A rare health condition that is caused by a genetic mutation (change) that negatively affects the glands in the endocrine system is called multiple endocrine neoplasia (MEN). Healthcare professionals have divided this disorder into 2 primary types. These include:
- Multiple endocrine neoplasia (MEN) type 1 – This type causes multiple tumors to develop in different parts of the endocrine system.
- Multiple endocrine neoplasia (MEN) type 2 – The second type of MEN is a genetic polyglandular cancer syndrome. People with MEN2 almost always develop medullary thyroid cancer (carcinoma) and are at increased risk for other tumors.
Both types of this condition have other names. For example, MEN1 is also known as MEN-1 syndrome, multiple endocrine adenomatosis, and Wermer’s syndrome. The second type can also be called MEN2 syndrome and Sipple syndrome.
Endocrine System
Typically, the endocrine system consists of multiple glands and organs that produce and release hormones. These hormones help the body function properly, including carrying messages through the blood to the organs, skin, muscles, and other structures. Check some examples of glands and organs that make up the endocrine system below:
- Hypothalamus – This is a very important gland that is located at the base of the brain and controls aspects of the endocrine system.
- Pituitary gland – This is a small gland that is attached to the hypothalamus. It also produces hormones that control multiple other glands in the endocrine system. These include the adrenal glands, thyroid gland, ovaries, and testicles.
- Thyroid – This is a butterfly-shaped gland located in the front of the neck. It is responsible for your metabolism (the way your body uses energy from food).
- Parathyroid glands – Normally, people have 4 small glands that are located next to the thyroid gland, which control Calcium and Phosphorus levels in the body.
- Adrenal glands – These glands from the endocrine system are located at the top of each kidney. They also control metabolism and blood pressure, sexual development, and your stress response.
- Pineal gland – This gland is responsible for the sleep cycle. It also releases Melatonin.
- Pancreas – This part of the endocrine system produces insulin, which is used to control blood sugar levels. Moreover, the pancreas is also a part of the digestive system.
- Ovaries – These are female sex organs that produce Estrogen, Progesterone, and Testosterone.
- Testes – The testicles (testes) are male sexual organs that produce sperm and release Testosterone.
What Parts of the Endocrine System are Affected by MEN1?
In most cases, people with the first type of MEN have problems with the parathyroid glands (the most common area affected by MEN1), the pituitary gland, and the gastroenteropancreatic tract. While most tumors caused by MEN1 are benign (noncancerous), some people may develop malignant (cancerous) ones. Furthermore, the endocrine glands in people with MEN1 often release excessive amounts of hormones in the bloodstream, which may also cause symptoms and health issues.
Nowadays, physicians have discovered more than 20 different endocrine and non-endocrine tumors that are caused by MEN1. Check some examples below:
- Neuroendocrine tumors of the thymus and bronchi
- Adrenocortical tumors
- Lipomas
- Visceral leiomyomas
- Truncal and facial collagenomas
- Facial angiofibromas
- Breast cancer
- Meningioma (a tumor that develops in the central nervous system, including the brain and spinal cord)
- Ependymomas
What Parts of the Endocrine system are Affected by MEN2?
Almost everyone who suffers from MEN2 will develop medullary thyroid cancer (MTC). This type of thyroid cancer accounts for about 1% to 2% of all diagnosed cases in the U.S. Usually, MTC is different from other types because it develops in the C cells of the thyroid gland. When it occurs, the thyroid gland begins to produce less hormone (especially Calcitonin) that reduces blood Calcium levels. Moreover, MTC may spread to nearby lymph nodes and other parts of the body if it is left untreated. Commonly, physicians recommend thyroidectomy (a surgery to remove the thyroid gland) for people with this type of cancer. In addition, most people with MEN2 will also develop the following health conditions. These include:
- Pheochromocytoma – This is a rare type of tumor that develops in the middle of one or both adrenal glands. The tumor is made up of certain cells called chromaffin cells that produce and release hormones. Most of the time, pheochromocytomas are benign, but about 10% to 15% of them can be malignant and spread quickly to other parts of the body.
- Hyperparathyroidism (overactive parathyroid glands) – This condition occurs when the parathyroid glands begin to produce and release too many hormones. As a result, it significantly increases the Calcium levels in the blood. It often occurs due to a non-cancerous tumor.
How Common is Multiple Endocrine Neoplasia?
Generally, MEN occurs rarely, and the first type affects about 1 in 30,000 people, and the second type affects about 1 in 35,000 people. According to some research, many cases can go undiagnosed or misdiagnosed.
Symptoms
Usually, people who develop MEN experience different symptoms because they depend on which part of the endocrine system is affected, the severity and type of MEN, existing health problems, gender, and age.
