Endocrinology 8 - Therapeutical Use Of Adrenal Steroids

Question 1

Compare glucocorticoid receptors and mineralocorticoid receptors

Answer 1

• GRs have a wide distribution, they are selective for glucocorticoids, and have a low affinity for cortisol
• MRs have discrete distribution (kidney), don’t distinguish between aldosterone and cortisol, and have a high affinity for cortisol

Question 2

How are mineralocorticoids protected from cortisol?

Answer 2

11beta-hydroxysteroid dehydrogenase 2 (11bHSD) breaks down cortisol to inactive cortisone

Question 3

Describe the selectivity of hydrocortisone

Answer 3

GR with MR activity at high doses, where 11bHSD is overwhelmed

Question 4

Describe the selectivity of prednisolone

Answer 4

GR with weak MR activity

Question 5

Describe the selectivity of dexamethasone

Answer 5

Synthetic glucocorticoid, with no mineralocorticoid activity

Question 6

Describe the selectivity of fludrocortisone

Answer 6

Aldosterone analogue - replaces aldosterone

Question 7

List the main routes of administration of corticosteroids

Answer 7

• Oral administration (hydrocortisone, prednisolone, dexamethasone, fludocortisone)
• Parentral (IV or IM - hydrocortisone or dexamethasone)

Question 8

Describe the distribution of corticosteroids

Answer 8

Bind to cotisol binding globulin and albumin

Question 9

List the duration of action of the main corticosteroid drugs

Answer 9

• Hydrocortisone 8 hours (multiple times a day)
• Prednisolone 12 hours (once a day)
• Dexamethasone 40 hours

Question 10

List the uses of corticosteroid replacement therapy

Answer 10

• Addisons disease (patients lack cortisol and aldosterone, so are treated by hydrocortisone and fludrocortisone by mouth)
• Secondary adrenocortical failure (ACTH deficiency, treated with hydrocortisone - aldosterone is normal)
• Acute adrenocortical failure (addisonian crisis - IV 0.9% sodium chloride, iv hydroxycortisone, and dextrose)
• Congenital adrenal hyperplasia (dexamethasone or hydrocortisone with a high dose at night to decrease ACTH, with fludrocortisone)

Question 11

List the objectives for therapy in congenital adrenal hyperplasia

Answer 11

• Replace cortisol
• Suppress ACTH (and adrenal androgen production)
• Replace aldosterone in salt wasting forms

Question 12

How is therapy monitored in congenital adrenal hyperplasia?

Answer 12

• Measure 17 OH progesterone
• Cushingoid means GC too high
• Hirsutism means GC too low (hence ACTH is still high)

Question 13

When are glucocorticoid dosage increased?

Answer 13

• When patients are vulnerable to stress (cortisol x10 when stressed)
• In minor illness (x2 normal dose)
• In surgery (intramuscular hydrocortisone with pre-med and at 6-8 hour intervals, oral once eating and drinking)

Question 14

What must patients with adrenocortical failure be told?

Answer 14

Should carry a steroid alert card and wear a MedicAlert bracelet.

Question 15

What is made in each part of the adrenal cortex?

Answer 15

• Zona fasciculata makes cortisol
• Zona glomerulosa makes aldosterone (outermost)
• Zona reticularis makes androgens and oestrogens (innermost)

Question 16

What stimulates the renin aldosterone pathway?

Answer 16

• Hyperkalaemia
• Hyponatraemia
• Decreased renal blood flow
• Sympathetic beta1 adrenoreceptor stimulation

Question 17

What happens in cushings with regards to cortisol and the aldosterone receptor?

Answer 17

• There are such high levels of cortisol that 11bHSD is overwhelmed by cortisol
• This means some cortisol is not converted to cortisone and cortisol will have mineralocorticoid effects (hypernatraemia)

Question 18

How is an addisonian crisis treated?

Answer 18

• With a large dose of IV hydrocortisone to replace cortisol (and also binds to mineralocorticoid receptor, overwhelming 11b-HSD) and fludrocortisone to replace aldosterone
• Dextrose if hypoglycaemic
• Saline to replace sodium

Question 19

How is congenital adrenal hyperplasia diagnosed?

Answer 19

• Measuring the level of 17a-hydroxyprogesterone (this accumulates in 21-hydroxylase deficiency)
• High ACTH (causing increased sex steroids)