8. Therapeutic use of adrenal steroids Flashcards
where is aldosterone produced?
zona glomerulosa
where is cortisol produced?
zona fasciculata
where are androgens + oestrogens produced?
zona reticularis
other than cortisol what else is under the control of ACTH?
adrenal sex steroids
what controls aldosterone release?
stimulated by renin-angiotensin system
renin from kidneys converts angiotensinogen to angiotensin 1 and angiotensin converting enzyme (ACE) converts angiotensin 1 to angiotensin 2 which stimulates the release of aldosterone from the adrenal cortex
what are the triggers of aldosterone release?
- hyperkalaemia - because aldosterone increases urinary potassium excretion
- hyponatraemia
- decreased renal blood flow - juxtaglomerular apparatus detect a fall in renal blood flow and releases renin
- 𝛽1 adrenoreceptor stimulation
what are the principle physiological actions of adrenal steroids?
cortisol - essential for life
aldosterone - promotes sodium retention and potassium loss
androgens/oestrogens - main source are gonads
what family do receptors for corticosteroids fall into?
members of the nuclear receptor super-family including glucocorticoid receptors and mineralocorticoid receptors
describe glucocorticoid receptors
- wide distribution
- selective for glucocorticoids
- low affinity for cortisol
describe mineralocorticoid receptors
- discrete distribution (kidneys)
- don’t distinguish between aldosterone and cortisol
- high affinity for cortisol
describe the protection of mineralocorticoid receptors from cortisol by 11𝛽-hydroxysteroid dehydrogenase
mineralocorticoid receptors don’t distinguish between aldosterone and cortisol which can cause problems because cortisol can stimulate them
the enzyme 11𝛽-hydroxysteroid dehydrogenase deactivates cortisol into cortisone so the mineralocorticoids are not stimulated
what happens when there is excessive cortisol?
excessive cortisol will outcompete 11𝛽-hydroxysteroid dehydrogenase, bind to mineralocorticoids and cause hypokalaemia
what is hydrocortisone?
a glucocorticoid with mineralocorticoid activity at high doses
it has the same structure as cortisol but is the synthetic version
what is prednisolone?
a glucocorticoid with weak mineralocorticoid activity
immunosuppressive
what is dexamethasone?
potent synthetic glucocorticoid with no mineralocorticoid activity
used for brain metastases where there is a lot of oedema
what is fludrocortisone?
aldosterone analogue that can be used as an aldosterone substitute
what are the routes of administration of corticosteroids?
oral - hydrocortisone, prednisolone, dexamethasone, fludrocortisone
parenteral (intravenous or intramuscular) - hydrocortisone, dexamethasone
what is the distribution of corticosteroids like?
- bind to plasma proteins (cortisol binding globulin and albumin) like circulating cortisol
- fludrocortisone can only only bind to albumin
what is the duration of action of corticosteroids before hepatic breakdown?
hydrocortisone - approx. 8h
prednisolone - approx. 12h
dexamethasone - approx. 40h
what is primary adrenal failure (addison’s disease) treated with?
hydrocortisone and fludrocortisone by mouth for cortisol and aldosterone replacement
what is secondary adrenocortical failure?
patient lacks cortisol but aldosterone is normal (renin-angiotensin system is working normally)
what is secondary adrenocortical failure treated with?
oral hydrocortisone
- titrate dose and adjust throughout the day to mimic normal physiology
what is acute adrenocortical failure (addisonian crisis) treated with?
- rehydrate with normal saline
- give dextrose (5%) to prevent hypoglycaemia
- give high dose hydrocortisone (which will also effect mineralocorticoid receptor)
what is congenital adrenal hyperplasia (CAH) treated with and why?
a large dose of cortisol (dexamethasone 1/day or hydrocortisone 2-3/day high dose) to replace cortisol but also suppress ACTH production and hence reduce sex steroid production as less 17𝛼-hydroxyprogesterone is pushed onto the adrenal androgen pathway
fludrocortisone to replace aldosterone
how can therapy for CAH be optimised?
by monitoring:
- 17𝛼-hydroxyprogesterone levels
- what they are complaining about: cushingoid = dose too high, hirsutism/acne = dose too low
what additional measures can be done in subjects with adrenocortical failure?
increasing glucocorticoid dosage when patients are unwell (and vulnerable to stress):
- minor illness - 2x normal dose
- surgery - hydrocortisone intramuscular injection at 6-8hr intervals
what is iatrogenic adrenocortical failure?
- occurs in patients on long-term high dose corticosteroid treatment
- suppressed adrenal function because they don’t have to produce cortisol themselves
- patients need to increase their dose when they experience stresses to the body
what must patients with adrenocortical failure carry and wear?
carry a steroid alert card
wear a MedicAlert bracelet/necklace
