No hope for HPAS screening in pediatric asthma
medwireNews: The authors of a South African study say that the search for a screening test for hypothalamic–pituitary–adrenal axis suppression (HPAS) in corticosteroid-treated children with asthma should be abandoned after they failed to identify any parameter that is universally useful for this purpose.
The study involved 143 children with asthma who were taking inhaled corticosteroids, with or without additional corticosteroid therapy. Those with a fasting morning serum cortisol level of more than 83 nmol/L underwent an overnight metyrapone test (ONMTPT) – the gold-standard test of HPA axis function.
The authors found only weak correlations between the three postmetapyrone outcomes – adrenocorticotropic hormone (ACTH), 11-deoxycortisol (11DOC), and 11DOC + cortisol – and potential screening variables. These included height, weight, height and weight velocity, change in blood pressure from supine to standing, and morning cortisol or ACTH; the only significant correlations were with dehydroepiandrosterone sulfate (DHEAS) and urinary free cortisol (UFC).
However, DHEAS showed an age effect, indicating that it was useful only in children aged 5 to 9 years old. In this age group, a cut-off value of 0.2 µmol/L could discriminate children with and without HPAS with a sensitivity of 0.88, a specificity of 0.61, and an accuracy of 0.67.
Noting that DHEAS in this group was more useful for ruling HPAS out than in (negative predictive value, 0.95), the authors say it may therefore be inadequate as a screening test. Furthermore, they speculate that, as adult DHEAS levels are substantially higher than those in children, analyzers used in clinical settings may not be calibrated with sufficient sensitivity for samples from younger patients.
Additionally, because less than 1% of free cortisol is excreted in the urine, they conclude that they would “not encourage the use of any screen based on UFC, as it is extremely unlikely to accurately predict which child will appropriately respond to stress.”
A recent study found that two-thirds of children with asthma who were taking corticosteroids in South Africa had some degree of HPA axis dysfunction, yet dynamic adrenal function tests are impractical in the allergy clinic, says the team, led by Ekkehard Werner Zöllner (University of Cape Town, South Africa).
But, on the basis of their results, the researchers conclude that the outlook for a future screening test is dim: “Continuing the search for a suitable screening test to detect HPAS is at this point unlikely to be successful.”
All that physicians can do, they say, is attempt to predict which children are likely to develop HPAS, something that could be assisted by the identification of genetic factors that predispose to, or protect against, the condition.
medwireNews (www.medwirenews.com) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013
By Kirsty Oswald, medwireNews Reporter