Screening for hypothalamic–pituitary–adrenal axis suppression in asthmatic children remains problematic: a cross-sectional study

Abstract

ObjectiveTo determine which parameter is the most useful screening test for hypothalamic–pituitary–adrenal suppression in asthmatic children.DesignCross-sectional study.SettingPaediatric allergy clinics in Cape Town, South Africa.Participants143 asthmatic children of mostly mixed ancestry, aged 5–12 years.Outcome measuresPrimary outcome measures included Spearman correlation coefficients (r) calculated between the postmetyrapone (PMTP) serum adrenocorticotropic hormone (ACTH), 11-deoxycortisol (11DOC), 11DOC+ cortisol (C) and height, weight, height velocity, weight velocity, change in systolic blood pressure from supine to standing, early morning urinary free cortisol (UFC), morning C, ACTH and dehydroepiandrosterone sulfate (DHEAS). Secondary outcome measures were the receiver operating characteristics (ROC) curve and the diagnostic statistics for the most promising test.ResultsAll screening variables were weakly correlated with the three PMTP outcomes. Only DHEAS and UFC (nmol/m2) were statistically significant—DHEAS for PMTP ACTH and 11DOC (r=0.20, p=0.025 and r=0.21, p=0.017); UFC (nmol/m2) for PMTP 11DOC and 11DOC+C (r=0.19, p=0.033 and r=0.20, p=0.022). The area under ROC curve for DHEAS in the 5-year to 9-year age group was 0.69 (95% CI 0.47 to 0.92). At DHEAS cut-off of 0.2 µmol/L: sensitivity=0.88 (CI 0.47 to 1.00), specificity=0.61 (CI 0.42 to 0.78), positive predictive value=0.37 (CI 0.16 to 0.62), negative predictive value=0.95 (CI 0.75 to 1.00), accuracy=0.67 (CI 0.50 to 0.81), positive likelihood ratio=2.26 (CI 1.35 to 3.78), negative likelihood ratio=0.20 (CI 0.03 to 1.30).ConclusionsNo parameter is useful as a universal screening test. DHEAS may be suitable to exclude HPAS before adrenarche. Further research is needed to confirm these findings and identify factors, for example, genetic that may predict or protect against HPAS.

Symptomatic adrenal suppression among children in Canada

“…The majority of cases were children being treated with ICS for asthma—the most common chronic illness of childhood 28. By identifying only symptomatic cases, our findings demonstrate the clinical significance of the previously reported high prevalence of biochemical AS in children with ICS-treated asthma19 24 27 and support recommendations for screening patients receiving ≥400–500 µg of ICS daily for 3–6 months 29 30. For those who were not in adrenal crisis, presentation was variable; growth failure, non-specific symptoms or both being the most common (35%, 28% and 13%, respectively).…”

“…Diagnosis of and confirmatory testing for AS are not straightforward. While there are multiple ways to test the HPA axis (all of which have pitfalls),24 33 34 only first morning cortisol levels or ACTH stimulation tests were used by reporting physicians; these are the most widely used tests in practice and in the literature 35. The most sensitive, specific and safe test for AS is a low-dose ACTH stimulation test.…”

Children with asthma have significantly lower long‐term cortisol levels in their scalp hair than healthy children

“…We cannot draw any conclusion about the clinical relevance of the lower long‐term cortisol levels in children with asthma, as we did not assess the adrenal function by dynamic tests in these children . Therefore, hair cortisol may not accurately predict HPA axis response to stress at a specific time point.…”

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

“…Urinary measurements of cortisol may span up to 24 h and provide a rough estimate of cortisol levels over time. However, the collection of urine is often unpractical and unreliable [13, 14]. A more suitable, relatively new technique is to measure the long-term cortisol concentration in scalp hair [15, 16].…”