Multiple Endocrine Neoplasia Syndromes
- Group of genetically inherited diseases resulting in proliferative lesions (hyperplasia, adenomas, carcinomas) of multiple endocrine organs
- Associated with distinct features;
- Occur at a younger age than sporadic cancers
- Arise in multiple endocrine organs either synchronously or at different times
- Even in only affected one organ they are multifocal
- Tumour are often preceded by an asymptomatic stage of endocrine hyperplasia
- Tumours are more aggressive and recur in a higher proportion than sporadic tumours
Multiple endocrine neoplasia Type I
- Also called Wermer syndrome
- Characterised by abnormalities in the Parathyroid, Pancreas and Pituitary
- Primary hyperparathyroidism is the most common manifestation due to both hyperplasia and adenomas. Hyperplasias are monoclonal
- Endocrine tumours of the pancreas are usually aggressive and are often functional
- In the pituitary there are frequently prolactinomas
- There are also gastinomas in the duodenum
- Associated with germline mutation I the MEN1 gene on chromosome 11q13 which acts as a TSG
Multiple Endocrine Neoplasia Type 2
- Classified into three distinct syndromes;
- MEN-2A
- MEN-2B
- Familial medullary thyroid cancer
- MEN-2A
MEN-2A (Sipple syndrome)
- Characterised by phaeochromocytoma, medullary carcinoma and parathyroid carcinoma
- Linked to germ line mutations in the RET protooncogene on chromosome 10. RET is a tyrosine kinase which binds glial derived neurotrophic factor (GDNF). Disease is associate with a gain of function mutation
MEN-2B
- Patients develop medullary thyroid carcinomas which are usually multifocal and more aggressive than in MEN-2A
- They also develop phaeochromocytomas
- However unlike MEN-2A, primary hyperparathyroidism is not present
- Also accompanied by neuromas and ganglioneuromas involving the skin, oral muscosa, respiratory tract and GI tract
- Also have a marfanoid habitus
- Also associated with a mutation in RET but a different one from MEN-2A
Familial Medullary thyroid cancer