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Treatment Multiple Endocrine Neoplasia Type 1

Multiple endocrine neoplasia is part of a group of disorders that affect the body's hormone-producing glands. It has two major forms: type 1 and type 2. The multiple endocrine neoplasia type 1 (MEN1) is caused by mutations in the MEN1 gene. It affects parathyroid, pancreas and pituitary glands. The prevalence of MEN1 is about 1 in 30,000 people.

Symptoms

The Parathyroid Glands

The parathyroid glands 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. 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 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.

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:

  • insulin—lowers blood sugar;
  • glucagon—raises blood sugar;
  • somatostatin—inhibits many cells.
  • Gastrin is another hormone that can be over secreted in MEN1. The gastrin comes from one or more tumors in the pancreas and small intestine. Gastrin normally circulates in the blood, causing the stomach to secrete enough acid needed for digestion. If exposed to too much gastrin, the stomach releases excess acid, leading to the formation of severe ulcers in the stomach and small intestine. Too much gastrin can also cause serious diarrhea.

About one in three patients with MEN1 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.

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:

  • prolactin—controls formation of breast milk, influences fertility, and influences bone strength;
  • growth hormone—regulates body growth, especially during adolescence;
  • adrenocorticotropin (ACTH)—stimulates the adrenal glands to produce cortisol;
  • thyrotropin (TSH)—stimulates the thyroid gland to produce thyroid hormones;
  • luteinizing hormone (LH)—stimulates the ovaries or testes to produce sex hormones that determine many features of "maleness" or "femaleness"; and
  • follicle stimulating hormone (FSH)—regulates fertility in men through sperm production and in women through ovulation.

The pituitary gland becomes overactive in about one of four persons with MEN1. This overactivity can usually be traced to a very small, benign tumor 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.

Causes

Mutations in the MEN1 gene cause multiple endocrine neoplasia type 1. This gene provides instructions for producing a protein called menin. Menin acts as a tumor suppressor, which means it normally keeps cells from growing and dividing too rapidly or in an uncontrolled way. Although the exact function of menin is unknown, it is likely involved in cell functions such as copying and repairing DNA and regulating the activity of other genes. If mutations inactivate both copies of the MEN1 gene, it is no longer able to control cell growth and division. The loss of functional menin allows cells to divide too frequently, leading to the formation of tumors characteristic of multiple endocrine neoplasia type 1.

 

Reference:

Endocrine and Metabolic Diseases Information Service, USA

Genetics Home Reference, U. S. National Library of Medicine