Multiple Endocrine Neoplasia:
The term Multiple Endocrine Neoplasia (MEN) contains several distinct syndromes featuring tumors of endocrine glands, each with its own characteristic pattern. In some cases, the tumors are malignant, in others, benign. If the tumors become cancerous, the condition can be life-threatening. Benign or malignant tumors of nonendocrine tissues occur as components of some of these tumor syndromes. MEN syndromes are inherited as autosomal dominant disorders. The major forms of multiple endocrine neoplasia are called type 1, type 2, and type 4. These types are distinguished by the genes involved, the types of hormones made, and the characteristic signs and symptoms.
- Pituitary tumors
- Parathyroid tumors
- Pancreatic endocrine tumors (e.g. Zollinger-Ellison syndrome, Insulinomas, VIPomas, Glucagonomas)
- Parathyroid tumor
- Medullary thyroid carcinoma
- Mucosal neuromas/Marfanoid habitus
- Medullary thyroid Carcinoma
- A useful mnemonic to remember the associated neoplasias is below:
- MEN I (3 Ps) – Pituitary, Parathyroid, Pancreas
- MEN IIa (1M,2Ps) – Medullary Thyroid Carcinoma, Pheochromocytoma, Parathyroid
- MEN IIb (2Ms,1P) – Medullary Thyroid Carcinoma, Marfanoid habitus/mucosal neuroma, Pheochromocytoma
Multiple endocrine neoplasia type 1 affects about 1 in 30,000 people; multiple endocrine neoplasia type 2 affects an estimated 1 in 35,000 people. Among the subtypes of type 2, type 2A is the most common form, followed by FMTC. Type 2B is relatively uncommon, accounting for about 5 percent of all cases of type 2. The prevalence of multiple endocrine neoplasia type 4 is unknown, although the condition appears to be rare.
Mutations in the MEN1, RET, and CDKN1B genes can cause multiple endocrine neoplasia.
Mutations in the MEN1 gene cause multiple endocrine neoplasia type 1. This gene provides instructions for producing a protein called menin. Menin acts as a tumor suppressor, which means it normally keeps cells from growing and dividing too rapidly or in an uncontrolled way. Although the exact function of menin is unknown, it is likely involved in cell functions such as copying and repairing DNA and regulating the activity of other genes. When mutations inactivate both copies of the MEN1 gene, menin is no longer available to control cell growth and division. The loss of functional menin allows cells to divide too frequently, leading to the formation of tumors characteristic of multiple endocrine neoplasia type 1. It is unclear why these tumors preferentially affect endocrine tissues.
Mutations in the RET gene cause multiple endocrine neoplasia type 2. This gene provides instructions for producing a protein that is involved in signaling within cells. The RET protein triggers chemical reactions that instruct cells to respond to their environment, for example by dividing or maturing. Mutations in the RET gene overactivate the protein’s signaling function, which can trigger cell growth and division in the absence of signals from outside the cell. This unchecked cell division can lead to the formation of tumors in endocrine glands and other tissues.
Mutations in the CDKN1B gene cause multiple endocrine neoplasia type 4. This gene provides instructions for making a protein called p27. Like the menin protein, p27 is a tumor suppressor that helps control the growth and division of cells. Mutations in the CDKN1B gene reduce the amount of functional p27, which allows cells to grow and divide unchecked. This unregulated cell division can lead to the development of tumors in endocrine glands and other tissues.
Read more about the CDKN1B, MEN1, and RET genes.
Symptoms vary from person to person, and depend on which gland is involved. They may include:
- Abdominal pain
- Black, tarry stools
- Bloated feeling after meals
- Burning, aching, or hunger discomfort in the upper abdomen or lower chest that is relieved by antacids, milk, or food
- Decreased sexual interest
- Lack of menstrual periods (in women)
- Loss of appetite
- Loss of body or facial hair (in men)
- Mental changes or confusion
- Muscle pain
- Nausea and vomiting
- Sensitivity to the cold
- Unintentional weight loss
- Vision problems
- Blood cortisol level
- CT scan of abdomen
- CT scan of the head
- Fasting blood sugar
- Genetic testing
- Insulin test
- MRI of the abdomen
- MRI of the head
- Parathyroid biopsy
- Serum adrenocorticotropic hormone
- Serum calcium
- Serum follicle stimulating hormone
- Serum gastrin
- Serum glucagon
- Serum luteinizing hormone
- Serum parathyroid hormone
- Serum prolactin
- Serum thyroid stimulating hormone
- Ultrasound of the neck
Surgery to remove the diseased gland is the treatment of choice. A medication called bromocriptine may be used instead of surgery for pituitary tumors that release the hormone prolactin.
The parathyroid glands, which control calcium production, can be removed. However, because it is difficult for the body to regulate calcium levels without these glands, a total parathyroid removal is usually not done initially.
Medicine is available to decrease the excess stomach acid production caused by some tumors, and to reduce the risk of ulcers.
Hormone replacement therapy is given when entire glands are removed or do not produce enough hormones.