Therapeutic Use of Adrenal Steroids

Question 1

Name the 3 parts of the adrenal cortex and the steroids that each produces.

Answer 1

Zona Glomerulosa: Aldosterone
Zona Fasciculata: Cortisol
Zona Reticularis: Sex Steroids

Question 2

What hormone controls the production of adrenal sex steroids and cortisol?

Answer 2

ACTH

Question 3

What controls the production of aldosterone?

Answer 3

Angiotensin II

Question 4

State 4 triggers of aldosterone release

Answer 4

Hyperkalaemia
Hyponatraemia
Drop in renal blood flow
Beta-1 adrenoceptor stimulation

Question 5

What is the principle action of aldosterone?

Answer 5

Increases Na+ reabsorption

Increases K+ excretion

Question 6

State 3 differences between glucocorticoid receptors and mineralocorticoid receptors.

Answer 6

GRs are widely distributed, MRs have a discrete distribution (kidney)
GRs are selective for glucocorticoids, MRs can’t distinguish between cortisol + aldosterone
GRs have a low affinity for cortisol, MRs have a high affinity for cortisol

Question 7

Describe how MRs are protected from cortisol stimulation.

Answer 7

11-beta hydroxysteroid dehydrogenase-2 converts cortisol to the inactive cortisone to prevent it from interacting with MRs

Question 8

Why do you get hypokalaemia in Cushing’s syndrome?

Answer 8

Excess cortisol overloads the 11-beta-HSD-2 system so the cortisol binds to MRs + has mineralocorticoid effects.

Question 9

Name 3 glucocorticoid drugs in order of decreasing mineralocorticoid activity.

Answer 9

Hydrocortisone (highest mineralocorticoid activity)
Prednisolone
Dexamethasone (no mineralocorticoid activity)

Question 10

What does prednisolone tend to be used for?

Answer 10

Immunosuppression

Used in asthma, RA + other inflammatory diseases

Question 11

What does dexamethasone tend to be used for?

Answer 11

Acute anti-oedema

E.g. used clinically for brain metastases where there is a lot of oedema

Question 12

Name an aldosterone analogue.

Answer 12

Fludrocortisone

Question 13

How are the steroid drugs administered?

Answer 13

Orally

Hydrocortisone + Dexamethasone can be administered parenterally (IV or IM) in high doses

Question 14

Describe the extent of plasma protein binding in each of the 4 steroid drugs.

Answer 14

They bind to plasma proteins: corticosteroid binding globulin + albumin
Hydrocortisone is extremely plasma protein bound ~90-95%
Prednisolone is less bound
Dexamethasone + fludrocortisone are even less bound
Fludrocortisone only binds to albumin

Question 15

Where are the corticosteroid drugs metabolised and how are they excreted?

Answer 15

Hepatic metabolism

Excreted in the bile + urine

Question 16

Describe the half-lives of the 3 glucocorticoid drugs in order of increasing half-life (shortest half-life first):

Answer 16

Hydrocortisone (8 hours)
Prednisolone (12 hours)
Dexamethasone (40 hours)

Question 17

State 4 reasons for giving corticosteroid replacement therapy

Answer 17

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

Question 18

State 2 causes of primary adrenocortical failure.

Answer 18

Addison’s disease

Chronic adrenal insufficiency

Question 19

What is the usual treatment for primary adrenocortical failure?

Answer 19

Lack of cortisol + aldosterone so need to give:
Hydrocortisone
Fludrocortisone

Question 20

What is secondary adrenocortical failure?

Answer 20

Adrenal gland itself is fine but there is a problem with the pituitary gland (ACTH deficiency)
There is NORMAL aldosterone production (because aldosterone isn’t dependent on ACTH)
So only cortisol needs to be replaced

Question 21

Describe the treatment of secondary adrenocortical failure.

Answer 21

HYDROCORTISONE (titrate dose to mimic normal physiology)

Question 22

What is the treatment for acute adrenocortical failure (Addisonian Crisis)?

Answer 22

IV saline (0.9% sodium chloride) (suffering from a salt losing crisis) 
High dose hydrocortisone (IV): binds GR + overwhelms 11B HSD 2 thus binds to MR 
5% Dextrose (if hypoglycaemic)

Question 23

What is the most common cause of congenital adrenal hyperplasia?

Answer 23

21-hydroxylase deficiency

Question 24

Describe the ACTH levels in CAH and explain the effect this has on steroid synthesis.

Answer 24

High ACTH: because no cortisol is being produced so there is no negative feedback on the hypothalamo-pituitary axis
High ACTH means that the sex steroid synthesis pathway is turned on + there is an increase in adrenal sex steroids

Question 25

What are the consequences of CAH in childhood?

Answer 25

CAH caused by partial enzyme deficiency can result in virilisation + precocious puberty

Question 26

How do you treat CAH?

Answer 26

Replace cortisol with high dose hydrocortisone (2-3/day) or dexamethasone (1/day)
Replace aldosterone with fludrocortisone
To replace cortisol + to suppress the ACTH axis to reduce adrenal sex steroid production

Question 27

How do you monitor/ diagnose CAH?

Answer 27

Measure 17a-hydroxyprogesterone levels
Monitor them clinically – are they complaining of hirsuitism/acne (GC dose too low) or cushingoid (GC dose too high) symptoms?

Question 28

When would you change the dose of hydrocortisone in CAH?

Answer 28

Minor illness

Surgery

Question 29

How does cortisol production change when placed under stress e.g. when ill?

Answer 29

We make 10X more to aid recovery

Question 30

What should patients with adrenocortical failure do to prevent a crisis?

Answer 30

Wear a MedicAlert bracelet + carry a steroid alert card