Can a Short Synacthen Test Be Performed in a Patient on Prednisone?
No, you should not perform a short Synacthen test while a patient is actively taking prednisone or other therapeutic corticosteroids, as exogenous steroids suppress the HPA axis and will confound the results, leading to false-negative findings. 1, 2
Why the Test Cannot Be Reliably Interpreted on Prednisone
Exogenous steroids including prednisone suppress endogenous cortisol production and interfere with cortisol assays. The measurement of therapeutic steroids varies in cortisol assays, making morning cortisol levels unreliable in patients on corticosteroids. 1 Additionally, therapeutic glucocorticoid use causes iatrogenic secondary adrenal insufficiency by suppressing the hypothalamic-pituitary-adrenal axis. 2
Key Evidence from Studies
Research directly addressing this question shows that approximately one-third to one-half of patients taking 5-20 mg prednisolone daily fail to achieve target cortisol concentrations on short Synacthen testing, even when they may have adequate adrenal reserve. 1 A specific study comparing the short Synacthen test to the insulin tolerance test in 22 patients on long-term prednisolone (<10 mg/day) found that 8 patients passed the insulin tolerance test but failed the short Synacthen test, demonstrating the test's unreliability in this population. 3
How to Properly Assess Adrenal Function in Patients on Prednisone
Timing of Steroid Withdrawal
Hydrocortisone must be held for 24 hours before testing, while other steroids including prednisone require longer washout periods before endogenous adrenal function can be accurately assessed. 1 The exact duration for prednisone is not specified in guidelines, but given its longer half-life compared to hydrocortisone, at least 48-72 hours would be prudent.
Alternative Approach: Test After Discontinuation
Laboratory confirmation of adrenal insufficiency should not be attempted in patients given high-dose corticosteroids until treatment is ready to be discontinued. 1 The recommended approach is:
- Wait until the patient has been weaned off corticosteroids before performing definitive HPA axis testing 1
- Test for HPA axis recovery after 3 months of maintenance therapy with hydrocortisone in patients with isolated central adrenal insufficiency from steroid use 1
- Consider endocrinology consultation for recovery and weaning protocols using hydrocortisone in patients with symptoms of adrenal insufficiency after weaning off corticosteroids 1
If Urgent Assessment Is Needed
If you suspect adrenal insufficiency in a patient currently on prednisone and cannot wait for steroid washout:
In cases of clinical uncertainty with ongoing steroid use, opt for empiric glucocorticoid replacement and test for ongoing need at 3 months rather than attempting diagnostic testing while on steroids. 1 This approach prioritizes patient safety over diagnostic certainty.
Critical Clinical Scenarios Requiring Immediate Action
If a patient on prednisone develops unexplained hypotension, collapse, or signs of adrenal crisis, treatment should NEVER be delayed for diagnostic testing. 2 Give IV hydrocortisone 100 mg immediately plus 0.9% saline infusion. 2
Exception: Using Dexamethasone for Emergent Treatment
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 This allows you to stabilize the patient while preserving the ability to perform a short Synacthen test afterward.
Common Pitfalls to Avoid
- Do not rely on a "normal" short Synacthen test result in a patient taking prednisone to rule out adrenal insufficiency—the test is unreliable in this context 1, 3
- Do not assume that low-dose prednisone (<5 mg daily) is safe from causing HPA axis suppression—even 5 mg prednisolone can cause inadequate adrenal reserve in a significant number of patients 1
- Do not perform the test without adequate steroid washout unless using dexamethasone for acute management 1, 2
Practical Algorithm for Decision-Making
Is the patient clinically unstable or showing signs of adrenal crisis?
- Yes → Treat immediately with IV hydrocortisone 100 mg (or dexamethasone 4 mg if you want to test later) 2
- No → Proceed to step 2
Can you safely discontinue prednisone for adequate washout (≥48-72 hours)?
- Yes → Hold prednisone, then perform short Synacthen test 1
- No → Proceed to step 3
Is there clinical suspicion of adrenal insufficiency despite ongoing prednisone use?
- Yes → Opt for empiric replacement therapy and test for recovery at 3 months 1
- No → Continue current management and reassess when steroids can be safely discontinued