How long after the last dose of hydrocortisone (cortisol replacement therapy) can cortisol levels be checked?

Timing of Cortisol Testing After Hydrocortisone Administration

Cortisol levels should be checked at least 24 hours after the last dose of hydrocortisone to obtain accurate results that reflect endogenous adrenal function. 1

Rationale for 24-Hour Washout Period

• The American College of Clinical Oncology recommends holding hydrocortisone for at least 24 hours before assessing endogenous adrenal function, as exogenous steroids interfere with cortisol assays 1
• Hydrocortisone has a relatively short half-life (mean 76.5 minutes, range 40-225.3 minutes), but complete clearance from the circulation takes significantly longer 2
• After oral hydrocortisone administration, serum cortisol typically reaches undetectable levels within 7 hours (range: 5-12 hours) following morning doses and 9 hours (range: 5-12 hours) following evening doses 3

Pharmacokinetic Considerations

• Following oral hydrocortisone administration, cortisol levels typically peak at approximately 1.2 hours (range: 0.3-3.3 hours) and then decline monoexponentially 3
• The bioavailability of oral hydrocortisone is high (94.2% in the morning), which can result in supraphysiological cortisol concentrations within 1-2 hours after administration 3
• Individual variation in absorption and half-life significantly influences overall exposure to glucocorticoids, with time to reach cortisol levels <100 nmol/L ranging from 140-540 minutes 2

Best Practices for Cortisol Testing

• Morning cortisol samples should ideally be collected between 7:30-8:00 AM when cortisol levels are naturally at their highest 1
• For patients requiring ongoing hydrocortisone therapy who need cortisol testing, the following approach is recommended:
  • Hold hydrocortisone for at least 24 hours before testing 1
  • For longer-acting steroids (e.g., prednisone), a longer washout period is necessary 1
  • Schedule the test early in the morning to capture the natural peak of cortisol production 1

Special Considerations

• Patients with known adrenal insufficiency should not discontinue hydrocortisone for testing without medical supervision due to risk of adrenal crisis 4
• For patients undergoing diagnostic evaluation for possible adrenal insufficiency, a standard-dose ACTH stimulation test may be more appropriate than a single cortisol measurement 4
• In cases where holding hydrocortisone is not feasible, interpretation of results should account for the interference of exogenous steroids 1

Pitfalls to Avoid

• Testing cortisol levels too soon after hydrocortisone administration will lead to falsely elevated results that do not reflect true endogenous adrenal function 1
• Failing to consider the circadian rhythm of cortisol when scheduling tests can lead to misinterpretation of results 5
• Not accounting for individual variations in hydrocortisone pharmacokinetics may lead to inappropriate timing of cortisol measurements 6, 2