Syndromes

Question 1

MEN 1

Answer 1

Rare AD disorder that causes tumours in the pituitary, parathyroid and pancreatic NETs

Mutation in the MEN1 gene of chromosome 11q13 causing loss of function of the Menin protein needed for DNA repair and cytoskeleton formation.

Primary hyperparathyroidism - half under age 20, most multiglandular with multiple parathyroid adenomas

Pancreatic NETs - 80% have tumours, most non functional
- 40% gastrinomas causing ZES - high gastrin, high gastric acid PUD and diarrhoea
- 20% insulinomas

Pituitary tymours - 40% - can include prolactinomas

Other - foregut NETs, benign adrenal tumours, lipomas

Work up - Ca, PTH, MRI brain and gastrin, insulin

Tx - parathyroid OT, octreotide and PNET OT, pit - bromocriptine for prolactinoma and OT

Question 2

MEN2

Answer 2

AD disorders with tumours of neural crest derived cells - medullary thyroid ca, parathyroid and phaeochromocytoma
- (Phe, Me, P)

Mutation in the RET proto oncogene on chromosome 10q11 causing constitutive activation of the receptor.

RET mutations occur in MEN2A, MEN2B and FMTC, with different codon mutations

MEN 2A
- All 3 present - phaeo, med thyroid ca and hyper parathyroidism (4 gland hyperplasia)
- Med thyroid Ca in 20 - can be bilateral/multicentric
- Phaeo 50%, hyperparathyroid 30%

MEN 2B
- Phaeo (in 50%) and MTC
- Also get mucosal neuromas, megacolon, motility problems, marfanoid

FMTC - Just get the MTC

Dx - genetic screen for RET after FH,
Dx and surveillance Biochem - plasma mentanephrines, Ca/PTH and Calcitonin

Tx - tx MTC, prophylactic at 6m MEN2B and 5y MEN2A and FMTC
- Phaeos - medication and operation before the thyroid
- Parathyroid - 4 gland parathyroidectomy and reimplantation

Question 3

VHL

Answer 3

AD disorder of vascular tumour including phaeo and PNET

Mutation in the VHL tumour suppressor gene

Other tumours include CNS haemangioblastomas, RCCs, retinal angiomas

Types
- 1 - PNET, CNS, (low risk phaeo RCC)
- 2 - Phaeo (variable risk RCC and haemangioblastoma)

Dx - Genetic testing