Adrenal gland pt 2 Flashcards
what are the clinical features of Cushing’s
Too much cortisol Centripetal obesity Moon face and buffalo hump Proximal myopathy Hypertension and hypokalaemia Red striae, thin skin and bruising osteoporosis, diabetes
What causes Cushing’s
( hypersecretion of hormones of the adrenal cortex aka too much cortisol)
Taking too many steroids
Pituitary dependent Cushing’s disease
Ectopic ACTH from lung cancer
adrenal adenoma secreting cortisol
What investigations can be done to determine the cause of Cushing’s
1) 24 h urine collection for urinary free cortisol
2) Blood diurnal cortisol levels
(cortisol usually highest at 9am and lowest at midnight, if asleep) ( in Cushing’s this will always be high
( to diagnose Cushing’s need basal 9am cortisol of 800nm )
3) Lose dose dexamethasone suppression test
( will fail to suppress in Cushing’s)
( to diagnose cushing’s need end of LDDST: 680nm)
What is the dexamethasone suppression test
Dexamethasone = artificial steroid
given 0.5mg 6 hourly for 48hours
in normal people = will suppress cortisol to 0
cushing’s ( any cause) = fail to supress
what results are needed to diagnose cushing’s
Basal (9am) cortisol 800 nM
End of LDDST: 680 nM
What steroids if taken in excess can cause Cushing’
Hydrocortisone
Prednisone
How can you use drugs to manipulate steroids
1) Enzyme inhibitors
2) Receptor blocking drugs
What can be used to treat Conn’s syndrome
Mr antagonists
- spironolactone
- epleronone
What does metryrapone’s do
Inhibition of 11b-hydroxylase
this prevents formation of corticosterone and cortisol
See google docs
What if the mechanism of action of metyrapone
inhibition of 11b-hydroxylase (refer also to first year notes on steroid biosynthesis)
steroid synthesis in the zona fasciculata [and reticularis] is arrested at the 11-deoxycortisol stage
11-deoxycortisol has no negative feedback effect on the hypothalamus and pituitary gland.
What is metyrapone used for ?
1) Control of Cushing’s syndrome prior to surgery.
- adjust dose (oral) according to cortisol (aim for mean serum cortisol 150-300 nmol/L)
- improves patient’s symptoms and promotes better post-op recovery (better wound healing, less infection etc)
2) Control of Cushing’s symptoms after radiotherapy (which is usually slow to take effect)
What are some unwanted side effects of metyrapone
1) Hypertension on long-term administration
due to accumulation of deoxycortisone ( which has mineralocorticoid activity leading to salt retention)
2) Hirsutism in women due to increased adrenal androgen production
What does ketoconazole do?
Mainly blocks 17 alpha hydroxylase inhibiting cortisol production
When do you used ketoconazole?
main use as an antifungal agent – although withdrawn in 2013 due to risk of hepatotoxicity
at higher concentrations, inhibits steroidogenesis – off-label use in Cushing’s syndrome
How is ketoconazole used in Cushing’s syndrome
USES (similar to metyrapone)
Cushing’s syndrome
- treatment and control of symptoms prior to surgery
orally active
