How can I interpret cortisol levels after administering 50 mg of hydrocortisone (cortisol replacement therapy) every 6 hours?

Interpreting Cortisol Levels After Hydrocortisone Administration

Cortisol levels measured at 8 AM after administering 50 mg of hydrocortisone every 6 hours will be artificially elevated and cannot be used to assess endogenous adrenal function. 1

Pharmacokinetics of Hydrocortisone and Cortisol Measurement

When administering hydrocortisone as replacement therapy, the exogenous hydrocortisone will significantly affect measured cortisol levels:

• Hydrocortisone (synthetic cortisol) is identical to endogenous cortisol and cannot be distinguished in laboratory tests
• After oral administration of 50 mg hydrocortisone, plasma cortisol levels increase approximately 3-fold, while salivary cortisol increases about 10-fold 2
• The half-life of hydrocortisone is approximately 1.5 hours 3
• Peak cortisol concentrations after oral hydrocortisone are uniformly supraphysiological 4

Why 8 AM Cortisol Testing After Hydrocortisone Is Invalid

Several factors make this approach problematic:

• With q6h dosing (50 mg every 6 hours), the last dose would have been given at 2 AM, meaning the 8 AM measurement occurs 6 hours after administration
• Even after 6 hours, significant exogenous hydrocortisone remains in circulation
• The normal diurnal rhythm of cortisol (highest in early morning) is disrupted by exogenous administration 5
• The administered dose (50 mg q6h = 200 mg/day) is substantially higher than physiological cortisol production (typically 20 mg/day) 1

Proper Assessment of Adrenal Function

To accurately assess endogenous adrenal function:

1. Discontinue hydrocortisone: Hydrocortisone should be held for at least 24 hours before testing
2. Use appropriate testing methods:
   • Morning cortisol measurement (after holding hydrocortisone)
   • ACTH stimulation test
   • Cortisol day curve measurements

Hydrocortisone Dosing Considerations

The current regimen of 50 mg q6h (200 mg/day) is significantly higher than standard replacement:

• Standard replacement dosing is typically 15-25 mg/day in divided doses 6
• For perioperative stress coverage, guidelines recommend 50 mg q6h as appropriate for major surgery 1, 7
• This high-dose regimen is intended for short-term use during periods of physiological stress

Clinical Implications

If attempting to assess adrenal function:

• The 8 AM cortisol will reflect primarily exogenous hydrocortisone
• The measurement cannot differentiate between endogenous production and administered medication
• Any interpretation of adrenal function would be invalid

Alternative Approaches

For monitoring hydrocortisone replacement:

• Salivary cortisol and urinary cortisol:creatinine ratio correlate well with plasma cortisol 4
• Clinical symptoms (fatigue, weight changes, blood pressure) may guide dosing
• Cortisol day curves can help optimize replacement dosing 5

Common Pitfalls

• Assuming measured cortisol reflects endogenous production when exogenous hydrocortisone has been administered
• Failing to account for the pharmacokinetics of hydrocortisone when interpreting results
• Using cortisol measurements to adjust dosing without considering the timing of last hydrocortisone dose
• Not recognizing that high-dose hydrocortisone (50 mg q6h) is a stress-dose regimen, not maintenance therapy

Remember that proper assessment of adrenal function requires temporary discontinuation of exogenous glucocorticoids when clinically safe to do so, with appropriate monitoring for adrenal crisis.