Screening for hypothalamic–pituitary–adrenal axis suppression in asthmatic children remains problematic

BMJ Open 2013;3:e002935 doi:10.1136/bmjopen-2013-002935

• Epidemiology

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

1. Ekkehard Werner Zöllner1,2, 
2. Carl J Lombard3, 
3. Ushma Galal3, 
4. Stephen Hough4,
5. Elvis M Irusen5, 
6. Eugene Weinberg6

+Author Affiliations

1. ¹Paediatric Endocrine Unit, Department of Paediatrics, Stellenbosch University, Tygerberg Children's Hospital, Cape Town, South Africa
2. ²Endocrine Unit, Red Cross Children's Hospital, University of Cape Town, Cape Town, South Africa
3. ³Biostatistics Unit, Medical Research Council, Cape Town, South Africa
4. ⁴Division of Endocrinology, Department of Medicine, Tygerberg Hospital, Stellenbosch University, Cape Town, South Africa
5. ⁵Pulmonology Division, Department of Medicine, Tygerberg Hospital, Stellenbosch University, Cape Town, South Africa
6. ⁶Allergy Unit, Red Cross Children's Hospital, University of Cape Town, Cape Town, South Africa

1. Corresponding toDr Ekkehard Werner Zöllner; zollner@sun.ac.za

• Received 22 March 2013
• Revised 28 June 2013
• Accepted 3 July 2013
• Published 1 August 2013

Abstract

Objective To determine which parameter is the most useful screening test for hypothalamic–pituitary–adrenal suppression in asthmatic children.

Design Cross-sectional study.

Setting Paediatric allergy clinics in Cape Town, South Africa.

Participants 143 asthmatic children of mostly mixed ancestry, aged 5–12 years.

Outcome measures Primary 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.

Results All 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).

Conclusions No 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.

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