Endo 8 - Therapeutic use of adrenal steroids Flashcards
Explain how adrenal steroids are formed
- Hypothalamus releases CRH to APG
- APG releases ACTH
- ACTH to zona fasciculate of adrenal gland - produces cortisol
Negative feedback throughout
Which 2 things control CRH release from Hypothalamus
- Circadian stimuli
2. Stress
Androgens and oestrogens are also somewhat regulated by ACTH to the adrenal gland. Where are they produced
Zona reticularis
Where is aldosterone produced
Zona glomerulosa
Explain how aldosterone release is stimulated
Angiotensinogen (liver) –> AI (via renin from the kidney) –> A2 (via ACE)
A2 acts on zona glomerulosa for aldosterone secretion
What are the 4 triggers for aldosterone secretion
- Hyperkalaemia
- Hyponatraemia
- Decreased RBF
- B1-adrenoceptor stimulation
Cortisol is what type of corticoid and aldosterone is what type of corticoid
Cortisol = Glucocorticoid
Aldosterone = Mineralocorticoid
Compare Glucocorticoid receptor and mineralocorticoid receptors
GR :
- Wide distribution
- Selective for GCs
- But low affinity for cortisol
MR:
- Discrete distribution
- They do not distinguish between aldosterone and cortisol
- High affinity for cortisol
Which receptors can cortisol bind to, and which receptors can aldosterone bind to?
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
Hydrocortisone is used as treatment for?
Addisons
Describe the receptor selectivity of hydrocortisone
GC with MC activity at high doses
What corticoid class is prednisolone
GC with weak MC activity
Describe dexamethasone
Synthetic GC with no MR activity (it is a pure GC)
Name an aldosterone analogue
Fludrocortisone - used as an aldosterone substitute
What are the GC drugs that can be taken orally
Hydrocortisone, prednisolone, dexamethasone, fludrocortisone
Corticosteroids bind to plasma proteins, which are
Cortisol Binding Globulin (CBG)
and a bit to albumin
Which Corticosteroids can be given IV
Hydrocortisone (e.g. in an Addisonian crisis) or dexamethasone
Describe the relative durations of action of Hydrocortisone, prednisolone, dexamethasone
Dexamethasone > prednisolone > hydrocortisone
Addisons disease is primary adrenocortical failure. Which hormones are not made
Aldosterone, cortisol, sex steroids (produced by gonads mainly anyway so not that deep)
What is the treatment for Addisons disease
- Hydrocortisone to replace cortisol
2. Fludrocortisone to replace aldosterone
What does secondary adrenocortical failure mean?
ACTH deficiency (problem usually APG/hypothalamus)
Patients lack cortisol but normal aldosterone
How do you treat someone with secondary adrenocortical failure
With hydrocortisone (to replace cortisol, no need to replace aldosterone)
What is an addisonian crisis
What is the treatment for this condition
Acute adrenocortical failure
Treat with giving 0.9% NaCl IV, then giving high dose hydrocortisone
Congenital adrenal hyperplasia (CAH) is another example of?
Primary adrenocortical failure
Congenital lack of enzymes needed for adrenal steroid synthesis
What enzyme is mainly lacking in Congenital adrenal hyperplasia?
What are the problems associated with this
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
Cholesterol is the precursor for all of the steroid biosynthesis pathways. What are the 3 arms
Aldosterone, Cortisol, Sex steroids (oestradiol)
What are the 3 objectives in treating someone with CAH and how are they met
- Replace cortisol
- Suppress ACTH - thus suppressing adrenal androgen production - dexamethasone/hydrocortisone given
- Replace aldosterone in salt wasting forms - fludrocortisone given
How is CAH treatment monitored
By monitoring 17-OH progesterone (should decrease)
What is the sticky one regarding treating CAH
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
What must you tell patients to do who take GC
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
