Therapeutic use of adrenal steroids

Question 1

What are the reasons for giving corticosteroid replacement therapy?

Answer 1

1. Primary adrenocortical failure
2. Secondary adrenocortical failure
3. Acute adrenocortical failure
4. Congenital adrenal hyperplasia
5. Iatrogenic adrencortical failure

Question 2

Why is corticosteroid replacement therapy used in primary adrenocortical failure?

Answer 2

• Addison’s disease + chronic adrenal insufficiency
• Adrenal cortex isn’t work - not making any hormones
• Need replacement of cortisol + aldosterone
• Loss of production of adrenal sex steroids isn’t an issue - gonads make most anyway
• Hydrocortisone (oral) + fludrocortisone (oral)

Question 3

Why is corticosteroid replacement therapy used in secondary adrenocortical failure?

Answer 3

• ACTH deficiency
• Adrenals fine, adenohypophysis not working
• Normal aldosterone production (RAS is normal)
• Need replacement of cortisol
• ACTH controls sex steroid release too but not worth treating
• Hydrocortisone (oral)
• Titrate dose to mimic circadian rhythm

Question 4

How do you treat an Addisonian crisis (acute adrenocortical failure)

Answer 4

1. IV SALINE to rehydrate patient
2. High dose hydrocortisone (iv/im every 6h)
   - No need to give fludrocortisone bc hydrocortisone dose so high that has MR effect
3. 5% dextrose if hypoglycaemic

Question 5

How do you treat congenital adrenal hyperplasia?

Answer 5

1. Replace cortisol - dexamethasone 1/day or hydrocortisone 2-3/day
   - Suppress ACTH and tf adrenal androgen production
2. Replace aldosterone in salt wasting forms - fludrocortisone
3. Monitor therapy by measuring 17a-hydroxyprogesterone levels

Question 6

How do exogenous corticosteroids differ?

Answer 6

1. Hydrocortisone
   - Same structure as cortisol
   - At high doses, can cause MR activation - overwhelsm 11BHSD
2. Prednisolone
   - Immunosuppressive glucocorticoid
   - Weak mineralocorticoid activity
3. Dexamethasone
   - Very potent glucocorticoid
   - Actue anti-oedema agent
   - NO mineralocorticoid effect
4. Fludrocortisone
   - Aldosterone analogue

Question 7

What are the receptors for corticosteroids?

Answer 7

1. Glucocorticoid receptor (GR)
   - Wide distribution
   - Selective for glucocorticoids
   - Low affinity for cortisol
2. Mineralocorticoid receptor (MR)
   - Discrete distribution
   - Do not distinguish btwn aldosterone + cortisol
   - High affinity for cortisol

Question 8

How are MRs protected from cortisol?

Answer 8

11B-hydroxysteroid dehydrogenase

• Deactivates cortisol by converting it to cortisone
• Cortisone is inactive and can’t stimulate MR