Therapeutic use of adrenal steroids. Flashcards
What is the primary stimulator of cortisol and androgen/oestrogen release from the adrenals?
ACTH
What stimulates aldosterone release from the adrenals?
Angtiotensin II.
What parts of the adrenals are cortisol, sex steroids and aldosterone released from?
Cortisol - zona fasciculata.
Sex steroids - zona reticularis.
Aldosterone - zona glomerulosa
Draw a diagram to show feedback loop for cortisol, stimulation of cortisol secretion and stimulation of aldosterone secretion
What enzyme family is responsible for steroid hormone synthesis?
Cytochrome p450c family.
What are the primary actions of cortisol and aldosterone?
Aldosterone - salt balance - promote Na+ retention, K+ loss, water retention, indirect effect on BP.
Cortisol - memory, blood glucose control, inflammation mediator, metabolism regulator.
What are the two types of corticosteroid receptors, what binds to them?
Glucocorticoid Receptors (GR) - cortisol
Mineralocorticoid receptors (MR) - aldosterone.
Compare the distribution of GRs and MRs.
GR - wide distribution, MR - in kidneys.
Compare the selectivity of GRs and MRs.
GRs - selective for glucocorticoids, MRs - do not distinguish between aldosterone and cortisol.
Compare the affinity of MRs and GRs for cortisol.
MRs - high affinity, GRs - low affinity.
Considering cortisols high affinity for MRs, why doesn’t it have the same effects as aldosterone?
Enzyme 11 beta-hydroxysteroid dehydrogenase 2 (11 beta HSD).
Catalyses cortisol –> inactive cortisone.
11 beta HSD found in kidneys - protects MR receptor from cortisol at site of aldosterone action
Why is hypokalaemia a symptom of Cushing’s?
Cushing’s = high cortisol.
Excess cortisol leaves 11 beta HSD unable to inactivate all of it, so some persists and binds to MR receptor with aldosterone like effects.
What is hydrocortisone used for?
Glucocorticoid - cortisol receptor. High doses give aldosterone like effects.
What is prednisolone used for?
Glucocorticoid - cortisol replacement.
Asthma, rheumatoid arthritis and other inflammatory diseases.
What is dexamethasone used for?
Glucocorticoid - cortisol replacement.
How do hydrocortisone, prednisolone and dexmethasone differ?
Hydrocortisone - mineralocorticoid activity at high doses.
Prednisolone - weak mineralocorticoid activity.
Dexamethasone - no mineralocorticoid activity.
What is fludrocortisone used for?
Aldosterone replacement.
How might corticosteroids be administered?
Oral - hydrocortisone, prednisolone, dexamathasone, fludrocortisone.
Parenteral (iv or im) - hydrocortisone, dexamethasone.
Compare the durations of hydrocortisone, prednisolone and dexamathasone in the blood.
–Hydrocortisone – duration ~ 8h
–Prednisolone – duration ~ 12h
–Dexamethasone – duration ~ 40h
How are corticosteroid drugs distributed through the body?
In the blood bound to plasma proteins - cortisol binding globuline and albumin.
Why might corticosteroid replacement therapy be used to treat a patient with Addison’s disease and how?
Addison’s disease - loss of functional adrenal gland –> cortisol, aldosterone deficiency.
Oral hydrocortisone and fludrocortisone.
Why is a large dose of iv hydrocortisone given in acute conditions?
It overwhelms 11 beta HSD allowing MR binding and aldosterone like effects, helping Na reabsorption.
How can corticosteroid replacement therapy be used to treat secondary adrenocortical failure (ACTH deficiency)?
Administration of oral hydrocortisone (aldosterone is normal).
RAAS system functional.
How is an Addisonian crisis treated?
iv 0.9% sodium chloride to rehydrate patient
High dose hydrocortisone
–i.v. infusion or i.m. every 6h, mineralocorticoid effect at high dose (11bHSD overwhelmed)
l5% dextrose if hypoglycaemic
Define congenital adrenal hyperplasia (CAH).
congenital lack of enzymes
needed for adrenal steroid synthesis
what enzyme converts testosterone to oestrogen/17 beta oestrodial?
aromatase.
In CAH, which enzyme is most commonly lacking?
21 hydroxylase - 95% of cases.
How might CAH with 21 hydroxylase deficiency be diagnosed?
17 alpha-hydroxyprogesterone build up which can be measured.
Why can hirsutism and virilisation result from 21 hydroxylase deficiency?
cortisol not being produced, so ACTH rises which stimulates adrenal androgen production.
What are the objectives of corticosteroid replacement therapy in patients with CAH?
Replace cortisol,
suppress ACTH in order to suppress adrenal androgen secretion.
Replace aldosterone.
How is CAH treated?
Dexamethasone 1/day in the evening (when cortisol should be low)
Or hydrocortisone 2-3/day, evening.
Aim to suppress androgen production.
Also fludrocortisone to replace aldosterone.
How can effectiveness of CAH therapy be monitored and optimised?
Regularly measure 17 OH progesterone - adjust dose of glucocorticoid accordingly if not within desired range/patient isn’ happy.
What difficulties can arise when administering large doses of glucocorticoid to suppress ACTH?
Androgen production decreases but excess cortisol can cause Cushing’s.
Why else can glucocorticoid management be difficult in corticosteroid replacement therapy? How is this handled?
cortisol = stress hormones -
normally approx. 20mg/day
in stress approx. 200-300mg/day (e.g. illness).
Patient only receiving fixed dose of cortisol, so no additional response to stress.
In minor illness - give 2x normal dose.
What is given to Addison’s patients during surgery?
I.m hydrocortisone before and at 6-8 hours intervals until recovery.
What should patients with Addison’s wear and carry at all times?
Steroid alert card, MedicAlert bracelet.
