Multiple endocrine neoplasia (MEN) syndromes received their name because they predispose people to develop tumors of the endocrine glands. The endocrine system is comprised of glands that secrete hormones into the bloodstream that control numerous processes within the body. The endocrine system is instrumental in regulating mood, growth and development, metabolism, as well as sexual function and reproductive processes.
The major glands of the endocrine system affected by the MEN syndromes are the pituitary, thyroid, parathyroids, adrenals and pancreas. Currently, there are two distinct MEN syndromes, MEN1 and MEN2. In some ways, the two syndromes are similar, but there are important differences.
Multiple endocrine neoplasia type 1 (MEN1) is characterized by development of tumors in the parathyroid glands, pituitary and pancreas. Nearly 100% of MEN1 patients will develop parathyroid tumors; 30-75% will develop pancreatic tumors and between 10% and 60% will develop a pituitary tumor. MEN1 is diagnosed when two of these three tumors are present. MEN1 is also diagnosed when an individual has one of the major tumors and has a first degree relative with two of the three endocrine tumors. More rarely, individuals with MEN1 will develop tumors of the adrenal cortex and carcinoid tumors of the thymus gland, lung or stomach. Adrenal tumors are typically benign, while carcinoid tumors can be cancerous. Other features include lipomas, facial angiofibromas, collagenomas or benign thyroid adenomas.
Hyperparathyroidism is usually the first sign of MEN1 and typically occurs between the ages 20 and 25. Nearly 100% of people with MEN1 will develop hyperparathyroidism by the age of 50. Hyperparathyroidism caused by MEN1 is typically treated with surgical removal of three-and-a-half of the four parathyroid glands, although sometimes all four glands are removed, with a portion of the parathyroid gland inserted into the forearm.
MEN1 also causes tumors in the islet cells of the pancreas and the lining of the duodenum (the first portion of the small intestine), which can secrete several hormones involved with endocrine function. Tumors that develop in the pancreas can be benign (non-cancerous) or malignant (cancerous). However, malignancy is rare before the age of 30.
Tumors that secrete hormones are named for the hormone they produce (i.e., gastrinoma, insulinoma, glucagonoma, VIPoma). Gastrinomas are the most common functional pancreatic tumor in individuals with MEN1 and can cause Zollinger-Ellison syndrome (ZES). Symptoms of ZES include elevated levels of gastrin, ulcers, inflammation of the esophagus, diarrhea and abdominal pain. The second most common functional pancreatic tumor in MEN1 is insulinoma. Surgery is the main treatment for hypoglycemia due to an insulinoma.
Except for insulinoma, the effects of hormone-secreting pancreatic tumors are typically well-managed with medication. The role of surgery in the treatment of other pancreatic tumors is debatable and depends greatly on the clinical history of the individual.
MEN1 can also cause benign (non-cancerous) tumors to develop in the anterior portion of the pituitary gland. The most common pituitary tumor is a prolactinoma; however, people with MEN1 can develop other pituitary tumors that are non-functional or that secrete hormones such as growth hormone, adrenocorticotropin hormone and thyroid stimulating hormone. Symptoms of a pituitary tumor are usually due to the tumor pressing on other nearby structures and can include headaches and changes in vision. However, prolactinomas can interfere with sexual function and fertility, and tumors secreting growth hormone over time can cause acromegaly (enlargement of the bones). Adrenocorticotropin-producing tumors can cause Cushing’s syndrome. Pituitary tumors generally respond well to medication; however, in some instances surgical removal of the tumor or radiation will be necessary.
Multiple endocrine neoplasia type 2 (MEN2) is characterized by a very high risk of developing medullary thyroid cancer (MTC). Individuals with MEN2 have a greater than 95% chance of developing MTC in their lifetime. MEN2 is divided into three clinical subtypes:
MEN2A is characterized by the presence of medullary thyroid cancer in early adulthood, pheochromocytoma and hyperparathyroidism. About 50% of people with MEN2A will develop a pheochromocytoma and 20-30% will develop hyperparathyroidism.
MEN2B is characterized by medullary thyroid carcinoma in early childhood, and pheochromocytomas (50% frequency). Hyperparathyroidism is almost never seen in people with MEN2B. People with MEN2B often have other physical characteristics, including being tall and slender, having small benign (non-cancerous) tumors on the lips and tongue and a condition where the large intestine becomes enlarged and irritated.
Familial Medullary Thyroid Carcinoma (FMTC) is medullary thyroid cancer occurring in multiple members of the same family without the presence of pheochromocytoma and/or hyperparathyroidism.