Usual Oral Hydrocortisone Dose for Primary Adrenal Insufficiency
For adults with primary adrenal insufficiency, use hydrocortisone 15-25 mg daily divided into 2-3 doses, with the highest dose given in the morning upon awakening. 1
Dosing Regimen
The Endocrine Society Clinical Practice Guideline provides clear recommendations for glucocorticoid replacement:
- Hydrocortisone: 15-25 mg/day divided into 2 or 3 oral doses 1
- Alternative: Cortisone acetate 20-35 mg/day in divided doses 1
Timing of Doses
The dosing schedule should mimic physiological cortisol secretion:
- Highest dose: Morning at awakening
- Two-dose regimen: Second dose in early afternoon (2 hours after lunch)
- Three-dose regimen: Doses at morning, lunch, and afternoon 1
This timing is critical because it attempts to replicate the natural diurnal cortisol rhythm, though current oral formulations cannot perfectly achieve physiological fluctuations 2.
Alternative Glucocorticoid Options
Prednisolone 3-5 mg/day (once or twice daily) is suggested as an alternative, particularly for patients with compliance issues 1. Recent evidence shows prednisolone 2-4 mg once daily is safe and effective, with the convenience of single daily dosing potentially improving adherence 3.
Avoid dexamethasone due to difficulty in dose titration and risk of Cushingoid side effects 1.
Monitoring and Dose Adjustment
Monitor clinically, not hormonally 1. The guideline explicitly recommends against hormonal monitoring for dose adjustment. Instead, assess:
- Body weight
- Postural blood pressure
- Energy levels
- Signs of glucocorticoid excess (Cushingoid features)
- Signs of insufficiency (fatigue, hypotension, salt craving) 1
Important Caveats
Individual variation exists: While the 15-25 mg range is standard, some patients may require higher frequency regimens or size-based dosing 1. Recent evidence suggests non-obese individuals may do well with even lower doses (10-15 mg/24h) 2, though the guideline maintains the 15-25 mg recommendation as the evidence-based standard.
Don't forget mineralocorticoid replacement: All patients with confirmed aldosterone deficiency require fludrocortisone 50-100 μg starting dose plus unrestricted salt intake 1.
The FDA labeling indicates a broader range (20-240 mg/day) for various conditions 4, but for replacement therapy specifically in primary adrenal insufficiency, the narrower 15-25 mg range from the Endocrine Society guideline is the appropriate target, as this reflects physiological cortisol production rather than pharmacological dosing for other conditions.