What is Multiple Endocrine Neoplasia (MEN)?
Multiple Endocrine Neoplasia is a group of hereditary disorders that causes tumors to grow in the body’s endocrine organs, the glands that produce hormones. Multiple endocrine neoplasia (commonly referred to by the acronym MEN) is an inherited tendency to develop cancer that is passed from one generation to the next in dominant fashion.
The term Multiple Endocrine Neoplasia itself summarizes this tendency to have cancer (neoplasia) in several different (multiple) endocrine organs.
What are the different types of Multiple Endocrine Neoplasia?
Depending upon which abnormal gene is passed from parent to child and which specific endocrine organs are affected, MEN is separated into two distinct types:
- In MEN type 1 (aka: Wermer’s Syndrome), the defective gene is menin. When menin is abnormal, tumors can grow in different areas of the body. The pattern of growth most often seen in MEN type 1 is tumors arising in the “3 P” glands: the Pituitary, the Parathyroid, and the Pancreas. Less often, tumors can grow in the adrenal glands and the thymus gland. Even more rarely, tumors are seen in the lung. Additionally, it is quite common for small, shiny red spots (called angiofibroma) to emerge over the nose and cheeks by age 40.
- In MEN type 2 (aka: Sipple’s Syndrome), the defective gene is RET. When RET is abnormal, the affected organs are the thyroid, adrenal, and parathyroid glands. The thyroid gland in MEN type 2 patients almost always develops medullary thyroid cancer. Less often, MEN type 2 patients will develop tumors in their adrenal glands called pheochromocytomas. A smaller fraction of MEN type 2 patients will develop benign tumors in their parathyroid glands called adenomas (the same kind of parathyroid growths seen in MEN type 1).
Complicating the classification of the disease even further, MEN type 2 is divided into type 2a and type 2b. In type 2b, patients tend to be tall and thin, with a narrow face, long fingers, and very flexible joints. Bumps can appear over their lips, tongues, and inner cheeks; these bumps are called mucosal neuromas. Patients with MEN type 2b almost never develop problems with their parathyroid glands.
How do doctors make the diagnosis of MEN?
It depends upon whether or not there is a known family history of MEN. If you are the first person in your family to have MEN, then the diagnosis process is more complicated. A genetic syndrome has to be suspected before it can ever be diagnosed. So at the beginning, your doctor will appropriately focus on your most bothersome problem, such as a high calcium level in MEN type 1, and then realize, in the process of investigating that single problem, that you have abnormalities in other areas. For instance, the diagnosis of hyperparathyroidism as the cause of high calcium in an MEN type 1 patient might then lead the doctor to find that all four parathyroid glands are overactive (patients without MEN type 1 usually have only one overactive gland causing their hyperparathyroidism).
Because it is unusual to see all the parathyroid glands making too much hormone, the doctor might then look for abnormalities in other endocrine organs like the pituitary gland (this typically requires a magnetic resonance imaging, or MRI, scan of the brain to look at the gland) and in the pancreas (which may require MRI or computerized tomography (CT) scans of the abdomen, or endoscopic ultrasound (EUS) in which an ultrasound probe is placed through the mouth while the patient is sedated and then advanced down the gut into the small intestine, where very detailed pictures of the pancreas can be taken). In this manner, the doctor might find tumors in the pituitary gland or pancreas which had not yet come to the attention of the patient or their physician. When abnormalities are seen in more than one endocrine organ, the diagnosis of Multiple Endocrine Neoplasia is strongly suspected.
What testing is available for MEN?
To confirm the MEN diagnosis, genetic testing can be performed.
- Test Menin: In MEN type 1, special blood tests are done to look for mutations in the menin gene. However, even if no mutations in menin are found, it is still possible to have MEN type 1, because we do not yet know all the changes in the menin gene that can lead to this condition. The gene was first identified in 1997, and, since then, over 1300 changes within the gene have been found which can result in a person having MEN type 1.
- Test RET: Special blood tests are conducted to test for mutations in RET. There are over 130 identified errors in the RET gene that can lead to MEN type 2, and new research is happening all the time to recognize more disease-causing mutations in both kinds of MEN and improve the accuracy of diagnostic tests.
- Test Calcitonin: In MEN type 2 patients with medullary thyroid cancer, there is a very specific blood test for a chemical called calcitonin. When calcitonin levels in the blood are high, it almost always means that there is a medullary thyroid cancer present in the body, and this can lead to the diagnosis both of the tumor and the MEN type 2 syndrome.
If I have MEN, how do I get my family tested?
If you have MEN, then genetic counseling is needed to determine when and how it is most appropriate to have your family tested for the same defective gene. The earliest reported symptoms in a child with MEN type 1 were at age 5, but it is uncommon to become symptomatic before adulthood and the first symptoms are usually related to high calcium levels. Children with MEN type 2 should see an endocrinologist and an endocrine surgeon to discuss preventive removal of the thyroid gland before it can develop cancer, which often happens before age 30.
Is there always a family history?
No, there is not always a family history of endocrine cancer in patients with MEN. There is always a possibility, particularly in MEN type 2b, that you are the first person in your family to be affected with the disease, by what as known as a “de novo” or new mutation that did not affect your father or mother but that occurred by chance in their sperm or eggs.
However, a parent affected with the disease has a 50% chance of passing it on to each one of their children.