Decreased morning serum cortisol levels in children with asthma treated with inhaled fluticasone propionate.
OBJECTIVE
In an observational long-term study, we followed 62 children (37 males, 25 females; mean age: 11.6 +/- 2.9 years) with moderate-to-severe asthma for 2 years and studied the effects of fluticasone propionate (176-1320 microg/day) on the function of the hypothalamic-pituitary-adrenal axis.


METHODS
Morning cortisol levels were monitored after patients had been on fluticasone for a mean of 8.0 +/- 5.2 months. Patients who had abnormal low morning cortisol levels (<5.5 microg/dL) were then switched either to lower fluticasone dosage or to other inhaled steroid formulation. Exact methods based on the binomial distribution were used to construct a 95% confidence interval for the true proportion of abnormal readings among those treated, and the Wilcoxon signed rank test was used to test for a significant difference between cortisol levels taken before and after the switch.


RESULTS
Twenty-two patients (36%) had abnormal morning cortisol levels while on fluticasone. Of the patients on a low dose (176 microg/day), 17% had abnormal values, whereas 43% of patients on a high dose (> or =880 microg/day) were abnormal. Patients with abnormal results (17/22) had their morning cortisol levels repeated 3 months after the switch. Thirteen of these patients (77%) had normal levels. A stratified analysis of the difference in morning cortisol levels before and after the switch showed significant increase in morning cortisol levels in the group receiving 440 microg/day or less of fluticasone (median difference: 5.25; confidence interval: 3.60-8.15), as well as in the group receiving 440 microg/day or more (median difference: 3.85; confidence interval: 1.00-7.60).


CONCLUSIONS
Inhaled fluticasone, even at conventional doses, may have greater effects on the adrenal function than previously recognized, but the clinical significance of this suppression still remains to be established.
Eid
Nemr
N
Department of Pediatrics, University of Louisville School of Medicine, Louisville, Kentucky, USA. nseid@louisville.edu
Morton
Ronald
R
Olds
Bradley
B
Clark
Pamela
P
Sheikh
Shahid
S
Looney
Stephen
S
D000280:Administration, Inhalation; D000730:Androstadienes / Q000008:administration & dosage / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000097:blood* / Q000188:drug therapy*; D002648:Child; D002940:Circadian Rhythm / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D000068298:Fluticasone; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male
D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D000068298:Fluticasone; D006854:Hydrocortisone