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Multiple Endocrine Neoplasia Syndromes
Multiple endocrine neoplasia syndromes are rare, inherited disorders in which several endocrine glands develop noncancerous (benign) or cancerous (malignant) tumors or grow excessively without forming tumors.
Multiple endocrine neoplasia syndromes are caused by gene mutations, so they tend to run in families.
Symptoms vary depending on which glands are affected.
Genetic screening tests can be done to detect disease in family members of people who have multiple endocrine neoplasia syndromes.
No cure is available, but doctors treat the changes in each gland as they occur with surgery or with drugs to control excess hormone production.
Multiple endocrine neoplasia syndromes can appear in infants or in people as old as age 70. These syndromes are usually inherited.
Multiple endocrine neoplasia syndromes occur in three patterns, called types 1, 2A, and 2B, although the types occasionally overlap. The tumors and the abnormally large glands often produce excess hormones. Although tumors or abnormal growth may occur in more than one gland at the same time, changes often take place over time.
Multiple endocrine neoplasia syndromes are caused by inherited genetic mutations. A single gene responsible for type 1 disease has been identified. Abnormalities in a different gene have been identified in people with types 2A and 2B disease.
People with multiple endocrine neoplasia type 1 develop tumors, or excessive growth and activity, of two or more of the following glands:
Almost all people with multiple endocrine neoplasia type 1 have tumors of the parathyroid glands. Most of the tumors are noncancerous, but they cause the glands to produce too much parathyroid hormone (hyperparathyroidism—see What Is Hyperparathyroidism?). The excess parathyroid hormone usually raises the levels of calcium in the blood, sometimes causing kidney stones.
Many (30 to about 80%) of people with type 1 disease also develop tumors of the hormone-producing cells (islet cells) of the pancreas.
More than half of islet cell tumors produce excessive gastrin, which stimulates the stomach to overproduce acid. People with tumors that produce gastrin generally develop peptic ulcers that often bleed, develop holes (perforate), and leak stomach contents into the abdomen, or block the stomach. The high acid levels commonly interfere with the activity of enzymes from the pancreas, resulting in diarrhea and fatty, smelly stools (steatorrhea). Some of these tumors produce high levels of insulin and, consequently, very low levels of sugar in the blood (hypoglycemia), especially if the person has not eaten for several hours. The remaining islet cell tumors may produce other hormones, such as vasoactive intestinal polypeptide, which can cause severe diarrhea and lead to dehydration. Some islet cell tumors produce no hormones at all.
Some of the islet cell tumors are cancerous and able to spread (metastasize) to other areas of the body. In people who have type 1 disease, cancerous islet cell tumors tend to grow more slowly than cancerous islet cell tumors that develop in people who do not have type 1 disease.
Some people with type 1 disease develop pituitary gland tumors. Some of these tumors produce the hormone prolactin, causing menstrual abnormalities and often breast secretions in women who are not nursing and decreased sexual desire and erectile dysfunction (impotence) in men. Other tumors produce growth hormone, leading to acromegaly (see Gigantism and Acromegaly.). A small percentage of pituitary tumors produce corticotropin, which overstimulates the adrenal glands, leading to high levels of corticosteroid hormones and Cushing syndrome (see Cushing Syndrome). A few pituitary tumors produce no hormones at all. Some pituitary tumors cause headaches, impaired vision, and decreased pituitary gland function by pressing against nearby parts of the brain.
In some people with type 1 disease, tumors or excessive growth and activity of the thyroid and adrenal glands develop. A small percentage of people develop a different type of tumor, known as carcinoid tumors (see Carcinoid Tumors and Carcinoid Syndrome). Some people also develop noncancerous growths just below the skin.
People with multiple endocrine neoplasia type 2A develop tumors or excessive growth and activity in two or three of the following glands:
Occasionally, an itchy skin condition called cutaneous lichen amyloidosis occurs in people with type 2A disease. Hirschsprung disease is present in 2 to 5% of people with type 2A disease.
Almost everyone with type 2A disease develops medullary thyroid cancer (see Medullary cancer). About 40 to 50% develop certain tumors of the adrenal glands (pheochromocytomas—see Pheochromocytoma), which usually raise blood pressure because of the epinephrine and other substances they produce. The high blood pressure may be intermittent or constant and is often very severe.
Some people with type 2A disease have overactive parathyroid glands. High levels of parathyroid hormone cause increased levels of calcium in the blood. The increased calcium often causes no symptoms but leads to kidney stones in about 25% of people.
Multiple endocrine neoplasia type 2B can consist of
Many people with type 2B disease have no family history of it. In these people, the disease is the result of a new gene defect (genetic mutation).
The medullary thyroid cancer that occurs in type 2B disease tends to develop at an early age and has been found in infants as young as 3 months of age. The medullary thyroid tumors in type 2B disease grow faster and spread more rapidly than those in type 2A disease.
Most people with type 2B disease develop neuromas in their mucous membranes. The neuromas appear as glistening bumps around the lips, tongue, and lining of the mouth. Neuromas may also occur on the eyelids and glistening surfaces of the eyes, including the conjunctiva and cornea. The eyelids and lips may thicken, and the lips may turn inside out (become everted).
Digestive tract abnormalities cause constipation and diarrhea. Occasionally, the colon develops large, dilated loops (megacolon). These abnormalities probably result from neuromas growing on the intestinal nerves.
People with type 2B disease often develop spinal abnormalities, especially curvature of the spine. They may also have abnormalities of the bones of the skull, feet, and thighs. Many people have long limbs and loose joints. Some of these abnormalities are similar to those that occur in Marfan syndrome (see Marfan Syndrome).
Conditions That Occur With Certain Multiple Endocrine Neoplasia Syndromes
Tests are available to identify the genetic abnormality present in each of the multiple endocrine neoplasia syndromes. Doctors usually do these genetic tests in people who have one of the tumors typical of multiple endocrine neoplasia and in family members of people already diagnosed with one of the syndromes. Screening of family members, sometimes even before birth, is particularly important because about half of the children of people with a multiple endocrine neoplasia syndrome inherit the disease.
Blood and urine tests are done to detect elevated hormone levels. Imaging tests, such as ultrasonography or computed tomography (CT), are also needed to help doctors determine locations of the tumors.
No cure is known for any of the multiple endocrine neoplasia syndromes. Doctors treat the changes in each gland individually. A tumor is treated by removing it surgically when possible. Before removal or if removal is not possible, doctors give drugs to correct the hormone imbalance caused by gland overactivity. An excessively large and overactive gland without a tumor is treated with drugs to counteract the effects of gland overactivity.
Because medullary thyroid cancer is ultimately fatal if untreated, doctors will most likely recommend preventive surgical removal of the thyroid gland if genetic testing has revealed evidence of multiple endocrine neoplasia type 2A or type 2B. This preventive surgery is done even if the diagnosis of medullary thyroid cancer has not been made before the surgery. Unlike other types of thyroid cancer, this aggressive type of thyroid cancer cannot be treated with radioactive iodine. Once the thyroid is removed, people must take thyroid hormone for the rest of their life. If thyroid cancer has spread, other treatments (such as drugs or vaccines) can sometimes help the person live longer. Pheochromocytomas must be removed surgically after the person’s blood pressure has been controlled with appropriate drugs.
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