PharmacologyTier 1Medical Sciences concept

Corticosteroid potency and mineralocorticoid activity comparison

Core concept

Two independent axes: glucocorticoid (anti-inflammatory) potency and mineralocorticoid (Na-retaining) activity
Cortisol and aldosterone both bind the mineralocorticoid receptor with equal affinity
- Specificity comes from 11-beta-hydroxysteroid dehydrogenase type 2 in the distal nephron, which converts cortisol -> inactive cortisone
- Synthetic steroids modified at C11 or with a 9-alpha-fluoro group resist this -> fludrocortisone has potent MR activity; dexamethasone and betamethasone have essentially none

Drug	Equivalent dose	Glucocorticoid potency	Mineralocorticoid	Biological t-half
Hydrocortisone	20 mg	1	1 (highest of the glucocorticoids)	8-12 h
Cortisone acetate	25 mg	0.8	0.8	8-12 h
Prednisolone	5 mg	4	0.6	12-36 h
Methylprednisolone	4 mg	5	0.5	12-36 h
Triamcinolone	4 mg	5	0	12-36 h
Dexamethasone	0.75 mg	25-30	0	36-72 h
Betamethasone	0.75 mg	25-30	0	36-72 h
Fludrocortisone	-	10	125	12-36 h

Useful conversions
- Prednisolone 25 mg = hydrocortisone 100 mg = dexamethasone 4 mg
- Hydrocortisone 100 mg IV three times daily is roughly prednisolone 75 mg daily equivalent
Choose by the axis you need
- Adrenal replacement -> hydrocortisone (physiological pattern, MR activity) + fludrocortisone in primary adrenal insufficiency
- Cerebral oedema, antiemesis, croup, fetal lung maturation, myeloma -> dexamethasone (long-acting, no fluid retention)
- Chronic inflammatory disease -> prednisolone
- Intra-articular -> triamcinolone (poorly soluble, long local action)
Dexamethasone suppresses the HPA axis most powerfully and for longest - hence its use in the 1 mg overnight suppression test, and its greater axis-suppression risk
Hydrocortisone is not "weaker" in a useful clinical sense - it is shorter-acting and more mineralocorticoid

Adrenal crisis: hydrocortisone 100 mg IV then 50 mg 6-hourly (or 200 mg/24 h infusion) with fluid resuscitation - never dexamethasone as maintenance replacement (no MR activity)
- Dexamethasone is the exception when a short Synacthen test is planned - it does not cross-react in the cortisol assay
Sick day rules - double the usual replacement dose for febrile illness; parenteral for vomiting or surgery
Any patient on >5 mg prednisolone (or equivalent) for >3-4 weeks has a suppressed axis - taper, and provide stress cover
Fludrocortisone is also used for neurogenic orthostatic hypotension and for type 4 RTA/hyperkalaemia
Adverse effects scale with cumulative dose and duration: hyperglycaemia, osteoporosis, myopathy, cataract, infection, avascular necrosis, skin atrophy, psychiatric effects
- Fluid retention, hypertension and hypokalaemia only with the mineralocorticoid-active agents

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