What is the conversion of prednisone to cortisol and what is the daily cortisol requirement?

Prednisone to Cortisol Conversion and Daily Cortisol Requirements

Prednisone has approximately 4 times the potency of cortisol, meaning 5 mg of prednisone is equivalent to about 20 mg of cortisol. The normal daily cortisol production in adults is 15-20 mg per day. 1

Prednisone to Cortisol Conversion

Prednisone is a synthetic glucocorticoid that requires conversion to its active form, prednisolone, in the liver. When comparing potency:

• Prednisone is approximately 4 times more potent than cortisol (hydrocortisone)
• 5 mg of prednisone ≈ 20 mg of cortisol
• This conversion factor is important when calculating replacement doses

Normal Daily Cortisol Production

The human body produces cortisol following a distinct diurnal rhythm:

• Total daily cortisol production: 15-20 mg per day
• Peak production: Between 2 am and 8 am
• Lowest production: Around midnight 1

This natural rhythm is important for normal physiological function and explains why:

• Exogenous corticosteroids suppress adrenocortical activity least when given in the morning (before 9 am)
• Single morning doses cause less adrenal suppression than divided doses throughout the day 1

Clinical Implications

Understanding the prednisone-cortisol relationship is critical for:

1. Replacement therapy: When treating adrenal insufficiency, doses should approximate normal physiological production

2. Pharmacologic therapy: When treating inflammatory conditions, doses typically exceed physiologic replacement (often 0.5-1 mg/kg/day of prednisone) 2

3. Adrenal suppression: Doses of prednisone exceeding 5 mg daily for more than a few weeks can suppress the hypothalamic-pituitary-adrenal (HPA) axis

4. Tapering: Abrupt withdrawal should be avoided; gradual tapering is necessary to allow recovery of the HPA axis 1

Minimizing Adrenal Suppression

To minimize adrenal suppression while maintaining therapeutic effect:

• Administer prednisone as a single morning dose (before 9 am) when possible
• Consider alternate-day therapy for long-term treatment when appropriate
• Use the lowest effective dose for the shortest duration possible 1

Cautions

• Patients on long-term prednisone therapy may require stress-dose steroids during illness or surgery
• Adrenal recovery after prolonged therapy can take months
• Monitoring for signs of adrenal insufficiency during tapering is essential

Understanding the relationship between prednisone and cortisol helps clinicians balance therapeutic benefits against the risk of adrenal suppression when prescribing corticosteroid therapy.