Recommended Prednisolone Dosing for Adrenal Insufficiency
For adrenal insufficiency, the recommended prednisolone dose is 4-5 mg once daily upon awakening, or alternatively 3 mg on awakening and 1-2 mg at 14:00h for patients experiencing marked fluctuations in energy levels throughout the day. 1
Primary vs. Alternative Glucocorticoid Options
Hydrocortisone (15-25 mg daily in divided doses) is generally the preferred first-line glucocorticoid replacement therapy for adrenal insufficiency due to its shorter half-life and closer mimicry of physiological cortisol secretion. However, prednisolone has specific indications:
- Indications for prednisolone use:
- Patients with compliance problems with multiple daily dosing
- Patients experiencing marked fluctuations in energy levels throughout the day
- Patients who cannot tolerate hydrocortisone/cortisone acetate 1
Dosing Regimens
Standard Prednisolone Regimens:
- Single daily dose: 4-5 mg upon awakening (07:00)
- Divided dose option: 3 mg on awakening and 1-2 mg at 14:00 1
Special Circumstances:
- Long work shifts: Consider divided dosing (3 mg + 2 mg or 3 mg + 1 mg) 1
- Night shift workers: Adjust timing to take first dose upon awakening before work 1
Monitoring and Dose Adjustment
Clinical assessment is the primary method for monitoring adequacy of glucocorticoid replacement, as plasma ACTH and serum cortisol measurements are not useful parameters for dose adjustment 1.
Signs of under-replacement:
- Lethargy
- Nausea
- Poor appetite
- Weight loss
- Increased pigmentation (especially with uneven distribution)
Signs of over-replacement:
- Weight gain
- Insomnia
- Peripheral edema
Special Considerations
Stress Dosing
During periods of stress, illness, or surgery, glucocorticoid doses must be increased:
- Minor illness/stress: Double or triple usual daily dose
- Moderate stress: Equivalent to hydrocortisone 50-75 mg/day in divided doses
- Severe stress/major surgery: Hydrocortisone 100 mg IV immediately followed by 200-300 mg/day as continuous infusion or divided doses 1, 2
- Post-major surgery: Double oral doses for 48 hours or up to a week 1
- Post-minor surgery: Double oral doses for 24 hours 2
Mineralocorticoid Replacement
For primary adrenal insufficiency, mineralocorticoid replacement with fludrocortisone (0.05-0.2 mg daily) is essential in addition to glucocorticoid therapy 1, 2, 3.
Drug Interactions
Be aware of medications that can affect glucocorticoid metabolism:
- May increase glucocorticoid requirements: Anti-epileptics, barbiturates, antituberculosis drugs, etomidate, topiramate
- May decrease glucocorticoid requirements: Grapefruit juice, licorice 1
Important Precautions
Adrenal crisis prevention: All patients should wear a medical alert bracelet and carry a steroid card 1, 2
Malabsorption: In suspected cases, serum or salivary cortisol day curve monitoring may guide dosing 1
Avoid dexamethasone: Dexamethasone is not adequate for primary adrenal insufficiency as it lacks mineralocorticoid activity 1, 2
Morning symptoms: For patients with morning nausea/vomiting, consider waking earlier to take medication and then returning to sleep 1
Transitioning from IV to oral therapy: When transitioning from IV hydrocortisone to oral maintenance therapy, double the usual maintenance oral dose for 24-48 hours 2
Long-term Considerations
Approximately 15-48% of patients on long-term prednisolone therapy (even at doses as low as 5 mg/day) may develop secondary adrenal insufficiency 4, 5. This highlights the importance of appropriate stress dosing protocols and careful monitoring, especially when considering glucocorticoid withdrawal.