multiple endocrine neoplasia (MEN types 1,2a and 2b)
type 2 features/ associated with?
addison's disease/ type 1 DM/ autoimmune thyroid disease - hypothyroidism or graves disease/ also associated with primary hypogonadism, vitiligo, alopecia, pernicious anaemia, chronic atrophic gastritis, coeliac disease, dermatitis herpetiformis.
Autoimmune polyendocrine syndromes?
autoimmune disorders cluster into 2 defined syndromes, type 1 and type 2.
type 1 causes?
mutations of AIRE (auto immuneregulator) gene on chromosome 21
MEN -1?
-95% are parathyroid hyperplasia/adenoma (most increase calcium) - pancreas endocrine tumours 70% are gastrinoma or insulinoma or rarely somatostatinoma (DM + steatorrhoea + gallstones/ cholangitis) or vipoma or glucagonomas (+/- glucagon syndrome: migrating rash; glossitis; cheilitis; anaemia; reduced weight ; increased plasma glucagon; increased glucose) -50% are pituitary prolactinoma or GH secreting tumour (acromegaly); also, adrenal and carcinoid tumours are associated.
What is the gene involvement in MEN-2a and b?
the ret proto-oncogene, a receptor tyrosine kinase
What is MEN syndromes?
these are functioning hormone producing tumours in multiple organs
What is the MEN-1 gene?
this is a tumour suppressor gene
What comprises the MEN syndromes?
-MEN-1 and 2 - neurofibromatosis - von hippel- lindau - peutz- jeghers syndromes - carney complex (spotty skin pigmentation, schwannomas, myxoma of skin, mucosa, or heart, especially atrial myxoma) - and endocrine tumours eg: pituitary adenoma, adrenal hyperplasia, and testicular tumour
Type 1 features?
-addison's disease -chronic mucocutaneous candidiasis - hypoparathyroidism
What do mucosal neuromas consist of?
Bumps on the lips, cheeks, tongue, glottis, eyelids, and visible corneal nerves.
Type 2 genetics?
HLA D3 and D4 linked, common and the cause is polygenic.
How is MEN syndrome inherited?
MEN syndrome is inherited as a autosomal dominants
MEN-1 gene codes for what?
Menin is the protein and it alters transcription activation, many are sporadic , presenting in the 3rd and 5th decades
MEN-2a
Thyroid: medullary thyroid carcinoma adrenal: pheochromocytoma (50% usually benign and bilateral) Parathyroid hyperplasia
Type 1 genetics?
autosomal recessive and rare
look at page 215 for the pics?
for the pics
Type 1 is associated with?
hypogonadism, pernicious anaemia, autoimmune primary hypothyroidism, chronic active hepatitis, vitiligo, alopecia
Describe the appearance seen in MEN-2b?
it has similar features to MEN-2a plus mucosal neuromas and marfanoid appearance, but no hyperparathyroidism.
