Overview of MEN1

  • Definition & Prevalence
    • Rare autosomal dominant disorder
    • Estimated incidence: ~2 per 100,000
    • Characterized by neoplasms in the pituitary, parathyroid, and pancreas
    • May also involve adrenal glands, duodenum (gastrinoma), and thoracic organs (carcinoid tumors)
  • Genetics
    • Caused by mutations in the MEN1 tumor suppressor gene, which encodes the protein menin
    • Most individuals inherit one mutated MEN1 allele from an affected parent
    • Tumor formation requires a second, somatic inactivation (“two-hit” hypothesis) of the remaining normal allele in each susceptible endocrine cell

Common Endocrine Tumors in MEN 1

  1. Parathyroid Hyperplasia/Adenomas
    • Most common feature (100% penetrance by age 50)
    • Presentation: Primary hyperparathyroidism (hypercalcemia + inappropriately high PTH)
    • Treatment: Surgical removal of 3.5 parathyroid glands; sometimes further reoperations or ethanol injections if recurrent hypercalcemia
  2. Pituitary Adenomas
    • Occur in ~20% of patients with MEN 1
    • Prolactinoma is most frequent pituitary tumor; GH- or ACTH-secreting adenomas also possible
    • Management: Similar to sporadic pituitary adenomas (medical therapy with dopamine agonists for prolactinomas, or surgery/radiation as indicated)
  3. Gastroenteropancreatic (GEP) Tumors
    • Major source of morbidity and mortality in MEN 1
    • Commonly found in the duodenum or pancreas; may be multiple and malignant
    • Gastrinomas (Zollinger-Ellison syndrome)
      • Often small and multifocal, typically in the duodenum
      • Cause severe peptic ulcer disease, especially if combined with hypercalcemia
      • Proton pump inhibitors effectively control acid hypersecretion
      • Surgical resection if feasible, especially if identified during a pancreatic operation
    • Pancreatic islet tumors
      • May secrete insulin, glucagon, vasoactive intestinal polypeptide (VIP), or pancreatic polypeptide (PP)
      • Insulinomas can be small and numerous; resection for symptomatic ones
      • Nonfunctioning pancreatic tumors ≥2 cm warrant surgical resection (risk of malignancy rises with size)

Additional Features

  • Other Tumors
    • Adrenal tumors (often nonfunctioning)
    • Lung and thymic carcinoids
    • Esophageal leiomyomas
    • Spinal cord ependymomas (rare)
  • Cutaneous Manifestations
    • Angiofibromas (small vascular lesions on face/body)
    • Collagenomas (dermal nodules)
    • Lipomas (subcutaneous fatty growths)
    • These lesions are benign but can be numerous

Screening & Management

  • Clinical Suspicion
    • Combination of two or more primary MEN 1 tumors (parathyroid, pituitary, or GEP tumors)
    • Family history of MEN 1–related neoplasms
  • Genetic Testing
    • MEN1 germline mutation analysis for high-risk individuals
  • Biochemical Monitoring
    • Annual blood tests for hypercalcemia (PTH, calcium), pituitary hormones (prolactin, IGF-1, etc.), and GEP tumor markers (gastrin, glucagon, VIP, pancreatic polypeptide, chromogranin A)
    • Imaging (MRI, endoscopic ultrasound) for tumor localization
  • Therapeutic Approaches
    • Parathyroid tumors: Surgical resection (3.5 glands) to manage hyperparathyroidism
    • Pituitary adenomas: Medical (dopamine agonists), surgical, or radiotherapy, depending on hormone secretion and size
    • GEP tumors: Proton pump inhibitors for Zollinger-Ellison syndrome; resect symptomatic or large pancreatic tumors

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