MEN-1 Syndrome
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Multiple Endocrine Neoplasia Type 1 (MEN-1) is an autosomal dominant inherited disorder characterized by tumours in specific endocrine glands.
It is famously remembered by the "3 Ps":
- Parathyroid (95%)
- Pancreas (40-70%)
- Pituitary (30-40%)
Clinical Scenario: Stones and Ulcers
A 35-year-old man presents with recurrent kidney stones. Blood tests show mild hypercalcaemia. Review of his records reveals he has been on omeprazole for years for 'bad indigestion'. His father died of a 'hormone tumour'.
Key Teaching Points
- The combination of **Hyperparathyroidism** (Stones/Hypercalcaemia) and **Gastrinoma** (Indigestion from acid hypersecretion) is classic MEN-1.
- Hyperparathyroidism in a young patient (<40) should always trigger genetic testing.
- The most likely cause of death in MEN-1 is malignant neuroendocrine tumour (Pancreatic/Carcinoid).
Image Integration Plan
| Image Type | Source | Status |
|---|---|---|
| Management Algorithm | AI-generated | PENDING |
| Pathophysiology (3 Ps Diagram) | AI-generated | PENDING |
| MRI Pituitary (Macroadenoma) | Web Source | PENDING |
| CT Abdomen (Pancreatic Mass) | Web Source | PENDING |
[!NOTE] Image Generation Status: Diagrams illustrating the Chromosome 11q13 defect are queued.
MEN-1 vs MEN-2
| Feature | MEN-1 | MEN-2A | MEN-2B |
|---|---|---|---|
| Gene | MEN1 (Chr 11) | RET (Chr 10) | RET (Chr 10) |
| Features | 3 Ps: Parathyroid, Pituitary, Pancreas | 2 Ps, 1 M: Parathyroid, Phaeo, Medullary Thyroid CA | 1 P, 2 Ms: Phaeo, Medullary Thyroid CA, Marfanoid/Mucosal Neuromas |
| Thyroid | Rare | MTC (100%) | MTC (100%) |
- Prevalence: 1 in 30,000.
- Inheritance: Autosomal Dominant with high penetrance (almost 100% by age 50).
- Genetics: Mutation of MEN1 gene on Chromosome 11q13. This encodes Menin (a tumour suppressor protein).
Loss of the tumour suppressor function of Menin leads to uncontrolled cell division in specific neuroendocrine tissues.
- Parathyroid: Usually involves hyperplasia of all 4 glands (unlike sporadic hyperparathyroidism which is usually a single adenoma).
- Pancreas: Islet cell tumours (Gastrinoma/Insulinoma). Can be multicentric.
- Pituitary: Anterior pituitary adenomas.
1. Parathyroid (95%)
2. Enteropancreatic Tumours (30-70%)
3. Pituitary Adenomas (30-40%)
Other Features
- General: Acromegalic features? Renal scar (stones)?
- Visual Fields: Bitemporal hemianopia (Pituitary mass).
- Skin: Check for lipomas or angiofibromas.
Screening
- Genetic Testing: For MEN1 mutation. Offered to all 1st degree relatives.
- Biochemical Screening (Annually for carriers): Calcium, PTH, Fasting Gastrin, Glucose, Insulin, Prolactin, IGF-1.
Imaging
- MRI Pituitary.
- CT / MRI Abdomen: For pancreatic NETs.
- Octreotide Scan / Gallium-68 PET: Functional imaging for NETs.
Requires massive Multi-Disciplinary Team (Endocrinologist, Surgeon, Geneticist).
A. Parathyroid
- Subtotal Parathyroidectomy: Removal of 3.5 glands. (Leave half a gland to prevent permanent hypocalcaemia).
- Alternately: Total parathyroidectomy + Autotransplantation into forearm muscle.
- Recurrence is common (50% at 10 years).
B. Pituitary
- Prolactinoma: Medical therapy (Dopamine agonists - Cabergoline) is first line.
- Others: Transsphenoidal surgery.
C. Pancreatic
- Gastrinoma: High dose PPIs (Omeprazole). Surgery can be curative but tumours are often multiple/metastatic.
- Insulinoma: Surgical resection (Enucleation).
- Non-functioning: Surveillance vs Surgery (Whipple's procedure) if >2cm or growing.
- Malignancy: Pancreatic/Thymic Neuroendocrine Tumours are the leading cause of death.
- Osteoporosis: From chronic hyperparathyroidism.
- Pituitary Apoplexy.
- Life expectancy is reduced (median age of death 55-60) due to malignant NETs.
- Early screening improves outcomes.
- Endocrine Society Guidelines: Clinical Practice Guidelines for MEN1.
What is MEN-1? It is a rare genetic condition passed down in families (50% chance if a parent has it). It causes benign tumours to grow in three specific hormone glands:
- Parathyroid (in neck): Controls calcium.
- Pituitary (in brain): Controls other hormones.
- Pancreas (in tummy): Controls digestion and sugar.
Is it cancer? Most of the tumours are "benign" (not cancer), but they cause problems by producing too much hormone (like too much acid causing ulcers, or too much calcium causing kidney stones). Some pancreatic tumours can become cancerous, so we watch them closely.
How is it managed? We cannot "cure" the gene, but we can treat the tumours.
- We often remove the parathyroid glands surgically.
- We use tablets to control pituitary hormones or acid.
- We do yearly blood tests and scans to catch any new tumours early.
- Thakker RV, et al. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012.
- Brandi ML, et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. 2001.
- Goudet P, et al. Causes of death and prognostic factors in multiple endocrine neoplasia type 1. World J Surg. 2010.