.
Treatment of Pancreatic Endocrine Cancer in FMEN1. 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 tumor that is secreting too much hormone. Another school advocates early surgery, perhaps when a tumor grows to a certain size, to remove pancreatic endocrine cancer in FMEN1 (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 FMEN1. Doctors agree that excessive release of certain hormones (such as gastrin) from pancreatic endocrine cancer in FMEN1 needs to be treated, and medications are often effective in blocking the effects of these hormones. Some tumors, such as insulin-producing tumors 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 FMEN1 the Same in Everyone? |
Although FMEN1 tends to follow
certain patterns, it can affect a person's health in many
different ways. Not only do the features of FMEN1 vary among
members of the same family, but some families with FMEN1 tend to
have a higher rate of prolactin-secreting pituitary tumors and a
much lower frequency of gastrin-secreting tumors. In addition, the age at which FMEN1 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 tumors of the parathyroid, pancreas, and pituitary by age 20. Sometimes a patient with MEN1 knows of no other case of FMEN1 among relatives. The commonest explanations are that knowledge about the family is incomplete or that the patient carries a new MEN1 gene mutation. |
Can FMEN1 Be Cured? |
There is no cure for FMEN1
itself, but most of the health problems caused by FMEN1 can be
recognized at an early stage and controlled or treated before
they become serious problems. If you have been diagnosed with FMENl, it is important to get periodic checkups because FMEN1 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 FMEN1. |
How Is FMEN1 Detected? |
Each of us has millions of genes
in each of our cells, which determine how our cells and bodies
function. In people with FMEN1, 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 very recently identified. As of 1998, a small number of centers around the world have begun to offer MEN1 gene testing on a research basis. The likelihood of finding a mutation in an MEN1 family has varied from 60 percent to 94 percent depending on methods. When a mutatioin 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. In the meantime, though, screening of close relatives of persons with FMEN1, who are at high risk, generally involves testing for hyperparathyroidism, the most common and usually the earliest sign of FMEN1. Any doctor can screen for hyperparathyroidism by testing the blood for calcium and sometimes one or two other substances such as ionized calcium and parathyroid hormone. An abnormal result indicates that the person probably has FMEN1, but a normal finding cannot rule out the chance that he or she will develop hyperparathyroidism at a later time. Blood testing can usually show signs of early hyperparathyroidism many years before symptoms of hyperparathyroidism occur. |
What is the Role for Genetic Counseling with MEN1 Gene Testing? |
Genetic counseling, 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 counseling, 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
counseling, 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 counseling
to the family member(s), may be a professional from the
disciplines of genetics, nursing, or medicine. |
Why Screen for FMEN1? |
FMEN1 is not an infectious or contagious disease, nor is it
caused by environmental factors. Because FMEN1 is a genetic
disorder inherited from one parent, and its transmission pattern
is well understood, family members at high risk for the disorder
can be easily identified. Testing can detect the blood chemical problems caused by FMEN1 many years before their later complications develop. Finding these hormonal imbalances early enables your doctor to begin preventive treatment, reducing the chances that FMEN1 will cause problems later. |
Who Should Consider MEN1 Screening? |
Who Should Consider MEN1 Screening by Gene Testing?Screening may be offered to persons with MEN1 or FMEN1 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 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. Delaying the gene testing until adulthood preserves the free choice of the person to accept or refuse a test that might have important effects on their job opportunities and insurance status.
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 or FMEN1, can usually be detected by blood tests between the ages of 15 and 50. Periodic testing should begin around age 10 and be repeated every year. There is no age at which periodic testing should stop, since doctors cannot rule out the chance that a person has inherited the MEN1 gene mutation. However, a person with normal testing beyond age 50 is very unlikely to have inherited the MEN1 gene mutation.
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Should a Person Who Has FMEN1 Avoid Having Children? |
A person who has FMEN1 or who has
a positive 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:
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Research in FMEN1 |
The National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK) was
established by Congress in 1950 as part of the National
Institutes of Health (NIH), whose mission is to improve human
health through biomedical research. The NIH is the research arm
of the Public Health Service under the U.S. Department of Health
and Human Services. The NIDDK conducts and supports a variety of research in endocrine disorders, including FMEN1. NIDDK and other NIH researchers isolated the MEN1 gene in 1997. Researchers have also shown that the MEN1 gene contributes to common endocrine tumors outside of the familial setting. |
Additional Information |
After reading this e-text, you may think of questions that you
would like answered. Some sources of additional information are
medical textbooks, physicians, nurses, and genetic counselors. The following articles about FMEN1 can be found in medical libraries, some college and university libraries, and through interlibrary loan in most public libraries. Chandrasekharappa, S.C., Guru, S.C., Manickam, P., Olufemi, S., Collins, F.S. Emmert-Buck, M.R., Debelenko, L.V., Zhuang, Z., Lubensky, I.A., Liotta, L.A., Crabtree, J.S., Wang, Y., Roe, B.A., Weisemann, J., Boguski, M.S., Agarwal, S.K., Kester, M.B., Kim, Y.S., Heppner, C., Dong, Q., Spiegel, A.M., Burns, A.L., Marx, S.J., "Positional cloning of the gene for multiple endocrine neoplasia-type 1 as many copies as needed. Printed single copies may be obtained from the Office of Communications and Public Liaison, NIDDK, 31 CENTER DRIVE, MSC 2560, Bethesda, Maryland 20892-2560.
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NIH Publication No. 97-3048 June 1997 e-text last updated: January 2000 |
In FMEN1, 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. Unrecognized hypercalcemia can
cause excess calcium to spill into the urine, leading to kidney
stones or kidney damage.