Evidence of hypothalamic-pituitary-adrenal axis suppression during moderate-to-high-dose inhaled corticosteroid use

Eur J Pediatr. 2015 Nov;174(11):1421-31. doi: 10.1007/s00431-015-2610-9. Epub 2015 Aug 9.

Abstract

The possible risk of adverse effects due to regular use of inhaled corticosteroids (ICS) is a real concern. Our aim was to describe the factors that have an impact on hypothalamic-pituitary-adrenal axis suppression (HPA-AS) in children and adolescents taking ICS regularly. The HPA axis status of patients who were on moderate-to-high-dose ICS [>176 and >264 μg/day fluticasone propionate-hydrofluoroalkane (FP-HFA) for patients 0-11 and ≥12 years, respectively] was investigated. Various types of ICS were converted to FP-HFA equivalent according to National Asthma Education and Prevention Program (NAEPP) guidelines. Participants with a baseline (8 a.m.) serum cortisol <15 μg/dL underwent a low-dose ACTH stimulation test (LDAT) to diagnose HPA-AS. Among 91 patients, 60 (75.9 %) participants underwent LDAT, and seven (7.7, 95 % CI 3.5-15.3 %) were diagnosed with HPA-AS. Ciclesonide was more frequently used by the participants with HPA-AS compared to patients with a normal HPA axis (42.9 vs. 4.8 %, p = 0.009). Use of ICS at moderate-to-high doses for at least 7 months distinguished participants with HPA-AS from those with a normal HPA axis. Among the duration, type, and dose of ICS, solely the use of ICS with a body mass index (BMI)-adjusted daily dose of ≥22 μg FP was found to increase the risk for HPA-AS (odds ratio (OR) 7.22, 95 % confidence interval (CI) 1.23-42.26, p = 0.028). The receiver operating characteristics (ROC) curve analysis revealed a cutoff value of 291 μg/day FP (area under the curve (AUC) = 0.840, p = 0.003) for predicting HPA-AS Conclusion: The prevalence of HPA-AS was found to be 7.7 % in children taking not only high-dose ICS but also moderate-dose ICS. Dose alone was found to be an actual risk factor for HPA-AS.

Keywords: Adverse effect; Asthma; Hypothalamic-pituitary-adrenal axis; Low-dose ACTH stimulation test; Treatment.

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Anti-Asthmatic Agents / administration & dosage
  • Anti-Asthmatic Agents / adverse effects*
  • Asthma / drug therapy*
  • Child
  • Child, Preschool
  • Female
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / adverse effects*
  • Humans
  • Hypothalamo-Hypophyseal System / drug effects*
  • Infant
  • Male
  • Pituitary-Adrenal System / drug effects*

Substances

  • Anti-Asthmatic Agents
  • Glucocorticoids