Inhaled beclomethasone dipropionate suppresses the hypothalamo-pituitary-adrenal axis in a dose dependent manner.
OBJECTIVE
Little is known about the dose-response relationship of potential, unwanted, effects of inhaled beclomethasone (BDP) on the hypothalamo-pituitary-adrenal (HPA) axis, particularly in nonspecialist clinic settings. The purpose of our study was to investigate the dose-response 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.


METHODS
Controlled observational study employing 21 patients on inhaled BDP recruited from general practice, with minimal past and no present exposure to other corticosteroids, and 21 age and gender-matched controls.


METHODS
Twenty-four-hour urinary free cortisol excretion (UFC), serum cortisol before and 30 minutes after injection of 1 microgram and 250 micrograms of tetracosactrin, serum IGF-I and serum osteocalcin were measured. BDP use was estimated by inhaler weighing and prescription count.


RESULTS
In subjects on inhaled BDP, 24-hour UFC (P < 0.008), serum cortisol 30 minutes after 250 micrograms tetracosactrin (P < 0.05) and the serum cortisol rise after 250 micrograms tetracosactrin (P < 0.04) were significantly lower when compared with controls. Measurements of HPA function correlated inversely with BDP dose estimated by inhaler weighing (all P < 0.03). Serum IGF-I and osteocalcin levels did not differ.


CONCLUSIONS
We have demonstrated hypothalamo-pituitary-adrenal axis suppression in nonspecialist-clinic asthma patients on moderate to large doses of inhaled beclomethasone dipropionate. When accurate measurements of inhaled steroid dose are used, there is an exponential relationship between dose and hypothalamo-pituitary-adrenal axis suppression. There appears to be no 'safe' threshold, and around 15% of patients may have clinically significant suppression. However, the significance of hypothalamo-pituitary-adrenal axis suppression as a marker for concomitant corticosteroid effects on other organ systems remains uncertain.
Grebe
S K
SK
Department of Pathology, Wellington School of Medicine, New Zealand.
Feek
C M
CM
Durham
J A
JA
Kljakovic
M
M
Cooke
R R
RR
D000280:Administration, Inhalation; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000097:blood / Q000188:drug therapy / Q000652:urine; D001507:Beclomethasone / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D016022:Case-Control Studies; D003366:Cosyntropin; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005194:Family Practice; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010913:Pituitary-Adrenal System / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D015675:Osteocalcin; D003366:Cosyntropin; D007334:Insulin-Like Growth Factor I; D001507:Beclomethasone; D006854:Hydrocortisone