How long should a patient stop exogenous glucocorticoids before drawing a morning (8 a.m.) serum cortisol, based on the steroid’s duration of action?

Timing of Last Steroid Before Morning Cortisol Testing

For short-acting glucocorticoids (prednisone, prednisolone, methylprednisolone, hydrocortisone), stop the medication on the day of testing and draw the 8 a.m. cortisol the following morning—this represents approximately 12-24 hours off the steroid. For long-acting glucocorticoids (dexamethasone, betamethasone), a longer washout period of at least 2 weeks is required before cortisol testing can reliably assess hypothalamic-pituitary-adrenal (HPA) axis recovery. 1, 2, 3

Understanding Steroid Duration of Action and HPA Suppression

The duration of adrenocortical suppression varies dramatically based on the specific glucocorticoid used:

• Short-acting steroids (prednisone, prednisolone, methylprednisolone, hydrocortisone) produce adrenocortical suppression for 1.25 to 1.5 days following a single dose 1
• Long-acting steroids (dexamethasone, betamethasone) produce adrenocortical suppression for 2 or more days following a single dose 1
• The maximal activity of the adrenal cortex occurs between 2 a.m. and 8 a.m., which is why morning cortisol testing is performed during this window 1

Practical Algorithm for Cortisol Testing During Glucocorticoid Weaning

For Patients on Short-Acting Glucocorticoids (Prednisone, Prednisolone, Methylprednisolone)

1. Stop glucocorticoids on the day of testing 2
2. Draw 8 a.m. serum cortisol the following morning (approximately 12-24 hours after last dose) 2, 3
3. Interpret results:
   • Morning cortisol >290 nmol/L (10.5 µg/dL) in adults predicts the patient can stop glucocorticoid therapy and will recover adrenal function 4
   • Morning cortisol >278 nmol/L (10.1 µg/dL) in children has 95% sensitivity for predicting HPA axis recovery 4
   • Morning cortisol <290 nmol/L suggests ongoing HPA suppression and requires continued glucocorticoid therapy with repeat testing later 4

For Patients on Long-Acting Glucocorticoids (Dexamethasone, Betamethasone)

1. Stop glucocorticoids for at least 2 weeks before testing 1, 2
2. These agents are specifically not recommended for alternate-day therapy precisely because of their prolonged suppressive effect on adrenal activity 1
3. The extended washout period is necessary because a single dose can suppress the HPA axis for 2+ days 1

Duration of Glucocorticoid Therapy and Testing Requirements

Short-Term Use (<3-4 Weeks)

• Patients can stop glucocorticoids abruptly without tapering 3
• Morning cortisol testing is generally not required 3
• HPA axis suppression is unlikely with such brief exposure 3

Prolonged Use (>3-4 Weeks)

• Prolonged glucocorticoid use causes HPA axis suppression, necessitating gradual tapering 3
• Morning serum cortisol testing should be used to assess HPA axis recovery and guide glucocorticoid cessation 3
• For some patients, dosage can be tapered and stopped without testing serum cortisol concentrations, but testing provides objective guidance 3

When to Proceed to ACTH Stimulation Testing

If morning cortisol results are equivocal or repeatedly low despite prolonged periods at physiological glucocorticoid doses:

• Perform a short synacthen test (SST) with cosyntropin 2, 3, 4
• Morning cortisol cut-offs that predict SST passage with 99% sensitivity are 316 nmol/L (11.5 µg/dL) in children and 349 nmol/L (12.7 µg/dL) in adults 4
• Consider endocrinology referral for patients with repeated low cortisol concentrations 3

Critical Pitfalls to Avoid

Do not test morning cortisol while the patient is still taking glucocorticoids—exogenous glucocorticoids will falsely elevate plasma cortisol levels and make the test uninterpretable. 2 The FDA label for cosyntropin explicitly states that glucocorticoids should be stopped on the day of testing, and long-acting glucocorticoids should be stopped for a longer period. 2

Do not rely on fasting cortisol alone in patients on spironolactone or estrogen-containing medications—these drugs can falsely elevate or alter cortisol binding globulin levels, respectively. 2 Spironolactone should be stopped on the day of testing, and estrogen-containing drugs should be stopped 4-6 weeks before testing. 2

Do not assume all glucocorticoids have the same washout period—the pharmacokinetics vary substantially, with dexamethasone requiring weeks of discontinuation while prednisone requires only 12-24 hours. 1

Special Considerations for Specific Clinical Scenarios

Patients on Alternate-Day Therapy

• Test on the morning after the "off-steroid day" 1
• This represents approximately 36-48 hours since the last dose 1
• Short-acting steroids are specifically recommended for alternate-day therapy because their suppressive effect is limited to 1.25-1.5 days 1

Patients Requiring Urgent Assessment

• If clinical suspicion for adrenal insufficiency is high and the patient cannot safely stop glucocorticoids, proceed directly to ACTH stimulation testing with appropriate interpretation caveats 2, 3
• The cosyntropin stimulation test can be performed while on glucocorticoids, though results must be interpreted cautiously 2