Therapeutic Use Of Adrenal Steroids

Question 1

Describe the production of adrenal steroids and their locations

Answer 1

Hypothalamus > CRH > anterior pituitary > ACTH > adrenal gland > cortisol.

1. Zona fasiculata: cortisol
2. Zona reticularis: androgens (oestrogen)
3. Zona glomerulosa: aldosterone

Question 2

Describe the process of release of aldosterone and its triggers

Answer 2

Aldosterone stimulated by the renin-angiotensin system. Renin from the juxtaglomerular cells in the kidneys converts angiotensinogen to angiotensin-1 and then ACE then angiotensin-II which stimulates the release of aldosterone from adrenal cortex

Triggers of aldosterone release: hyperkalaemia, hyponatraemia, drop in renal blood flow, beta 1 adrenoreceptor stimulation

Question 3

What are the principle physiological actions of adrenal steroids

Answer 3

Cortisol, aldosterone (na retention, K loss)

Question 4

Summarise the role of glucocorticoid and mineralcorticoid receptors.

Answer 4

Glucocorticoid:

1. Wide distributions
2. Selective for glucocorticoid
3. Low affinity for cortisol

Mineralcorticoid

1. Discrete distribution (kidneys)
2. Do not distinguish between aldosterone and cortisol
3. High affinity for cortisol

Question 5

Discuss the drug-receptor selectivity of hydrocortisone, prednisolone, dexamethasone, fludocortisone

Answer 5

1. Hydrocortisone (like cortisol GR, MR activity - overwhelms 11bhsd)
2. Prednisolone (GR with little MR)
3. Dexamethasone (synthetic glucocorticoid no MR)
4. Fludocortisone (aldosterone analogues)

Question 6

Describe the corticosteroid replacement therapy

Answer 6

1. Primary adrenocortico failure: addisons: patients lack cortisol and aldosterone (treat with hydrocortisone and fludrocortisone)
2. Secondary adrenocortical failure: ACTH deficiency (low cortisol), treat with hydrocortisone
3. Acute adrenocortical failure: addisonian crisis
4. congenital adrenal hyperplasia (CAH)

Question 7

Explain CAH

Answer 7

Lecture