FFinalistSouthampton · 2027
Endocrine
AKT · Endocrine/Paraneoplastic & neuroendocrine

MEN 2 (2a/2b)

Autosomal-dominant RET proto-oncogene mutation

Overview

Multiple Endocrine Neoplasia type 2 — autosomal-dominant RET proto-oncogene mutation. MEN2A: medullary thyroid cancer + phaeochromocytoma + parathyroid hyperplasia. MEN2B: medullary thyroid cancer + phaeochromocytoma + mucosal neuromas/marfanoid habitus (NO parathyroid disease). Medullary thyroid cancer is near-universal — RET-positive carriers are offered prophylactic thyroidectomy.

Recognise

  • MEDULLARY thyroid cancer (calcitonin-secreting — near-universal, often the lethal component)
  • PHAEOCHROMOCYTOMA (catecholamine excess — must be excluded before any surgery)
  • MEN2A: + primary hyperparathyroidism; MEN2B: + mucosal neuromas (lips/tongue), marfanoid habitus, NO parathyroid disease

Red flags

  • Operating on a patient with an undiagnosed phaeochromocytoma can be fatal — always exclude phaeo first
  • RET-positive → prophylactic thyroidectomy (timing by mutation risk)

Differentials & how to tell them apart

MEN1parathyroid + pituitary + pancreas (3 Ps), no medullary thyroid cancer/phaeo
Sporadic medullary thyroid cancer/phaeoisolated, RET-negative, no syndromic features/family history
Marfan syndromemarfanoid habitus but no neuromas/medullary cancer/phaeo (different genetics)

Investigations

Calcitonin/CEA (medullary cancer), plasma/urinary metanephrines (phaeo), calcium/PTH (2A); RET genetic testing and family cascade screening.

Management

Exclude/treat phaeo first → (prophylactic) thyroidectomy; family RET screening

  1. 1RET testing in suspected cases and relatives. Screen for and treat the components — but ALWAYS exclude and treat a phaeochromocytoma before any other surgery.Gate: Exclude a PHAEOCHROMOCYTOMA (metanephrines) and alpha-block it BEFORE any thyroid/parathyroid surgery — operating with an untreated phaeo can precipitate a fatal hypertensive crisis; RET-positive carriers are offered PROPHYLACTIC thyroidectomy
  2. 2Total thyroidectomy (medullary cancer — no radioiodine role); adrenalectomy after alpha-blockade; parathyroidectomy (2A); lifelong surveillance and family cascade testing.
Thyroidectomy (prophylactic in RET carriers; total for cancer) — medullary cancer does not respond to radioiodine
Alpha- then beta-blockade + adrenalectomy (phaeo) — alpha before beta — exclude/treat phaeo BEFORE thyroid surgery
Parathyroidectomy (2A) — for hyperparathyroidism

Key points

RET. Medullary thyroid cancer + phaeo ± parathyroid (2A) or mucosal neuromas/marfanoid (2B). THE rule: exclude and treat the phaeo before any surgery; offer prophylactic thyroidectomy to RET carriers.

Monitor & prognosis

Calcitonin/metanephrines/calcium; family screening.

Good if medullary cancer caught/prevented early.

Source: Endocrine Society; British Thyroid Association