Multiple Endocrine Neoplasia Type 1

Overview

Multiple endocrine neoplasia, type 1 (MEN 1), sometimes called Wermer's syndrome, is a rare disorder that causes tumors in the endocrine glands and parts of the small intestine and stomach. In MEN 1, the endocrine glands — usually the parathyroids, pancreas and pituitary — grow tumors and release excessive amounts of hormones that can lead to disease. However, the tumors are usually noncancerous (benign).

The excess hormones can cause a wide variety of signs and symptoms. These can include tiredness, bone pain, broken bones, kidney stones, and ulcers in the stomach or intestines. MEN 1 can't be cured. But regular testing can detect problems, and doctors can provide treatment as needed.

MEN 1 is an inherited disorder. This means people who have the gene mutation can pass it on to their children. Each child has a 50% chance of inheriting the disorder.

Symptoms 

Signs and symptoms of MEN 1 include the following:

MEN type 1-associated symptoms depend on which glands are affected by the overgrowth of tissue (hyperplasia) or tumor formation. Although most tumors are benign (noncancerous), tissue overgrowth or tumor formation causes the affected glands to become hyperactive and produce excess hormones. Elevated hormone levels are the main cause of MEN type 1-associated signs and symptoms. Certain tumors, such as gastrinomas and carcinoid tumors can potentially become malignant. The clinical expression of MEN type 1 is highly variable even within members of the same family and identical twins.

More than 20 different endocrine and non-endocrine tumors have been identified in individuals with MEN type 1. Affected individuals will not necessarily develop tumors at the same age or in the same locations and, therefore, they can manifest variable spectra of clinical signs and symptoms during their lifetime. Some individuals may only develop mild symptoms; others may develop serious, life-threatening complications. Some individuals may develop symptoms as young adults or adolescents; other may not develop symptoms until middle-age or older. It is important to note that individual cases are highly variable and that affected individuals will not develop all of the symptoms discussed below.

*Tiredness

*Bone pain

*Broken bones

*Kidney stones

*Ulcers in the stomach or intestines

Symptoms are caused by the release of too many hormones in the body.

causes

MEN type 1 is a rare genetic disorder caused by mutations of the MEN1 gene. The MEN1 gene encodes a nuclear protein known as menin. The exact role of menin is not fully understood. The MEN1 gene is a tumor suppressor gene, a gene that when it operates normally may have several functions including inhibiting cell division, repairing and replicating DNA, and instructing cells when to die (a normal process called apoptosis). When tumor suppressor genes malfunction, certain cells may continue to grow and reproduce causing tumor formation.

This genetic mutation may be inherited in an autosomal dominant pattern or occur as a new gene mutation in the affected person.

Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual at the embryo level. The risk of passing the abnormal gene from affected parent to offspring is 50 percent for each pregnancy. The risk is the same for males and females.

Diagnosis

To diagnose multiple endocrine neoplasia, type 1 (MEN 1), your doctor will perform a physical exam and review your medical history and family history. You may have a blood test and imaging tests, including the following:

• Magnetic resonance imaging (MRI)
• Computerized tomography (CT) scan
• Positron emission tomography (PET) scan
• Nuclear medicine scans
• Endoscopic ultrasound of the pancreas and other scans

Genetic testing may determine whether someone has a genetic mutation causing MEN 1. If someone has a mutation, his or her children are at risk of inheriting the mutation and developing MEN 1. Parents and siblings also are at risk of having the mutation even if they have not yet developed symptoms.

If no related genetic changes are found in family members, then no further screening tests are needed. However, genetic testing doesn't uncover all MEN 1 genetic mutations. If genetic testing doesn't confirm MEN 1, but it's likely a person has it, that person and their family members still need close follow-up with appropriate blood and imaging tests.

Treatment

In MEN 1, tumors can grow on the parathyroids, pancreas and pituitary gland. These tumors can lead to various conditions, all of which can be treated. These conditions and treatments may include:

Pituitary tumors. These types of tumors may be treated with surgery or drug therapy.

Hyperparathyroidism. Surgery to remove most of the parathyroid glands is the usual treatment for too much parathyroid hormone.

Neuroendocrine tumors. These are usually located in the pancreas or small intestine (duodenum). Treatment depends on the type and stage of the tumor.

Hypoglycemic syndrome. This condition results when tumors produce too much insulin (insulinomas), causing severely low levels of glucose, which can be life-threatening. Doctors usually recommend surgery and possibly removal of a portion of the pancreas.

Zollinger-Ellison syndrome (ZES). ZES can result in tumors that overproduce gastric acid (gastrinomas), leading to ulcers and diarrhea. Doctors may prescribe medication or surgery.

Other pancreatic neuroendocrine tumors. These tumors sometimes produce other hormones that can cause various health issues. Treatment of these types of tumors may involve medication, surgery or an ablation procedure. In an ablation procedure your doctor destroys abnormal tissue that may be present.

Metastatic neuroendocrine tumors. Disease that has spread to the lymph nodes or liver may be treated with surgery. Surgery options include liver surgery, radiofrequency ablation, cryoablation or chemoembolization.

Radiofrequency ablation uses high-frequency energy that passes through a needle and causes the surrounding tissue to heat up, killing the nearby cells. Cryoablation involves freezing tumors. And chemoembolization involves injecting strong chemotherapy drugs directly into the liver. When surgery isn't an option, doctors may use other forms of chemotherapy or hormone-based treatments.

Adrenal tumors. Most of these tumors can be observed and not treated. However, if the tumors produce hormones or they're large and thought to be cancerous, doctors recommend removing them, usually with minimally invasive surgery.

Carcinoid tumors. Carcinoid tumors in people with MEN 1 can develop in the lungs, thymus gland and digestive tract. Surgeons remove these tumors when they haven't spread to other areas. Doctors may use chemotherapy, radiation therapy or hormone-based therapy for advanced cases.