tumors occur in 15 to 42% of MEN 1 patients. From 25 to 90% are prolactinomas. About 25% of pituitary tumors secrete growth hormone or growth hormone and prolactin. Excess prolactin may cause galactorrhea, and excess growth hormone causes acromegaly clinically indistinguishable from sporadically occurring acromegaly. About 3% of tumors secrete ACTH, producing Cushing's disease. Most of the remainder are nonfunctional. Local tumor expansion may cause visual disturbance, headache, and hypopituitarism. Pituitary tumors in MEN 1 patients appear to be larger and behave more aggressively than sporadic pituitary tumors. Other manifestations Adenomas of adrenal glands occurs occasionally in MEN 1 patients. Hormone secretion is rarely altered as a result, and the significance of these abnormalities is uncertain. Carcinoid tumors, particularly those derived from the embryologic foregut (lungs, thymus), occur in isolated cases. Multiple subcutaneous and visceral lipomas, angiofibromas, and collagenomas may also occur. Genetic People with multiple endocrine neoplasia type 1 are born with one mutated copy of the MEN1 gene in each cell. Then, during their lifetime, the other copy of the gene is mutated in a small number of cells. These genetic changes result in no functional copies of the MEN1 gene in selected cells, allowing the cells to divide with little control and form tumors. This is known as Knudson's two-hit hypothesis and is a common feature seen with inherited defects in tumor suppressor genes. Oncogenes can become neoplastic with only one activating mutation, but tumor suppressors inherited from both mother and father must be damaged before they lose their effectiveness. The exception to the "two-hit hypothesis" occurs when suppressor genes exhibit dose-response, such as ATR. The exact function of MEN1 and the protein, menin, produced by this gene is not known, but following the inheritance rules of the "two-hit hypothesis" indicates that it acts as a tumor suppressor. Diagnosis In a diagnostic workup individuals with a combination of endocrine neoplasias suggestive of the MEN1 syndrome are recommended to have a mutational analysis of the MEN1 gene if additional diagnostic criteria are sufficiently met, mainly including: age <40 years positive family history including a first degree relative proving to have the MEN1 gene. multifocal or recurrent neoplasia two or more organ systems affected Types Multiple endocrine neoplasia or MEN 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