MEN1
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.
Risk Factors
MEN1 is caused by mutations in the MEN1 gene, which is a tumor suppressor gene. Mutations of the MEN1 gene "disable" tumor suppression, causing unregulated cell division that leads to tumor formation. All children of a parent with MEN1 have a 50% chance of developing the disease.
Genetic testing of a blood sample can identify MEN1 gene mutations in about 75-90% of people with clinical symptoms. A positive test result can confirm a diagnosis in an affected individual, or identify family members at risk of developing MEN1. However, a negative test result cannot definitively rule out MEN1 in patients when a mutation has not been previously identified in another family member. Genetic testing is offered to adults. Children with symptoms are also tested on case-by-case basis, but testing is typically not done on children who don't have symptoms, because there are currently no preventive treatments. A genetic counselor will discuss testing with you and your family, answer any questions and help you make an informed decision regarding testing.
Screening Guidelines
Screening guidelines may vary depending on the patient's age and clinical history, but some annual screening recommendations apply to all adults with MEN1 or who are at risk for MEN1. These include assessment of calcium, parathyroid hormone, gastrin and prolactin levels. Occasionally, individuals will need additional imaging tests such as ultrasound, CT or MRI to screen for carcinoid, pancreatic, pituitary and other tumors. Screening has been recommended as early as age five for children at risk for MEN1.