Therapeutic uses of adrenal steroids Flashcards
What do the different parts of the adrenal glands make?
Zona fasciculata – cortisol
Zona glomerulosa – aldosterone
Zona reticularis – sex steroids
What does angiotensin 2 do?
stimulates aldosterone production and vasoconstriction
What are the actions of aldosterone?
Promotes Na+ retention and K+ excretion – i.e. water retention
Describe the distribution, selectivity and affinity of glucocorticoid receptors
- wide distribution
- selective for GC
- low affinity for cortisol
Describe the distribution, selectivity and affinity of mineralocorticoids
- discrete distribution (kidneys)
- non selective between aldosterone and cortisol
- high affinity for cortisol
How does Cushing’s syndrome cause hypertension?
- Normally an enzyme called 11 beta hydroxysteroid dehydrogenase 2 (HSD2) inactivates cortisol by forming cortisone
- In Cushing’s, you are producing too much cortisol and so 11 beta HSD2 is overwhelmed and cortisol binds too much to the MR causing hypertensive episodes
What are some drugs used to mimic human hormones?
- Hydrocortisone
- Prednisolone
- Dexamethasone
- Fludrocortisone
What is hydrocortisone and describe its activity?
Glucocorticoid with mineralocorticoid activity at high doses
What is prednisolone and describe its activity?
Glucocorticoid with weak mineralocorticoid activity
What is dexamethasone and describe its activity?
Synthetic glucocorticoid with no mineralocorticoid activity
What is fludrocortisone and describe its activity?
Aldosterone analogue (used as a subsititute for deficiencies)
What are the routes of admission for corticosteroids?
Oral – hydrocortisone, prednisolone, dexamethasone, fludrocortisone
Parenteral (IV or IM) – hydrocortisone, dexamethasone e.g. in an Addisonian crisis
How are corticosteroids distributed in the blood?
Often bind to plasma binding proteins (e.g. CBG and albumin) as cortisol does in the blood
What is the duration of activity of hydrocortisone, prednisolone and dexamethasone?
Hydrocortisone - ~8 hours
Prednisolone – ~12 hours
Dexamethasone - ~40 hours
What is primary adrenocortical failure?
Addison’s disease
How is primary adrenocortical failure treated?
- Patients lack cortisol and aldosterone
- Treated with hydrocortisone (for cortisol) and fludrocortisone (for aldosterone) orally
What is secondary adrenocortical failure?
ACTH Deficiency
How is secondary adrenocortical failure treated?
- Patients lack cortisol but aldosterone is normal
- Treat with hydrocortisone
What is CRT?
corticosteroid replacement therapy
What is congenital adrenal hyperplasia?
Larger and missing an enzyme to make cortisol e.g. 21 hydroxylase deficiency
What % of CAH are due to 21 hydroxylase deficiency?
95%
What happens in 21 hydroxylase deficiency to 17a hydroxyprogesterone and also what does ACTH drive?
- In 21-hydroxylase deficiency, 17a-hydroxyprogesterone accumulates as this is immediately before the enzyme block
- There is no cortisol production so ACTH rises and high ACTH drives further androgen production
What is the therapy for 21 hydroxylase deficiency?
Replace cortisol – dexamethasone/hydrocortisone
Supress ACTH (and thus adrenal androgen production)
Replace aldosterone – fludrocortisone
How is 21 hydroxylase deficiency treatment monitored?
Clinical assessments:
GC dose too high – cushingoids (symptoms caused by cushing’s)
GC dose too low – hirsutism (as androgens still in excess)
