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Multiple endocrine neoplasia type 1
Classification and external resources
ICD-10 D44.8
ICD-9 258.01
ICD-O: 8360/1
OMIM 131100
DiseasesDB 7971
MedlinePlus 000398
eMedicine med/2404
MeSH D018761

Multiple endocrine neoplasia type 1 (MEN-1 syndrome) or Wermer syndrome is part of a group of disorders that affect the endocrine system.

Contents

Explanation

These disorders greatly increase the risk of developing multiple cancerous and noncancerous tumors in glands such as the parathyroid, pituitary, and pancreas. Multiple endocrine neoplasia occurs when tumors are found in at least two endocrine glands. Tumors can also develop in organs and tissues other than endocrine glands. If the tumors become cancerous, some cases can be life-threatening. The disorder affects 1 in 30,000 people.

Although many different types of hormone-producing tumors are associated with multiple endocrine neoplasia, tumors of the parathyroid gland, pituitary gland, and pancreas are most frequent in multiple endocrine neoplasia type 1. Tumors cause an overactivation of these hormone-producing glands, leading to serious health problems such as severe ulcers (Due to gastrin hypersecretion, which stimulates secretion of hydrochloric acd). Overactivity of the parathyroid gland (hyperparathyroidism) is the most common sign of this disorder. Hyperparathyroidism disrupts the normal balance of calcium in the blood, which can lead to kidney stones, thinning of bones, weakness, and fatigue.

Neoplasia in the pituitary gland can manifest as prolactinomas whereby too much prolactin is secreted, suppressing the release of gonadotropins, causing a decrease in sex hormones such as testosterone.

Pancreatic tumors usually form in the islet cells, which over-secrete insulin, causing a decrease in blood glucose levels.


Multiple endocrine neoplasia is part of a group of disorders that affect the body's network of hormone-producing glands (the endocrine system). Hormones are chemical messengers that travel through the bloodstream and regulate the function of cells and tissues throughout the body. Multiple endocrine neoplasia involves tumors in at least two endocrine glands; tumors can also develop in other organs and tissues. These growths can be noncancerous (benign) or cancerous (malignant). If the tumors become cancerous, some cases can be life-threatening.

The two major forms of multiple endocrine neoplasia are called type 1 and type 2; they are often confused because of their similar names. Type 1 and type 2 are distinguished by the genes involved, the types of hormones made, and the characteristic signs and symptoms.

Many different types of tumors are associated with multiple endocrine neoplasia. Type 1 frequently involves tumors of the parathyroid gland, pituitary gland, and pancreas. Tumors in these glands lead to the overproduction of hormones. The most common sign of multiple endocrine neoplasia type 1 is overactivity of the parathyroid gland (hyperparathyroidism). Hyperparathyroidism disrupts the normal balance of calcium in the blood, which can lead to kidney stones, thinning of bones, nausea and vomiting, high blood pressure (hypertension), weakness, and fatigue.

The most common sign of multiple endocrine neoplasia type 2 is a form of thyroid cancer called medullary thyroid carcinoma. Some people with this disorder also develop a pheochromocytoma, which is a tumor of the adrenal glands that can cause dangerously high blood pressure. Multiple endocrine neoplasia type 2 is divided into three subtypes: type 2A, type 2B, and familial medullary thyroid carcinoma (FMTC). These subtypes differ in their characteristic signs and symptoms and risk of specific tumors; for example, hyperparathyroidism occurs only in type 2A. The features of this disorder are relatively consistent within any one family.

Genetic effects

People with multiple endocrine neoplasia type 1 are born with one mutated copy of the MEN1 gene in each cell. Then, during their lifetime, the other copy of the gene is mutated in a small number of cells. These genetic changes result in no functional copies of the MEN1 gene in selected cells, allowing the cells to divide with little control and form tumors. Parathyroid: Hyperparathyroidism is present in ≥ 90% of patients. Asymptomatic hypercalcemia is the most common manifestation: about 25% of patients have evidence of nephrolithiasis or nephrocalcinosis. In contrast to sporadic cases of hyperparathyroidism, diffuse hyperplasia or multiple adenomas are more common than solitary adenomas.

