Multiple Endocrine Neoplasia

Multiple endocrine neoplasia (MEN), including Werner's syndrome and Sipple's syndrome, is a hereditary disorder in which two or more endocrine glands develop hyperplasia, adenoma, or carcinoma, concurrently or consecutively.

Two of the types that occur are well documented: MEN I (Werner's syndrome), the most common form, involves hyperplasia and adenomatosis of the parathyroid glands, islet cells of the pancreas, pituitary and, rarely, thyroid and adrenal glands; MEN II (Sippie's syndrome) involves medullary carcinoma of the thyroid, with hyperplasia and adenomatosis of the adrenal medulla (pheochromocytoma) and parathyroid glands.

Causes

MEN1 is caused by mutation at the PYGM gene, one of a group of tumor suppressor genes. If you inherit one defective copy of a tumor suppressor gene from either parent, there's a high probability of having a second mutation in at least one dividing cell. Then, that cell no longer possesses even one normal copy of the gene. When both copies are defective, tumors develop.

Both types of MEN2 are caused by mutations in the RET gene. A mutation in only one copy of the RET gene is enough to cause the disease.

Signs and symptoms

Symptoms vary greatly from person to person and may be related to peptic ulcer disease, hypoglycemia, hypercalcemia, or pituitary dysfunction.

• Abdominal pain
• Burning, aching, or hunger discomfort in the upper abdomen or lower chest that is relieved by antacids, milk, or food
• Black, tarry stools
• Nausea and vomiting
• Bloated feeling after meals
• Weakness
• Headache
• Loss of coordination
• Anxiety
• Mental changes or confusion
• Coma if hypoglycemia is untreated
• Loss of appetite
• Muscle pain
• In women, cessation of menses , infertility , or failure to lactate
• In men, decreased sexual interest, loss of body or facial hair.

Diagnosis

Investigating symptoms of pituitary tumor, hypoglycemia, hypercalcemia, or GI hemorrhage may lead to a diagnosis of MEN.

Diagnostic tests must be used to carefully evauate each affected endocrine gland. For example, radioimmunoassay showing increased levels of gastrin in patients with peptic ulceration and Zollinger-Ellison syndrome suggests the need for follow up studies for MEN I because 50% of patients with Zollinger-Ellison syndrome have MEN. After confirmation of MEN, family members must also be assessed for this inherited syndrome.

Treatment

Treatment must eradicate the tumors. Subsequent therapy controls residual symptoms.

MEN I

In patients with MEN I, peptic ulceration is usually the most urgent clinical feature, so primary treatment emphasizes control of bleeding or resection of necrotic tissue. In hypoglycemia caused by insulinoma, oral administration of diazoxide or glucose can keep blood glucose levels within acceptable limits. Subtotal (partial) pancreatectomy is required to remove the tumor.

Because all parathyroid glands have the potential for neoplastic enlargement, subtotal parathyroidectomy may also be required. Transsphenoidal surgery may be required for pituitary lesions.

MEN II

In MEN II, treatment of an adrenal medullary tumor includes antihypertensives and resection of the tumor.

Prevention

Screening of close relatives of people affected with this disorder is recommended.