Multiple endocrine neoplasia type 1
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant tumor-suppressor syndrome causing parathyroid, pancreatic, and pituitary tumors, the '3 Ps.' First-line treatment is organ-specific: parathyroidectomy for hyperparathyroidism, dopamine agonists for prolactinoma, and surgical resection or acid suppression for pancreatic neuroendocrine tumors.
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What this article covers
- Overview
Definition: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome of endocrine tumors caused by germline mutation of the MEN1 tumor suppressor gene, which encodes the protein menin.
- Epidemiology
Rarity: MEN1 is a very rare syndrome, accounting for a small minority of all cases of primary hyperparathyroidism, pituitary tumors, and pancreatic neuroendocrine tumors.
- Risk factors
Germline MEN1 mutation: an inherited or de novo pathogenic variant in the MEN1 gene is both necessary and sufficient to confer syndrome risk.
- Pathophysiology
Tumor suppressor loss: the MEN1 gene on chromosome 11 encodes menin, a protein involved in transcriptional regulation and genome stability; a germline loss-of-function mutation combined with somatic…
- Clinical features
Diagnostic core feature: the defining clinical pattern is tumors arising in two or more of the three classic endocrine organs (parathyroid, pancreas, pituitary) in the same patient, or in relatives across a family.
- Differential diagnosis
Sporadic (non-MEN) primary hyperparathyroidism: a solitary parathyroid adenoma without pituitary or pancreatic tumors and no family history, unlike the multiglandular disease and family clustering typical of MEN1.
- Diagnosis
Diagnostic criteria: MEN1 is diagnosed clinically by two or more of the characteristic tumors (parathyroid, pancreatic, or pituitary) in one patient, or by one such tumor plus a first-degree relative…
- Management
First, manage primary hyperparathyroidism surgically when symptomatic or meeting criteria: subtotal or total parathyroidectomy with autotransplantation is the definitive treatment for parathyroid…
- Complications
Malignant pancreatic neuroendocrine tumors: gastrinomas and other pancreatic tumors in MEN1 can metastasize, most often to the liver, and are the leading cause of MEN1-related death.
- Prognosis
Variable penetrance and timing: the great majority of MEN1 mutation carriers develop at least one manifestation during adulthood, but the specific tumors and their severity vary widely even within the same family.
- Prevention
Cascade genetic testing: once a familial MEN1 mutation is identified, test first-degree relatives so carriers can begin surveillance before symptomatic disease develops.
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Related articles
- Primary hyperparathyroidism
Primary hyperparathyroidism is autonomous PTH oversecretion, most often from a solitary parathyroid adenoma, producing hypercalcemia with an elevated or inappropriately normal PTH and low or low-normal phosphorus. Most patients are asymptomatic and identified on routine labs; parathyroidectomy is curative and is first-line for symptomatic disease or when specific biochemical, skeletal, or renal criteria are met, while observation with annual monitoring suffices for mild, asymptomatic disease.
- Prolactinoma
Prolactinoma is a prolactin-secreting pituitary adenoma, the most common functional pituitary tumor, presenting with hypogonadism and galactorrhea from prolactin excess or with headache and visual loss from mass effect in larger tumors. Diagnosis requires an elevated prolactin with a pituitary mass on dedicated MRI after excluding pregnancy, medication effect, and hypothyroidism, and first-line treatment is a dopamine agonist, most often cabergoline, which lowers prolactin and shrinks the tumor without surgery in most patients.
- Pancreatic neuroendocrine tumors (PanNETs)
Pancreatic neuroendocrine tumors (PanNETs) are islet-cell tumors that may be functional, producing a hormone-excess syndrome such as insulinoma or gastrinoma, or nonfunctioning and detected by mass effect or incidentally. First-line treatment is surgical resection when localized, with somatostatin analogues and acid suppression used to control hormone-excess symptoms before or in place of surgery.
- Multiple endocrine neoplasia type 2A
Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal dominant RET-mutation syndrome causing medullary thyroid carcinoma, pheochromocytoma, and primary hyperparathyroidism. First-line treatment is total thyroidectomy for medullary thyroid carcinoma and surgical resection of pheochromocytoma, always after preoperative alpha-then-beta adrenergic blockade if pheochromocytoma coexists.