Makindo Medical Notes

🔬 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.

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%).

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).