Prednisolone Washout Period Before Adrenal Insufficiency Screening
Wait 48 hours after stopping prednisolone before performing the cosyntropin stimulation test to allow accurate cortisol measurement and avoid false-positive results from iatrogenic HPA axis suppression. 1
Pharmacokinetic Rationale
- Prednisolone has a plasma half-life of only 2-4 hours, but its biological effects on HPA axis suppression persist much longer than the drug's presence in circulation 1
- The 48-hour washout period allows prednisolone to clear sufficiently so that measured cortisol reflects endogenous adrenal function rather than exogenous steroid interference 1
- Morning cortisol measurements in patients actively taking prednisolone are not diagnostic because the assay measures both endogenous cortisol and therapeutic steroids, with cross-reactivity varying by assay 2
Critical Testing Protocol
- The Endocrine Society recommends never attempting diagnostic testing while the patient is actively taking prednisolone, as morning cortisol will be falsely low due to iatrogenic secondary adrenal insufficiency 1
- After the 48-hour washout, perform the standard cosyntropin stimulation test using 0.25 mg IV or IM, with cortisol measurements at baseline and 30 minutes post-administration 1
- A peak cortisol level of less than 500 nmol/L (18 μg/dL) at 30 minutes is diagnostic of adrenal insufficiency 1, 3
Important Safety Considerations
- The 48-hour washout is only safe for stable outpatients—if a patient is acutely ill or unstable, immediately treat with IV hydrocortisone 100 mg without waiting for testing 1, 4
- Treatment of suspected acute adrenal insufficiency should never be delayed for diagnostic procedures 1, 4, 3
- Patients on more than 7.5 mg prednisolone equivalent daily for more than 3 weeks should be anticipated to have HPA axis suppression, with approximately 39-48% having adrenal insufficiency 1, 5
Alternative Approach for Chronic Steroid Users
- For patients on chronic prednisolone who cannot safely stop for 48 hours, consider empiric glucocorticoid replacement and defer definitive testing for 3 months after switching to physiologic hydrocortisone replacement 1, 2
- After 3 months on stable hydrocortisone maintenance therapy, perform ACTH stimulation testing to assess HPA axis recovery, prioritizing patient safety over immediate diagnostic certainty 1
- Laboratory confirmation of adrenal insufficiency should not be attempted until corticosteroid treatment is ready to be discontinued and sufficient washout time has elapsed 2
Common Pitfalls to Avoid
- Do not test while the patient is still on prednisolone or immediately after stopping—this will yield false-positive results showing "adrenal insufficiency" that simply reflects expected HPA suppression 2
- Hydrocortisone must be held for 24 hours before testing, while other steroids including prednisolone require longer washout periods (48 hours minimum) 2
- If you need to treat suspected adrenal crisis but still want to perform diagnostic testing later, use dexamethasone 4 mg IV instead of hydrocortisone, as dexamethasone does not interfere with cortisol assays 2, 6
- In cases of long-term steroid exposure, consult endocrinology for a recovery and weaning protocol using hydrocortisone rather than attempting abrupt discontinuation and early testing 2