MEN-1 Symptoms
The symptoms of people with MEN1 appear according to the location of the tumor. In this case, the symptoms appear due to overproduction of hormones. Usually, the symptoms are related to the following tumor types and disorders that are associated with MEN1. For example:
- Gastrinomas
- Prolactinomas
- Insulinomas
- Hyperparathyroidism
Symptoms Related to Parathyroid Gland Hyperplasia
Most of the time, MEN1 affects the parathyroid glands, and approximately 90% of people with this type of multiple endocrine neoplasia develop hyperparathyroidism. Check some symptoms below:
- Difficulty concentrating
- Depression
- Extreme tiredness (fatigue)
- Appetite changes
- Muscle weakness
- Joint pain
- Nausea
- Vomiting
- Bone pain
- Confusion
- Temporary memory problems
- Increased thirst and frequent urination
- Constipation
Symptoms Related to Pancreas and Duodenum Tumors
About 40% of adults with MEN1 will develop multiple gastrinomas and noncancerous tumors that release a hormone called gastrin. This tumor often appears in the first part of the duodenum (small intestine). Check some symptoms of gastrinomas below:
- Esophageal reflux (also known as acid reflux)
- Peptic ulcers
- Diarrhea
- Abdominal (belly) pain
Furthermore, people with MEN1 may also develop a tumor called an insulinoma. It appears in about 10% of people, and it secretes insulin. Without immediate treatment, it may lead to hypoglycemia (low blood sugar) and the following symptoms. Examples include:
- Heart palpitations
- Anxiety
- Hunger
- Sweating
- Shakiness
- Confusion
- Temporary vision changes
Symptoms Related to Pituitary Gland Tumors
These tumors often appear in about 25% of people with MEN1. They cause an increased release of several important hormones, including growth hormone, prolactin, and thyroid-stimulating hormone. One of them is prolactinomas, which cause an increased production and release of prolactin in the blood, and they are the most common pituitary gland tumors associated with MEN1. Check some symptoms of prolactinomas below:
- Infertility in men and women
- Reduced libido
- Milky discharge from the nipples (also known as galactorrhea)
- Changes in menstruation that are not related to menopause (including irregular periods or a lack of periods)
- Reduced levels of Testosterone in men
- Erectile dysfunction (ED)
- Nausea
- Vomiting
- Headaches
- Vision problems (such as reduced peripheral vision, double vision, blurred vision, and others)
What Are The Symptoms of MEN2?
The symptoms in people with MEN2 are also different because they depend on which glands and organs are affected by the disease. Mostly, people with MEN2 have symptoms due to medullary thyroid cancer, but they can also occur due to pheochromocytomas and hyperparathyroidism.
Symptoms Related to Medullary Thyroid Cancer
This is the most common disorder that people with MEN2 develop. Check some symptoms of MTC below:
- Neck pain
- A lump in the neck
- Voice changes (such as hoarseness)
- Difficult swallowing
- Cough
- Dyspnea (shortness of breath)
Symptoms Related to Pheochromocytomas
According to some research, about 50% of people with MEN2 also develop a pheochromocytoma. This is a noncancerous tumor that appears in one or both adrenal glands. The symptoms often appear due to increased production of Adrenaline or Noradrenaline in the blood. In rare cases, pheochromocytomas do not cause any symptoms. Check some symptoms of this type of tumor below:
- Excessive sweating
- Headaches
- Shakiness
- Fast or irregular heartbeats
- Hypertension (high blood pressure)
Symptoms Related to Hyperparathyroidism
Usually, people who develop this condition experience the following symptoms. These include:
- Constipation
- Problems with concentrating or focusing
- Muscle weakness and joint pain
- Fatigue
- Kidney stones
- Polyuria (excessive urination)
- Osteoporosis (brittle bones)
- Blurred vision
- Anxiety
If any of the previous symptoms occur, immediately contact your physician. Otherwise, it may lead to unpleasant results.
Causes
This is a genetic disease that occurs due to specific gene mutations that can be inherited (passed from the biological parents to their biological children). Sometimes, these gene mutations may occur due to a new gene mutation during fetal development. Usually, there is a 50% chance of passing the abnormal gene to your children.
The first type of multiple endocrine neoplasia happens due to a mutation in the MEN1 gene, which is a tumor suppressor. It means that this gene helps prevent tumors from forming by controlling cell division and instructing cells. When this gene does not work properly, some cells may grow and reproduce without control, causing tumors.
The MEN2 syndrome happens due to mutations of the RET gene. It plays an important role in the development of cancer. In normal circumstances, this gene helps control cell growth and multiplication and regulates cell death.
How to Prevent Multiple Endocrine Neoplasia?
There is no way to prevent this disorder because it occurs due to a gene mutation that is inherited during pregnancy or happens randomly for unknown reasons. In any case, you can perform genetic tests before pregnancy to make sure you do not have this abnormal gene.
Diagnosis
Usually, doctors diagnose MEN when a person has at least 2-3 endocrine tumors associated with this disorder. These include a parathyroid tumor, pituitary tumor, and/or gastrointestinal tumor. They may also ask some questions about your symptoms and family history to get more clues about your disease.
However, doctors usually perform multiple blood tests to check for increased hormone levels that are often present in people with MEN1. Most of the time, doctors perform imaging tests to identify the exact location and size of the tumor. These include CT (computerized tomography) scans, MRI (magnetic resonance imaging) scans, ultrasounds, and others. Moreover, the same tests are used to diagnose MEN2. The only difference is that doctors can confirm MEN2 when the affected person has MTC (medullary thyroid cancer) and other types of tumors.
Treatment
Typically, treatment for MEN involves a healthcare team, including endocrinologists, surgeons, oncologists, pediatricians, and others. They often recommend the following options to reduce the symptoms and improve your quality of life. Examples include:
- Medications to reduce the effects of excessive hormone levels
- Surgery to remove tumors
- Hormone replacement therapy to supply hormone levels when an endocrine gland is removed
- Cancer treatments – These include chemotherapy, radiation therapy, immunotherapy, or targeted therapy.
Frequently Asked Questions
Is there a cure for multiple endocrine neoplasia?
Unfortunately, there is no way to cure this disorder. That’s why the treatment goal is to ease the symptoms, prevent life-threatening complications, and improve your quality of life.
What is the life expectancy of multiple endocrine neoplasia?
Usually, people with MEN1 live between the ages of 55 and 70, especially if the disorder is found in the early stages. For more details, discuss it with your physician.
What is the most common cause of multiple endocrine neoplasia?
While most of the time, people develop MEN due to an abnormal gene that passes from their biological parents, it may also happen due to a new gene mutation that occurs for unknown reasons. Ask your healthcare provider if you have any other questions.
