Multiple endocrine neoplasia type 1 (MEN 1)
Multiple endocrine neoplasia type 1 (MEN 1), also known as Wermer syndrome, is a hereditary condition characterized by the development of endocrine and nonendocrine tumors, predominantly benign. The condition is marked by tumors in critical areas such as the parathyroid glands, pituitary gland, pancreas, and duodenum. Individuals with MEN 1 have a 50% chance of inheriting the disorder if a parent is affected, as it is caused by mutations in the MEN1 gene, a tumor-suppressor gene crucial for regulating cell growth. The incidence of MEN 1 is approximately 1 in 30,000, with many affected individuals experiencing hyperparathyroidism, gastrinomas, pituitary tumors, or insulinomas.
Symptoms can vary widely, with parathyroid tumors leading to high calcium levels and associated complications, while pancreatic and pituitary tumors present a range of hormonal disturbances and other health issues. Diagnosis typically involves identifying tumors in at least two of the three affected systems and may include genetic testing and various imaging techniques. Treatment often requires a combination of surgical intervention and medication, depending on the tumor type. While many tumors are benign, monitoring is essential as some may metastasize, particularly pancreatic tumors.
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Multiple endocrine neoplasia type 1 (MEN 1)
ALSO KNOWN AS: Wermer syndrome, multiple endocrine adenomatosis
RELATED CONDITIONS: Hyperparathyroidism, pituitary tumor, pancreatic tumor, duodenal tumor, Zollinger-Ellison syndrome (ZES), Hypoglycemic syndrome
DEFINITION: Multiple endocrine neoplasia type 1 (MEN 1) is a hereditary tumor syndrome characterized by endocrine and nonendocrine tumors, most of which are benign. The characteristic findings include tumors of the parathyroid glands, pituitary gland, pancreas, and duodenum (part of the small intestine). Neuroendocrine tumors (nerve-cell tumors that may produce hormones) in the pancreas and duodenum are the main cause of tumor-related death. The severity varies within families and between families.
Risk factors: Because MEN 1 is hereditary, the main is having a family history of this disorder. Each child of a person with MEN 1 has a 50 percent chance of inheriting the disorder. The condition is equally present in men and women of all ages.
Etiology and the disease process: The underlying genetic cause of MEN 1 is a mutation or a genetic change in the MEN1 gene. MEN1 is a tumor-suppressor gene, and the protein it encodes helps stop uncontrolled cell growth and proliferation.
Usually, each person has two normal copies of the MEN1 gene. A mutation in one copy of the gene is sufficient to cause MEN 1, which is why this condition is referred to as autosomal dominant (autosomal means the MEN1 gene is located on one of the twenty-two pairs of autosomes, which are the nonsex chromosomes). An affected person has a MEN1 gene mutation from the time of conception in the womb; however, symptoms of the disease may not manifest until later in life. Most mutations are inherited from a parent, but new mutations do occur.
Incidence: Approximately 1 per 30,000 people have MEN 1. Approximately 90 percent of individuals with MEN 1 develop hyperparathyroidism (overactive parathyroid), 40 percent develop multiple gastrinomas, 25 percent pituitary gland tumors, and 10 percent insulinoma. Some researchers believe the incidence of MEN 1 and MEN 2 is higher than the diagnoses indicate.
Symptoms: Parathyroid tumors can cause high calcium levels in the blood, nausea, fatigue, muscle pains, constipation, abdominal pain, peptic ulcer disease, kidney stones, and bone fractures. Symptoms of pituitary tumors vary depending on the type of hormone made by the tumor. Tumors of the pancreas and duodenum cause many symptoms depending on the tumor type. Other symptoms include anxiety, bloating after meals, decreased sexual drive, vision problems, and mental changes such as confusion.
Screening and diagnosis: Physicians diagnose MEN 1 in a person with an endocrine tumor in two of the three tissue systems this syndrome affects—parathyroid glands, gastroenteropancreatic tract, and pituitary gland. Because mutations in the MEN1 gene cause MEN 1, genetic testing can confirm a suspected diagnosis or test a family member at risk for the disease but with no symptoms. A blood test measuring cortisol, parathyroid hormone, hypercalcemia, insulin, or fasting blood sugar levels is also commonly used in diagnosing MEN 1. Imaging tests include magnetic resonance imaging (MRI), computerized tomography (CT) scan, positron emission tomography (PET) scan, and endoscopic ultrasound of the pancreas.
Treatment and therapy: To treat MEN 1 tumors, a combination of surgery and medication may be used. In some pituitary tumors, bromocriptine may be used instead of surgery. Hormone replacement therapy is an effective treatment in some patients.
Prognosis, prevention, and outcomes: Because MEN 1 is a genetic condition, its manifestations cannot be prevented. However, physicians recommend monitoring that includes blood testing for hormone levels and imaging of the head and abdomen. Though most MEN 1 tumors are benign, some pancreatic tumors metastasize and spread to the liver.
Bibliography
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