Therapeutic Use of Adrenal Steroids

Question 1

What stimulus have an impact on cortisol production?

Answer 1

Stress & Circadian stimuli

Question 2

What controls aldosterone release and what are the triggers for it?

Answer 2

AGTII

x Hyperkalaemia
x Hyponatraemia
x LOW RBF (renal)
x Beta-1 adrenoceptio stimulation

Question 3

Principal physiological actions of aldosterone?

Answer 3

Promotes:
Na+ RETENTION

K+ LOSS

Question 4

Main receptors for corticosteroids?

Answer 4

GR

MR

Question 5

Properties of GR?

Answer 5

Glucocorticoid Receptors

x Wide distribution
x SELECTIVE for glucocorticoids
x LOW AFFINITY for cortisol

Question 6

Properties of MR?

Answer 6

Mineralcorticoid Receptors

x Discrete distribution (kidney)
x Does NOT distinguish betw. aldosterone & cortisol
x HIGH AFFINITY for cortisol

Question 7

What is an issue with MR having a high affinity for cortisol?

Answer 7

Cortisol can bind to the MR and behave like aldosterone!

Question 8

What prevents cortisol binding to both GR & MR?

Answer 8

11beta-hydroxsteroid dehydrogenase 2!

Converts cortisol to the inactive CORTISONE

Question 9

What issues arises with Cushings’ in terms of GR and MR?

Answer 9

Patients suffer from HYPOKALAEMIA

This is as:
In excess cortisol, the enzyme 11betaHSD2 become overwhelmed so cortisol goes on to bind to MR, acting like aldosterone

Question 10

4 drugs that can be used in regards to the GR and MR and why?

Answer 10

Hydrocortisone

Prednisolone

Dexamethasone

Fludrocortisone

RECEPTOR SELECTIVITY

Question 11

Hydrocortisone?

Answer 11

Glucocorticoid

w. mineralcorticoid activity at high doses

Question 12

Prednisolone?

Answer 12

Glucocorticoid

w. WEAK mineralcorticoid acitivty

Question 13

Dexamethasone?

Answer 13

Synthetic glucocorticoid

w. NO mineralcorticoid activity

Question 14

Fludrocortisone?

Answer 14

Aldosterone analogue

used as an aldosterone substitute i.e. 21/11-hydroxylase deficiencies

Question 15

Routes of administration of the corticosteroid drugs?

Answer 15

Oral - ALL 4

Parenteral (i.v or i.m) - hydrocortisone & dexamethasone*

*i.e. in an Addisonian crisis

Question 16

Distribution of the corticosteroid drugs in the body?

Answer 16

Binds to plasma proteins (CBG) as cortisol does in the blood

Question 17

Duration of action of the corticosteroid drugs in the body?

Answer 17

x Hydrocortisone - 8hrs
(hence why is re-administered several times a day in Addison’s patients)

x Prednisolone - 12hrs

x Dexamethasone - 40hrs

Question 18

1o vs. 2o adrenocortical failure?

Answer 18

1o - Addison’s Disease/Syndrome

2o - ACTH deficieny

Question 19

CRT in 1o adrenocortical failure?

Answer 19

Patient lack cortisol & aldosterone

SO

Treat w. hydrocortisone & fludrocortisone ORALLY

Question 20

If admitted to hospital for 1o adrenocortical failure, do you always need to give BOTH drugs?

Answer 20

NO

If given LARGE doses of hydrocortisone, do NOT need to give fludrocortisone as the excess cortisol can also bind to MR

Question 21

CRT in 2o adrenocortical failure?

Answer 21

Patients LACK CORTISOL but aldosterone is fine (as AGTII still working just not ACTH!)

SO

treat w. hydrocortisone (does NOT need saline/fluid replacement as aldosterone is fine!)

Question 22

CRT is Acute Adrenocortical Failure?

Answer 22

i.e. Addisonian Crisis

In this order:
1. IV SALINE (0.9% NaCl) - rehydrate paitnet

2. High dose of i.v/i.m HYDROCORTISONE every 6hr - ensures theres a MR effect
3. 5% DEXTROSE - if hypoglycaemic (due to lack of cortisol)

Question 23

CAH?

Answer 23

Cogenital Adrenal Hyperplasia

i.e. 95% due to 21-hydroxylase deficiency

Question 24

How can CAH be diagnosed?

Answer 24

If due to 21-hydroxylase deficiency:

17alpha-hydroxyprogesterone accumulates so can measure this

Question 25

CRT in CAH?

Answer 25

1. Replace cortisol - dexamethasone (1/day) OR hydrocortisone (2-3/day) 2. Supress ACTH (and thus adrenal androgen production) - this is the real problem so want to stop this! 3. Replace aldosterone - flucrocortisone

Question 26

How can you monitor/optimise CRT for CAH?

Answer 26

Measure 17alpha-hydroxyprogesterone x If GC too HIGH = Cushings' x If GC too LOW (and hence ACTH risen) = Hirsutism

Question 27

What additional precautions should be kept in place for those with adrenocortical failure?

Answer 27

Cortisol levels go up/down depending on STRESS so GC dosage should be INCREASES when patients are vulnerable to stress e.g. surgery

Question 28

Normal cortisol levels vs. in stress?

Answer 28

Normal cortisol production = 20mg/day Stress production = 200-300 mg/day

Question 29

When should you increase GC dosage in CRT?

Answer 29

x In minor illness - 2x normal dose x Surgery - hydrocortisone i.m both before & after