The Adrenal Gland And Hyperadrenalism Flashcards
How is cortisol released?
Has a diurnal rhythm
Highest in morning (8am) lowest at midnight
No point in measuring cortisol in the morning for people with hyperadrenalism as it will be high anyways
What is Cushing’s syndrome?
Any cause of High cortisol
Commonest cause Is Cushing’s disease - pituitary tumour causes excess ACTH which causes excess cortisol
Causes if Cushing’s syndrome: Cushing’s disease Too much oral steroids Ectopic ACTH from lung cancer Adrenal adenoma aecreting cortisol
What are the symptoms of Cushing disease?
Moon face Centripetal obesity Proximal myopathy (weakness and wasting) Hypertension (causing pitting oedema) and hypokalaemia Red striae, thin skin, bruising Osteoporosis Diabetes
What investigations are done to diagnose Cushing’s syndrome?
24hr urine collection for urinary free cortisol (would be high in Cushing’s)
Blood diurnal cortisol levels - done in hospital day and night, while they are asleep as not to stress them. (In Cushing’s, cortisol may not be high in the morning as it is highest then anyway but it will be consistently at this level)
Low dose dexamethasone suppression test
What is the low dose dexamethasone test?
0.5 mg dexamethasone hourly for 48 hrs (artificial steroid)
In normal people this triggers the pituitary to completely stop making ACTH, so adrenal stops making cortisol
ANY causes of Cushing’s will fail the test, cortisol won’t go down
What are the diagnosis criteria for Cushing’s syndrome?
Basal (9am) cortisol 800nM (high)
End of LDDST (low dose dexamethasone suppression test): 680 nM
If both these are high then you know there is hyperadrenalism but you don’t know the cause
What are the categories of drug treatments of hyperadrenalism?
Treating excess cortisol (Cushing’s syndrome):
Inhibitors of steroid biosynthesis- metyrapone, ketaconazole
Excess aldosterone (conns syndrome): Spironolactone, epleronone
An operation should be arranged and these are used prior to this
What is the action of metyrapone?
Inhibition of 11-beta-hydroxylase (last step in cortisol synthesis). So synthesis is halted in the 11-deoxycortisol stage
11 deoxycortisol has no negative feedback effect on the hypothalamus and pituitary gland
When is metyrapone used?
Control of Cushing’s prior to surgery:
Adjust dose according to cortisol levels
It improves patients symptoms before surgery and promotes better post op recovery
Control of Cushing’s symptoms after radiotherapy
What are the side effects of metyrapone?
It causes deoxycorticosterone (a precursor of aldosterone, which acts like aldosterone) to accumulate in the zona glomerulosa - this leads to salt retention and hypertension
Also leads to increased sex steroid synthesis (increased adrenal androgen production) - causes hirsuitism in women
What is the mechanism of action of ketoconazole?
Originally marketed as an anti fungal but risk of hepatotoxicoty
At higher concentrations it inhibits steroidogenesis
Blocks the action of 17- alpha-hydroxylase (enzyme required for cortisol production)
When is ketoconazole used?
(Mostly same as metyrapone)
Treatment and control of symptoms prior to surgery
What are the side effects of ketoconazole?
Possibly fatal liver damage
So liver function must be monitored weekly, clinically and biochemically
How is Cushing’s syndrome treated?
DEPENDS ON CAUSE
Pituitary surgery (transsphenoidal hypophysectomy)
Bilateral adrenalectomy
Unilateral adrenalectomy for adrenal mass
Medical treatment: metyrapone or ketoconazole
What is conns syndrome?
Benign adrenal cortical tumour (in zona glomerulosa)
Causes excess aldosterone
This causes hypertension and hypokalaemia
(Aldosterone increases sodium reabsortpption, increases potassium excretion, raises blood pressure)
