WHAT IS MEN 2?
MEN2 describes a group of disorders that cause one or more glands in the body to develop tumors that produce excess hormones. These conditions usually run in families and can be passed from one generation to the next. There are two types: MEN2A and MEN2B. Individuals with MEN2A can develop medullary thyroid cancer (MTC), primary hyperparathyroidism, and pheochromocytoma (PHEO). Some may also develop a skin condition called cutaneous lichen amyloidosis (CLA) or a bowel condition called Hirschprung disease (HD). Individuals with MEN2B all develop MTC and about half develop PHEO, and they do not get primary hyperparathyroidism. Affected individuals may also have: difficulty making tears, thickened lips, eyelids that turn outward, tall and lanky body type, high-arched feet, and overgrowths (ganglioneuromatosis or neuromas) of mucosal surfaces (especially the tongue) and the gastrointestinal tract/bowel. Individuals commonly have symptoms of constipation or diarrhea due to an abnormally enlarged and poorly working large intestine.
MEDULLARY THYROID CANCER (MTC)
Medullary Thyroid Cancer is a rare tumor of the thyroid gland that comes from cells in the thyroid called parafollicular cells or C-cells. It accounts for 1-2% of thyroid cancers in North America. These cells can produce proteins called “calcitonin” and “carcinoembryonic antigen (CEA)”, which can be measured in the blood and help indicate the extent of C-cell growth and/or spread. In MTC, thyroid function tests such as thyroid hormone (T4) and thyroid stimulating hormone (TSH) levels are usually normal. MTC may spread to the lymph nodes or, in more advanced cases, to other areas of the body such as the lungs, liver, and bones.
A PHEO is a tumor of the adrenal glands, small glands located above the kidneys, that make high levels of catecholamines (epinephrine and norepinephrine; also known as adrenaline and noradrenaline). In MEN2, PHEOs are usually benign and do not spread beyond the adrenal glands. Symptoms of a PHEO may include palpitations, high blood pressure, severe headaches, increased sweatiness and paleness. Testing for PHEO includes collecting a urine sample (generally over a 24-hour period) or a blood sample to check for a metabolized products of catecholamines called metanephrines. High metanephrines are an indicator of a PHEO and require further investigation, usually with a CT scan or MRI.
The four parathyroid glands lie behind the thyroid gland and produce parathyroid hormone (PTH). PTH is responsible for maintaining normal calcium levels in the blood. Overproduction of PTH from benign tumors in the parathyroid glands can lead to high calcium levels. Symptoms may include irritability, kidney stones, constipation, increased urination, and osteoporosis (low bone strength) leading to broken bones.
CUTANEOUS LICHEN AMYLOIDOSIS (CLA)
This is a rare disorder with symptoms of skin darkening and itchy areas, typically on or between the shoulder blades. The itchiness may worsen with stress and improve with sun exposure. This area may become darkened with scratching. This symptom may start before a diagnosis of MTC.
HIRSCHPRUNG DISEASE (HD)
HD results from an undergrowth of nerve cells in the bowel. As a result, the muscles in the intestinal wall cannot contract and relax adequately, and affected individuals with HD have difficulty passing stools. This usually presents in infancy or early childhood.