What is the recommended time to wait after stopping oral prednisolone (corticosteroid) before checking early morning serum cortisol and Adrenocorticotropic Hormone (ACTH) levels in a patient?

Timing of Cortisol and ACTH Testing After Stopping Prednisolone

Wait at least 3-4 weeks after stopping oral prednisolone before checking early morning serum cortisol and ACTH levels to allow adequate time for HPA axis recovery and avoid false-positive results for adrenal insufficiency. 1

Rationale for the Waiting Period

The hypothalamic-pituitary-adrenal (HPA) axis requires time to recover after exogenous glucocorticoid suppression, and testing too early will yield misleadingly low cortisol levels that reflect ongoing suppression rather than true adrenal insufficiency. 2, 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
• Patients on corticosteroids will have low morning cortisol as a result of iatrogenic secondary adrenal insufficiency, with ACTH also suppressed—this is expected and not diagnostic. 2
• Morning cortisol measurements in patients actively taking or recently stopping corticosteroids are unreliable because therapeutic steroids can cross-react with cortisol assays, and the HPA axis remains suppressed. 1

Specific Washout Requirements

• 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 optimal approach is to wait until the patient has been completely weaned off corticosteroids, then test for HPA axis recovery after 3 months of being off steroids or after 3 months of maintenance physiologic replacement with hydrocortisone in cases of isolated central adrenal insufficiency from steroid use. 1

Evidence Supporting the Timeline

Research demonstrates that even brief high-dose glucocorticoid courses can suppress adrenal function for days to weeks:

• After just 5 days of prednisone 50 mg daily, adrenal response to ACTH remained reduced at 5 days post-discontinuation, though pituitary response to hypoglycemia recovered by day 5. 3
• Following a 14-day course of prednisone 0.5 mg/kg daily, 100% of healthy volunteers had suppressed adrenal function on day 1,50% on day 3,26.5% on day 7, and 32.4% still had suppression at day 21. 4
• In SLE patients on low-dose prednisolone (<5 mg/day), serum morning cortisol was collected after 72-hour glucocorticoid discontinuation before performing ACTH stimulation testing, though this short interval is only appropriate for very low doses. 5

Practical Clinical Algorithm

For patients on chronic prednisolone therapy:

1. Taper and discontinue prednisolone completely (or reduce to the lowest possible dose if complete discontinuation is not feasible). 1

2. Wait 3-4 weeks minimum after complete discontinuation before testing. For patients on higher doses (>10 mg daily) or longer duration (>3 months), consider waiting up to 3 months. 1, 4

3. Obtain early morning (8 AM) paired measurements of serum cortisol and plasma ACTH as the first-line diagnostic test. 1

4. Interpret results:

   • Morning cortisol <250 nmol/L (<9 μg/dL) with elevated ACTH suggests primary adrenal insufficiency 1
   • Morning cortisol <250 nmol/L with low or inappropriately normal ACTH suggests secondary adrenal insufficiency 1
   • Morning cortisol 140-500 nmol/L (5-18 μg/dL) requires ACTH stimulation testing for definitive diagnosis 1
   • Morning cortisol >500 nmol/L (>18 μg/dL) generally excludes adrenal insufficiency 1

5. If ACTH stimulation testing is needed: Perform the standard 250 mcg cosyntropin test with cortisol measurements at baseline, 30, and 60 minutes. Peak cortisol <500 nmol/L (<18 μg/dL) is diagnostic of adrenal insufficiency. 1

Critical Pitfalls to Avoid

• Do not attempt diagnostic testing while the patient is still on corticosteroids or immediately after stopping—you will get false-positive results showing "adrenal insufficiency" that simply reflects expected HPA suppression. 2, 1

• In cases of clinical uncertainty with ongoing low-dose steroid use, opt for empiric glucocorticoid replacement and test for ongoing need at 3 months rather than attempting diagnostic testing while on steroids. 1

• If the patient is clinically unstable with suspected adrenal crisis, never delay treatment for diagnostic testing—give hydrocortisone 100 mg IV immediately and draw cortisol/ACTH before treatment if possible. 1, 6

• For long-term steroid exposure, consult endocrinology for a recovery and weaning protocol using hydrocortisone rather than attempting abrupt discontinuation and early testing. 2