genetics of endocrine Flashcards
what are monogenic disorders?
-disorders caused due to defect in a single gene
what are polygenic disorders?
-disorders caused due to defect in multiple genes
what are the 6 different patterns of monogenic inheritence?
- AD
- AR
- XLD
- XLR
- Y linked
- mitochondrial
what does MEN1 affect (multiple endocrine noeplasia type 1)?
MAINLY 3 Ps
Pituitary
Parathyroid
Pancreas
angiofibromas= common!!
but can also have:
- gastric carcinoma
- thymic/ bronchial carcinoids
- adrenal
is MEN1 autosomal dominant or recessive?
MEN1 is autosomal dominant inheritance
what does MEN1 gene mutation typically result in?
-loss/reduced protein function
is MEN 2 (multiple endocrine neoplasia type 2) autosomal dominant or recessive?
autosomal dominant
what are the 2 types of MEN2 and which is more common?
MEN2a (more common)
MEN2b
what type of cancer occurs in almost every patient with MEN2?
MTC
medullary thyroid cancer
what mutation is associated with MEN2?
RET proto oncogene mutation
what type of MEN is associated with pheochromocytoma?
MEN2
what is neurofibromatosis type 1 characterised by?
- axillary freckling
- cafe au lait patches
- neurofibromas
- optic gliomas
- scoliosis
what mutation causes neurofibromatosis type 1?
-mutation in NF1 gene
what type of MEN is associated with parathyroid hyperplasia?
MEN2A and MEN1
what is phaechromocytoma?
-a rare tumour of the adrenal medulla
how may patients present if there is a MEN1 mutation causing a tumour in the parathyroid?
-may present with hypercalcaemia due to parathyroid hyperplasia
how may patients present if they have a MEN1 mutation causing a pituitary adenoma?
- If affecting mammotrophs (prolactin cells) may present with hyperprolactinaemia
- if affecting somatotrophs may present with excess GH
- if affecting corticotrophins may present with excess cortisol through excess ACTH
what is diagnostic criteria for MEN1 mutation?
-presence of two or more MEN1 tumour type
what are some investigations done if suspected MEN1?
- serum calcium (to detect asymptomatic hypercalcaemia)
- CT or MRI
- unlike MEN2 there is no clear evidence of benefit of using DNA testing in general screening
what is the management for parathyroid hyperplasia caused by MEN1 mutation?
PARATHYROIDECTOMY
-this is indicated when there are pathological features of excess PTH and raised Ca levels for example by osteopenia, nephroliathiasis (kidney stones) and symptomatic hypercalcaemia
what is management for pituitary adenoma caused by MEN1 mutation?
both surgical and medical options available
Transsphenoidal surgery!
what is the main cause of mortality in MEN1 mutations?
-pancreatic tumours :(
what is the management for insulinomas?
- may be treated pharmacologically with diazoxide (inhibits insulin release)
- surgery
what does diazoxide do?
inhibits insulin release
what is the treatment for a gastrinoma?
- PPIs
- surgical excisions in those who do not maintain symptomatic relief
what does MEN2A cause?
- phaechromocytoma
- medullary thyroid cancer
- parathyroid hyperplasia
what does MEN2B cause?
- phaeochromocytoma
- medullary thyroid cancer
- neuroma and ganglioneuroma
- marfanoid habitus
how many phaechromocytoma present?
- sweating
- increase BP
- irregular HB
- anxious
(basically increase in adrenaline as it affects chromaffin cells in adrenal )glands
how does medullary thyroid cancer typically present when there is a MEN2 mutation?
-bilateral and multifocal
how is MEN2 diagnosed?
-if there is presence of two or more MEN2 tumours
OR
-if there is presence of RET oncogene mutation
what should be done if someone is found to have a RET oncogene mutation?
- genetic testing of family
- screen patient and their family for tumours
what should be done if someone presents with MTC (medullary thyroid cancer)?
-screen for other tumours associated with MEN2
who is a prophylactic thyroidectomy offered to?
-patients with MEN2
what is treatment for parathyroid hyperplasia in a patient with MEN2 mutation?
parathyroidectomy
what is treatment for patient with phaechromocytoma due to MEN2 mutation?
- unilateral or bilateral adrenalectomy
- patients with adrenalectomy should be given synthetic glucocorticoids and mineralocorticoids
what is the treatment for a patient with MEN2 mutation who has developed MTC?
-thyroidectomy and lymph node dissection
