An Overview of Multiple Endocrine Neoplasias

Multiple endocrine neoplasia (MEN) is the name for a group of hereditary illnesses characterized by having more than one tumor of the endocrine organs at a time. There are several different combinations of endocrine tumors that are known to occur together, and each of these patterns is categorized as one of several different MEN syndromes.

Multiple endocrine neoplasia syndromes can affect these major endocrine glands:

• Pituitary
• Thyroid
• Parathyroid
• Adrenal
• Pancreas

The tumors that develop as part of each MEN syndrome may be benign or malignant. Benign tumors are self-limited tumors that can cause medical symptoms but grow slowly, do not spread to other parts of the body, and are not fatal. Malignant tumors are cancerous tumors that can grow rapidly, may spread to other parts of the body, and can be fatal if they are left untreated.

Each of the three syndromes that are considered the most common manifestations of MEN is caused by a specific genetic abnormality, which means that the tumor combination runs in families as a hereditary condition.

The MEN syndromes are called MEN 1, MEN 2A, and MEN 2B. Each has a unique set of symptoms to consider.

People diagnosed with MEN 1 have tumors of the pituitary gland, the parathyroid gland, and the pancreas. Generally, these tumors are benign, although it is not impossible for them to become malignant.

The symptoms of MEN 1 can begin during childhood or adulthood. The symptoms themselves are variable because the tumors involve endocrine organs that can produce a wide range of effects on the body. Each of the tumors causes abnormal changes related to hormonal overactivity. Possible symptoms of MEN 1 are:

• Hyperparathyroidism, in which the parathyroid gland produces too much hormone, can cause tiredness, weakness, muscle or bone pain, constipation, kidney stones, or thinning of bones. Hyperparathyroidism is usually the first sign of MEN1 and typically occurs between the ages 20 and 25. Nearly everyone with MEN1 will develop hyperparathyroidism by the age of 50.
• Ulcers, inflammation of the esophagus, diarrhea, vomiting, and abdominal pain
• Headaches and changes in vision
• Problems with sexual function and fertility
• Acromegaly (overgrowth of the bones)
• Cushing’s syndrome
• Infertility
• Excess production of breast milk

People with MEN 2 have thyroid tumors, adrenal gland tumors, and parathyroid tumors.

The symptoms of MEN 2A begin in adulthood, typically when a person is in his or her 30s. As with the other MEN syndromes, the symptoms result from overactivity of the endocrine tumors.

• Swelling or pressure in the neck region due to tumors on the thyroid
• High blood pressure, rapid heart rate, and sweating caused by adrenal gland tumors (pheochromocytoma) that specifically involve the section of the adrenal gland called the adrenal medulla
• Excessive thirst and frequent urination caused by high calcium levels due to parathyroid tumors
• Neuromas, which are growths around nerves of mucous membranes, such as the lips and tongue
• Thickening of the eyelids and lips
• Abnormalities of the bones in the feet and thighs
• Curvature of the spine
• Long limbs and loose joints
• Small benign tumors on the lips and tongue
• Enlargement and irritation of the large intestine

This is the least common of these rare tumor patterns and is characterized by thyroid tumors, adrenal gland tumors, neuromas throughout the mouth and digestive system, abnormalities of bone structure, and an unusually tall and skinny stature, indicating what are known as marfanoid features.

The symptoms can begin in childhood, often before age 10, and include:

• A very tall, lanky appearance
• Neuromas in and around the mouth
• Stomach and digestive problems
• Symptoms of thyroid cancer and pheochromocytoma

Your doctor may be concerned that you may have MEN syndrome if you have more than one endocrine tumor and your family history includes people with the syndrome. You do not need to have all of the signature tumors of one of the MEN syndromes for your doctor to consider the disease. If you have more than one tumor or characteristic, or even if you have one endocrine tumor that is associated with MEN, your doctor might evaluate you for other tumors before they become symptomatic.

Similarly, a family history is not necessary for MEN diagnosis because a person can be the first in the family to have the disease. The specific genes that cause MEN have been identified, and genetic testing may be an option in confirming the diagnosis.

Diagnostic tests may include:

• Blood tests
• Urine tests
• Imaging tests, which may include computed axial tomography (CT or CAT) scans or magnetic resonance imaging (MRI) scans

The treatment for the MEN syndromes depends on a few different factors. Not everyone who is diagnosed with MEN 1, MEN 2A, or MEN 2B experiences the same exact disease course. Generally, treatment is focused on three main objectives, which include reducing symptoms, detecting tumors early, and preventing the consequences of malignant tumors.

If you are diagnosed with multiple endocrine neoplasia, your treatment for MEN will be customized to your particular needs. One or more of the following therapies may be recommended to treat the disease or help relieve symptoms.

• Medications to help balance hormone levels or treat symptoms
• Surgery: Sometimes the affected gland can be surgically removed to treat symptoms. (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.)
• Radiation and/or chemotherapy, in the case of a malignancy

Active surveillance and monitoring to identify new tumors and to spot any malignancy as early as possible may also be recommended.

Finding out you have a tumor is distressing, and having more than one tumor is even more frightening. If you have been told that you have or might have multiple endocrine neoplasia, then you are probably quite concerned about which symptoms could pop up next and whether your overall health is in danger.

The fact that MEN syndromes are recognized and classified makes your situation more predictable than it may seem. Despite the fact that these are rare syndromes, they have been defined in great detail and there are well-established methods of managing these illnesses. While you will certainly need consistent medical follow up, there are effective ways of controlling your condition and with prompt diagnosis and appropriate treatment, you can live a healthy life.