“MEN, MEN, MEN, MEN, manly MEN MEN, MEN…” OK, not the long running TV comedy Two and a Half Men. Not the one that starred Charlie Sheen and Jon Cryer. MEN is short for “multiple endocrine neoplasia,” and, coincidentally enough, there are almost two and half kinds of them. They’re referred to as MEN 1, MEN 2a and 2b, and MEN 3. Some books actually postulate an MEN 4, but that’s another show for another season.
Multiple endocrine neoplasias are inherited disorders that include a variety of combinations of endocrine and nonendocrine tumors and affect different endocrine glands. The diseases run in families enough so that genetic counseling is advised when any first degree relative is affected. There are so many different systems and hormones affected that in many TV commercials for drugs (even not during just Two and a Half Men) the usual speed talk at the end that gives all the cautions involved in taking the medications often mentions multiple endocrine neoplasia by name as an instance when the drug shouldn’t be taken.
MEN type 1 is a syndrome that affects two or more of three principal endocrine systems. These are tumors of the parathyroid glands (which help control calcium and phosphorus levels in the body), pituitary tumors, and tumors of the pancreas and GI tract. The parathyroid growths may lead to elevated calcium levels in the serum and an overgrowth of the glands. Kidney stones and abdominal and bone pain may be associated. The pituitary tumors are usually adenomas and a primary presentation in affected women. These can result in menstrual dysfunction, enlarged breasts, or breast secretion as they secrete a hormone called prolactin. The endocrine tumors of the GI tract involve gastrinoma (hyper acid secretion), insulinoma (overproduction of insulin), glucagonoma, and some adrenocortical tumors as well. Hyperparathyroid tumors are the most common; the triad most seen in unison are the parathyroid, pituitary and pancreatic growths.
The risk of cancer development in MEN 1 generally depends on which organ is involved. Parathyroid abnormalities cause changes in calcium and phosphorus metabolism (and secondarily involve the bones) but are generally non-malignant. The GI tumors (gastrinoma) are very aggressive and may have metastasized even before they are initially found. The biggest problem with MEN 1 is the malignant changes that occur in up to a third of those affected, and there is no true prevention possible in that each of the organs in which they occur are not amenable to prophylactic surgical excision and removal.
MEN 2a and 2b (our half MEN) also involve genetic expression and tumors that include parathyroid and pituitary but substitute pheochromocytoma (a growth were blood pressure hormones are involved) and familial medullary cancer of the thyroid. The 2b type has an additional feature of mucosal neuromas of the lips, tongue and GI tract. The most ominous of the findings is the medullary cancer. In these cases, there can be actual prevention attempted by prophylactic removal of the thyroid gland at a young age, after which thyroid supplementation is given.
MEN 3 is also known by the MEN 2b surname. MEN 4, only recently described, is a much rarer familial tumor syndrome where almost any combination of the previous goes. Those with MEN 4 appear susceptible to adrenal tumors, kidney tumors, testicular cancer and cervical carcinoma. Thankfully this is the rarest of the bunch.
Risk classifications generally have an added mortality, first for the effects of all the inappropriate hormone secretion from the growths and, secondarily, for the increased occurrence of tumors. MEN 2 is the more insurable of the group as elective removal of the thyroid cuts down on major malignant potential. Again, genetic screening is a must in first degree relatives of affected individuals and early diagnosis is key.
