Therapeutic use of adrenal steroids Flashcards
What is produced by the zona glomerulosa?
Aldosterone
What is produced by the zona fasciculata?
Cortisol
What is produced by the zona reticularis?
Androgens and oestrogens
What is aldosterone release stimulated by?
The renin-angiotensin system.
Renin from the juxtaglomerular cells in the kidneys converts angiotensinogen to angiotensin I, which is converted to angiotensin II by ACE. Angiotensin II stimulates the release of aldosterone from the adrenal cortex.
Where are androgens and oestrogens mostly produced?
Gonads
What does aldosterone promote?
Sodium retention
Potassium loss via the kidneys
What can trigger aldosterone release?
Hyperkalaemia- because aldosterone increases urinary potassium excretion
Hyponatraemia
Drop in renal blood flow- juxtaglomerular apparatus detects drop in renal blood flow and releases renin
Beta-1 adrenoceptor stimulation
Compare features of glucocorticoid and mineralocorticoid receptors.
GRs have wide distribution, whereas MRs have discrete distribution (kidneys).
GRs are selective for glucocorticoids, whereas MRs do not distinguish between aldosterone and cortisol.
GRs have a low affinity for cortisol, whereas MRs have a high affinity for cortisol.
How are mineralocorticoid receptors protected from cortisol?
11 beta hydroxysteroid dehydrogenase 2 enzyme (11 beta HSD-2) converts cortisol to inactive cortisone.
Why does hypokalaemia occur in Cushing’s syndrome?
High levels of cortisol overwhelm the system- 11 beta HSD-2 can’t inactivate it all so some of the cortisol binds to mineralocorticoid receptors and causes hypokalaemia.
What is the selectivity of hydrocortisone?
Glucocorticoid with mineralocorticoid activity at high doses.
What is the selectivity of prednisone?
Glucocorticoid with weak mineralocorticoid activity.
Tends to be immunosuppressive.
What is the selectivity of dexamethasone?
Synthetic glucocorticoid with no mineralocorticoid activity- acute anti-oedemic agent, e.g. used for brain metastases.
What is the selectivity of fludrocortisone?
Aldosterone analogue- for primary adrenal failure.
How are corticosteroids administered?
All may be administered orally.
Hydrocortisone and dexamethasone may be administered parenterally (i.v. or i.m.).
What may corticosteroid replacement therapy be used for?
Primary adrenocortical failure (Addison’s disease)
Secondary adrenocortical failure (ACTH deficiency)
Acute adrenocortical failure (Addisonian crisis)
Congenital adrenal hyperplasia
Iatrogenic adrenocortical failure
How is primary adrenocortical failure (Addison’s disease) treated?
Patients lack cortisol and aldosterone, treat with oral hydrocortisone and fludrocortisone.
How is secondary adrenocortical failure (ACTH deficiency) treated?
Patients lack cortisol but aldosterone is normal, treat with hydrocortisone (no fludrocortisone).
How is acute adrenocortical failure (Addisonian crisis) treated?
i.v. 0.9% sodium chloride to rehydrate patient, then high dose hydrocortisone (i.v. or 6-hourly i.m.) and 5% dextrose if hypoglycaemic.
How are corticosteroids metabolised and excreted?
Breakdown is hepatic.
Excreted via bile and urine.
What is the order of shortest to longest half-life /duration of corticosteroids?
Hydrocortisone and fludrocortisone
Prednisolone
Dexamethasone
What is the treatment of congenital adrenal hyperplasia?
Replace cortisol- dexamethasone 1/day or hydrocortisone 2-3/day.
Suppress ACTH and thus adrenal androgen production.
Replace aldosterone in salt-wasting forms- fludrocortisone.
Monitor/optimise therapy by measuring 17 alpha hydroxyprogesterone levels.
If Cushingoid, glucocorticoid dose is too high.
If hirsutism/acne, glucocorticoid dose is too low.
What is the normal rate of production of cortisol?
20mg/day
What is the rate of production of cortisol under stress?
200-300mg/day
In patients with adrenocortical failure, what should be done when they are vulnerable to stress?
Dosage is increased.
2x normal dose if minor illness.
Surgery- hydrocortisone, i.m., with pre-medication and at 6-8hr intervals, oral once eating and drinking.
What precaution should patients with adrenocortical failure take?
Carry a steroid alert card and wear a MedicAlert bracelet/necklace in case of emergency (unwell and can’t communicate).
