Endocrine
AKT · Endocrine/Paraneoplastic & neuroendocrine

MEN 1 (Wermer syndrome)

Autosomal-dominant MEN1 tumour-suppressor mutation — the '3 Ps'

Overview

Multiple Endocrine Neoplasia type 1 — an autosomal-dominant syndrome (MEN1 gene) of tumours of the '3 Ps': Parathyroid (primary hyperparathyroidism — usually the first/commonest), Pituitary (adenoma, e.g. prolactinoma), and Pancreas (neuroendocrine — gastrinoma, insulinoma). Recognised by combinations of these and a family history; managed by surveillance and treating each tumour.

Recognise

  • Primary HYPERPARATHYROIDISM (hypercalcaemia — usually the earliest/most common feature)
  • PANCREATIC neuroendocrine tumours (gastrinoma → Zollinger-Ellison, insulinoma)
  • PITUITARY adenoma (prolactinoma commonest); autosomal-dominant family history

Red flags

  • Zollinger-Ellison ulcers/complications; hypercalcaemia
  • Index case → genetic testing and screening of the family

Differentials & how to tell them apart

Sporadic single endocrine tumourisolated hyperparathyroidism/prolactinoma without the multi-gland/family pattern
MEN2medullary thyroid cancer + phaeochromocytoma + parathyroid (RET) — different combination

Investigations

Biochemical screening (calcium/PTH, gut hormones/gastrin, prolactin/pituitary, fasting glucose-insulin), imaging (pituitary MRI, pancreatic imaging); MEN1 genetic testing and family cascade screening.

Management

Treat each component + lifelong surveillance + family genetic screening

  1. 1Recognise a combination of parathyroid, pituitary and pancreatic tumours (or one + family history) → MEN1 genetic testing. Treat each tumour and start lifelong surveillance.Gate: An index case mandates MEN1 genetic testing and CASCADE screening of relatives — and biochemical/imaging surveillance for the other components (the syndrome, not just the presenting tumour)
  2. 2Component-specific treatment (parathyroidectomy, dopamine agonist, gastrinoma management); periodic re-screening; family counselling.
Treat each tumourparathyroidectomy, dopamine agonist (prolactinoma), PPI/resection (gastrinoma) etc.
Lifelong biochemical/imaging surveillanceand family cascade screening

Key points

3 Ps — Parathyroid, Pituitary, Pancreas. Hyperparathyroidism usually comes first. One MEN1 tumour means screen for the others and test the family.

Monitor & prognosis

Periodic biochemistry/imaging; family screening.

Good with surveillance; gastrinoma drives morbidity.

Source: Endocrine Society; UKINETS