treating adrenal disorders

Question 1

control of adrenal steroid production- hypothalamus and aldosterone

Answer 1

CRH sent from hypothalamus

aldosterone controlled by renal blood flow, hyponatremia/hyperkalemi- angiotensinogen= ANG 1 ( by renin)= Ang 2 (by ACE)= aldosterone= NA absorption/K + excretion

Question 2

MR vs GR receptor

Answer 2

GR is all over body, and is selective for glucocorticoids although affinity for cortisol is LOW

MR is only in kidney, and is no selective for gluco or mineralocorticoids, although affinity for cortisol is HIGH

Question 3

why cortisol doesn’ t bind to aldosterone receptor

Answer 3

cortisol converted into inactive cortison (cannot bind to MR recepotr) due to 11beta-hydroxysteroid dehydrogenase (11 beta HSD)

Question 4

effect of cushings on 11beta HSD

Answer 4

enzyme is overwhelmed so some cortisol can bind to MR receptor= hypertension and HYPOKALAEMIA

Question 5

receptor selectivity of different drugs and similarity

Answer 5

hydrocortisone (medication for addisons)= glucocorticoid with mineralocorticoid activity at high doses

prednisolone- glucocorticoid with weak mineralocorticoid activity (use as immunosurpressant often)

dexamethasone (synthetic glucocorticoid with no MR activity)

fludrocortisone (aldosterone analogue)- replaces aldosterone

very similar in structure

Question 6

routes of administration of corticosteroids

Answer 6

the 4 drugs can be given orally as a tablet

hydrocortisone and dexamethasone can be given paraenterally (intravenously)- good way of getting large amount into system if someone acutely unwell

Question 7

binding of corticosteroids

Answer 7

drugs (apart from fludrocortisone) binds to cortisol binding globulin (CBG) and albumin like cortisol

Question 8

duration of action of drugs

Answer 8

hydrocortisone only lasts 8 hrs (given multiple times a day), prednisolone 12 hours, and dexamethasone very powerful- 40 hours

Question 9

adrenal steroids lost in addisons

Answer 9

due to autoimmune/TB, all 3 pathways lost, but sex steroids don’t need to be replaced as gonads can do it

Question 10

treatment of addisons- acute and long term

Answer 10

acute treatment (addisonina crisis)- give patient intravenous 0.9% NaCl solution to replace lost sodium (stops tiredness, diziness and hypotension), and large dose of intravenous hydrocortisone given (enzyme overwhelmed, so binds to both receptors- dextrose also given for hypoglycaemia

then give hydrocortisone and fludrocortisone orally

Question 11

secondary adrenocortical failure (ACTH deficiency)

Answer 11

renin system fine, so only sex steroids and cortisol are deficient

treat with hydrocortisone

Question 12

congenital adrenal hyperplasia- precursor build up and treatment

Answer 12

17alpha hydroxyprogesterone builds up before enzyme block, so can be measured

hydrocortisone and fludorcortisone given

ACTH high so sex steroids even higher along with back up of precursors- surpress ACTH using larger dose of dexamethasone or hydrocortisone at night (cortisol normally low)

Question 13

monitoring therapy problem with CAH treatment

Answer 13

can be monitored by 17 OH progesterone levels

surpressing ACTH with large dose of glucocorticoid can lead to cushings

Question 14

additional measures for corticosteroid therapy- dosage changes and what they wear

Answer 14

during stress, cortisol levels rise by 10 times (eg when feeling ill) to combat stress

thus dosage should increase when patient vulnerable to stress- double dosage with minor illness, and during surgery (anaesthetic causes stress), hydrocortison given intravenously before, during and after surgery until patient can eat/drink again

patients should carry steroid alert card and red bracelet- if emergency happens, it will show a large dosage of hydrocortisone needed