Endocrinology 8 - Therapeutical Use Of Adrenal Steroids Flashcards
Compare glucocorticoid receptors and mineralocorticoid receptors
- 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
How are mineralocorticoids protected from cortisol?
11beta-hydroxysteroid dehydrogenase 2 (11bHSD) breaks down cortisol to inactive cortisone
Describe the selectivity of hydrocortisone
GR with MR activity at high doses, where 11bHSD is overwhelmed
Describe the selectivity of prednisolone
GR with weak MR activity
Describe the selectivity of dexamethasone
Synthetic glucocorticoid, with no mineralocorticoid activity
Describe the selectivity of fludrocortisone
Aldosterone analogue - replaces aldosterone
List the main routes of administration of corticosteroids
- Oral administration (hydrocortisone, prednisolone, dexamethasone, fludocortisone)
- Parentral (IV or IM - hydrocortisone or dexamethasone)
Describe the distribution of corticosteroids
Bind to cotisol binding globulin and albumin
List the duration of action of the main corticosteroid drugs
- Hydrocortisone 8 hours (multiple times a day)
- Prednisolone 12 hours (once a day)
- Dexamethasone 40 hours
List the uses of corticosteroid replacement therapy
- 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)
List the objectives for therapy in congenital adrenal hyperplasia
- Replace cortisol
- Suppress ACTH (and adrenal androgen production)
- Replace aldosterone in salt wasting forms
How is therapy monitored in congenital adrenal hyperplasia?
- Measure 17 OH progesterone
- Cushingoid means GC too high
- Hirsutism means GC too low (hence ACTH is still high)
When are glucocorticoid dosage increased?
- 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)
What must patients with adrenocortical failure be told?
Should carry a steroid alert card and wear a MedicAlert bracelet.
What is made in each part of the adrenal cortex?
- Zona fasciculata makes cortisol
- Zona glomerulosa makes aldosterone (outermost)
- Zona reticularis makes androgens and oestrogens (innermost)
What stimulates the renin aldosterone pathway?
- Hyperkalaemia
- Hyponatraemia
- Decreased renal blood flow
- Sympathetic beta1 adrenoreceptor stimulation
What happens in cushings with regards to cortisol and the aldosterone receptor?
- 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)
How is an addisonian crisis treated?
- 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
How is congenital adrenal hyperplasia diagnosed?
- Measuring the level of 17a-hydroxyprogesterone (this accumulates in 21-hydroxylase deficiency)
- High ACTH (causing increased sex steroids)
