What is the recommended maintenance dose of prednisolone (glucocorticoid) for primary adrenal insufficiency?

Prednisolone Maintenance Dose in Primary Adrenal Insufficiency

The recommended maintenance dose of prednisolone for primary adrenal insufficiency is 4-5 mg daily, typically given as a single dose upon awakening (before 9 am), or alternatively as a divided regimen of 3 mg on awakening and 1-2 mg at 14:00h. 1, 2

Standard Dosing Regimens

Single Daily Dose (Preferred for Compliance)

• Prednisolone 4-5 mg taken upon awakening (before 9 am) 1, 2
• This single-dose approach should be considered when patients have compliance problems or marked fluctuations of energy 1

Divided Dose Regimen (For Long Shifts or Severe Symptoms)

• 3 mg on awakening and 1-2 mg at 14:00h 1, 2
• The second dose should not be taken later than 4-6 hours before bedtime to avoid insomnia 2
• This regimen is particularly useful for patients working long shifts (e.g., airline stewardesses, postmen) 1

Important Context: Prednisolone vs. Hydrocortisone

Prednisolone should only be considered as a second-line option when hydrocortisone or cortisone acetate is not tolerated or when there are compliance problems 1. The dose equivalence is approximately 20 mg hydrocortisone = 5 mg prednisolone 2.

Essential Mineralocorticoid Replacement

All patients with primary adrenal insufficiency require fludrocortisone 0.05-0.2 mg daily in addition to glucocorticoid replacement 2, 3. This is critical because:

• Primary adrenal insufficiency involves deficiency of all adrenocortical hormones, including mineralocorticoids 3
• Under-replacement of mineralocorticoids is common and may predispose patients to recurrent adrenal crises 1
• The dose should be adjusted based on blood pressure (supine and standing), salt cravings, and electrolyte levels 1

Monitoring and Dose Adjustment

Clinical Assessment (Not Laboratory Values)

Clinical symptoms are the primary method for monitoring adequacy of replacement 2:

Signs of over-replacement:

• Weight gain 2
• Insomnia 2
• Peripheral edema 2

Signs of under-replacement:

• Lethargy 2
• Nausea and poor appetite 2
• Weight loss 2
• Increased pigmentation 2

Drug Interactions Requiring Dose Adjustment

Several medications increase prednisolone requirements 1, 2:

• Anti-epileptics and barbiturates 1, 2
• Antituberculosis medications 1, 2
• Antifungal drugs may require medication changes 1, 2

Substances that may decrease prednisolone requirements:

• Grapefruit juice 1, 2
• Liquorice 1, 2

Critical Safety Considerations

Stress Dosing Education

All patients must be educated on stress dosing and prescribed injectable hydrocortisone 100 mg for emergencies 3. This is essential because:

• Adrenal crisis can cause hypotension, shock, and death if untreated 3
• Patients need to increase glucocorticoids during acute illness 3
• Injectable glucocorticoids prevent or treat adrenal crisis 3

Medical Alert Identification

Patients should wear a medical alert bracelet or necklace indicating adrenal insufficiency 2

Special Populations and Situations

Morning Nausea

• Patients can wake earlier to take the first dose, then return to sleep to relieve symptoms 2

Night Shift Workers

• Adjust dosing schedule according to sleep-wake pattern, taking the first dose upon awakening before work 2

Pregnancy

• Higher fludrocortisone doses (up to 500 µg daily) may be needed in the last trimester when progesterone counteracts mineralocorticoids 1

Common Pitfall to Avoid

Do not compensate for under-replacement of mineralocorticoids by over-replacing glucocorticoids 1. This practice is common but inappropriate and may lead to long-term adverse outcomes from glucocorticoid excess while still predisposing patients to adrenal crises from inadequate mineralocorticoid replacement 1.