Therapeutic use of adrenal steroids

Question 1

What are the layers of the cortex and what do they release?

Answer 1

Zona glomerularis = aldosterone
Zona fasticulata = cortisol
Zona reticularis = androgens + oestrogens#

The adrenal sex steroids are under the control of ACTH. This is important when considering congenital adrenal hyperplasia

Question 2

What controls aldosterone release?

Answer 2

Renin-angiotensin system:
Renin released from the juxtoglomerular cells in the kidney. Renin converts angiotensinogen to angiotensin 1. ACE converts A1 to to A2 which stimulates the release of aldosterone from the adrenal cortex.

Question 3

What triggers aldosterone release?

Answer 3

Hyperkalaemia
Hyponatraemia
Drop in renal blood flow
Beta-1 adrenoceptor stimulation

See notes - think about causes

Question 4

What are the principle actions of adrenal steroids?

Answer 4

Cortisol - essential for life
Aldosterone - important in salt balance. Na+ retention and K+ excretion
Androfens/oestrogens - unclear role since gonads are a bigger source of sex steroids

Question 5

What are the types of receptors for corticosteroids?

Answer 5

They are members of the nuclear receptor super family:
Glucocorticoid receptors (GR)
Mineralocorticoid receptors (MR)

See slides - for differences

Question 6

How are the MRs protected?

Answer 6

Cortisol can stimulate the MRs so to protect them 11b-hydroxysteroid dehydrogenase converts cortisol to cortisone.
Cortisone is inactive so it can’t stimulate the MR.

See notes - Cushing’s syndrome and hypkalaemia

Question 7

Drugs - receptor selectivity

Answer 7

Cortisol (hydrocortisone) -glucocorticoid with mineralocorticoid activity at high doses
Prednisolone - glucocorticoid with weak mineralocorticoid activity
Dexamethasone - glucocorticoid with no mineralocorticoid effect
These are all glucocorticoid substitutes.

Fludrocortisone - Aldosterone analogue

See notes - small differences in structure changes binding

Question 8

Describe the admission of corticosteroids

Answer 8

Orally - hydrocortisone, prednisolone, dexamethasone, fludrocortisone
In acute situations
parentral administration- IV or IM. hydrocortisone and dexamethosone. Dexamethosone isn’t really used in this situation

There are mineralocorticoid effects at high doses of hyrdocortisone (think about 11bhsd)

Question 9

Describe the distribution of corticosteroids

Answer 9

See notes - CBG

Question 10

List the corticosteroid drugs in order of shortest duration of action to longest

Answer 10

Hydrocortisone (8h) + Fludrocortisone -> Prednisolone (12h) -> Dexamethasome (40h)

Question 11

What are the reasons for giving corticosteroid replacement therapy?

Answer 11

Primary adrenocortical failure (Addison’s disease)
Secondary adrenocortical failure (ACTH deficiency)
Acute adrenocortical failure (Addisonian crisis)
Congenital adrenal hyperplasia

Question 12

Describe Addison’s disease and the treatment

Answer 12

See notes - Patients need cortisol and aldosterone.
Hydrocortisone and fludrocortisone is taken orally to treat primary adrenocortical failure.
You don’t need to worry about replacing the androgens since most of them are produced in the gonads anyway

Question 13

Describe secondary adrenal failure and treatment

Answer 13

See notes - problem with anterior pituitary = ACTH deficient. The adrenals work fine. There is normal aldosterone because its release is based off the renin-angiotensin system. However you need to replace the cortisol.
Treatment: hydrocortisone (orally)

Question 14

Describe acute adrenalcortical failure and treatment

Answer 14

1) IV saline (0.9% sodium chloride) to restore circulating volume and BP. Re-hydrates the patient.
2) High dose of hydrocortisone (deals with low cortisol) - fludrocortisone is not required because the dose of hydrocortisone is high enough that it has mineralocorticoid effects.
3) 5% dextrose if they are hypoglycaemic

Question 15

Describe congenital adrenal hyperplasia (CAH)

Answer 15

See notes - This is a congenitial problem where there is a lack of enzymes needed for adrenal steroid synthesis.
95% of cases is 21-hydroxylase
High levels of ACTH which keeps rising because no cortisol is being produced so no negative feed back.
There is a build up of precursor (17a-hydroxyprogesterone) which is pushed towards the production of adrenal androgens - this is driven further by the high levels of ACTH.

Treatment - big dose of cortisol to suppress the ACTH as well stopping the production of sex hormones. Dexamethasone 1/ day or Hydrocortisone 2/3 days. Fludrosterone is used to treat the low aldosterone.

Measure/optimise therapy by: Measuring the 17a-hydroxyprogesterone levels. Clinical assessment:
Cushingoid - GC dose is too high
Hirsutism - GC dose is too low (and hence ACTH has risen)

Question 16

What is the normal cortisol production daily?

Answer 16

20mg/day

Question 17

What is the cortisol production when stressed?

Answer 17

200-300mg/day
You must tell patients who to increase their GC dosage when they are vulnerable to stress (mimic what the body would do)
In minor illness you double the dose. Surgery - hydrocortisone i.m with pre-med and at 6-8 hour intervals, oral once eating and drinking