Endo 8 - Therapeutic use of adrenal steroids

Question 1

Explain how adrenal steroids are formed

Answer 1

1. Hypothalamus releases CRH to APG
2. APG releases ACTH
3. ACTH to zona fasciculate of adrenal gland - produces cortisol

Negative feedback throughout

Question 2

Which 2 things control CRH release from Hypothalamus

Answer 2

1. Circadian stimuli

2. Stress

Question 3

Androgens and oestrogens are also somewhat regulated by ACTH to the adrenal gland. Where are they produced

Answer 3

Zona reticularis

Question 4

Where is aldosterone produced

Answer 4

Zona glomerulosa

Question 5

Explain how aldosterone release is stimulated

Answer 5

Angiotensinogen (liver) –> AI (via renin from the kidney) –> A2 (via ACE)

A2 acts on zona glomerulosa for aldosterone secretion

Question 6

What are the 4 triggers for aldosterone secretion

Answer 6

1. Hyperkalaemia
2. Hyponatraemia
3. Decreased RBF
4. B1-adrenoceptor stimulation

Question 7

Cortisol is what type of corticoid and aldosterone is what type of corticoid

Answer 7

Cortisol = Glucocorticoid

Aldosterone = Mineralocorticoid

Question 8

Compare Glucocorticoid receptor and mineralocorticoid receptors

Answer 8

GR :

1. Wide distribution
2. Selective for GCs
3. But low affinity for cortisol

MR:

1. Discrete distribution
2. They do not distinguish between aldosterone and cortisol
3. High affinity for cortisol

Question 9

Which receptors can cortisol bind to, and which receptors can aldosterone bind to?

Answer 9

Cortisol can bind to GR and Aldosterone receptor (AR)

But usually cortisol is converted into a form that can’t bind to AR because 11 beta-hyroxysteroid dehydrogenase2 converts it into inactive cortisone

This is why in Cushings (XS cortisol), patients may present with hypertension, etc - due to activation of MR

Question 10

Hydrocortisone is used as treatment for?

Answer 10

Addisons

Question 11

Describe the receptor selectivity of hydrocortisone

Answer 11

GC with MC activity at high doses

Question 12

What corticoid class is prednisolone

Answer 12

GC with weak MC activity

Question 13

Describe dexamethasone

Answer 13

Synthetic GC with no MR activity (it is a pure GC)

Question 14

Name an aldosterone analogue

Answer 14

Fludrocortisone - used as an aldosterone substitute

Question 15

What are the GC drugs that can be taken orally

Answer 15

Hydrocortisone, prednisolone, dexamethasone, fludrocortisone

Question 16

Corticosteroids bind to plasma proteins, which are

Answer 16

Cortisol Binding Globulin (CBG)

and a bit to albumin

Question 17

Which Corticosteroids can be given IV

Answer 17

Hydrocortisone (e.g. in an Addisonian crisis) or dexamethasone

Question 18

Describe the relative durations of action of Hydrocortisone, prednisolone, dexamethasone

Answer 18

Dexamethasone > prednisolone > hydrocortisone

Question 19

Addisons disease is primary adrenocortical failure. Which hormones are not made

Answer 19

Aldosterone, cortisol, sex steroids (produced by gonads mainly anyway so not that deep)

Question 20

What is the treatment for Addisons disease

Answer 20

1. Hydrocortisone to replace cortisol

2. Fludrocortisone to replace aldosterone

Question 21

What does secondary adrenocortical failure mean?

Answer 21

ACTH deficiency (problem usually APG/hypothalamus)

Patients lack cortisol but normal aldosterone

Question 22

How do you treat someone with secondary adrenocortical failure

Answer 22

With hydrocortisone (to replace cortisol, no need to replace aldosterone)

Question 23

What is an addisonian crisis

What is the treatment for this condition

Answer 23

Acute adrenocortical failure

Treat with giving 0.9% NaCl IV, then giving high dose hydrocortisone

Question 24

Congenital adrenal hyperplasia (CAH) is another example of?

Answer 24

Primary adrenocortical failure

Congenital lack of enzymes needed for adrenal steroid synthesis

Question 25

What enzyme is mainly lacking in Congenital adrenal hyperplasia? What are the problems associated with this

Answer 25

21-hydroxylase lacking, so can't make cortisol This causes buildup of 17a-hydroxyprogesterone - which causes an increase in sex steroid production ACTH negative feedback not present, so MORE cortisol production drive causes more sex steroid to be formed

Question 26

Cholesterol is the precursor for all of the steroid biosynthesis pathways. What are the 3 arms

Answer 26

Aldosterone, Cortisol, Sex steroids (oestradiol)

Question 27

What are the 3 objectives in treating someone with CAH and how are they met

Answer 27

1. Replace cortisol 2. Suppress ACTH - thus suppressing adrenal androgen production - dexamethasone/hydrocortisone given 3. Replace aldosterone in salt wasting forms - fludrocortisone given

Question 28

How is CAH treatment monitored

Answer 28

By monitoring 17-OH progesterone (should decrease)

Question 29

What is the sticky one regarding treating CAH

Answer 29

There is a balance between causing Cushingoid symptoms by giving a high GC dose, and then lowering the GC dose the next time you see them may cause hirsutism

Question 30

What must you tell patients to do who take GC

Answer 30

Tell them to take GC when they are vulnerable to stress, or if they have surgery (w general anaesthetic) Body produces 10-15x more cortisol when stressed Also to give a steroid alert card - or wear a MedicAlert bracelet