title: Evidence of hypothalamic-pituitary-adrenal axis suppression during moderate-to-high-dose inhaled corticosteroid use.
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.
authors.affiliation: Department of Pediatric Allergy, Faculty of Medicine, Hacettepe University, Sıhhıye, 06100, Ankara, Turkey. ozlem.bircan@gmail.com.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Cavkaytar
authors.affiliation: Department of Pediatric Endocrinology, Faculty of Medicine, Hacettepe University, Sıhhıye, 06100, Ankara, Turkey. dvuralli@hotmail.com.
authors.forename: Dogus
authors.initials: D
authors.lastname: Vuralli
authors.affiliation: Department of Pediatric Allergy, Faculty of Medicine, Hacettepe University, Sıhhıye, 06100, Ankara, Turkey. ebruarik@yahoo.com.
authors.forename: Ebru
authors.initials: E
authors.lastname: Arik Yilmaz
authors.affiliation: Department of Pediatric Allergy, Faculty of Medicine, Hacettepe University, Sıhhıye, 06100, Ankara, Turkey. betulbuyuktiryaki@yahoo.com.
authors.forename: Betul
authors.initials: B
authors.lastname: Buyuktiryaki
authors.affiliation: Department of Pediatric Allergy, Faculty of Medicine, Hacettepe University, Sıhhıye, 06100, Ankara, Turkey. ozgeusoyer@gmail.com.
authors.forename: Ozge
authors.initials: O
authors.lastname: Soyer
authors.affiliation: Department of Pediatric Allergy, Faculty of Medicine, Hacettepe University, Sıhhıye, 06100, Ankara, Turkey. umsahner@yahoo.com.
authors.forename: Umit M
authors.initials: UM
authors.lastname: Sahiner
authors.affiliation: Department of Pediatric Endocrinology, Faculty of Medicine, Hacettepe University, Sıhhıye, 06100, Ankara, Turkey. nurgun.kandemir@gmail.com.
authors.forename: Nurgun
authors.initials: N
authors.lastname: Kandemir
authors.affiliation: Department of Pediatric Allergy, Faculty of Medicine, Hacettepe University, Sıhhıye, 06100, Ankara, Turkey. b_sekerel@yahoo.com.
authors.forename: Bulent E
authors.initials: BE
authors.lastname: Sekerel
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001249:Asthma / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007223:Infant; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects*
chemical_list: D018927:Anti-Asthmatic Agents; D005938:Glucocorticoids
keywords: Adverse effect; Asthma; Hypothalamic-pituitary-adrenal axis; Low-dose ACTH stimulation test; Treatment