Signs and symptoms M.E.N.1

Parathyroid: Hyperparathyroidism is present in ≥ 90% of patients. Asymptomatic hypercalcemia is the most common manifestation: about 25% of patients have evidence of nephrolithiasis or nephrocalcinosis. In contrast to sporadic cases of hyperparathyroidism, diffuse hyperplasia or multiple adenomas are more common than solitary adenomas.

Pancreas: Pancreatic islet cell tumors occur in 60 to 70% of patients. Tumors are usually multicentric. Multiple adenomas or diffuse islet cell hyperplasia commonly occurs; such tumors may arise from the small bowel rather than the pancreas. About 30% of tumors are malignant and have local or distant metastases. Malignant islet cell tumors due to MEN 1 syndrome often have a more benign course than do sporadically occurring malignant islet cell tumors.

About 40% of islet cell tumors originate from a β cell, secrete insulin (insulinoma), and can cause fasting hypoglycemia. β-Cell tumors are more common in patients < 40. About 60% of islet cell tumors originate from non-β-cell elements and tend to occur in patients > 40. Non-β-cell tumors are somewhat more likely to be malignant.

Most islet cell tumors secrete pancreatic polypeptide, the clinical significance of which is unknown.Gastrin is secreted by many non–β-cell tumors (increased gastrin secretion in MEN 1 also often originates from the duodenum). Increased gastrin secretion increases gastric acid, which may inactivate pancreatic lipase, leading to diarrhea and steatorrhea. Increased gastrin secretion also leads to peptic ulcers in > 50% of MEN 1 patients. Usually the ulcers are multiple or atypical in location, and often bleed, perforate, or become obstructed. Peptic ulcer disease may be intractable and complicated (Zollinger-Ellison syndrome—see Tumors of the GI Tract: Zollinger-Ellison Syndrome). Among patients presenting with Zollinger-Ellison syndrome, 20 to 60% have MEN 1.

A severe secretory diarrhea can develop and cause fluid and electrolyte depletion with non–β-cell tumors. This complex, referred to as the watery diarrhea, hypokalemia, and achlorhydria syndrome (WDHA; pancreatic cholera—see Tumors of the GI Tract: Vipoma), has been ascribed to vasoactive intestinal polypeptide, although other intestinal hormones or secretagogues (including prostaglandins) may contribute. Hypersecretion of glucagon, somatostatin, chromogranin, or calcitonin, ectopic secretion of ACTH (causing Cushing's syndrome), and hypersecretion of growth hormone–releasing hormone (causing acromegaly) sometimes occur in non–β-cell tumors. All of these are rare in MEN 1.

Nonfunctioning pancreatic tumors also occur in patients with MEN 1 and may be the most common type of pancreatoduodenal tumor in MEN 1. The size of the nonfunctioning tumor correlates with risk of metastasis and death.

Pituitary: Pituitary tumors occur in 15 to 42% of MEN 1 patients. From 25 to 90% are prolactinomas. About 25% of pituitary tumors secrete growth hormone or growth hormone and prolactin. Excess prolactin may cause galactorrhea (see Pituitary Disorders: Galactorrhea), and excess growth hormone causes acromegaly clinically indistinguishable from sporadically occurring acromegaly. About 3% of tumors secrete ACTH, producing Cushing's disease. Most of the remainder are nonfunctional. Local tumor expansion may cause visual disturbance, headache, and hypopituitarism. Pituitary tumors in MEN 1 patients appear to be larger and behave more aggressively than sporadic pituitary tumors.

Other manifestations: Adenomas and adenomatous hyperplasia of the thyroid and adrenal glands occurs occasionally in MEN 1 patients. Hormone secretion is rarely altered as a result, and the significance of these abnormalities is uncertain. Carcinoid tumors, particularly those derived from the embryologic foregut, occur in isolated cases. Multiple subcutaneous and visceral lipomas, angiofibromas, and collagenomas may also occur.

See also

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References

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