Asthma treatment in children: A guide to screening for and management of hypothalamic-pituitary-adrenal axis suppression

Zöllner, Ekkehard Werner

doi:10.7196/samj.2019.v109i5.13932

Cited by 5 publications

(4 citation statements)

References 24 publications

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“…The discrepancy in the findings between results of the two studies can be explained by the use of different adrenal function tests. In the Greek study, the low‐dose ACTH stimulation test (not the gold standard) was used without defining definitive cut‐offs 1,2 for basal and stimulated F levels. Relying on statistical differences of these levels vis‐a‐vis their respective genotypes may be misleading.…”

Section: Discussionmentioning

confidence: 99%

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Hypothalamic‐pituitary‐adrenal axis suppression in asthma: A glucocorticoid receptor polymorphism may protect

Akurugu

Heerden

Mulder

et al. 2020

Pediatric Allergy Immunology

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Background Asthmatic children on corticosteroids can develop hypothalamic‐pituitary‐adrenal axis suppression (HPAS). Single nucleotide polymorphisms (SNPs) rs242941 and rs1876828 of the corticotrophin‐releasing hormone receptor 1 (CRHR1) gene were associated with lower stimulated cortisol (F) levels, whereas rs41423247 of the glucocorticoid receptor (NR3C1) gene was associated with higher basal F levels. The objective of the current study was to confirm whether these three SNPs are associated with HPAS in asthmatic children. Methods DNA was extracted from saliva obtained from 95 asthmatic children, who had previously undergone basal F and metyrapone testing. Thirty‐six children were classified as suppressed. Non‐suppressed children were subclassified according to their post‐metyrapone adrenocorticotropin (PMTP ACTH) level into a middle (106‐319 pg/mL) and a high (>319 pg/mL) ACTH response group. TaqMan® polymerase chain reaction assays were utilized. Results Only rs41423247 was inversely associated with HPAS (OR = 0.27 [95% CI 0.06‐0.90]). Its GC genotype was inversely associated with HPAS (log odds = −1.28, P = .021). √PMTP ACTH was associated with CC (effect size = 10.85, P = .005) and GC genotypes (effect size = 4.06, P = .023). The C allele is inherited as a dominant trait (effect size = −1.31 (95% CI −2.39‐−0.33; P = .012). In the high ACTH response group, both genotypes affected the PMTP ACTH (effect sizes 1.41 and 15.46; P‐values .023 and <2 × 10−26 for GC and CC, respectively). Conclusions The C allele of rs41423247 was found to be protective against HPAS. CC genotype is associated with the highest PMTP ACTH response.

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Section: Discussionmentioning

confidence: 99%

“…Hypothalamic-pituitary-adrenal axis suppression (HPAS) is a wellrecognized adverse effect of corticosteroid therapy. 1,2 Whenever this is prescribed, endogenous cortisol (F) production is reduced.…”

Section: Backg Rou N Dmentioning

confidence: 99%

Hypothalamic‐pituitary‐adrenal axis suppression in asthma: A glucocorticoid receptor polymorphism may protect

Akurugu

Heerden

Mulder

et al. 2020

Pediatric Allergy Immunology

View full text Add to dashboard Cite

show abstract

“…5 Thediscrepancy in the findings between results of the two studies can be explained by the use of different adrenal function tests. In the Greek study the low dose ACTH stimulation test (not the gold standard) was used without defining definitive cut-offs 3,6 for basal and stimulated F levels. Relying on statistical differences of these levels vis-a-vis their respective genotypes could have led to erroneous conclusions.…”

Section: Discussionmentioning

confidence: 99%

Hypothalamic-pituitary-adrenal axis suppression in asthma: A glucocorticoid receptor polymorphism may protect

