Multiple Endocrine Neoplasia type II (MEN2)
🔬 Medullary thyroid cancer, characterised by stromal amyloid deposition, is a hallmark of MEN2 and is seen in nearly all affected patients.
⚠️ MEN2 is a rare but important hereditary cancer syndrome — early recognition and genetic screening save lives.
ℹ️ About
- 👥 MEN2A – affects ~60–90% of MEN2 families.
- 👥 MEN2B – rarer, ~5% of MEN2 families, often with distinctive marfanoid features.
- 📊 Rare overall: incidence ~1 in 30,000.
🧬 Aetiology
- 🧬 RET proto-oncogene mutation → abnormal cell signalling → predisposition to endocrine tumours.
- Inheritance is autosomal dominant.
- ~50% of MEN2B cases are de novo mutations (no family history).
🩺 Clinical Features
- MEN2A:
- 🦋 Medullary thyroid carcinoma (MTC): 98–100% affected.
- 🟢 Phaeochromocytoma: ~50% (usually benign adrenal tumour, but can cause life-threatening hypertension).
- 🦴 Parathyroid disease: hyperplasia or adenoma → 5–10%.
- MEN2B (Marfanoid type):
- 🦋 Medullary thyroid carcinoma: 98–100%.
- 🟢 Phaeochromocytoma: ~50%.
- 👄 Mucosal neuromas: lips, tongue, GI tract → 95–98%.
- 🍽️ GI dysmotility: constipation, diarrhoea, pseudo-obstruction → 75–90%.
- 🦴 Marfanoid habitus: long limbs, joint/spine abnormalities → ~95%.
- 😮 Distinctive facies: thick lips, prominent eyelids (75–90%).
MEN2B
🔎 Investigations
- 🧪 Bloods: U&E, calcium, PTH (hyperparathyroidism if ↑Ca with inappropriately normal/high PTH).
- 🟢 Phaeochromocytoma screen: urinary/plasma metanephrines annually from childhood.
- 📸 Imaging: CT/MRI abdomen if metanephrines abnormal (to detect adrenal tumours).
- 🧬 Genetic testing: RET mutation analysis is key for diagnosis, screening, and family cascade testing.
- 📈 CEA and calcitonin may be raised in medullary thyroid cancer.
💊 Management
- 🔪 Prophylactic thyroidectomy: indicated if RET mutation identified.
📌 In MEN2B, thyroidectomy often recommended in infancy; in MEN2A, usually before age 3–5.
- 🦋 Medullary thyroid cancer: total thyroidectomy + central neck dissection if nodes involved.
- 🟢 Phaeochromocytoma: surgical excision, but only after careful pre-op alpha-adrenergic blockade (to control BP).
- 🦴 Hyperparathyroidism: parathyroidectomy if symptomatic or biochemical disease.
- 🔄 Follow-up: annual calcium/PTH, metanephrines, and imaging as needed.
Clinical Pearls
- Always rule out phaeochromocytoma before thyroidectomy → prevents perioperative hypertensive crisis.
- MEN2A = "2 Ps" (Phaeo + Parathyroid) + MTC.
- MEN2B = "1 P" (Phaeo) + MTC + Marfanoid body + Mucosal neuromas.
References
- GeneReviews: MEN2
- BNF – Thyroid cancer management
- Oxford Handbook of Endocrinology & Diabetes (OHED).
🧾 Clinical Case – Multiple Endocrine Neoplasia Type II (MEN2)
A 29-year-old woman presents with a neck lump and episodes of flushing, palpitations, and hypertension.
Examination reveals a firm thyroid nodule, and labs show elevated calcitonin.
Further work-up identifies a pheochromocytoma on adrenal imaging.
Genetic testing confirms a RET proto-oncogene mutation.
👉 Diagnosis: MEN2A (medullary thyroid carcinoma + pheochromocytoma + parathyroid disease risk).
👉 Management: alpha-blockade and adrenalectomy for pheochromocytoma, followed by prophylactic thyroidectomy, and family genetic counselling.
