Multiple Endocrine Neoplasia Syndromes
Multiple endocrine neoplasia syndromes are rare conditions in which several endocrine glands develop noncancerous (benign) or cancerous (malignant) tumors or grow excessively without forming tumors.
Multiple endocrine neoplasia syndromes can appear in infants or in those as old as age 70. Almost all the multiple endocrine neoplasia syndromes are 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.
Types
Type 1 Disease: People with multiple endocrine neoplasia type 1 develop tumors, or excessive growth and activity, of two or more of the following glands: the parathyroid glands (the small glands located next to the thyroid gland), the pancreas, the pituitary gland, and, less often, the thyroid gland and the adrenal glands.
Almost all people with type 1 disease 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 Section 12, Chapter 155)). The excess parathyroid hormone usually raises the levels of calcium in the blood, sometimes leading to kidney stones.
Most people with type 1 disease also develop tumors of the hormone-producing cells (islet cells) of the pancreas. Some of these tumors produce high levels of insulin and, consequently, low levels of sugar in the blood (hypoglycemia), especially if the person has not eaten for several hours. 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, perforate and leak stomach contents into the abdomen, or obstruct the stomach. The high acid levels commonly interfere with the activity of enzymes from the pancreas, resulting in diarrhea and fatty, smelly stools (steatorrhea). The remaining islet cell tumors may produce other hormones, such as vasoactive intestinal polypeptide, which can cause severe diarrhea and lead to dehydration.
Some of the islet cell tumors are cancerous and able to spread (metastasize) to other areas of the body. Cancerous islet cell tumors tend to grow more slowly than other types of cancer that develop in the pancreas.
Most people with type 1 disease develop pituitary gland tumors. Some of these tumors produce the hormone prolactin, leading to menstrual abnormalities in women and erectile dysfunction (impotence) in men. Others produce growth hormone, leading to acromegaly (see Section 13, Chapter 162). A small percentage of pituitary tumors produce corticotropin, which overstimulates the adrenal glands, leading to high levels of corticosteroid hormones and Cushing's syndrome (see Section 13, Chapter 164). 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 Section 13, Chapter 168). Some people also develop soft, noncancerous fatty growths just below the skin (lipomas).
Type 2A Disease: People with multiple endocrine neoplasia type 2A develop tumors or excessive growth and activity in two or three of the following glands: the thyroid gland, the adrenal glands, and the parathyroid glands.
Almost everyone with type 2A disease develops medullary thyroid cancer (see Section 13, Chapter 163). About 50% develop pheochromocytomas, tumors of the adrenal glands (see Section 13, Chapter 164), 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 and therefore have increased levels of calcium in the blood, which may lead to kidney stones. In others, the parathyroid glands increase in size without producing large amounts of parathyroid hormone, so the people do not have problems related to high calcium levels.
Type 2B Disease: Multiple endocrine neoplasia type 2B can consist of medullary thyroid cancer, pheochromocytomas, and neuromas (growths around the nerves). Some people with type 2B disease have no family history of it.
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 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.
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 feet and thighs. Many people have long limbs and loose joints.
Screening
Because about half of the children of people with a multiple endocrine neoplasia syndrome inherit the disease, screening is important for early diagnosis and treatment. Tests for identification of each type of tumor are available. A single gene responsible for type 1 disease has been identified, and a test for abnormalities in this gene is available. Abnormalities in a different gene have been identified in people with types 2A and 2B disease, and tests for mutations in this gene are also available. These genetic tests permit earlier and more effective diagnosis and treatment in people who have a family history of multiple endocrine neoplasia syndromes.
Treatment
No cure is known for any of the multiple endocrine neoplasia syndromes. Doctors treat the changes in each gland individually. A tumor is treated either by removing it or by correcting the hormone imbalance, using drugs that counteract the effects of 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, a doctor will most likely recommend surgical removal of the thyroid gland if a person has evidence of type 2A or type 2B disease, even if the diagnosis of medullary thyroid cancer cannot be established 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, a person must take thyroid hormone for the rest of his life.
| 
