Effects of fluticasone propionate, triamcinolone acetonide, prednisone, and placebo on the hypothalamic-pituitary-adrenal axis

Background: Many clinicians are reluctant to prescribe inhaled corticosteroids because of concerns over potential effects on the hypothalamic-pituitary-adrenal axis. Objective: The purpose of this study was to compare the adrenal responses to 6-hour cosyntropin infusion after treatment with fluticasone propionate aerosol, triamcinolone acetonide aerosol, prednisone, and placebo for 4 weeks, a sufficient time interval to assess any effects on the adrenal response to stress. Methods: This double-blind, triple-dummy, randomized, placebo-controlled study was conducted in 128 patients to evaluate adrenal response to 6-hour cosyntropin infusion (a clinically relevant method for evaluating adrenal function) after 28 days of treatment with fluticasone propionate aerosol 88 mu g or 220 mu g twice daily, triamcinolone acetonide aerosol 200 mu g 4 times daily or 400 mu g twice daily, prednisone 10 mg once daily, and placebo. Results: After 28 days of treatment, mean plasma cortisol response to cosyntropin over 12 hours after initiation of the 6-hour infusion was similar among fluticasone, triamcinolone, and placebo groups; cortisol response was significantly (P < .05) reduced after treatment with prednisone compared with the other treatment groups. Mean I-hour area under the plasma cortisol concentration-time curves and peak plasma cortisol concentrations were significantly (P less than or equal to.003) lower with prednisone than any other treatment; no significant differences were noted between placebo and either of the fluticasone groups in any assessment. Mean reductions From baseline in area under the plasma cortisol concentration time curves and peak cortisol concentrations mere significantly (P <.05) greater with triamcinolone 400 pg twice daily compared with placebo. Conclusion: These results suggest that fluticasone propionate at therapeutic doses has effects on the hypothalamic-pituitary-adrenal axis comparable to that of placebo and has significantly less effect than prednisone as measured hy 6-hour cosyntropin infusion after 28 days of treatment.