adrenals

Question 1

two types of corticosteroid receptor

Answer 1

glucocorticoid (GR) and mineralocorticoid (MR)

Question 2

GR vs MR: distribution

Answer 2

GR widely distributed, MR discretely distributed (kidney)

Question 3

GR vs MR: selectivity

Answer 3

GR selective for glucocorticoids, MR unselective between aldosterone and cortisol

Question 4

GR vs MR: affinity for cortisol

Answer 4

GR low affinity, MR high affinity

Question 5

how are MRs protected from cortisol (preventing cortisol binding to it all the time); significance in Cushing’s

Answer 5

11B-hydroxysteroid dehydrogenase 2 (11BHSD) inactivates cortisol to cortisone before it binds, and cortisone cannot bind to MR; in Cushing’s, hypokalaemia as excess cortisol overwhelms 11BHSD, so this binds to MR, promoting Na+ reabsorption and K+ excretion

Question 6

4 drugs with receptor selectivity for GR and/or MR

Answer 6

hydrocortisone, prednisolone, dexamethasone, fludrocortisone

Question 7

GR and MR selectivity of hydrocortisone

Answer 7

glucocorticoid with mineralocorticoid activity at high dose (mimics cortisol)

Question 8

GR and MR selectivity of prednisolone

Answer 8

glucocorticoid with weak mineralocorticoid activity; used as immunosuppressant for inflammatory diseases

Question 9

GR and MR selectivity of dexamethasone; what does it help diagnose

Answer 9

synthetic glucocorticoid with no mineralocorticoid activity (used to diagnose Cushing’s)

Question 10

GR and MR selectivity of fludrocortisone

Answer 10

mineralocorticoid with no glucocorticoid activity; aldosterone analogue (used as aldosterone substitute)

Question 11

drug structures and varying affinities explained

Answer 11

have varying affinities to receptors by having subtle structural differences

Question 12

pharmacokinetics: 2 routes of administration of exogenous corticosteroids

Answer 12

oral, parenteral (IV or IM)

Question 13

pharmacokinetics: exogenous corticosteroids which are orally administered

Answer 13

all: hydrocortisone, prednisolone, dexamethasone, fludrocortisone

Question 14

pharmacokinetics: exogenous corticosteroids which are parenteral administered (IV or IM); why isn’t fludrocortisone given IV

Answer 14

hydrocortisone, dexamethasone; as hydrocortisone has mineralocorticoid effects at high doses, fludrocortisone doesn’t have to be given IV

Question 15

pharmacokinetics: distribution of exogenous corticosteroids

Answer 15

bind to plasma proteins (cortisol binding globulin and albumin) as circulating cortisol does

Question 16

pharmacokinetics: duration of hydrocortisone action

Answer 16

8 hours - quickly metabolised so several times a day

Question 17

pharmacokinetics: duration of prednisolone action

Answer 17

12 hours - once a day

Question 18

pharmacokinetics: duration of dexamethasone action

Answer 18

40 hours - potent so used in dexamethasone test for Cushing’s

Question 19

what is primary adrenocortical failure, and effect on production and release of steroid hormones

Answer 19

Addison’s disease, so no aldosterone, cortisol or sex steroids (sex steroids don’t need to be replaced as most produced by gonads)

Question 20

how is Addison’s disease treated (not Addisonian crisis)

Answer 20

hydrocortisone (cortisol replacement) and fludrocortisone (aldosterone replacement) by mouth

Question 21

what is secondary adrenocortical failure, and effect on production and release of steroid hormones

Answer 21

ACTH deficiency, so patient lacks cortisol but normal aldosterone (RAAS pathway as adrenal cortex fine)

Question 22

how is ACTH deficiency treated

Answer 22

hydrocortisone or prednisolone to replace cortisol

Question 23

what is an acute adrenocortical failure also known as

Answer 23

Addisonian crisis (more severe form of Addisons so severe hypotension)

Question 24

treatment of Addisonian crisis (3 things)

Answer 24

IV 0.9% NaCl to rehydrate (increase blood pressure, replace Na+ without K+), immediate high dose hydrocortisone (IV infusion or IM every 6 hours to produce mineralocorticoid effect by overwhelming 11BHSD; therefore fludrocortisone doesn’t need to be administered straight away), 5% dextrose if hypogylcaemic

Question 25

what is congenital adrenal hyperplasia

Answer 25

congenital lack of enzymes needed for adrenal steroid synthesis (95% cases lack 21-hydroxylase)

Question 26

effect of having a) partial and b) complete 21-hydroxylase deficiency on steroid production

Answer 26

a) aldosterone and cortisol deficient, excess sex steroids; b) aldosterone and cortisol absent, excess sex steroids

Question 27

what is measured to make congenital adrenal hyperplasia diagnosis if 21-hydroxylase deficiency

Answer 27

17a-hydroxyprogesterone; accumulates as ACTH drive but immediately before enzyme 'block', so high levels

Question 28

3 objectives of congenital adrenal hyperplasia therapy

Answer 28

replace cortisol, suppress ACTH (therefore suppressing adrenal androgen production), replace aldosterone in salt wasting forms

Question 29

treatment of congenital adrenal hyperplasia to stop ACTH drive

Answer 29

cortisol: dexamethasone 1/day, pm or hydrocortisone 2-3/day, high dose pm (try to reduce ACTH and adrenal androgen production); aldosterone: fludrocortisone

Question 30

what is measured to monitor and optimise therapy for congenital adrenal hyperplasia (if bigger dose of glucocorticoid to stop ACTH drive, can develop Cushing's)

Answer 30

17a-hydroxyprogesterone; clinical assessment: Cushingoid - GC dose too high; hirsutism - GC dose too low, causing ACTH (and therefore testosterone production) to rise

Question 31

additional measure in subjects with adrenocortical failure and vulnerable to stress (e.g. unwell) and why

Answer 31

increase glucocorticoid dosage, as if in stress e.g. unwell with pneumonia or UTI, 10x more cortisol produced than normal

Question 32

what 2 occasions is glucocorticoid dosage increased during stress when using corticosteriod replacement therapy for adrenocortical failure

Answer 32

in minor illness (2x normal dose to mimic what body would normally be doing), surgery (general anaesthetic is stress to body)

Question 33

how is glucocorticoid dosage increased before surgery

Answer 33

hydrocortisone (IM), with pre-med and at 6-8 hour intervals; oral once eating and drinking

Question 34

what should patients with adrenocortical failure carry and wear to ensure effective treatment if unwell

Answer 34

steroid alert card, MedicAlert bracelet/necklace to ensure adequate treatment as in time of stress