EFFECTS OF REPEATED ONCE-DAILY DOSING OF 3 INTRANASAL CORTICOSTEROIDSON BASAL AND DYNAMIC MEASURES OF HYPOTHALAMIC-PITUITARY-ADRENAL-AXIS ACTIVITY

Background: Intranasal corticosteroids are regarded as the first-line treatment for allergic rhinitis, but few studies have directly compare d their systemic effects. Objective: We sought to compare the hypothal amic-pituitary-adrenal (HPA)-axis suppression with three intranasal co rticosteroids in terms of basal and dynamic adrenocortical activity. M ethods: Sixteen healthy volunteers (mean age, 30.7 years) were studied in a single-blind, randomized, four-way crossover study comparing pla cebo with 200 mu g/day fluticasone propionate (FP), 220 mu g/day triam cinolone acetonide (TAA), anti 336 mu g/day beclomethasone dipropionat e (BDP), After 4 days or treatment, an overnight urine collection was taken for cortisol and creatinine excretion starting at 10 PM (14 hour s after the fourth dose), and blood was taken for serum cortisol at 8 AM (24 hours after the fourth dose) and after stimulation with adrenoc orticotrophic hormone (ACTH) (0.5 mu g). Results: For overnight urinar y cortisol excretion compared with placebo (20.8 nmol), there was a si gnificant (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% suppressio n). There was also a trend towards suppression of overnight, urinary c ortisol/creatinine excretion, but this was not statistically significa nt (placebo, 5.2 nmol/mmol; TAA, 5.0 nmol/mmol; BDP, 4.3 nmol/mmol; an d 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 dth 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 respon se to ACTH stimulation. Further studies are indicated to establish whe ther the systemic effects of inhaled and intraanasal corticosteroids a re additive.