Corticosteroid Selection: Dexamethasone vs Hydrocortisone vs Prednisone
The choice between dexamethasone, hydrocortisone, and prednisone depends primarily on the clinical indication: hydrocortisone is preferred for adrenal insufficiency due to its mineralocorticoid activity; prednisone is the standard for most inflammatory and autoimmune conditions; and dexamethasone is chosen when rapid onset, high potency, or lack of mineralocorticoid effects are needed.
Potency and Pharmacologic Differences
The three corticosteroids differ substantially in potency and duration of action:
- Hydrocortisone is the least potent, with the shortest duration of action and significant mineralocorticoid activity 1, 2
- Prednisone is 4-5 times more potent than hydrocortisone with intermediate duration and minimal mineralocorticoid effects 2
- Dexamethasone is approximately 25 times more potent than hydrocortisone, has the longest duration of action, and completely lacks mineralocorticoid activity 1, 2
The equivalent anti-inflammatory doses are: 20 mg hydrocortisone = 5 mg prednisone = 0.75 mg dexamethasone 3.
Indication-Specific Recommendations
Adrenal Insufficiency and Replacement Therapy
Hydrocortisone is the drug of choice for primary or secondary adrenocortical insufficiency because it is structurally identical to endogenous cortisol and provides necessary mineralocorticoid activity 1, 4, 1.
- For acute adrenal crisis or perioperative stress coverage, hydrocortisone 200-300 mg/day (as infusion or divided doses) is recommended 3
- Dexamethasone is inadequate for primary adrenal insufficiency because it lacks mineralocorticoid activity 3
- In congenital adrenal hyperplasia, nocturnal dexamethasone may provide superior ACTH suppression compared to standard hydrocortisone dosing, though longer-term safety data are needed 5
Sepsis and Septic Shock
Hydrocortisone is the preferred corticosteroid for sepsis, as it was the most commonly studied agent in randomized trials 3.
- Typical adult dosing: 200-300 mg/day as continuous infusion or divided boluses every 6 hours 3
- Treatment duration: 7-14 days or less if rapidly improving 3
- Dexamethasone, methylprednisolone, and prednisolone produced similar results and are acceptable alternatives 3
- Adding fludrocortisone for additional mineralocorticoid activity is speculative but potentially helpful 3
Immune Thrombocytopenia (ITP)
For newly diagnosed adult ITP, either prednisone (0.5-2.0 mg/kg/day) or dexamethasone (40 mg/day for 4 days) are acceptable first-line options 3.
- Prednisone is the traditional standard first-line therapy, typically given at 0.5-2 mg/kg/day until platelet count increases to 30-50 × 10⁹/L 3
- Dexamethasone provides faster platelet response at 7 days (RR 1.31; 95% CI 1.11-1.54) and may achieve higher sustained response rates (50-80% with multiple cycles) 3
- If rapid platelet count response is prioritized, dexamethasone is preferred over prednisone 3
- Corticosteroid duration should not exceed 6 weeks to minimize toxicity 3
Inflammatory and Autoimmune Conditions
Prednisone is the standard corticosteroid for most chronic inflammatory conditions including rheumatic disorders, collagen vascular diseases, and inflammatory bowel disease 1, 4.
- Prednisone provides intermediate potency with good oral bioavailability 2
- For acute exacerbations requiring parenteral therapy, methylprednisolone or hydrocortisone can be used 3
- Dexamethasone is reserved for specific situations requiring high potency or long duration 2
Sudden Sensorineural Hearing Loss
Prednisone 1 mg/kg/day (maximum 60 mg/day) is the standard oral corticosteroid, with equivalent doses of methylprednisolone (48 mg/day) or dexamethasone (10 mg/day) as alternatives 3.
- Treatment should begin within 14 days of onset, ideally immediately 3
- Duration: full dose for 7-14 days, then taper over similar period 3
- Intratympanic dexamethasone or methylprednisolone can be used as salvage therapy 3
Immune Checkpoint Inhibitor Toxicity
Prednisone 0.5-1 mg/kg/day (or equivalent methylprednisolone) is the standard for grade 2-3 immune-related adverse events 3.
- For dermatologic toxicity: topical corticosteroids (clobetasol for body, hydrocortisone 2.5% for face) are used for grade 1-2 reactions 3
- Systemic prednisone is escalated for grade 3 reactions covering >30% body surface area 3
- For colitis: prednisone 1 mg/kg/day initially, increased to 2 mg/kg/day if no improvement in 48 hours 3
Glomerular Diseases
Oral prednisolone or prednisone is the standard corticosteroid for most glomerular diseases including IgA nephropathy, membranous nephropathy, and nephrotic syndrome 3.
- In children with nephrotic syndrome, prednisolone dosing is typically 60 mg/m²/day until remission, then tapered 3
- Deflazacort and high-dose methylprednisolone are alternatives with similar efficacy 3
- Weight-based dosing (1.5 mg/kg, maximum 40 mg) versus body surface area dosing (40 mg/m²) show comparable outcomes 3
Critical Caveats
Mineralocorticoid Activity
Hydrocortisone is essential when mineralocorticoid effects are needed (primary adrenal insufficiency), while dexamethasone's lack of this activity makes it unsuitable for replacement therapy but advantageous when sodium retention must be avoided 3, 1.
Duration and Toxicity
Shorter corticosteroid courses minimize adverse effects including hyperglycemia, hypertension, mood disturbances, osteoporosis, and immunosuppression 3. The risk-benefit ratio shifts unfavorably with courses exceeding 6 weeks 3.
Tapering Requirements
Corticosteroids should be tapered rather than stopped abruptly, especially after courses longer than 14 days, to prevent adrenal insufficiency and rebound inflammation 3. Monitor for recurrence of symptoms after discontinuation 3.
Drug Interactions
Patients taking CYP3A4 inducers may require higher hydrocortisone doses due to increased metabolism 3. Conversely, critically ill patients may have prolonged elimination half-lives 3.