Multiple endocrine neoplasia

Multiple endocrine neoplasia is part of a group of disorders that affect the body's network of hormone-producing glands (the endocrine system). Hormones are chemical messengers that travel through the bloodstream and regulate the function of cells and tissues throughout the body. Multiple endocrine neoplasia involves tumors in at least two endocrine glands; tumors can also develop in other organs and tissues. These growths can be noncancerous (benign) or cancerous (malignant). If the tumors become cancerous, some cases can be life-threatening.

The two major forms of multiple endocrine neoplasia are called type 1 and type 2; they are often confused because of their similar names. Type 1 and type 2 are distinguished by the genes involved, the types of hormones made, and the characteristic signs and symptoms.

Many different types of tumors are associated with multiple endocrine neoplasia. Type 1 frequently involves tumors of the parathyroid gland, pituitary gland, and pancreas. Tumors in these glands lead to the overproduction of hormones. The most common sign of multiple endocrine neoplasia type 1 is overactivity of the parathyroid gland (hyperparathyroidism). Hyperparathyroidism disrupts the normal balance of calcium in the blood, which can lead to kidney stones, thinning of bones, nausea and vomiting, high blood pressure (hypertension), weakness, and fatigue.

The most common sign of multiple endocrine neoplasia type 2 is a form of thyroid cancer called medullary thyroid carcinoma. Some people with this disorder also develop a pheochromocytoma, which is a tumor of the adrenal glands that can cause dangerously high blood pressure. Multiple endocrine neoplasia type 2 is divided into three subtypes: type 2A, type 2B, and familial medullary thyroid carcinoma (FMTC). These subtypes differ in their characteristic signs and symptoms and risk of specific tumors; for example, hyperparathyroidism occurs only in type 2A. The features of this disorder are relatively consistent within any one family.

Each of the two major types of multiple endocrine neoplasia affects an estimated 1 in 30,000 people. Among the subtypes of multiple endocrine neoplasia type 2, type 2A is the most common form, followed by familial medullary thyroid cancer. Type 2B is relatively uncommon, accounting for about 5 percent of all cases of multiple endocrine neoplasia type 2.

Mutations in the MEN1 and RET genes cause multiple endocrine neoplasia.

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.

Multiple endocrine neoplasia type 2 results from mutations in the RET gene. This gene provides instructions for producing a protein that is involved in signaling within cells. The RET protein triggers chemical reactions that instruct cells to respond to their environment, for example by dividing or maturing. Mutations in the RET gene overactivate the protein's signaling function, which can trigger cell growth and division in the absence of signals from outside the cell. This unchecked cell division can lead to the formation of tumors in endocrine glands and other tissues.

Read more about the MEN1 and RET genes.

Most cases of multiple endocrine neoplasia type 1 are considered to have an autosomal dominant pattern of inheritance. People with this condition are born with one mutated copy of the MEN1 gene in each cell. In most cases, the altered gene is inherited from an affected parent. The remaining cases are a result of new mutations in the MEN1 gene, and occur in people with no history of the disorder in their family.

Unlike most other autosomal dominant conditions, in which one altered copy of a gene in each cell is sufficient to cause the disorder, two copies of the MEN1 gene must be altered to trigger tumor formation in multiple endocrine neoplasia type 1. A mutation in the second copy of the MEN1 gene occurs in a small number of cells during a person's lifetime. Almost everyone who is born with one MEN1 mutation acquires a second mutation in certain cells and develops tumors of the endocrine glands and other tissues.

Multiple endocrine neoplasia type 2 is also usually inherited in an autosomal dominant pattern. A person with multiple endocrine neoplasia type 2 often inherits the altered RET gene from one parent with the condition. Some cases, however, result from new mutations in the gene and occur in people without other affected family members.