MEN1 (Wermer Syndrome) - Causes, Symptoms, Diagnosis and Treatment

What Is MEN1?

MEN1 otherwise called multiple endocrine neoplasia type 1, is a rare inherited or genetic disorder that results in tumors in various endocrine glands and some parts of the stomach and small intestine. It is caused by mutations of the MEN1 tumor suppressor gene at the 11q13 locus and is characterized by the combination of tumors in the parathyroids, pancreas, and anterior pituitary. Tumor growth in these endocrine glands results in the release of excessive hormones, which results in various symptoms like bone pain, tiredness, and abdominal pain. It can increase the risk of fractures, stomach ulcers, and kidney stones. But, these tumors are usually benign or non-cancerous. There is no cure for MEN1, but regular testing can help prompt treatment.

People with multiple endocrine neoplasia type 1 can pass the causative gene mutation to their offspring as it is an inherited disorder. There is a 50 % chance of the child inheriting the disorder. Because of the non-aggressive nature of these tumors, most people do not develop any symptoms. But, if left untreated, MEN1 decreases life expectancy, with 50 % of patients dying by the age of 50 years. Wermer was first to describe the syndrome in 1954, which is why this syndrome is also called Wermer syndrome.

What Causes MEN1?

Mutations of the MEN1 gene cause MEN1. The MEN1 gene encodes menin, which is a nuclear protein. The MEN1 gene suppresses various tumors. With this gene malfunctioning, some cells grow abnormally and cause tumor formation.

Who Are Prone to Developing MEN1?

Men and women are equally affected by MEN1. It can affect people of all age groups, but the symptoms of overactive parathyroid glands are usually seen in people in their 20s.

What Are the Signs and Symptoms of MEN1?

The symptoms of MEN1 depend on the glands that are affected by the tumor formation. Even though these tumors are non-cancerous, tissue overgrowth makes these affected glands more active, resulting in excess hormone production. Around 20 different endocrine and non-endocrine tumors have been associated with MEN1. The patients might not show symptoms, while in others, the symptoms can vary. Depending on the type of tumors and their location, the symptoms include:

1) Parathyroid Gland Tumors:

The parathyroid glands are the most commonly affected endocrine glands in MEN type 1. Almost 90 % of individuals with MEN1 develop primary hyperparathyroidism (PHPT), which is the parathyroid gland producing too much PTH (parathyroid hormone). PHPT can result in -

• Hypercalcemia (elevated serum level of calcium).

• Kidney stones.

• Kidney damage.

• Fatigue.

• Weakness.

• Nausea.

• Constipation.

• Ulcers.

• Stomach discomfort.

• Hypertension.

• Muscular pain.

In later stages, depression and confusion can occur. The bones can become thin and result in fractures.

2) Pituitary Gland Tumors:

Around 25 % of MEN1 patients develop benign pituitary gland tumors. The pituitary secretes prolactin and various other hormones that influence fertility, growth, and several other functions. Non-cancerous pituitary tumors secreting prolactin (prolactinomas) are most commonly seen. In women, this tumor can result in -

• Irregular menstruation.

• Infertility.

• Low sex drive.

• Painful sex.

• Breast milk production without the women being pregnant.

In men, it can result in -

• Infertility.

• Gynecomastia.

The other symptoms include -

• Headaches.

• Blurred vision.

Tumors that release growth hormone (GH) are the second most commonly seen. Excess growth hormone causes acromegaly, where the bones and other tissues grow larger.

3) Pancreatic Tumors:

MEN1 patients, around 40 %, develop gastrinomas in the pancreas and duodenum. These tumors secrete gastrin, and high levels of gastrin make the stomach release a lot of acids, resulting in-

• Stomach pain.

• Diarrhea.

• Acid reflux.

• Peptic ulcers.

• Nausea and vomiting.

• Smelly stools.

If not treated promptly, peptic ulcers can lead to internal bleeding and bowel obstruction.

Insulinoma can also develop in the pancreas. This tumor secretes insulin and can cause-

• Low blood sugar.

• Confusion.

• Blurred vision.

• Anxiety.

• Palpitations.

• Hunger.

• Sweating.

Other Tumors:

Apart from endocrine tumors, MEN1 can also result in:

1. Lipomas - tumors arising from fat cells.

2. Adrenal gland tumors.

3. Carcinoid Tumors - these tumors are found in the stomach, lungs, and thymus and are slow-growing.

4. Skin tumors.

5. Tumors in the brain and spinal cord (meningiomas and ependymomas).

How Is MEN1 Diagnosed?

Multiple endocrine neoplasia type 1 or MEN 1 is diagnosed with the help of a physical examination and by taking a good medical and family history. The high levels of hormones in the blood can be diagnosed using blood tests, and imaging tests like MRI (magnetic resonance imaging), CT (computed tomography), and a PET (positron emission tomography) scan can help locate tumors.

Genetic testing can help diagnose MEN1 by identifying the gene mutation that causes MEN1.

How Is MEN1 Treated?

Treatment is done based on the type of tumor and the symptoms. The treatment options include:

1) Parathyroid Tumors - Surgical removal of the parathyroid glands (parathyroidectomy) is done. Either three parathyroid glands and a part of the fourth gland are removed (subtotal parathyroidectomy), or all four glands are totally removed (total parathyroidectomy).

2) Pituitary Tumors - These tumors are either treated with dopamine agonists, which lower the levels of prolactin and shrink the tumors. Sometimes, surgery (transsphenoidal) might be needed, where the pituitary tumors are removed through the nose.

3) Pancreas Tumors - Insulinomas are usually treated by surgical resection of pancreatic lesions.

Also, lipomas, carcinoid tumors, and people with multiple tumors are also treated by surgery.

Postsurgical Management:

In case a patient loses an entire endocrine gland or more than three parathyroid glands, you will be prescribed hormone replacement medicines, as the glands responsible for its production are absent. Other medicines and supplements like Calcium and Vitamin D might also be needed.

Genetic Counseling - Genetic counseling can help -

• You understand how genetic testing is done.

• Make you aware of the medical, financial, and social decisions involved in getting tested.

• Discuss the various treatment options to manage genetic diseases.

• You decide whether to have children and the chances of your children being born with MEN1.

• Identify the family members who are at risk or might benefit from getting tested for MEN1 mutation.

Conclusion:

MEN1 is a genetic disorder meaning the condition can be passed from generation to generation in a family. So people with a family history of MEN1 should consider a genetic counseling session if they are planning to have a baby.

For more information, consult a doctor online now.