For secondary adrenal insufficiency, is 5 mg of prednisolone or Hisone (prednisolone) 10 mg in the morning and 5 mg at 2 pm more effective?

Glucocorticoid Replacement for Secondary Adrenal Insufficiency

For secondary adrenal insufficiency, a divided-dose regimen of prednisolone (such as Hisone 10 mg morning and 5 mg at 2 pm, totaling 15 mg daily) is NOT appropriate and represents excessive dosing that increases mortality risk—the correct maintenance dose is 4-5 mg prednisolone daily, preferably given as a single morning dose or split as 3 mg morning and 1-2 mg at 2 pm. 1

The Critical Dosing Error in Your Question

The regimen "Hisone 10 mg morning and 5 mg at 2 pm" totals 15 mg prednisolone daily, which is 3 times the recommended maintenance dose for adrenal insufficiency. This is a stress-dose regimen, not maintenance therapy. 2, 1

• Standard maintenance dosing for secondary adrenal insufficiency is 4-5 mg prednisolone daily (equivalent to 15-20 mg hydrocortisone) 1, 3
• The 15 mg total daily dose you mentioned would only be appropriate for moderate acute illness requiring 2-3 times maintenance dosing, not routine replacement 2
• Chronic over-replacement with excessive prednisolone doses leads to weight gain, insomnia, peripheral edema, and increased cardiovascular mortality 1

Optimal Dosing Regimens

Single daily dose (preferred for simplicity):

• 4-5 mg prednisolone upon awakening (before 9 am) 1
• This mimics the physiological cortisol peak and reduces insomnia risk 1

Divided dose (for patients with symptoms):

• 3 mg prednisolone upon awakening + 1-2 mg at 2 pm 1
• The afternoon dose should never be taken later than 4-6 hours before bedtime to avoid sleep disruption 1
• Approximately two-thirds of the total dose should be given in the morning 1

Why Not 5 mg Prednisolone as a Single Dose?

While 5 mg prednisolone daily is within the acceptable range and mentioned in guidelines 2, recent evidence shows concerning mortality signals:

• In primary adrenal insufficiency, prednisolone was associated with significantly higher mortality compared to hydrocortisone (adjusted HR 2.92 vs 1.90, P=0.0020) 4
• Even 5 mg prednisolone daily can suppress adrenal function in 39-48% of patients, indicating it may be excessive for many individuals 5, 6
• The 4-5 mg range allows for individualization, with most patients doing well on 4 mg 1

Secondary vs Primary Adrenal Insufficiency: Key Difference

You do NOT need mineralocorticoid (fludrocortisone) replacement in secondary adrenal insufficiency because the renin-angiotensin-aldosterone system remains intact. 2, 3 This is a critical distinction from primary disease.

Monitoring Adequacy of Replacement

Clinical assessment is the primary monitoring method, not laboratory values: 1

Signs of under-replacement:

• Lethargy, nausea, poor appetite, weight loss 1
• These symptoms may prompt inappropriate dose increases

Signs of over-replacement:

• Weight gain, insomnia, peripheral edema 1
• Cushingoid features with chronic excessive dosing

Stress Dosing Education

All patients must understand when to increase their dose: 1, 3

• Minor illness (cold, low-grade fever): Double the usual dose 3
• Moderate illness (high fever, gastroenteritis): 20 mg prednisolone daily (or 60 mg hydrocortisone) 2
• Severe illness/surgery: Requires IV hydrocortisone 100 mg, not oral prednisolone 2
• Patients should wear medical alert identification 1

Common Pitfall: Confusing Maintenance with Stress Dosing

The "10 mg morning and 5 mg afternoon" regimen appears to be a stress-dose protocol that someone mistakenly prescribed for daily maintenance. This is a dangerous error that will lead to iatrogenic Cushing's syndrome over time. 1

Practical Algorithm for Dosing Decision

1. Start with 4 mg prednisolone as a single morning dose 1
2. Assess after 2-4 weeks: If patient reports afternoon fatigue, split to 3 mg morning + 1 mg at 2 pm 1
3. If symptoms persist: Consider switching to hydrocortisone (15-20 mg daily in divided doses) rather than increasing prednisolone, as hydrocortisone has a better safety profile 4, 7
4. Never exceed 5 mg prednisolone daily for maintenance unless during documented physiological stress 1, 3