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

What Is MEN1?

MEN1, or 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 parathyroids, pancreas, and anterior pituitary tumors. Tumor growth in these endocrine glands results in the release of excessive hormones, resulting in symptoms like bone pain, tiredness, and abdominal pain. It can increase the risk of fractures, stomach ulcers, and kidney stones. However, 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, a nuclear protein that suppresses various tumors. When this gene malfunctions, some cells grow abnormally and cause tumor formation.

What Are the Risk Factors Associated With MEN1?

• Genetic Mutation: MEN1 is a hereditary disorder due to the mutations in the MEN1 gene, which is a tumor suppressor gene. It is an autosomal dominant disease and therefore a person requires only one mutated gene from either of the parents to be affected.

• Family History: If one of the parents is affected with MEN1, the child has a 50 percent chance of developing the disease. Patients with a family history of MEN1 or other endocrine neoplasms are at greater risk.

What Is the Epidemiology of MEN1?

• Prevalence: MEN1 is estimated to occur in 1 of every 30,000 people, thus making it a rare disease. For gender, it impacts both the male and the female persons.

• Age of Onset: MEN 1 manifests in adulthood, most commonly in the third to fifth decade of life, but it is not age-limited.

Who Are Prone to Developing MEN1?

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

Which Structures of the Endocrine System Are Involved in MEN1?

MEN1 primarily affects the following parts of the endocrine system:

• Parathyroid Glands: In most patients with MEN1, the tumor is hyperparathyroidism, which is caused by benign tumors in the parathyroid gland. This causes a high level of calcium in the blood or hypercalcemia.

• Pancreatic Islet Cells: Tumors in the pancreas are called pancreatic neuroendocrine tumors (pNETs), which can produce hormones such as insulin, gastrin, or glucagon. They can result in states such as insulinomas (hypoglycemia) or gastrinomas (peptic ulcer).

• Pituitary Gland: In MEN1, pituitary adenomas are evident in 30-40% of patients. These tumors may produce prolactin, growth hormone, or ACTH, resulting in syndromes such as prolactinoma or acromegaly.

• Adrenal Glands: Far more rarely, adrenal tumors or hyperplasia may occur, which cause excess cortisol or other hormone secretion.

• Thymus and Lungs: Occasionally, MEN1 can cause carcinoid tumors in the thymus or lung, which can, at times, be malignant.

What Are the Signs and Symptoms of MEN1?

The symptoms of MEN1 depend on the glands 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. Some 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 percent 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 percent of MEN1 patients develop benign pituitary gland tumors. The pituitary secretes prolactin and other hormones that influence fertility, growth, and 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.

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

3) Pancreatic Tumors:

MEN1 patients, around 40 percent, 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 - It is found in the stomach, lungs, and thymus and is 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 (MEN 1) is diagnosed through physical examination and a good medical and family history. High hormone levels in the blood can be diagnosed using blood tests, and imaging tests like MRI (magnetic resonance imaging), CT (computed tomography), and PET (positron emission tomography) scans 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 - The parathyroid glands are surgically removed (parathyroidectomy). Either three parathyroid glands and part of the fourth gland are removed (subtotal parathyroidectomy), or all four glands are totally removed (total parathyroidectomy).

2) Pituitary Tumors - These tumors are 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 surgically by resectioning pancreatic lesions.

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

Postsurgical Management:

If 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 at risk or who might benefit from getting tested for the MEN1 mutation.

What Is the Prognosis of MEN1?

The prognosis of MEN1 differs depending on the tumor type and size, the localization of the tumor, and the efficiency of the treatment. If the disease is diagnosed early and the management is proper, many people can have normal life expectancies.

Nevertheless, the life expectancy of patients may decrease due to malignant tumors, especially in the case of pancreatic carcinoma and complications connected with hormone overproduction, such as severe hypercalcemia. Therefore, the syndrome must be monitored over the individual's lifetime to avoid such complications.

What Are the Complications Associated With MEN1?

• Hormonal Imbalances: Hormones released from endocrine tumors result in diverse symptoms, such as hypercalcemia due to parathyroid gland overactivity or gastric ulcers attributed to excess gastrin production.

• Malignancy: Some of the tumors that may be caused by MEN1 include carcinomas of the pancreas and the thymus gland.

• Metastasis: It is invasive, and the cancer cells may spread to other organs of the body, and thereby hampering the treatment procedures and lowering the survival ratio.

• Surgical Risks: Tumors sometimes have to be removed through surgery, and this entails that the patient may need several operations to get all the tumors removed, which are bound to have usual surgical risks as well as possible postoperative complications.

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.