8. Therapeutic Use of Adrenal Steroids

Question 1

Hormone produced in the zona glomerulosa

Answer 1

Aldosterone

Question 2

Hormone produced in the zona fasciculata

Answer 2

Cortisol

Question 3

Hormone produced in the zona reticularis

Answer 3

Androgens + Oestrogens

Also under the control of ACTH

Question 4

Triggers of Aldosterone release

Answer 4

• Hyperkalaemia- because aldosterone increases urinary potassium excretion
• Hyponatraemia
• Drop in Renal Blood Flow- Juxtaglomerular apparatus detects a drop in renal blood flow and renin release
• Beta-1 adrenoceptor stimulation

Question 5

Principle physiological actions of cortisol

Answer 5

Essential for life (stimulates gluconeogensis + anti inflammatory pathways)

Question 6

Actions of adrenal androgens/oestrogens

Answer 6

UNCLEAR role, since gonads are a much bigger source

Question 7

Corticosteroid receptor types

Answer 7

1. Glucocorticoid receptors- wide distribution, selective for glucocorticoids, low affinity for cortisol
2. Mineralocorticoid receptors- discrete distribution, no distinction between aldosterone and cortisol, high affinity for cortisol

MR lack of distinction between the two could lead to problems

Question 8

Protection of Mineralocorticoid receptors from cortisol

Answer 8

Achieved by 11b-hydroxysteroid dehydrogenase 2 (11þHSD)

deactivates cortisol by converting it to cortisone

Question 9

Why can cushing’s syndrome cause HYPOKLAEMIA

Answer 9

The system gets overwhelmed- cortisol binds to MR receptors

Question 10

Receptor selectivity of cortisol

Answer 10

Cortisol and hydrocortisone have the same structure (cortisol endogenous, hydrocortisone synthetic)

• Can cause MR activation at high doses

Question 11

Receptor sensitivity of prednisolone

Answer 11

This tends to be an immunosuppressive type of glucocorticoid

It is a glucocorticoid with weak mineralocorticoid activity

Question 12

Receptor sensitivity of dexamethasone

Answer 12

Very POTENT glucocorticoid- very good anti-oedema agent

NO mineralocorticoid effect

Question 13

Receptor sensitivity of fludrocortisone

Answer 13

ALDOSTERONE analogue/ substitute

Question 14

Pharmacoinetics and distribution of corticosteroids

Answer 14

• All drugs can be given orally
• Some acute situations where you need IV or IM
• Hydrocortisone is about 90-95% bound- unbound hormone is biologically inactive
• Only bound to albumin

Question 15

Metabolism and excretion of corticosteroids

Answer 15

Breakdown is hepatic it gets excreted via bile and urine

Question 16

Half lives common corticosteroids

Answer 16

Shortest to longest:

1. Hydrocortisone and Fludrocortisone
2. Prednisolone
3. Dexamethasone

Question 17

Reasons for giving corticosteroid replacement (and drugs of therapy)

Answer 17

• Primary Adrenocortical Failure (Addison’s- hydrocortisone, fludrocortisone)
• Secondary Adrenocortical Failure (ACTH deficiency so normal aldosterone- titrated dose (circadian) of hydrocortisone)
• Acute Adrenocortical Failure (addisonian crisis- IV SALINE, high dose hydrocortisone, so high you dont need fluro)
• Congenital Adrenal Hyperplasia (congenital lack of enzymes- most common cause abscence 21-hydroxylase- Dexamethasone 1/day OR Hydrocortisone 2-3/day)
• Iatrogenic Adrenocortical Failure (long term, high dose CORTICOSTEROID treatment- suppressd adrenal function since reliant on treatment)

Question 19

Causes and symptoms of congenital adrenal hyperplasia

Answer 19

• Congenital lack of steroid synthetic enzymes

Cause:

• Most commonly due to absence of 21-hydroxylase
• No negative feedback so increased ACTH
• 17a-hydroxyprogesterone is overproduced so pathway is pushed towards androgen production

Symptoms:

• Boys- precocious puberty
• Girls- virilisiation
• Women- hirtuism, acne

Question 20

Normal cortisol production

Answer 20

20 mg/day

Question 21

Stressed production of cortisol

Answer 21

200-300 mg/day

Question 22

Changing replacement treatment in times of stress

Answer 22

Minor illnesses= 2x normal hydrocortisone dose

Surgery= 6-8x normal dose with pre-med