How long should a patient with fluticasone (fluticasone propionate)-induced adrenal suppression be off the medication to avoid false positive results on a cosyntropin stimulation test?

Duration Off Fluticasone Before Cosyntropin Stimulation Test

Patients should discontinue fluticasone for at least 2-4 months before performing a cosyntropin stimulation test to allow adequate recovery of the hypothalamic-pituitary-adrenal (HPA) axis and avoid false-positive results.

Evidence for HPA Axis Suppression from Fluticasone

The concern about fluticasone interfering with adrenal testing is well-founded, as both inhaled and intranasal formulations can suppress the HPA axis:

• High-dose inhaled fluticasone (880 mcg/day) caused adrenal suppression in 14 of 19 patients (74%) on low-dose cosyntropin stimulation testing, with recovery taking 2-10 months after dose reduction or discontinuation 1
• Standard-dose inhaled fluticasone (220 mcg twice daily) caused complete adrenal insufficiency in a documented case, with cortisol levels normalizing only after 4 months of discontinuation 2
• The duration of fluticasone use correlates with the degree of adrenal impairment (r = 0.32, P = 0.01), meaning longer exposure requires longer recovery time 1

Practical Washout Recommendations

For accurate cosyntropin stimulation testing:

• Minimum washout period: 2 months for low-to-moderate dose fluticasone 2
• Recommended washout period: 4 months for high-dose or prolonged fluticasone use 2, 1
• Hydrocortisone must be held for 24 hours before testing, while other exogenous steroids including prednisolone require longer washout periods 3

Critical Considerations During the Washout Period

Do not attempt diagnostic testing while the patient remains on corticosteroids, as this will yield false-positive results showing "adrenal insufficiency" that simply reflects expected HPA suppression rather than true adrenal disease 3:

• Morning cortisol measurements in patients actively taking corticosteroids are not diagnostic because the assay measures both endogenous cortisol and therapeutic steroids 3
• Laboratory confirmation of adrenal insufficiency should not be attempted until corticosteroid treatment is discontinued and sufficient washout time has elapsed 3

If the patient has symptoms suggesting true adrenal insufficiency during the washout period:

• Consider empiric glucocorticoid replacement with hydrocortisone rather than risking adrenal crisis 3
• Consult endocrinology for a recovery and weaning protocol using hydrocortisone, rather than attempting abrupt discontinuation 3
• Test for HPA axis recovery after 3 months of maintenance therapy in patients with isolated central adrenal insufficiency from steroid use 3

Alternative Approach for Urgent Testing

If you must 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 3
• However, dexamethasone lacks mineralocorticoid activity and is inadequate for primary adrenal insufficiency 3

Common Pitfalls to Avoid

• Do not test immediately after stopping fluticasone—the HPA axis remains suppressed for months 2, 1
• Do not rely on the absence of symptoms to determine readiness for testing—one patient remained asymptomatic except for mild fatigue despite complete adrenal suppression 2
• Do not assume intranasal steroids are safe—while moderate-dose intranasal steroids had no effect on adrenal function in one study, high-dose inhaled formulations clearly suppress the axis 1
• Approximately one-third to one-half of patients taking 5-20 mg prednisolone daily fail to achieve target cortisol concentrations on cosyntropin testing, even when they may have adequate adrenal reserve 3

Updated Cortisol Cutoffs for Modern Assays

When interpreting the cosyntropin stimulation test after the appropriate washout period, use assay-specific cutoffs rather than the historical 18 μg/dL threshold:

• Abbott Architect assay: 14.6 μg/dL at 60 minutes (sensitivity 92%, specificity 96%) 4
• Roche Elecsys II assay: 14.6 μg/dL 5
• LC-MS/MS: 14.5 μg/dL 5
• The historical cutoff of 18 μg/dL was based on older polyclonal antibody assays and leads to false-positive diagnoses with newer monoclonal antibody-based assays 5, 4