Multiple Endocrine Neoplasia type 1 (MEN1)
Most patients with MEN1 present with hypercalcaemia due to primary hyperparathyroidism.
📖 About
- Inherited or sporadic condition, also called Wermer syndrome.
- Characterised by tumours in multiple endocrine glands – especially parathyroid, pituitary, and pancreas.
🧬 Aetiology
- Autosomal dominant disorder due to mutations in the MEN1 gene on chromosome 11q13.
- The MEN1 gene encodes a tumour suppressor protein called menin.
- Most cases present in the 3rd–5th decades; some are sporadic.
🩺 Clinical Features (see individual topics)
- Parathyroid tumours (95%): parathyroid hyperplasia or adenoma → primary hyperparathyroidism with hypercalcaemia.
- Pituitary tumours (≈60%):
- Prolactinomas → galactorrhoea, infertility.
- GH-secreting tumours → acromegaly.
- ACTH-secreting tumours → Cushing’s disease.
- Pancreatic / Duodenal Neuroendocrine tumours (50–75%):
- Gastrinoma → Zollinger–Ellison syndrome (multiple small duodenal tumours, severe peptic ulcers).
- Insulinoma → recurrent hypoglycaemia.
- Glucagonoma → hyperglycaemia + necrolytic migratory erythema.
- VIPoma → Verner–Morrison syndrome: watery diarrhoea, hypokalaemia, acidosis.
- Occasional: Carcinoid and adrenal tumours.
🧪 Investigations
- Routine: FBC, U&E, LFT, bone profile.
- 📈 Serum Ca²⁺ (high), PTH (inappropriately normal/high), DEXA scan for bone density.
- 🖥️ Imaging: CT abdomen (pancreatic/adrenal masses), MRI pituitary.
- Endoscopy for peptic ulcer disease.
- Functional testing:
- ↑ Fasting gastrin + ↑ gastric acid output → gastrinoma.
- Hypoglycaemia + ↑ Insulin, C-peptide, proinsulin → insulinoma.
- ↑ Serum glucagon → glucagonoma.
- ↑ VIP → VIPoma.
💊 Management
- Directed at each tumour: surgical resection where appropriate (e.g. parathyroidectomy for hyperparathyroidism).
- Medical therapy for hormone excess (e.g. PPIs for gastrinoma, dopamine agonists for prolactinomas).
- Genetic counselling for families.
- Regular surveillance (biochemical and imaging) due to lifelong tumour risk.
📚 References
- Royal College of Physicians Endocrinology guidance.
- Oxford Handbook of Endocrinology & Diabetes.
- BNF, NICE CKS – relevant tumour management pathways.
🧾 Clinical Case – Multiple Endocrine Neoplasia Type 1 (MEN1)
A 32-year-old man presents with recurrent peptic ulcers, abdominal pain, and diarrhoea.
Examination shows mild features of hypercalcaemia (thirst, constipation).
Blood tests reveal raised serum calcium and PTH, consistent with primary hyperparathyroidism, and elevated gastrin levels.
MRI pituitary later shows a prolactin-secreting adenoma.
Family history reveals his father had similar endocrine tumours.
👉 Diagnosis: MEN1 (parathyroid hyperplasia, pancreatic neuroendocrine tumour, pituitary adenoma).
👉 Management: surgery for hyperparathyroidism, proton pump inhibitors for gastrinoma, dopamine agonists for prolactinoma, and genetic counselling.
