Will Fluticasone (fluticasone) affect the results of a Dexamethasone Suppression Test (DST) for cortisol levels?

Will Fluticasone Affect a Dexamethasone Suppression Test?

Yes, fluticasone can interfere with cortisol testing and should be considered when interpreting DST results, though the mechanism is through actual HPA axis suppression rather than assay cross-reactivity.

Understanding the Interference Mechanism

Fluticasone affects cortisol measurements through two distinct pathways that must be differentiated:

Direct Assay Cross-Reactivity (Minimal Clinical Impact)

• Fluticasone does not cause clinically significant cross-reactivity in modern cortisol immunoassays, with studies showing no statistically or clinically significant interference at therapeutic concentrations of 0.1 and 1.0 µg/mL in the Roche cortisol immunoassay 1
• This means fluticasone molecules themselves will not falsely elevate the measured cortisol value on the laboratory test 1

Actual HPA Axis Suppression (Clinically Significant)

• The major concern is that fluticasone causes genuine suppression of endogenous cortisol production, which can confound interpretation of screening tests for Cushing's syndrome 2
• Inhaled fluticasone, even at conventional doses, can decrease morning serum cortisol levels, with 36% of children on fluticasone (176-1320 µg/day) showing abnormally low morning cortisol (<5.5 µg/dL) 3
• The suppressive effect is dose-dependent: 17% of patients on low-dose fluticasone (176 µg/day) had abnormal cortisol levels, while 43% on high-dose (≥880 µg/day) showed suppression 3
• Fluticasone accumulates with repeated dosing due to slow elimination, leading to marked plasma cortisol suppression—47% suppression after a single 1000 µg dose versus 95% suppression with repeated dosing 4

Clinical Implications for DST Interpretation

When Screening for Cushing's Syndrome

• Patients on fluticasone may have falsely normal or low cortisol levels after DST, potentially masking true Cushing's syndrome or creating confusion about baseline HPA axis function 2
• The Endocrine Society explicitly warns that exogenous steroids including fluticasone inhalers can confuse interpretation of serum cortisol levels 2
• Guidelines recommend considering the patient's medication history, particularly use of exogenous steroids, when interpreting screening tests for hypercortisolism 5

When Assessing Adrenal Insufficiency

• Fluticasone can cause iatrogenic adrenal suppression, making it difficult to distinguish between medication-induced suppression and true adrenal insufficiency 3
• After switching from fluticasone to lower doses or alternative steroids, 77% of patients with previously abnormal morning cortisol levels normalized within 3 months, confirming the reversible nature of fluticasone-induced suppression 3

Practical Recommendations

Before Performing DST

• Ideally, discontinue fluticasone for an appropriate washout period before performing DST if the clinical situation permits and alternative asthma management is feasible 2
• If fluticasone cannot be stopped, document its use and dosage, as this will be critical for interpretation 2

Interpreting DST Results in Patients on Fluticasone

• If cortisol suppresses "too well" (very low post-DST cortisol), consider that fluticasone may be contributing to HPA axis suppression rather than indicating normal feedback 3, 4
• Use additional screening tests (late-night salivary cortisol, 24-hour urinary free cortisol) to triangulate the diagnosis, as these may be less affected by inhaled steroid use 5
• Consider measuring dexamethasone levels concomitantly with cortisol to ensure adequate drug exposure and rule out pharmacokinetic causes of abnormal results 6, 7

Critical Pitfall to Avoid

• Do not assume a normal or low post-DST cortisol definitively rules out Cushing's syndrome in patients on fluticasone—the inhaled steroid may be masking autonomous cortisol production by adding its own suppressive effect 2, 3
• Conversely, if screening for adrenal insufficiency, recognize that low cortisol may be iatrogenic from fluticasone rather than representing true pathology 3

When Fluticasone Must Continue During Testing

If clinical circumstances require ongoing fluticasone therapy during diagnostic evaluation:

• Perform multiple screening tests (2-3 collections of each modality) to account for variability and medication effects 5, 2
• Consider the Dex-CRH test or desmopressin test to distinguish true Cushing's syndrome from medication-induced HPA axis alterations 5
• Monitor for 3-6 months if results are equivocal and clinical suspicion is low, as treatment adjustments may clarify the picture 5