Timing of Cortisol Sampling After Hydrocortisone Administration
After administering 50 mg of hydrocortisone, you should wait at least 24 hours before taking a cortisol sample to accurately assess endogenous adrenal function. 1
Why 24 Hours Is Necessary
Hydrocortisone administration significantly affects cortisol measurements in several important ways:
- Exogenous hydrocortisone (50 mg) produces cortisol levels that are substantially higher than physiological production (typically 20 mg/day) 1
- Plasma cortisol measurements taken before 24 hours will primarily reflect the administered medication rather than endogenous production 1
- Cortisol concentrations after a 50 mg dose remain elevated for many hours, with significant interference in laboratory measurements 2
Pharmacokinetics of 50 mg Hydrocortisone
Understanding the pharmacokinetics helps explain why 24 hours is necessary:
- After a 50 mg oral dose, peak cortisol concentrations (Cmax) occur at approximately 1.7 hours 3
- These peak levels are supraphysiological and can reach 419 ng/mL or higher 3
- Even with a half-life of approximately 1.5 hours, multiple half-lives are needed for the exogenous hydrocortisone to clear sufficiently 3
- Studies show that after IV administration of 50 mg hydrocortisone, cortisol levels at 30 minutes are extremely high and remain elevated for hours 2
Clinical Implications
When assessing adrenal function:
- Any cortisol sample taken before 24 hours will be artificially elevated and cannot differentiate between endogenous production and administered medication 1
- This applies to all forms of cortisol measurement (plasma, salivary, or urinary) 2
- For accurate assessment of the hypothalamic-pituitary-adrenal axis, hydrocortisone must be completely cleared from the system 1
Alternative Assessment Methods
If you need to assess adrenal function after hydrocortisone administration:
- Wait at least 24 hours after the last dose 1
- Consider using an ACTH stimulation test after the washout period 1
- Cortisol day curve measurements may be helpful for optimizing replacement dosing 1, 4
Common Pitfalls to Avoid
- Taking cortisol samples too soon (especially at 2 hours post-dose when levels are uniformly supraphysiological) 2
- Misinterpreting elevated cortisol levels as adequate endogenous production when they actually reflect exogenous medication 1
- Failing to recognize that even "low-dose" hydrocortisone therapy produces cortisol concentrations that considerably exceed both basal and ACTH-stimulated levels 5
Remember that accurate assessment of adrenal function is critical for appropriate management of patients with adrenal insufficiency, and premature testing can lead to incorrect clinical decisions.