Multiple Endocrine Neoplasia - Types, Causes, Symptoms, Diagnosis, and Treatment

Introduction:

Multiple endocrine neoplasia (MEN) is a condition that causes the growth of tumors in the endocrine system, which comprises different glands that produce, store, and secrete hormones into the bloodstream. Hormones are chemical messengers released by the endocrine glands to carry out specific functions in different parts of the body. Growth of tumors occurs in different endocrine glands in MEN, leading to an excess hormone production from the affected glands, causing symptoms. The tumors may be benign (harmless) or malignant (cancerous). The condition affects about one in every 30,000 to 35,000 people.

What Are the Types of Multiple Endocrine Neoplasia (MEN)?

There are many types of MEN, type 1 and type 2 being the most common.

• Multiple Endocrine Neoplasia Type 1:

MEN type 1 involves tumors occurring in the pancreas, parathyroid glands, and the pituitary glands. Commonly, the parathyroid glands are involved first, causing symptoms of overactive parathyroid glands that cause excess calcium to be released into the bloodstream. In persons with hyperparathyroidism, symptoms may not occur for many years. However, they may present with symptoms like thinning of bones, making them more prone to fractures, kidney stones, nausea and vomiting, high blood pressure, and weakness. People with a genetic trait for MEN type 1 tend to develop hyperparathyroidism by the age of 50.

• Multiple Endocrine Neoplasia Type 2:

MEN type 2 is further classified into three subtypes, namely:

1. Type 2A.
2. Type 2B.
3. Familial medullary thyroid carcinoma (FMTC).

About 90 percent of all the cases are of type 2A. People affected with MEN type 2 tend to develop familial medullary thyroid carcinoma (FTMC) irrespective of the subtype. People with type 2A can develop hyperparathyroidism, which causes an increase in blood calcium levels. People with type 2B can develop tumors in the nerve cells of the GI (gastrointestinal) tract, lips, eyelids, and tongue, which usually occur before ten years of age.

What Are the Causes of Multiple Endocrine Neoplasia (MEN)?

Both MEN type 1 and type 2 are inherited, which means that a defective gene passed down in families is the cause. MEN type 1 occurs due to an abnormality in the MEN1 (menin 1) gene, whereas MEN type 2 occurs due to an abnormality in RET (ret proto-oncogene) gene. Sometimes, a patient without a family history can develop MEN due to a new genetic change that develops due to unknown reasons.

Who Are at an Increased Risk of Developing MEN?

MEN is an inherited condition that is passed down in families. Either of the parents with a genetic mutation (changes in genes) can transmit it to their children. The genes that change are MEN1 (menin 1) and RET (ret proto-oncogene).

Both men and women are at equal risk. Also, people of any geographical or racial group can develop MEN.

What Are the Symptoms of Multiple Endocrine Neoplasia (MEN)?

Symptoms in multiple endocrine neoplasia occur due to an increase in the hormone levels that are released.

The following symptoms are noted in MEN type1, which include:

• Bone pain.

• Increased tendency to fractures.

• Kidney stones.

• Stomach or intestinal ulcers.

• Fatigue.

• Vision changes.

• Headache.

• Infertility.

• Increased production of breast milk.

• Acromegaly (occurs due to excess production of growth hormone secreted by the pituitary gland).

• Cushing’s syndrome (occurs due to abnormally high levels of the hormone cortisol).

The following symptoms are noted in MEN type 2 that includes:

• Neuromas are benign (harmless) growths of the nerve tissues of the lips and tongue.

• Overgrowth of thyroid cells leads to thyroid carcinoma.

• Thickening of the lips and eyelids.

• The curvature of the spine.

• Abnormalities of feet and thigh bones.

• Loose bones.

• Enlarged large intestine.

How Is Multiple Endocrine Neoplasia (MEN) Diagnosed?

A doctor diagnoses MEN based on physical examination and taking the medical and family history. Few tests may be ordered to get a better picture of the condition, which include:

1. Magnetic resonance imaging (MRI) scans use magnetic fields and radio waves to provide precise details of the soft tissues of the body.
2. Computerized tomography (CT) scans to create cross-sectional images using several X-rays and computer processing techniques.
3. Positron emission tomography (PET) scan uses tiny particles called positrons to create images of the body tissues. Body images are obtained by detection of radiation from the emission of positron particles.
4. Nuclear medicine scans use radioactive substances for the diagnosis and treatment of diseases.
5. Ultrasound scans of the pancreas use high-frequency sound waves to create images of the body parts.

Genetic testing helps determine if a person has MEN. Children of the affected person are at a higher risk of inheriting the mutation (change). Also, parents and siblings of the affected persons may be having the condition without showing noticeable symptoms.

How Is Multiple Endocrine Neoplasia (MEN) Treated?

Treatment of multiple endocrine neoplasia depends on the type and the development of the tumors. The following pattern may be considered in treating MEN.

• Screening for tumors.

• Surgery to remove tumors that have developed.

• Chemotherapy.

• Radiation therapy.

• Genetic counseling for parents who are planning pregnancy.

The treatments for specific tumors include:

1. Pituitary Tumors: They can be treated by surgery or medications.
2. Hyperparathyroidism: It is treated by removal of the overactive parathyroid glands.
3. Hypoglycemic Syndrome: A tumor of the pancreas results in the production of excess insulin (a condition called insulinoma), which leads to very low blood glucose levels that can be life-threatening. Surgery is done to remove a part of the pancreas.
4. Neuroendocrine Tumors: These types of tumors occur in the pancreas or small intestine. Surgery, medications, or an ablation procedure are the preferred modes of treatment. The ablation procedure destroys the tumors using extreme heat or cold.
5. Zollinger-Ellison Syndrome (ZES): ZES involves tumors that produce excess gastric acid that can lead to diarrhea and ulcers. Medications or surgery are the treatment options.
6. Adrenal Tumors: In most cases, adrenal tumors are treated by a wait and watch approach. However, if the tumors are cancerous (harmful), minimally invasive surgery is advised to remove them.
7. Carcinoid Tumors: These types of tumors develop in the lungs, digestive tract, and thymus gland. Radiation, chemotherapy, or hormone-based therapy is recommended for advanced cases of carcinoid tumors.

Conclusion:

Multiple endocrine neoplasia (MEN) is an inherited condition that is passed down in families. Symptoms may occur based on the gland affected and also the number of hormones circulating in the bloodstream. Early screening based on family history can help start early treatment for the tumors. Also, regular check-ups with the endocrinologist are advised post-treatment to keep a check on the regrowth of tumors. Genetic counseling is advised for families who plan on starting a family.