Therapeutic uses of adrenal steroids

Question 1

describe the adrenal gland structure and the products produced?

why is the medulla of the gland not affected the same way?

Answer 1

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

Question 2

what stimulated aldosterone production

Answer 2

ANG II

Question 3

glucocorticoid receptors (GR)

Answer 3

widely distributed
selective for GC
low affinity for cortisol

Question 4

mineralocorticoid receptors (MR)

• where are they located mainly?
• selectivity and affinity?

Answer 4

mainly in kidney (discrete distribution)
non-selective for cortisol and aldosterone
high affinity for cortisol

Question 5

what cause hypertensive episodes and hypokalaemia ,in Cushing’s, in terms of MR?

Answer 5

• 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

Question 6

deactivating enzyme of cortisol

Answer 6

11 beta hydroxysteroid dehydrogenase 2 (11beta HSD2)

converts cortisol to cortisone

Question 7

which hormone has a higher affinity to MR?

Answer 7

cortisol > aldosterone

Question 8

4 drugs used to mimic cortisol or aldosterone

Answer 8

1) hydrocortisone (GC)
2) prednisolone (GC)
3) dexamethasone (GC)
4) fludrocortisone (MC)

all four are structurally similar with very fine differences

Question 9

hydrocortisone

Answer 9

glucocorticoid with mineralocorticoid activity at high doses

Question 10

prednisolone

Answer 10

GC with weak MC activity

Question 11

dexamethasone

Answer 11

synthetic glucocorticoid

with no mineralocorticoid activity (only binds with GR)

Question 12

fludrocortisone

Answer 12

aldosterone analogue

Question 13

two methods of administration

Answer 13

1) oral- all 4 drugs

2) parenteral i.m or i.v.- hydrocortisone and dexamethasone

Question 14

when would parenteral administration be used?

Answer 14

in an Addisonian Crisis to provide a large dose systemically very quickly

Question 15

how are the drugs distributed in the body?

Answer 15

binds to CBG and albumin just like the cortisol itself

Question 16

duration of action of the drugs

Answer 16

hydrocortisone ~ 8hours (therefore administered multiple times in a day)

prednisolone ~12 hours

dexamethosone ~40 hours

Question 17

treatment of primary adrenocortical failure (Addison’s disease/Syndrome)

Answer 17

may need acute care first

later, due to lack of cortisol and aldosterone they need :

• hydrocortisone (cortisol)
• fludrocortisone (aldosterone)

orally

Question 18

treatment of secondary adrenocortical failure (ACTH deficiency, issue at the pituitary)

Answer 18

due to lack of cortisol, hydrocortisone/prednisolone needs to be given

aldosterone is normal

Question 19

treatment of Acute Adrenocortical Failure i.e. Addisonian Crisis

Answer 19

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

Question 20

common cause of Congential Adrenal Hyperplasia

Answer 20

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

Question 21

therapy for CAH

Answer 21

• replace cortisol with dexamethasone or hydrocortisone
• suppress ACTH to indirectly reduce sex steroid production
• replace aldosterone with fludrocortisone

Question 22

importance of correct dosage when treating CAH

Answer 22

• use 17 OH progesterone levels for administration
• too much GC will cause cushingoids
• too low a dose still enables hirsutism

Question 23

normal cortisol production

Answer 23

20 mg/day

Question 24

cortisol level at stress

Answer 24

200-300 mg/day

Question 25

important of cortisol dosage for Addison’s patients under stress

Answer 25

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.

Question 26

when does cortisol dosage also need to be increased?

Answer 26

for those undergoing surgery

IM hydrocortisone given at 6-8 hour intervals before an after surgery to adjust to and recover from anaesthetic.

Question 27

medi alert bracelets

Answer 27

worn by Addison’s patients in case of emergency

Question 28

what is Congenital Adrenal Hyperplasia?

Answer 28

21-hydroxylase deficiency (genetic)

Not able to produce aldosterone or cortisol so progesterone builds up –> sex hormone arm

no negative feedback

Question 29

what investigations can be done for Congenital Adrenal Hyperplasia?

Answer 29

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

Question 30

how is Addison’s Crisis treated?

Answer 30

IV saline (dehyradtion)
dextrose
fludrocortisone (aldosterone analogue)
hydrocortisone

aim to replace missing hormones and suppress the high hormones levels

Question 31

what steroid replacement must be done pre trans-sphenoidal pituitary surgery?

Answer 31

Hydrocortisone IM at 6-8 hour intervals.

Question 32

what happens to steroid dosage when undergoing physiological stress?

Answer 32

doubled

Question 33

what is the insulin induced hypoglycaemia test?

Answer 33

• 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

Question 34

what is the normal response to an insulin induced hypoglycaemia test?

Answer 34

• blood glucose decrease

- cortisol increase (to mobilise glucose in the body in response)

Question 35

what is an abnormal response to an insulin induced hypoglycaemia test?

Answer 35

• blood glucose decrease

- cortisol does not increase meaning adrenal insufficiency therefore needing of replacement therapy