Endocrine System >
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