Multiple Endocrine Neoplasia

“In MEN syndromes there are functioning hormone-producing tumours in multiple organs with three subtypes: MEN 1 (Wemer syndrome), MEN 2A (Sipple syndrome) and MEN 2B”

Aetiology

• MEN1 gene is a tumour suppressor gene which can cause an altered menin protein expression if mutated
• MEN 2A and MEN 2B are caused by a mutated RET proto-oncogeneà elevated tyrosine kinase activity

Pathophysiology

• MEN 1
  • Primary hyperparathyroidism (90%, most ↑ ­Ca)
  • Pancreas endocrine tumours (70%) such as gastrinoma and insulinoma or glucagonomas
  • Pituitary prolactinoma (50%)
  • GH secreting tumour
  • Carcinoid tumour
• MEN 2A
  • Medullary Thyroid Carcinoma (95-100%)
  • Pheochromocytoma (50%)
  • Parathyroid hyperplasia
• MEN 2B
  • Similar to MEN 2A plus mucosal neuromas and Marfanoid appearance but no hyperparathyroidism

Clinical Presentation

• MEN 1
  • Hyperparathyroidism → ↑ Ca, bone abnormalities, weak, tired, thirsty, dehydrated but polyuric, abdominal pain.
  • Gastrinoma → Z-E syndrome, diarrhoea, upper abdominal pain due to ulcers.
  • Insulinoma → fasting hypoglycaemia with Whipple’s triad.
  • Glucagonomas → migrating rash, glossitis, cheilitis, anaemia, wt loss.
  • Carcinoid tumour → flushing, diarrhoea, bronchospasm
• MEN 2A
  • Palpable neck mass, hypertension, episodic sweating, diarrhoea, elevated BP and HR in Pheochromocytoma
• MEN 2B
  • Mucosal neuromas → bumps on lips, cheeks tongue glottis, eyelids and visible corneal nerves.
  • Marfanoid habitus → high arched palate, pectus excavatum, bilateral pescavus and scoliosis

Investigations

• Genetic screening for RET mutations.
  • If mutations are identified, also screen family members at risk.
• Serum calcium and PTH levels.
• Screen for different hormones associated with potential MEN tumours (e.g fasting gastrin in gastrinomas).
• DEXA scan and urinary tract imaging in hypercalcaemia to evaluate BMD.

Management

• Parathyroidectomy to control hypercalcaemia.
• Surgical removal of tumours with symptomatic treatment relating to the specific endocrine glands affected

Complications

• Constant surveillance to identify any development of an additional tumour.
• Associated with neurofibromatosis, Von Hippel- Lindau syndrome, Peutz- Jeghers syndrome and Carney complex.
• Overall MEN1 has a reduced life expectancy and the outlook is dependent on which tumours a patient develops