Therapeutic use of adrenal steroids Flashcards
What does the zona glomerulosa produce?
Aldosterone
What does the zona fasciculata produce?
Cortisol
What does the zona reticular produce?
Androgens and oestrogens
Which hormones are under the control of ACTH?
Cortisol and androgens
What stimulates aldosterone release?
Renin-angiotensin system
Where is renin produced?
Juxtaglomerular cells
What does renin do?
Converts angiotensinogen to angiotensin I
What does ACE do?
Converse angiotensin I to angiotensin II
What does angiotensin II do?
Stimulates release of aldosterone from adrenal cortex
What triggers aldosterone release?
Hyperkalaemia
Hyponatraemia
Drop in renal blood flow
Beta-1 adrenoceptor stimulation
Which adrenal steroid is essential for life?
Cortisol
Why are the principle physiological actions of adrenal androgens unknown?
Gonads are a much bigger source of androgens
What are the difference between glucocorticoid and mineralocorticoid receptors?
Glucocorticoid:
Wide distribution
Selective for glucocorticoids
Low affinity for cortisol
Mineralocorticoid:
Discrete distribution
Don’t distinguish between aldosterone and cortisol
High affinity for cortisol
Why is MRs lack of selectivity a problem?
Cortisol can stimulate them
How are MRs protected from cortisol?
Cortisol is converted to cortisone by 11beta hydroxysteroid dehydrogenase
Why do you have hypokalaemia in Cushing’s?
The system gets overwhelmed, when there is lots of cortisol, 11 betahydroxysteroid dehydrogenase can’t inactivate it all so some binds to mineralocorticoid receptors and causes hypokalaemia
How does cortisol compare to hydrocortisone?
They have the same structure but hydrocortisone is synthetic and cortisol is endogenous
What sort of steroid is prednisolone?
Immunosuppressive glucocorticoid with weak mineralocorticoid activity
What sort of steroid is dexamethasone?
Very potent glucocorticoid- used clinically for things like brain metastases where there is a lot of oedema- an acute anti-oedema agent
What sort of steroid is fludrocortisone?
Aldosterone analogue
What percentage of hydrocortisone in the body is bound to plasma proteins?
90-95%
Which plasma proteins do corticosteroids bind to?
Corticosteroid binding globulin and albumin
In terms of binding, how do the other corticosteroids (prednisolone, dexamethasone and fludrocortisone) compare?
They are less bound and fludrocortisone is only bound to albumin
What is the order of the corticosteroids from shortest to longest half life?
Hydrocortisone and fludrocortisone
Prednisolone
Dexamethasone
What are reasons for giving replacement corticosteroid?
Primary adrenocortical failure Secondary adrenocortical failure Acute adrenocortical failure Congenital adrenal hyperplasia Iatrogenic adrenocortical failure
What are the two main causes of primary adrenocortical failure?
Addison’s disease
Chronic adrenal insufficiency
What is wrong in primary adrenocortical failure?
Their adrenal cortex just isn’t working, they can’t make any hormones and need replacement cortisol and aldosterone
Why do primary adrenocortical failure patients not need replacement androgens?
The loss of production from adrenal cortex isn’t a big deal because most androgens are made in gonads
How is primary adrenocortical failure treated?
Hydrocortisone and fludrocortisone
What is wrong in secondary adrenocortical failure?
Lack of ACTH- problem in adenohypophysis
What is the difference between a patient with primary and secondary adrenocortical failure?
Secondary have aldosterone because RAS works properly
How do you treat secondary adrenocortical failure?
Hydrocortisone (oral)- titrate dose throughout day to mimic normal physiology
What is there a lack of congenital adrenal hyperplasia?
Steroid synthetic enzymes
What are most cases of congenital adrenal hyperplasia due to?
Lack of 21-hydroxylase
How do you treat congenital adrenal hyperplasia?
Replace cortisol:
Dexamethasone 1/day or hydrocortisone 2-3/day
Suppress ACTH and thus adrenal androgen production
Replace aldosterone- fludrocortisone
Monitor optimise therapy by measuring 17alpha-hydroxyprogesterone
Do a clinical assessment of what they are complaining about:
Cushingoid- too much glucocorticoid
Hirsutism/acne- too little glucocorticoid (high ACTH)
What is the normal cortisol production?
20mg/day
When does iatrogenic adrenocortical failure occur?
Happens in patients on long term high dose corticosteroid treatment
Why does iatrogenic adrenocortical failure occur?
If they’re on glucocorticoids for a long term, they will stop producing cortisol as they don’t need to anymore
