Endocrine Diseases

Introduction
Hormones
Parathyroid Glands
Pancreas Gland
Pituitary Gland
Rare complications of MEN1
Is MEN1 the same in everyone?

Endocrine system includes eight major glands throughout your body. These glands make hormones. Hormones are chemical messengers. They travel through your bloodstream to tissues or organs. Hormones work slowly and affect body processes from head to toe. These include

• Growth and development
• Metabolism - digestion, elimination, breathing, blood circulation and maintaining body temperature
• Sexual function
• Reproduction
• Mood

If your hormone levels are too high or too low, you may have a hormone disorder. Hormone diseases also occur if your body does not respond to hormones the way it is supposed to. Stress, infection and changes in your blood's fluid and electrolyte balance can also influence hormone levels.

In the United States, the most common endocrine disease is diabetes. There are many others. Hormone imbalance are usually treated by controlling how much hormone your body makes. Hormone supplements can help if the problem is too little of a hormone.

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 recognize 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.

Hormones are your body's chemical messengers. They travel in your bloodstream to tissues or organs. They work slowly, over time, and affect many different processes.

Endocrine glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, thymus, thyroid, adrenal glands and pancreas. In addition, men produce hormones in their testes and women produce them in their ovaries.

Hormones are powerful. It takes only a tiny amount to cause big changes in cells or even your whole body. That is why too much or too little of a certain hormone can be serious. Laboratory tests can measure the hormone levels in your blood, urine or saliva. Your health care provider may perform these tests if you have symptoms of a hormone disorder. Home pregnancy tests are similar - they test for pregnancy hormones in your urine.

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. 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.

Treatment of Hyperparathyroidism.

It is sometimes difficult to decide whether hyperparathyroidism in MEN1 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 of blood calcium should continue, since the small piece of remaining parathyroid tissue can grow larger 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).

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.

Treatment of Gastrinomas

The gastrinomas associated with MEN1 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. The mainstay of treatment is now very powerful medicines that block stomach acid release, called acid pump inhibitors. Taken by mouth, these have proven effective in controlling the complications from high gastrin in most cases of Zollinger-Ellison syndrome.

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.

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.

The overactive endocrine glands associated with MEN1 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 MEN1. 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 MEN1.

Another type of benign tumor often seen in people with MEN1 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.

Eventually, about half of MEN1 cases will develop a cancerous pancreatic tumor or a cancerous carcinoid tumor.

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 tumors and a much lower frequency of gastrin-secreting tumors.

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 tumors 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.