INHALED BECLOMETHASONE DIPROPIONATE SUPPRESSES THE HYPOTHALAMO-PITUITARY-ADRENAL AXIS IN A DOSE-DEPENDENT MANNER

OBJECTIVE Little is known about the dose-response relationship of pote ntial, unwanted, effects of inhaled beclomethasone (BDP) on the hypoth alamo-pituitary-adrenal (HPA) axis, particularly in nonspecialist clin ic settings, The purpose of our study was to investigate the dose-resp onse relationship of inhaled BDP on the HPA axis in a general practice patient population, We also explored the optimal testing strategy in this population and correlated effects of inhaled BDP on the HPA axis with other systemic corticosteroid side effects. PATIENTS AND DESIGN C ontrolled observational study employing 21 patients on inhaled BDP rec ruited from general practice, with minimal past and no present exposur e to other corticosteroids, and 21 age and gender-matched controls. ME ASUREMENTS Twenty-four-hour urinary free cortisol excretion (UFC), ser um cortisol before and 30 minutes after injection of 1 mu g and 250 mu g of tetracosactrin, serum IGF-I and serum osteocalcin were measured, BDP use was estimated by inhaler weighing and prescription count. RES ULTS In subjects on inhaled BDP, 24-hour UFC (P < 0.008), serum cortis ol 30 minutes after 250 mu g tetracosactrin (P < 0.05) and the serum c ortisol rise after 250 mu g tetracosactrin (P < 0.04) were significant ly lower when compared with controls. Measurements of HPA function cor related inversely with BDP dose estimated by inhaler weighing (all P < 0.03). Serum IGF-I and osteocalcin levers did not differ. CONCLUSIONS We have demonstrated hypothalamo-pituitary-adrenal axis suppression i n nonspecialist-clinic asthma patients on moderate to large doses of i nhaled beclomethasone dipropionate, When accurate measurements of inha led steroid dose are used, there is an exponential relationship betwee n dose and hypothalamo-pituitary-adrenal axis suppression, There appea rs to be no 'safe' threshold, and around 15% of patients may have clin ically significant suppression. However, the significance of hypothala mo-pituitary-adrenaI axis suppression as a marker for concomitant cort icosteroid effects on other organ systems remains uncertain.