Effects of repeated once daily dosing of three intranasal corticosteroids on basal and dynamic measures of hypothalamic-pituitary-adrenal–axis activity

Abstract

Background: Intranasal corticosteroids are regarded as the first-line treatment for allergic rhinitis, but few studies have directly compared their systemic effects. Objective: We sought to compare the hypothalamic-pituitary-adrenal (HPA)–axis suppression with three intranasal corticosteroids in terms of basal and dynamic adrenocortical activity. Methods: Sixteen healthy volunteers (mean age, 30.7 years) were studied in a single-blind, randomized, four-way crossover study comparing placebo with 200 μg/day fluticasone propionate (FP), 220 μg/day triamcinolone acetonide (TAA), and 336 μg/day beclomethasone dipropionate (BDP). After 4 days of treatment, an overnight urine collection was taken for cortisol and creatinine excretion starting at 10 pm (14 hours after the fourth dose), and blood was taken for serum cortisol at 8 am (24 hours after the fourth dose) and after stimulation with adrenocorticotrophic hormone (ACTH) (0.5 μg). Results: For overnight urinary cortisol excretion compared with placebo (20.8 nmol), there was a significant ( p < 0.05) degree of suppression with FP (11.8 nmol) but not with TAA (16.0 nmol) or BDP (16.5 nmol). In terms of fold difference (95% CI for difference) from placebo, this amounted to 1.75-fold (1.01 to 3.03) for FP (43% suppression), 1.30-fold (0.75 to 2.25) for TAA (23% suppression), and 1.26-fold (0.73 to 2.18) for BDP (21% suppression). There was also a trend towards suppression of overnight urinary cortisol/creatinine excretion, but this was not statistically significant (placebo, 5.2 nmol/mmol; TAA, 5.0 nmol/mmol; BDP, 4.3 nmol/mmol; and FP, 4.3 nmol/mmol). Values for serum cortisol before and after ACTH stimulation showed no significant suppression. Conclusion: Suppression of overnight urinary cortisol occurred with intranasal FP (43%), TAA (23%), and BDP (21%), although this was only statistically significant with FP. None of the drugs were associated with blunting of the response to ACTH stimulation. Further studies are indicated to establish whether the systemic effects of inhaled and intranasal corticosteroids are additive.