Therapeutic uses of adrenal steroids Flashcards
describe the adrenal gland structure and the products produced?
why is the medulla of the gland not affected the same way?
z. fasciculata- cortisol
z. glomerulosa- aldosterone (water retention, Na retention)
z. reticularis- sex steroids
medulla makes catecholamines and is not affected as it is not under ACTH control
what stimulated aldosterone production
ANG II
glucocorticoid receptors (GR)
widely distributed
selective for GC
low affinity for cortisol
mineralocorticoid receptors (MR)
- where are they located mainly?
- selectivity and affinity?
mainly in kidney (discrete distribution)
non-selective for cortisol and aldosterone
high affinity for cortisol
what cause hypertensive episodes and hypokalaemia ,in Cushing’s, in terms of MR?
- MR can have cortisol bind to it.
- The cortisol deactivating enzyme is overwhelmed and therefore cortisol binds to MR
- cortisol has a higher affinity than aldosterone to MR therefore deactivation is required
deactivating enzyme of cortisol
11 beta hydroxysteroid dehydrogenase 2 (11beta HSD2)
converts cortisol to cortisone
which hormone has a higher affinity to MR?
cortisol > aldosterone
4 drugs used to mimic cortisol or aldosterone
1) hydrocortisone (GC)
2) prednisolone (GC)
3) dexamethasone (GC)
4) fludrocortisone (MC)
all four are structurally similar with very fine differences
hydrocortisone
glucocorticoid with mineralocorticoid activity at high doses
prednisolone
GC with weak MC activity
dexamethasone
synthetic glucocorticoid
with no mineralocorticoid activity (only binds with GR)
fludrocortisone
aldosterone analogue
two methods of administration
1) oral- all 4 drugs
2) parenteral i.m or i.v.- hydrocortisone and dexamethasone
when would parenteral administration be used?
in an Addisonian Crisis to provide a large dose systemically very quickly
how are the drugs distributed in the body?
binds to CBG and albumin just like the cortisol itself
duration of action of the drugs
hydrocortisone ~ 8hours (therefore administered multiple times in a day)
prednisolone ~12 hours
dexamethosone ~40 hours
treatment of primary adrenocortical failure (Addison’s disease/Syndrome)
may need acute care first
later, due to lack of cortisol and aldosterone they need :
- hydrocortisone (cortisol)
- fludrocortisone (aldosterone)
orally
treatment of secondary adrenocortical failure (ACTH deficiency, issue at the pituitary)
due to lack of cortisol, hydrocortisone/prednisolone needs to be given
aldosterone is normal
treatment of Acute Adrenocortical Failure i.e. Addisonian Crisis
firstly treat hypotension (due to low aldosterone) at admission with 0.9% NaCl (saline) to rehydrate
and I.V. hydrocortisone (high dosage)
provide 5% dextrose if hypoglycaemic
common cause of Congential Adrenal Hyperplasia
95% of cases due to lack of 21-hydroxylase enzyme
accumulation of 17 alpha hydroxyprogesterone leads to excess sex steroid production
no cortisol production, ACTH goes high, driving further androgen production
therapy for CAH
- replace cortisol with dexamethasone or hydrocortisone
- suppress ACTH to indirectly reduce sex steroid production
- replace aldosterone with fludrocortisone
importance of correct dosage when treating CAH
- use 17 OH progesterone levels for administration
- too much GC will cause cushingoids
- too low a dose still enables hirsutism
normal cortisol production
20 mg/day
cortisol level at stress
200-300 mg/day
important of cortisol dosage for Addison’s patients under stress
dose needs doubling for patients with minor illnesses to help recovery
Usually cortisol needs to be high to recover but as there is low cortisol, the dose needs to altered.
when does cortisol dosage also need to be increased?
for those undergoing surgery
IM hydrocortisone given at 6-8 hour intervals before an after surgery to adjust to and recover from anaesthetic.
medi alert bracelets
worn by Addison’s patients in case of emergency
what is Congenital Adrenal Hyperplasia?
21-hydroxylase deficiency (genetic)
Not able to produce aldosterone or cortisol so progesterone builds up –> sex hormone arm
no negative feedback
what investigations can be done for Congenital Adrenal Hyperplasia?
1) Genetic testing for the gene that encodes 21-hydroxylase (if absent then confirmed).
2) Measure 17alpha-hydroxyprogesterone levels (should be high due to build up).
3) Short synacthen test – give ACTH and observe cortisol does not rise.
summary:
- 21 hydroxylase levels
- progesterone precursor levels
- cortisol suppression test
how is Addison’s Crisis treated?
IV saline (dehyradtion)
dextrose
fludrocortisone (aldosterone analogue)
hydrocortisone
aim to replace missing hormones and suppress the high hormones levels
what steroid replacement must be done pre trans-sphenoidal pituitary surgery?
Hydrocortisone IM at 6-8 hour intervals.
what happens to steroid dosage when undergoing physiological stress?
doubled
what is the insulin induced hypoglycaemia test?
- used to determine how the hypothalamus, pituitary and adrenal glands respond to stress
- blood is drawn to measure the blood glucose and cortisol levels, followed by an injection of fast-acting insulin
what is the normal response to an insulin induced hypoglycaemia test?
- blood glucose decrease
- cortisol increase (to mobilise glucose in the body in response)
what is an abnormal response to an insulin induced hypoglycaemia test?
- blood glucose decrease
- cortisol does not increase meaning adrenal insufficiency therefore needing of replacement therapy
