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
- 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
- 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)
- 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