Therapeutic use of adrenal steroids

Question 1

draw out the HPA axis

Answer 1

see slide

Question 2

what contributes too the release of cortisol?

Answer 2

circadian rhythm

Question 3

what do each of the following sections produce?
Zona fasciculata –
Zona glomerulosa –
Zona reticularis –

Answer 3

o Zona glomerulosa – aldosterone.
Zona fasciculata – cortisol.
o Zona reticularis – sex steroids.

Question 4

what contributes to the release of aldosterone from the adrenal gland?

Answer 4

RAS

Question 5

what do the following hormones do?
§ Cortisol –
§ Aldosterone –
§ Androgens/oestrogens –

Answer 5

§ Cortisol – essential for life.
§ Aldosterone – promotes Na+ retention and K+ excretion – i.e. water retention.
§ Androgens/oestrogens – main source is the gonads

Question 6

what are the differences between glucocorticoid receptors and mineralocorticoid receptors?

Answer 6

glucocorticoid receptors:

• widely distributed
• selective for glucocorticoids
• low affinity for cortisol

mineralocorticoid receptors:

• discrete distribution (kidneys)
• non selective between aldosterone and cortisol
• high affinity for cortisol

Question 7

why doesn’t all the cortisol bind to the MR receptors normally?

Answer 7

11 beta-hydroxysteroid dehydrogenase 2 turns cortisol into an inactive form- cortisone

Question 8

what happens in cushing’s with reference to cortisol?

Answer 8

So in Cushing’s, you are producing too much cortisol and so 11bHSD2 is overwhelmed and cortisol binds too much to the MR causing hypertensive episodes.

Question 9

which hormones do we use to following drugs for?

• hydrocortisone
• prednisolone
• dexamethasone
• fludrocortisone

Answer 9

Hydrocortisone – glucocorticoid with mineralocorticoid activity at HIGH DOSES.
§ Prednisolone – glucocorticoid with WEAK mineralocorticoid activity.
§ Dexamethasone – glucocorticoid (synthetic) with NO mineralocorticoid activity.
§ Fludrocortisone – Aldosterone analogue.
o Used as an aldosterone substitute.
§ I.E. 21/11-hydroxylase deficiencies.

Question 10

routes of administration:

oral?
parenteral (IV or IM)

Answer 10

§ Oral – hydrocortisone, prednisolone, dexamethasone, fludrocortisone.
§ Parenteral (IV or IM) – hydrocortisone, dexamethasone. I.E. in an Addisonian crisis

Question 11

what is the duration of action for

• hydrocortisone
• prednisolone
• dexamethasone

Answer 11

§ Hydrocortisone - ~8 hours. (Hence why hydrocortisone is re-administered several times a day in Addison’s patients.)
§ Prednisolone – ~12 hours.
§ Dexamethasone - ~40 hours.

Question 12

• what is primary adrenocortical failure
• what hormones are they lacking?
• how is it treated?

Answer 12

CRT: Primary Adrenocortical Failure – i.e. Addison’s Disease/Syndrome
§ Patients lack cortisol and aldosterone (sex steroids can be produced from the gonads)
§ Treated with hydrocortisone (for cortisol) and fludrocortisone (for aldosterone) orally

Question 13

• what is secondary adrenocortical failure
• what hormones are they lacking?
• how is it treated?

Answer 13

CRT: Secondary Adrenocortical Failure – i.e. ACTH Deficiency as the pituitary cannot stimulate the release of hormones from the adrenal gland
§ Patients lack cortisol but aldosterone is normal since it can be stimulated by the RAS
§ Treat with hydrocortisone.

Question 14

what is acute adrenocortical failure?

Answer 14

Addisonian crisis

Question 15

what is the protocol for treating someone with Addisonian crisis?

Answer 15

1. IV saline (0.9% NaCl) – rehydrate.
2. High dose hydrocortisone – IV or IM every 6h. The high dose ensures there is a mineralocorticoid effect as the 11bHSD2 is overwhelmed.
3. 5% dextrose – if hypoglycaemic.

Question 16

• what is congenital adrenal hyperplasia?
• what hormones are they lacking?
• how is it treated?

Answer 16

CRT: Congenital Adrenal Hyperplasia – i.e Approx. 95% of cases are due to a lack of enzyme 21-hydroxylase.

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.

§ Therapy includes:
o Replace cortisol – dexamethasone/hydrocortisone.
o Supress ACTH (and thus adrenal androgen production).
o Replace aldosterone – by administering fludrocortisone.

Question 17

what do you have to monitor during therapy for congenital adrenal hyperplasia?

Answer 17

Monitor/optimise therapy by measuring:

17-hydroxyprogesterone levels.

Question 18

what happens if the GC dose is too high or too low in congenital adrenal hyperplasia?

Answer 18

Clinical assessments:
§ GC dose too high – cushingoids.
§ GC dose too low – hirsutism (as androgens still in excess)

Question 19

when should cortisol dosage be increased in patients?

Answer 19

Cortisol levels go up and down depending also upon stress levels so the glucocorticoid dosage should be increased when patients are vulnerable to stress (e.g. surgery).
o Normal cortisol production ~20mg/day.
o Stress cortisol production ~200/300mg/day.

Question 20

how much should the cortisol dosages be changed to in minor illness and surgery?

Answer 20

When to increase glucocorticoid dosage:
o Minor illness – 2x normal dose.
o Surgery – IM hydrocortisone at 6-8 hour intervals.