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, usually 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.
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.
Nearly everyone who inherits a susceptibility to FMEN1 will develop overactive parathyroid glands (hyperparathyroidism) by age 60, but the disorder can often be detected before age 20. Hyperparathyroidism may cause problems such as tiredness, weakness, muscle or bone pain, constipation, indigestion, kidney stones, or thinning of bones.
Treatment of Hyperparathyroidism. It is sometimes difficult to decide whether hyperparathyroidism in FMEN1 is severe enough to need treatment, especially in a person who has no symptoms. The usual treatment is an operation to remove the three largest parathyroid glands and all but a small part of the fourth. After parathyroid surgery, regular testing should continue, since the small piece of parathyroid tissue can grow back and cause recurrent hyperparathyroidism. People whose parathyroid glands have been completely removed by surgery must take daily supplements of calcium and vitamin D to prevent hypocalcemia (low blood calcium).
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 gastrinomas associated with FMEN1 are difficult to cure by surgery, because it is difficult to find the multiple small gastrinomas in the pancreas and small intestine. In the past, the standard treatment for gastrinomas was the surgical removal of the entire stomach to prevent acid production. Recently, however, researchers have identified very powerful blockers of stomach acid release, called acid pump inhibitors. Taken by mouth, these have proven effective in controlling most cases of ZollingerEllison syndrome.
Treatment of Prolactinomas. Most 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.
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.
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. Since the type of pancreatic endocrine cancer associated with FMEN1 can be difficult to recognize, difficult to treat, and very slow to progress, doctors have different views about the value of surgery in managing these tumors.
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 cancers in FMEN1 before they spread and become 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 insulinproducing 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.
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.
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.
In the next few years, scientists hope to develop a simple test that will identify the abnormal FMEN1 gene. Such a test would be given once in a person's lifetime to find out whether he or she has inherited the FMEN1 gene.
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.
Testing can detect the blood chemical problems caused by FMEN1 many years before these complications develop. Finding these hormonal imbalances early enables your doctor to begin preventive treatment, reducing the chances that FMEN1 will cause problems later.
The NIDDK conducts and supports a variety of research in endocrine disorders, including FMEN1. Researchers have begun to locate the FMEN1 gene by showing that it is on chromosome 11. Researchers have also suggested that the FMEN1 gene contributes to common endocrine tumors outside of the familial setting.
The following articles about FMEN1 can be found in medical libraries, some college and university libraries, and through interlibrary loan in most public libraries.
Metz, D. C., Jensen, R. T., Bale, A., Skarulis, M.C., Eastman, R.C., Nieman, L., Norton, J.A. Friedman, E., Larson, C., Amorosi, A., Brandi, M.L., Marx, S.J., "Multiple endocrine neoplasia type 1: Clinical features and management," in The Parathyroids, ed by Bilezekian, J.P., Levine, M.A., and Marcus R. Raven Press, 1994, 591-646.
Friedman, E., Larsson, C., Amorosi, A., Brandi, M.L., Bale, A., Metz, D., Jensen, R.T., Skarulis, M., Eastman, R.C., Nieman, L., Norton, J.A., Marx, S.J., "Multiple endocrine neoplasia type 1: Pathology, pathophysiology, and differential diagnosis," in Bilezekian et al, 647-680.
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This publication was written by Stephen J. Marx, M.D. and reviewed by Robert T. Jensen, M.D., both of the National Institute of Diabetes and Digestive and Kidney Diseases. It is based in part on the booklet, "Understanding Multiple Endocrine Neoplasia Type 1," published by the NIH Clinical Center's Communications Office.
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