8. Therapeutic use of adrenal steroids

Question 1

Draw the axis of adrenal steroid production (liver + hypothalamus)

Answer 1

.

Question 2

Difference between MR and GR receptors

Answer 2

GR = widely distributed, SELECTIVE for glucocorticoids but low affinity for cortisol

MR = only in kidney, can bind both aldosterone AND cortisol. High affinity for cortisol but cortisol normally metabolised into inactive form by 11-b-HSD. So only aldosterone binds to MR

Question 3

What happens to cortisol in cushings

Answer 3

Excess cortisol -> 11bHSD gets overwhelmed.

Cortisol that isn’t deactivated binds to MR

Causes hypertension + hypokalaemia

Question 4

Example of primary adrenocortical failure? Treatment?

Answer 4

Addison’s
Low cortisol + aldosterone

Hydrocortisone/prednisolone + fludrocortisone tablets

Question 5

Example of secondary adrenocortical failure? Treatment?

Answer 5

ACTH deficiency
Low cortisol but normal aldosterone (since its controlled by renin-angiotensin system which is separate)

Hydrocortisone/prednisolone tablets

Question 6

Example of acute adrenocortical failure? Treatment?

Answer 6

Addisonian crisis

IV 0.9% sodium chloride (to rehydrate)
HIGH DOSE iv/im hydrocortisone every 6hrs
5% dextrose (if hypoglycaemic)

Question 7

Treatment for congenital adrenal hyperplasia

Answer 7

Dexamethasone 1/day or hydrocortisone 2-3/day
Fludrocortisone
Monitor treatment by measuring 17-OH prog.
If GC too high -> will cause cushingoid
If GC too low -> will cause hirsutism

Question 8

Patient with adrenocortical failure also has minor illness. How would you change their treatment?

Answer 8

Double the dose, since cortisol production increases 10-fold when under stress

Question 9

Patient with adrenocortical failure and is undergoing GC treatment. He is going into surgery involving general anaesthetic. What should the doctor do during surgery?

Answer 9

Give patient IV hydrocortisone at 6-8hr intervals. Switch back to oral when patient can eat/drink again.

Question 10

What is hydrocortisone?

Answer 10

Glucocorticoid (cortisol replacement)

Also has MR (aldosterone) activity at HIGH doses - floods 11bHSD

Question 11

Difference between hydrocortisone and prednisolone?

Answer 11

They’re both tablets but hydrocortisone can be given parenterally in emergencies

Prednisolone has higher DOA (12hrs) so only need 1 tablet in morning.
Hydrocortisone has shorter DOA (hrs) so multiple throughout the day

Question 12

What is fludrocortisone?

Answer 12

Aldosterone analogue

Given to addison’s patients together with cortisol replacement

Question 13

What is dexamethasone?

Answer 13

Synthetic GC with NO MR activity

Only used in congenital adrenal hyperplasia

1 per day
Very long DOA (40hrs)

Question 14

What do all the cortisol/aldosterone replacement drugs bind to in the blood?

Answer 14

Cortisol binding globulin (CBG) or albumin