Therapeutic uses of adrenal steroids

Question 1

What do the different parts of the adrenal glands make?

Answer 1

Zona fasciculata – cortisol

Zona glomerulosa – aldosterone

Zona reticularis – sex steroids

Question 2

What does angiotensin 2 do?

Answer 2

stimulates aldosterone production and vasoconstriction

Question 3

What are the actions of aldosterone?

Answer 3

Promotes Na+ retention and K+ excretion – i.e. water retention

Question 4

Describe the distribution, selectivity and affinity of glucocorticoid receptors

Answer 4

• wide distribution
• selective for GC
• low affinity for cortisol

Question 5

Describe the distribution, selectivity and affinity of mineralocorticoids

Answer 5

• discrete distribution (kidneys)
• non selective between aldosterone and cortisol
• high affinity for cortisol

Question 6

How does Cushing’s syndrome cause hypertension?

Answer 6

• Normally an enzyme called 11 beta hydroxysteroid dehydrogenase 2 (HSD2) inactivates cortisol by forming cortisone
• In Cushing’s, you are producing too much cortisol and so 11 beta HSD2 is overwhelmed and cortisol binds too much to the MR causing hypertensive episodes

Question 7

What are some drugs used to mimic human hormones?

Answer 7

• Hydrocortisone
• Prednisolone
• Dexamethasone
• Fludrocortisone

Question 8

What is hydrocortisone and describe its activity?

Answer 8

Glucocorticoid with mineralocorticoid activity at high doses

Question 9

What is prednisolone and describe its activity?

Answer 9

Glucocorticoid with weak mineralocorticoid activity

Question 10

What is dexamethasone and describe its activity?

Answer 10

Synthetic glucocorticoid with no mineralocorticoid activity

Question 11

What is fludrocortisone and describe its activity?

Answer 11

Aldosterone analogue (used as a subsititute for deficiencies)

Question 12

What are the routes of admission for corticosteroids?

Answer 12

Oral – hydrocortisone, prednisolone, dexamethasone, fludrocortisone

Parenteral (IV or IM) – hydrocortisone, dexamethasone e.g. in an Addisonian crisis

Question 13

How are corticosteroids distributed in the blood?

Answer 13

Often bind to plasma binding proteins (e.g. CBG and albumin) as cortisol does in the blood

Question 14

What is the duration of activity of hydrocortisone, prednisolone and dexamethasone?

Answer 14

Hydrocortisone - ~8 hours

Prednisolone – ~12 hours

Dexamethasone - ~40 hours

Question 15

What is primary adrenocortical failure?

Answer 15

Addison’s disease

Question 16

How is primary adrenocortical failure treated?

Answer 16

• Patients lack cortisol and aldosterone

- Treated with hydrocortisone (for cortisol) and fludrocortisone (for aldosterone) orally

Question 17

What is secondary adrenocortical failure?

Answer 17

ACTH Deficiency

Question 18

How is secondary adrenocortical failure treated?

Answer 18

• Patients lack cortisol but aldosterone is normal

- Treat with hydrocortisone

Question 19

What is CRT?

Answer 19

corticosteroid replacement therapy

Question 20

What is congenital adrenal hyperplasia?

Answer 20

Larger and missing an enzyme to make cortisol e.g. 21 hydroxylase deficiency

Question 21

What % of CAH are due to 21 hydroxylase deficiency?

Answer 21

95%

Question 22

What happens in 21 hydroxylase deficiency to 17a hydroxyprogesterone and also what does ACTH drive?

Answer 22

• In 21-hydroxylase deficiency, 17a-hydroxyprogesterone accumulates as this is immediately before the enzyme block
• There is no cortisol production so ACTH rises and high ACTH drives further androgen production

Question 23

What is the therapy for 21 hydroxylase deficiency?

Answer 23

Replace cortisol – dexamethasone/hydrocortisone

Supress ACTH (and thus adrenal androgen production)

Replace aldosterone – fludrocortisone

Question 24

How is 21 hydroxylase deficiency treatment monitored?

Answer 24

Clinical assessments:
GC dose too high – cushingoids (symptoms caused by cushing’s)

GC dose too low – hirsutism (as androgens still in excess)

Question 25

Why may glucocorticoids be given when patients are under stress e.g. surgery?

Answer 25

Cortisol levels go up and down depending also upon stress levels so the glucocorticoid dosage should be increased when patients are vulnerable to stress (

Question 26

What is normal cortisol production and cortisol produced during stress?

Answer 26

Normal cortisol production ~20mg/day

Stress cortisol production ~200/300mg/day

Question 27

When is glucocorticoid dosage increased?

Answer 27

Minor illness – 2x normal dose

Surgery – IM hydrocortisone at 6-8 hour intervals

Question 28

What should patients with Addison’s for example carry?

Answer 28

Identification bracelet or necklace with them but not in their wallets as paramedics cannot check that