Adrenal responses to a low‐dose short synacthen test in children with asthma

Hawcutt, Daniel B; Jorgensen, Andrea; Wallin, Naomi; Thompson, B. D.; Peak, Matthew; Lacy, David; Newland, Paul; Didi, Mo; Couriel, Jon; Blair, Jo; Pirmohamed, Munir; Smyth, Rosalind L

doi:10.1111/cen.13069

Cited by 6 publications

(10 citation statements)

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“…In our study, the prevalence of HPA-AS was 7.7 %, much lower than in previously published studies [18,37,38]. This discrepancy might result from differences in inclusion criteria, diagnostic tests for a suppressed HPA axis, cutoff values for LDAT, and statistical analysis.…”

Section: Discussioncontrasting

confidence: 85%

“…They are instructed on signs and symptoms of adrenal crisis in stressful conditions and how to use oral hydrocortisone under these circumstances. Along with the data of our study and the other relevant studies [18,30,37,38], it would be very instructive to learn about the prognosis of patients with ICS-associated HPA axis suppression in future studies.…”

Section: Discussionmentioning

confidence: 67%

“…This discrepancy might result from differences in inclusion criteria, diagnostic tests for a suppressed HPA axis, cutoff values for LDAT, and statistical analysis. In a recent study by Hawcutt et al, asthma patients who had been using corticosteroids for a minimum period of 6 months were studied irrespective of consumption of oral steroids as a controller therapy [18]. They used log-transformed cortisol values to normalize the data in some of the statistical models.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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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.

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Section: Discussioncontrasting

confidence: 85%

Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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“…8 Although higher doses of corticosteroids are associated significantly with lower baseline and peak cortisol values, [8][9][10] at a population level, the reduction in peak cortisol seen with increasing total dose of corticosteroids is small (<1 nmol/L per 200 µg/day). 8 However, symptomatic adrenal suppres sion has been reported at doses as low as 200 µg of inhaled beclometasone per day, 11 and one in three children with asthma using corticosteroids has a peak cortisol lower than 500 nmol/L. 8 Adrenal suppression is also seen in adults with asthma and COPD treated with ICS.…”

Section: Introductionmentioning

confidence: 99%

“…8 However, symptomatic adrenal suppres sion has been reported at doses as low as 200 µg of inhaled beclometasone per day, 11 and one in three children with asthma using corticosteroids has a peak cortisol lower than 500 nmol/L. 8 Adrenal suppression is also seen in adults with asthma and COPD treated with ICS. 5 The reasons for the interindividual variability in both adults and children remain unclear, because clinical factors only account for a small proportion of the variance.…”

Section: Introductionmentioning

confidence: 99%

Susceptibility to corticosteroid-induced adrenal suppression: a genome-wide association study

DB¹,

Francis²,

DF³

et al. 2019

ESPE

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Background A serious adverse effect of corticosteroid therapy is adrenal suppression. Our aim was to identify genetic variants affecting susceptibility to corticosteroid-induced adrenal suppression.Methods We enrolled children with asthma who used inhaled corticosteroids as part of their treatment from 25 sites across the UK (discovery cohort), as part of the Pharmacogenetics of Adrenal Suppression with Inhaled Steroids (PASS) study. We included two validation cohorts, one comprising children with asthma (PASS study) and the other consisting of adults with chronic obstructive pulmonary disorder (COPD) who were recruited from two UK centres for the Pharmacogenomics of Adrenal Suppression in COPD (PASIC) study. Participants underwent a low-dose short synacthen test. Adrenal suppression was defined as peak cortisol less than 350 nmol/L (in children) and less than 500 nmol/L (in adults). A case-control genome-wide association study was done with the control subset augmented by Wellcome Trust Case Control Consortium 2 (WTCCC2) participants. Single nucleotide polymorphisms (SNPs) that fulfilled criteria to be advanced to replication were tested by a randomeffects inverse variance meta-analysis. This report presents the primary analysis. The PASS study is registered in the European Genome-phenome Archive (EGA). The PASS study is complete whereas the PASIC study is ongoing.Findings Between November, 2008, and September, 2011, 499 children were enrolled to the discovery cohort. Between October, 2011, and December, 2012, 81 children were enrolled to the paediatric validation cohort, and from February, 2010, to June, 2015, 78 adults were enrolled to the adult validation cohort. Adrenal suppression was present in 35 (7%) children in the discovery cohort and six (7%) children and 17 (22%) adults in the validation cohorts. In the discovery cohort, 40 SNPs were found to be associated with adrenal suppression (genome-wide significance p<1 × 10 -⁶), including an intronic SNP within the PDGFD gene locus (rs591118; odds ratio [OR] 7·32, 95% CI 3·15-16·99; p=5·8 × 10 -⁸). This finding for rs591118 was validated successfully in both the paediatric asthma (OR 3·86, 95% CI 1·19-12·50; p=0·02) and adult COPD (2·41, 1·10-5·28; p=0·03) cohorts. The proportions of patients with adrenal suppression by rs591118 genotype were six (3%) of 214 patients with the GG genotype, 15 (6%) of 244 with the AG genotype, and 22 (25%) of 87 with the AA genotype. Meta-analysis of the paediatric cohorts (discovery and validation) and all three cohorts showed genome-wide significance of rs591118 (respectively, OR 5·89, 95% CI 2·97-11·68; p=4·3 × 10 -⁹; and 4·05, 2·00-8·21; p=3·5 × 10 -¹⁰).Interpretation Our findings suggest that genetic variation in the PDGFD gene locus increases the risk of adrenal suppression in children and adults who use corticosteroids to treat asthma and COPD, respectively.

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Optimizing the corticosteroid dose in steroid-sensitive nephrotic syndrome

Christian¹,

Maxted²

2021

Pediatr Nephrol

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The use of corticosteroids in the treatment of steroid-sensitive nephrotic (SSNS) syndrome in children has evolved surprisingly slowly since the ISKDC consensus over 50 years ago. From a move towards longer courses of corticosteroid to treat the first episode in the 1990s and 2000s, more recent large, well-designed randomized controlled trials (RCTs) have unequivocally shown no benefit from an extended course, although doubt remains whether this applies across all age groups. With regard to prevention of relapses, daily ultra-low-dose prednisolone has recently been shown to be more effective than low-dose alternate-day prednisolone. Daily low-dose prednisolone for a week at the time of acute viral infection seems to be effective in the prevention of relapses but the results of a larger RCT are awaited. Recently, corticosteroid dosing to treat relapses has been questioned, with data suggesting lower doses may be as effective. The need for large RCTs to address the question of whether corticosteroid doses can be reduced was the conclusion of the authors of the recent corticosteroid therapy for nephrotic syndrome in children Cochrane update. This review summarizes development in thinking on corticosteroid use in SSNS and makes suggestions for areas that merit further scrutiny.

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Adrenal responses to a low‐dose short synacthen test in children with asthma

Abstract: Clinical Endocrinology (Oxford), 82, 648-656.

Cited by 6 publications

References 1 publication

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

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

Susceptibility to corticosteroid-induced adrenal suppression: a genome-wide association study

Optimizing the corticosteroid dose in steroid-sensitive nephrotic syndrome

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