Akurugu

Heerden

Mulder

et al. 2020

Preprint

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Background: Asthmatic children on corticosteroids can develop hypothalamic-pituitary-adrenal axis suppression (HPAS). Single nucleotide polymorphisms (SNPs) rs242941 and rs1876828 of the corticotrophin-releasing hormone receptor 1 (CRHR1) gene were associated with lower stimulated cortisol (F) levels, whereas rs41423247 of the glucocorticoid receptor (NR3C1) gene was associated with higher basal F levels. The objective of the current study was to confirm whether these three SNPs are associated with HPAS in asthmatic children. Methods: DNA was extracted from saliva obtained from 95 asthmatic children, who had previously undergone basal F and metyrapone testing. Thirty-six children were classified as suppressed. Non-suppressed children were sub-classified according to their post-metyrapone ACTH (PMTP ACTH) level into a middle (106-319 pg/ml) and a high (>319 pg/ml) ACTH response group. TaqMan® polymerase chain reaction assays were utilized. Results: Only rs41423247 was inversely associated with HPAS (OR = 0.27 [95% CI 0.06-0.90]). Its GC genotype was inversely associated with HPAS (log odds =-1.28, p = 0.021). [?]PMTP ACTH was associated with CC (effect size = 10.85, p = 0.005) and GC genotypes (effect size = 4.06, p = 0.023). The C allele is inherited as a dominant trait (effect size =-1.31 (95% CI-2.39-0.33; p = 0.012). In the high ACTH response group, both genotypes affected the PMTP ACTH (effect sizes 1.41 and 15.46; p-values 0.023 and < 2x10-26 for GC and CC respectively). Conclusions: The C allele of rs41423247 was found to be protective against HPAS. CC genotype is associated with the highest PMTP ACTH response.

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“…The study subjects were referred to the Pediatric Endocrine Outpatient Clinic. After being evaluated by a pediatric endocrine specialist, subjects were scanned for baseline fasting blood cortisol levels at 08:00 am (14,15).…”

Section: Cortisol Testmentioning

confidence: 99%

The Prevalence of Hypothalamic-Pituitary-Adrenal Axis Suppression in Children with Persistent Asthma

et al. 2019

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Background: Hypothalamic-pituitary-adrenal (HPA) axis suppression is the most important systemic side effect associated with inhaled corticosteroids (ICS) therapy.Objectives: To evaluate the prevalence and determinants of hypothalamic-pituitary-adrenal (HPA) axis suppression in asthmatic children on ICSs.Methods: A total of 92 children aged 6 to 18 years, diagnosed with persistent asthma, and receiving regular ICS therapy for a minimum of 3 months, without any systemic steroid therapy within the last 3 months, were enrolled in the study. Clinical and demographic variables were recorded. HPA axis suppression was measured by morning cortisol levels and confirmed by low-dose adrenocorticotropic hormone stimulation test.Results: Of 92 enrolled patients, 51 (55.4%) were male. The mean age was 10.1 ± 2.6 years. HPA axis suppression was observed in two (2.1%) patients. The body mass index (BMI) values were significantly lower in the HPA axis suppression group compared to the other enrollees. No relationship was observed between the HPA axis suppression and the ICS dose, duration of therapy or coadministration of long-acting beta-agonists or nasal steroids. Conclusions:In our study, the prevalence of HPA axis suppression was 2.1%. Children with persistent asthma who has been treated with regular ICS should be screened for HPA axis suppression.

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Asthma treatment in children: A guide to screening for and management of hypothalamic-pituitary-adrenal axis suppression

Abstract: This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

Cited by 5 publications

References 24 publications

Hypothalamic‐pituitary‐adrenal axis suppression in asthma: A glucocorticoid receptor polymorphism may protect

Hypothalamic‐pituitary‐adrenal axis suppression in asthma: A glucocorticoid receptor polymorphism may protect

Hypothalamic-pituitary-adrenal axis suppression in asthma: A glucocorticoid receptor polymorphism may protect

The Prevalence of Hypothalamic-Pituitary-Adrenal Axis Suppression in Children with Persistent Asthma

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