Therapeutic use of adrenal steroids

Question 1

What is produced by the zona glomerulosa?

Answer 1

Aldosterone

Question 2

What is produced by the zona fasciculata?

Answer 2

Cortisol

Question 3

What is produced by the zona reticularis?

Answer 3

Androgens and oestrogens

Question 4

What is aldosterone release stimulated by?

Answer 4

The renin-angiotensin system.
Renin from the juxtaglomerular cells in the kidneys converts angiotensinogen to angiotensin I, which is converted to angiotensin II by ACE. Angiotensin II stimulates the release of aldosterone from the adrenal cortex.

Question 5

Where are androgens and oestrogens mostly produced?

Answer 5

Gonads

Question 6

What does aldosterone promote?

Answer 6

Sodium retention

Potassium loss via the kidneys

Question 7

What can trigger aldosterone release?

Answer 7

Hyperkalaemia- because aldosterone increases urinary potassium excretion
Hyponatraemia
Drop in renal blood flow- juxtaglomerular apparatus detects drop in renal blood flow and releases renin
Beta-1 adrenoceptor stimulation

Question 8

Compare features of glucocorticoid and mineralocorticoid receptors.

Answer 8

GRs have wide distribution, whereas MRs have discrete distribution (kidneys).
GRs are selective for glucocorticoids, whereas MRs do not distinguish between aldosterone and cortisol.
GRs have a low affinity for cortisol, whereas MRs have a high affinity for cortisol.

Question 9

How are mineralocorticoid receptors protected from cortisol?

Answer 9

11 beta hydroxysteroid dehydrogenase 2 enzyme (11 beta HSD-2) converts cortisol to inactive cortisone.

Question 10

Why does hypokalaemia occur in Cushing’s syndrome?

Answer 10

High levels of cortisol overwhelm the system- 11 beta HSD-2 can’t inactivate it all so some of the cortisol binds to mineralocorticoid receptors and causes hypokalaemia.

Question 11

What is the selectivity of hydrocortisone?

Answer 11

Glucocorticoid with mineralocorticoid activity at high doses.

Question 12

What is the selectivity of prednisone?

Answer 12

Glucocorticoid with weak mineralocorticoid activity.

Tends to be immunosuppressive.

Question 13

What is the selectivity of dexamethasone?

Answer 13

Synthetic glucocorticoid with no mineralocorticoid activity- acute anti-oedemic agent, e.g. used for brain metastases.

Question 14

What is the selectivity of fludrocortisone?

Answer 14

Aldosterone analogue- for primary adrenal failure.

Question 15

How are corticosteroids administered?

Answer 15

All may be administered orally.

Hydrocortisone and dexamethasone may be administered parenterally (i.v. or i.m.).

Question 16

What may corticosteroid replacement therapy be used for?

Answer 16

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

Question 17

How is primary adrenocortical failure (Addison’s disease) treated?

Answer 17

Patients lack cortisol and aldosterone, treat with oral hydrocortisone and fludrocortisone.

Question 18

How is secondary adrenocortical failure (ACTH deficiency) treated?

Answer 18

Patients lack cortisol but aldosterone is normal, treat with hydrocortisone (no fludrocortisone).

Question 19

How is acute adrenocortical failure (Addisonian crisis) treated?

Answer 19

i.v. 0.9% sodium chloride to rehydrate patient, then high dose hydrocortisone (i.v. or 6-hourly i.m.) and 5% dextrose if hypoglycaemic.

Question 20

How are corticosteroids metabolised and excreted?

Answer 20

Breakdown is hepatic.

Excreted via bile and urine.

Question 21

What is the order of shortest to longest half-life /duration of corticosteroids?

Answer 21

Hydrocortisone and fludrocortisone
Prednisolone
Dexamethasone

Question 22

What is the treatment of congenital adrenal hyperplasia?

Answer 22

Replace cortisol- dexamethasone 1/day or hydrocortisone 2-3/day.
Suppress ACTH and thus adrenal androgen production.
Replace aldosterone in salt-wasting forms- fludrocortisone.
Monitor/optimise therapy by measuring 17 alpha hydroxyprogesterone levels.
If Cushingoid, glucocorticoid dose is too high.
If hirsutism/acne, glucocorticoid dose is too low.

Question 23

What is the normal rate of production of cortisol?

Answer 23

20mg/day

Question 24

What is the rate of production of cortisol under stress?

Answer 24

200-300mg/day

Question 25

In patients with adrenocortical failure, what should be done when they are vulnerable to stress?

Answer 25

Dosage is increased.
2x normal dose if minor illness.
Surgery- hydrocortisone, i.m., with pre-medication and at 6-8hr intervals, oral once eating and drinking.

Question 26

What precaution should patients with adrenocortical failure take?

Answer 26

Carry a steroid alert card and wear a MedicAlert bracelet/necklace in case of emergency (unwell and can’t communicate).