Impact of inhaled corticosteroids on cortisol suppression in adults with asthma: a quantitative review.
BACKGROUND
Studies examining the effects of inhaled corticosteroids (ICSs) on cortisol suppression show inconsistent results, and there is uncertainty regarding the dose-response relationship between ICSs and cortisol suppression.


OBJECTIVE
To determine, using meta-analysis, the extent of cortisol suppression after administration of clinically relevant ICS doses in adults with asthma.


METHODS
Database searches (MEDLINE, EMBASE, and The Cochrane Library) using appropriate indexed terms were performed to identify eligible articles for review. Articles reporting the effects of ICSs on cortisol levels in asthmatic adults, measured using the cumulative serum or plasma cortisol, morning serum or plasma cortisol, or cumulative overnight urinary free cortisol method, were identified. All available cortisol measurements were extracted. Cortisol suppression was estimated, and treatment arms were grouped into low-, medium-, and high-dose ranges according to the Global Initiative for Asthma guidelines. A multivariate model was used to determine relationships between ICS dose and cortisol suppression and to explore sources of heterogeneity among trials.


RESULTS
Thirty-one studies providing information on 216 measures of cortisol suppression were included in this meta-analysis. Cortisol suppression in the low-, medium-, and high-dose groups were estimated to be 17.92% (95% confidence interval [CI], 11.08%-24.77%), 26.55% (95% CI, 17.29%-35.80%), and 36.31% (95% CI, 26.48%-46.13%), respectively.


CONCLUSIONS
Statistically significant cortisol suppression was evident at low doses of ICSs and increased with dose. These results support an impact of all ICSs on endogenous cortisol levels and underscore the importance of titrating ICS doses to the minimum required to maintain symptom control.
Wlodarczyk
John H
JH
John Wlodarczyk Consulting Services, New Lambton, New South Wales, Australia. john@jwcs.com.au
Gibson
Peter G
PG
Caeser
Manfred
M
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D001249:Asthma / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D002986:Clinical Trials as Topic; D016206:Databases, Bibliographic; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism* / Q000652:urine; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D006854:Hydrocortisone