What is MEN1?

Multiple Endocrine Neoplasia Type 1 (MEN1) is a rare inherited syndrome characterized by tumors in multiple endocrine glands. The classic "3 P's" are: Parathyroid tumors, Pituitary tumors, and Pancreatic NETs.

Genetics:

• Autosomal Dominant: 50% chance of passing to each child
• MEN1 Gene: Tumor suppressor gene on chromosome 11
• High Penetrance: >90% develop symptoms by age 50
• ~10% are de novo mutations (no family history)

Classic MEN1 Triad - "The 3 P's":

1. Parathyroid Tumors (90-95% - Usually First Manifestation):

• Multiglandular hyperplasia/adenomas (all 4 glands affected)
• Primary Hyperparathyroidism: High calcium, high PTH
• Onset: 20s-30s (earlier than sporadic hyperparathyroidism)
• Symptoms: Kidney stones, bone pain, fatigue, hypercalcemia complications
• Recurrence Common After Surgery (30-50% recur within 10 years)

2. Pancreatic Neuroendocrine Tumors (NETs) (30-80%):

• Often Multiple, Small Tumors
• Types:
  • Non-Functional (40-50%): Don't secrete hormones; found incidentally
  • Gastrinoma (40%): Most common functional NET in MEN1 → Zollinger-Ellison syndrome
  • Insulinoma (10%): Hypoglycemia
  • Glucagonoma, VIPoma, somatostatinoma (rare)
• Malignant Potential: ~50% (especially non-functional tumors >2 cm)
• Leading Cause of Death in MEN1

3. Pituitary Tumors (15-50%):

• Prolactinoma (Most Common): High prolactin → irregular periods, infertility, galactorrhea
• Growth Hormone Adenoma: Acromegaly (enlarged hands, feet, facial features)
• ACTH Adenoma: Cushing's disease (rare)
• Non-Functional Adenomas: Mass effects (headaches, vision loss)
• Often larger and more aggressive than sporadic pituitary tumors

Other Associated Tumors/Features:

• Adrenal Gland Abnormalities (20-73%): Usually non-functional adenomas or hyperplasia
• Thyroid Nodules/Adenomas (25%)
• Carcinoid Tumors: Bronchial (5%), thymic (2-8%), gastric
• Lipomas, Angiofibromas, Collagenomas (Skin Lesions)
• Thymic and Bronchial NETs: More aggressive
• Meningiomas, Ependymomas (CNS Tumors)

Diagnosis:

Clinical Diagnosis (ANY of the following):

• Two or more MEN1-associated tumors: In a single patient
• One MEN1-associated tumor + family history: First-degree relative with MEN1

Genetic Testing:

• Confirms diagnosis (identifies MEN1 gene mutation)
• Screen at-risk relatives
• Detects mutation in ~90% of clinical MEN1 cases

Biochemical/Imaging Surveillance (For Affected Patients):

• Annually Starting Age 5-10:
  • Calcium, PTH (screen for hyperparathyroidism)
  • Fasting glucose (insulinoma screening)
  • Prolactin, IGF-1 (pituitary tumors)
  • Gastrin (gastrinoma)
  • Chromogranin A, pancreatic polypeptide (pancreatic NETs)
• Imaging:
  • MRI pituitary (every 3-5 years or if symptoms)
  • MRI or CT abdomen (every 1-3 years—pancreatic NETs)
  • CT chest (every 1-3 years after age 20—thymic/bronchial NETs, especially smokers)

Treatment (Tumor-Specific):

Hyperparathyroidism:

• Surgery: Subtotal parathyroidectomy (remove 3.5 glands) or total parathyroidectomy with autotransplantation
• High recurrence rate → may need re-operation
• Calcimimetics (cinacalcet) if surgery refused/failed

Pancreatic NETs:

• Functional Tumors (gastrinoma, insulinoma): Surgery if localized; somatostatin analogs for symptom control
• Non-Functional Tumors:
  • <1 cm: Surveillance
  • 1-2 cm: Controversial (surgery vs. surveillance)
  • >2 cm: Surgery (high malignancy risk)
• Metastatic: Somatostatin analogs, everolimus, PRRT, chemotherapy

Pituitary Tumors:

• Prolactinoma: Dopamine agonists (cabergoline, bromocriptine)
• GH Adenoma: Surgery, somatostatin analogs, radiation
• ACTH Adenoma: Surgery (transsphenoidal resection)

Prognosis:

• Life Expectancy: Reduced compared to general population (median survival ~55 years)
• Main Causes of Death: Malignant pancreatic NETs, thymic carcinoids (especially in smokers)
• Early detection and surveillance improve outcomes