8. Therapeutic use of adrenal steroids

Question 1

where is aldosterone produced?

Answer 1

zona glomerulosa

Question 2

where is cortisol produced?

Answer 2

zona fasciculata

Question 3

where are androgens + oestrogens produced?

Answer 3

zona reticularis

Question 4

other than cortisol what else is under the control of ACTH?

Answer 4

adrenal sex steroids

Question 5

what controls aldosterone release?

Answer 5

stimulated by renin-angiotensin system

renin from kidneys converts angiotensinogen to angiotensin 1 and angiotensin converting enzyme (ACE) converts angiotensin 1 to angiotensin 2 which stimulates the release of aldosterone from the adrenal cortex

Question 6

what are the triggers of aldosterone release?

Answer 6

• hyperkalaemia - because aldosterone increases urinary potassium excretion
• hyponatraemia
• decreased renal blood flow - juxtaglomerular apparatus detect a fall in renal blood flow and releases renin
• 𝛽1 adrenoreceptor stimulation

Question 7

what are the principle physiological actions of adrenal steroids?

Answer 7

cortisol - essential for life

aldosterone - promotes sodium retention and potassium loss

androgens/oestrogens - main source are gonads

Question 8

what family do receptors for corticosteroids fall into?

Answer 8

members of the nuclear receptor super-family including glucocorticoid receptors and mineralocorticoid receptors

Question 9

describe glucocorticoid receptors

Answer 9

• wide distribution
• selective for glucocorticoids
• low affinity for cortisol

Question 10

describe mineralocorticoid receptors

Answer 10

• discrete distribution (kidneys)
• don’t distinguish between aldosterone and cortisol
• high affinity for cortisol

Question 11

describe the protection of mineralocorticoid receptors from cortisol by 11𝛽-hydroxysteroid dehydrogenase

Answer 11

mineralocorticoid receptors don’t distinguish between aldosterone and cortisol which can cause problems because cortisol can stimulate them

the enzyme 11𝛽-hydroxysteroid dehydrogenase deactivates cortisol into cortisone so the mineralocorticoids are not stimulated

Question 12

what happens when there is excessive cortisol?

Answer 12

excessive cortisol will outcompete 11𝛽-hydroxysteroid dehydrogenase, bind to mineralocorticoids and cause hypokalaemia

Question 13

what is hydrocortisone?

Answer 13

a glucocorticoid with mineralocorticoid activity at high doses

it has the same structure as cortisol but is the synthetic version

Question 14

what is prednisolone?

Answer 14

a glucocorticoid with weak mineralocorticoid activity

immunosuppressive

Question 15

what is dexamethasone?

Answer 15

potent synthetic glucocorticoid with no mineralocorticoid activity

used for brain metastases where there is a lot of oedema

Question 16

what is fludrocortisone?

Answer 16

aldosterone analogue that can be used as an aldosterone substitute

Question 17

what are the routes of administration of corticosteroids?

Answer 17

oral - hydrocortisone, prednisolone, dexamethasone, fludrocortisone

parenteral (intravenous or intramuscular) - hydrocortisone, dexamethasone

Question 18

what is the distribution of corticosteroids like?

Answer 18

• bind to plasma proteins (cortisol binding globulin and albumin) like circulating cortisol
• fludrocortisone can only only bind to albumin

Question 19

what is the duration of action of corticosteroids before hepatic breakdown?

Answer 19

hydrocortisone - approx. 8h

prednisolone - approx. 12h

dexamethasone - approx. 40h

Question 20

what is primary adrenal failure (addison’s disease) treated with?

Answer 20

hydrocortisone and fludrocortisone by mouth for cortisol and aldosterone replacement

Question 21

what is secondary adrenocortical failure?

Answer 21

patient lacks cortisol but aldosterone is normal (renin-angiotensin system is working normally)

Question 22

what is secondary adrenocortical failure treated with?

Answer 22

oral hydrocortisone

- titrate dose and adjust throughout the day to mimic normal physiology

Question 23

what is acute adrenocortical failure (addisonian crisis) treated with?

Answer 23

1. rehydrate with normal saline
2. give dextrose (5%) to prevent hypoglycaemia
3. give high dose hydrocortisone (which will also effect mineralocorticoid receptor)

Question 24

what is congenital adrenal hyperplasia (CAH) treated with and why?

Answer 24

a large dose of cortisol (dexamethasone 1/day or hydrocortisone 2-3/day high dose) to replace cortisol but also suppress ACTH production and hence reduce sex steroid production as less 17𝛼-hydroxyprogesterone is pushed onto the adrenal androgen pathway

fludrocortisone to replace aldosterone

Question 25

how can therapy for CAH be optimised?

Answer 25

by monitoring:

• 17𝛼-hydroxyprogesterone levels
• what they are complaining about: cushingoid = dose too high, hirsutism/acne = dose too low

Question 26

what additional measures can be done in subjects with adrenocortical failure?

Answer 26

increasing glucocorticoid dosage when patients are unwell (and vulnerable to stress):

• minor illness - 2x normal dose
• surgery - hydrocortisone intramuscular injection at 6-8hr intervals

Question 27

what is iatrogenic adrenocortical failure?

Answer 27

• occurs in patients on long-term high dose corticosteroid treatment
• suppressed adrenal function because they don’t have to produce cortisol themselves
• patients need to increase their dose when they experience stresses to the body

Question 28

what must patients with adrenocortical failure carry and wear?

Answer 28

carry a steroid alert card

wear a MedicAlert bracelet/necklace