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.

Evaluation of Hypothalamic-Pituitary-Adrenal Axis Suppression following Cutaneous Use of Topical Corticosteroids in Children: A Meta-Analysis

“…To the best of our knowledge, no previous meta-analysis has been performed on AI from TCS use in pediatrics, although other forms of systemically absorbed CS have been studied. Children with asthma, another atopic condition commonly treated with CS, show a higher percentage of HPA axis suppression following the use of inhaled CS at rates of 7.7–42% depending on the potency and duration of use [39-43]. These findings prompted new Pediatric Endocrine Society guidelines recommending dynamic HPA axis testing for children with asthma treated with chronic high-dose inhaled CS or those with specific clinical features suggestive of AI [44, 45].…”

Long-Term Cortisol Concentration in Scalp Hair of Asthmatic Children Using Inhaled Corticosteroids: A Case-Control Study

“…Clinicians are often aware of possible HPA-axis suppression that may occur in cases of long-term or high-dose ICS therapy [9, 10]. However, recent studies show that HPA-axis suppression may already occur at low-to-moderate ICS doses [11, 12]. In clinical practice, screening for HPA-axis suppression remains challenging since current tests fall short in several aspects.…”

Oral corticosteroids for asthma exacerbations might be associated with adrenal suppression: Are physicians aware of that?

“…25,26 It seems that for both OCS and ICS, corticosteroid dose and duration of treatment, despite being important risk factors, are not good predictors of which patients will actually develop adrenal insufficiency. 15,16,27 Surprisingly, the most reliable predictors of AS described in asthmatic children are related to clinical features such as low body mass for age, 28 decreased lung function and poor symptom control. 29 Impaired adrenal function in asthmatic children was believed to contribute to the development of more severe asthma, but current data suggest that asthma itself may down regulate the HPA activity so that ICS treatment may actually improve adrenal function in well-controlled patients.…”