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Multiple Endocrine Neoplasia Type 1.

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GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
2005 Aug 31 [updated 2017 Dec 14].

Author information

1
Department of Surgery and Translational Medicine, University of Florence and Regional Center for Hereditary Endocrine Tumors, Unit of Metabolic Bone Diseases, University Hospital of Careggi, Florence, Italy

Excerpt

CLINICAL CHARACTERISTICS:

Multiple endocrine neoplasia type 1 (MEN1) syndrome includes varying combinations of more than 20 endocrine and non-endocrine tumors. Endocrine tumors become evident either by overproduction of hormones by the tumor or by growth of the tumor itself. Parathyroid tumors are the main MEN1-associated endocrinopathy; onset in 90% of individuals is between ages 20 and 25 years with hypercalcemia evident by age 50 years; hypercalcemia causes lethargy, depression, confusion, anorexia, constipation, nausea, vomiting, diuresis, dehydration, hypercalciuria, kidney stones, increased bone resorption/fracture risk, hypertension, and shortened QT interval. Pituitary tumors include prolactinoma (the most common), which manifests as oligomenorrhea/amenorrhea and galactorrhea in females and sexual dysfunction in males. Well-differentiated endocrine tumors of the gastro-entero-pancreatic (GEP) tract can manifest as Zollinger-Ellison syndrome (gastrinoma); hypoglycemia (insulinoma); hyperglycemia, anorexia, glossitis, anemia, diarrhea, venous thrombosis, and skin rash (glucagonoma); and watery diarrhea, hypokalemia, and achlorhydria syndrome (vasoactive intestinal peptide [VIP]-secreting tumor). Carcinoid tumors are non-hormone-secreting and can manifest as a large mass after age 50 years. Adrenocortical tumors can be associated with primary hypercortisolism or hyperaldosteronism. Non-endocrine tumors include facial angiofibromas, collagenomas, lipomas, meningiomas, ependymomas, and leiomyomas.

DIAGNOSIS/TESTING:

Clinical diagnostic criteria for MEN1 syndrome include the presence of two endocrine tumors that are parathyroid, pituitary, or GEP tract tumors. Biochemical testing detects an increased serum concentration of parathyroid hormone and calcium in primary hyperparathyroidism, increased serum concentrations of prolactin from a prolactinoma, and increased serum concentrations of gastrin, insulin, and VIP from tumors of the GEP tract. Prolactinomas are imaged by MRI, neuroendocrine tumors (NETs) are detected by somatostatin receptor scintigraphy, and pancreatic endocrine tumors are detected by endoscopic ultrasound. Molecular genetic testing of MEN1, the only gene in which pathogenic variants are known to cause MEN1 syndrome, detects a heterozygous MEN1 pathogenic variant in approximately 80%-90% of probands with familial MEN1 syndrome and in approximately 65% of simplex cases (i.e., a single occurrence of MEN1 syndrome in the family).

MANAGEMENT:

Treatment of manifestations: Hyperparathyroidism is treated with subtotal parathyroidectomy and cryopreservation of parathyroid tissue or total parathyroidectomy and autotransplantation of parathyroid tissue; calcimimetics are used to treat primary hyperparathyroidism in those for whom surgery is contraindicated or has failed; prior to surgery, bone antiresorptive agents are used to reduce hypercalcemia and limit bone resorption. Prolactinomas are treated with dopamine agonists (cabergoline being the drug of choice). Growth hormone-secreting tumors causing acromegaly are treated by transsphenoidal surgery; medical therapy for growth hormone-secreting tumors includes somatostatin analogs, octreotide, and lanreotide. ACTH-secreting pituitary tumors associated with Cushing syndrome are surgically removed; non-secreting pituitary adenomas are treated by transsphenoidal surgery. Proton pump inhibitors or H2-receptor blockers reduce gastric acid output caused by gastrinomas. Surgery is indicated for insulinoma and most other pancreatic tumors. Long-acting somatostatin analogs can control the secretory hyperfunction associated with carcinoid syndrome. Surgical removal of adrenocortical tumors that exceed 3.0 cm in diameter can prevent malignancy. Prevention of primary manifestations: Thymectomy may prevent thymic carcinoid in males, particularly in smokers. Prevention of secondary complications: Measure PTH and/or serum calcium to assess for hypoparathyroidism following subtotal or total parathyroidectomy. Measure urinary catecholamines prior to surgery to diagnose and treat a pheochromocytoma to avoid blood pressure peaks during surgery. Surveillance: Serum concentrations of calcium from age eight years, gastrin from age 20 years, and prolactin from age five years; abdominal CT or MRI from age 20 years and head MRI from age five years. Consider fasting serum PTH concentration and yearly chest CT. Evaluation of relatives at risk: Because early detection affects management, molecular genetic testing is offered to at-risk members of a family in which a germline MEN1 pathogenic variant has been identified. Pregnancy management: Women with primary hyperparathyroidism from any cause are at increased risk of developing preeclampsia; infants born to women with primary hyperparathyroidism should be monitored for postnatal hypocalcemia.

GENETIC COUNSELING:

MEN1 syndrome is inherited in an autosomal dominant manner. Approximately 10% of cases are caused by a de novo pathogenic variant. Each child of an individual with MEN1 syndrome has a 50% chance of inheriting the pathogenic variant. Prenatal diagnosis for pregnancies at increased risk is possible if the pathogenic variant in a family is known.

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