Therapeutic use of adrenal steroids

Question 1

What does the zona glomerulosa produce?

Answer 1

Aldosterone

Question 2

What does the zona fasciculata produce?

Answer 2

Cortisol

Question 3

What does the zona reticular produce?

Answer 3

Androgens and oestrogens

Question 4

Which hormones are under the control of ACTH?

Answer 4

Cortisol and androgens

Question 5

What stimulates aldosterone release?

Answer 5

Renin-angiotensin system

Question 6

Where is renin produced?

Answer 6

Juxtaglomerular cells

Question 7

What does renin do?

Answer 7

Converts angiotensinogen to angiotensin I

Question 8

What does ACE do?

Answer 8

Converse angiotensin I to angiotensin II

Question 9

What does angiotensin II do?

Answer 9

Stimulates release of aldosterone from adrenal cortex

Question 10

What triggers aldosterone release?

Answer 10

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

Question 11

Which adrenal steroid is essential for life?

Answer 11

Cortisol

Question 12

Why are the principle physiological actions of adrenal androgens unknown?

Answer 12

Gonads are a much bigger source of androgens

Question 13

What are the difference between glucocorticoid and mineralocorticoid receptors?

Answer 13

Glucocorticoid:
Wide distribution
Selective for glucocorticoids
Low affinity for cortisol

Mineralocorticoid:
Discrete distribution
Don’t distinguish between aldosterone and cortisol
High affinity for cortisol

Question 14

Why is MRs lack of selectivity a problem?

Answer 14

Cortisol can stimulate them

Question 15

How are MRs protected from cortisol?

Answer 15

Cortisol is converted to cortisone by 11beta hydroxysteroid dehydrogenase

Question 16

Why do you have hypokalaemia in Cushing’s?

Answer 16

The system gets overwhelmed, when there is lots of cortisol, 11 betahydroxysteroid dehydrogenase can’t inactivate it all so some binds to mineralocorticoid receptors and causes hypokalaemia

Question 17

How does cortisol compare to hydrocortisone?

Answer 17

They have the same structure but hydrocortisone is synthetic and cortisol is endogenous

Question 18

What sort of steroid is prednisolone?

Answer 18

Immunosuppressive glucocorticoid with weak mineralocorticoid activity

Question 19

What sort of steroid is dexamethasone?

Answer 19

Very potent glucocorticoid- used clinically for things like brain metastases where there is a lot of oedema- an acute anti-oedema agent

Question 20

What sort of steroid is fludrocortisone?

Answer 20

Aldosterone analogue

Question 21

What percentage of hydrocortisone in the body is bound to plasma proteins?

Answer 21

90-95%

Question 22

Which plasma proteins do corticosteroids bind to?

Answer 22

Corticosteroid binding globulin and albumin

Question 23

In terms of binding, how do the other corticosteroids (prednisolone, dexamethasone and fludrocortisone) compare?

Answer 23

They are less bound and fludrocortisone is only bound to albumin

Question 24

What is the order of the corticosteroids from shortest to longest half life?

Answer 24

Hydrocortisone and fludrocortisone
Prednisolone
Dexamethasone

Question 25

What are reasons for giving replacement corticosteroid?

Answer 25

``` Primary adrenocortical failure Secondary adrenocortical failure Acute adrenocortical failure Congenital adrenal hyperplasia Iatrogenic adrenocortical failure ```

Question 26

What are the two main causes of primary adrenocortical failure?

Answer 26

Addison's disease | Chronic adrenal insufficiency

Question 27

What is wrong in primary adrenocortical failure?

Answer 27

Their adrenal cortex just isn't working, they can't make any hormones and need replacement cortisol and aldosterone

Question 28

Why do primary adrenocortical failure patients not need replacement androgens?

Answer 28

The loss of production from adrenal cortex isn't a big deal because most androgens are made in gonads

Question 29

How is primary adrenocortical failure treated?

Answer 29

Hydrocortisone and fludrocortisone

Question 30

What is wrong in secondary adrenocortical failure?

Answer 30

Lack of ACTH- problem in adenohypophysis

Question 31

What is the difference between a patient with primary and secondary adrenocortical failure?

Answer 31

Secondary have aldosterone because RAS works properly

Question 32

How do you treat secondary adrenocortical failure?

Answer 32

Hydrocortisone (oral)- titrate dose throughout day to mimic normal physiology

Question 33

What is there a lack of congenital adrenal hyperplasia?

Answer 33

Steroid synthetic enzymes

Question 34

What are most cases of congenital adrenal hyperplasia due to?

Answer 34

Lack of 21-hydroxylase

Question 35

How do you treat congenital adrenal hyperplasia?

Answer 35

Replace cortisol: Dexamethasone 1/day or hydrocortisone 2-3/day Suppress ACTH and thus adrenal androgen production Replace aldosterone- fludrocortisone Monitor optimise therapy by measuring 17alpha-hydroxyprogesterone Do a clinical assessment of what they are complaining about: Cushingoid- too much glucocorticoid Hirsutism/acne- too little glucocorticoid (high ACTH)

Question 36

What is the normal cortisol production?

Answer 36

20mg/day

Question 37

When does iatrogenic adrenocortical failure occur?

Answer 37

Happens in patients on long term high dose corticosteroid treatment

Question 38

Why does iatrogenic adrenocortical failure occur?

Answer 38

If they're on glucocorticoids for a long term, they will stop producing cortisol as they don't need to anymore