Screening for hypothalamic-pituitary-adrenal suppression in - - PowerPoint PPT Presentation

Screening for hypothalamic-pituitary-adrenal suppression in asthmatic children on corticosteroids is not possible when employing clinical & static biochemical parameters

• E. Zöllner1), C. Lombard2), U. Galal2) ,

S.F Hough1), E.M. Irusen1), E. Weinberg3)

1) Endocrine & Allergy Units, Tygerberg Hospital, 2) Biostatistics Unit, Medical Research Council, Cape Town, South Africa

3) UCT Lung Institute & Red Cross Children’s Hospital

Background

• Up to 2/3 of all asthmatic children on corticosteroid (CS)

therapy were found to have a degree of hypothalamic pituitary adrenal axis suppression (HPAS).

• HPAS may not be recognised until the child presents with an

adrenal crisis or non-specific symptoms.

• Only dynamic testing will identify which children are at risk
• f adrenal crisis, but this is impractical.
• A screening test should thus be identified.

Objective

To determine which clinical/biochemical parameter is

the most useful screening test for HPAS in asthmatic children.

Methods

• 143 asthmatic children, 5-18 years old, on inhaled

corticosteroids (ICS), with/without additional CS therapy, were recruited from the allergy units of Tygerberg & Red Cross Children’s Hospitals and the UCT Lung Institute.

• Height, weight, height velocity (HV), weight velocity (WV),

change in systolic BP from recumbent to standing (ΔSBP) were recorded.

• Early morning urine (06:00-07:00h) for urinary free cortisol

(UFC) was collected.

• Morning serum (08:00-09:00h) cortisol (C), ACTH &

dehydroepiandrosterone sulphate (DHEAS) was obtained.

• Overnight metyrapone (MTP) test was performed if C > 83nmol/l.

Screening Variable ACTH 11DOC 11DOC+C r P r P r P Height SDS 0.12 0.186 -0.13 0.120 -0.05 0.542 Weight SDS 0.10 0.262 -0.01 0.195 -0.10 0.279 HV SDS 0.999 0.07 0.420 0.07 0.452 WV SDS

• 0.04 0.638 0.07

0.421 0.09 0.302 ΔSBP 0.992 0.05 0.538 -0.04 0.616 C 0.05 0.538 0.08 0.374 0.12 0.176 ACTH 0.10 0.248 0.04 0.640 0.10 0.263 DHEAS 0.20 0.025 0.21 0.017 0 0.995 UFC (nmol/m2) 0.08 0.379 0.19 0.033 0.20 0.022 UFC (nmol/mmolCr) 0.08 0.397 0.14 0.111 0.16 0.064

Table 1: Spearman correlations between PMTP ACTH, 11 DOC, 11DOC+C and screening variables

Category

Age (years)

5-9 10-14 15-18 Total Males No HPAS 18 32 9 59 HPAS 2 6 2 10 Total 20 38 11 69 Females No HPAS 14 25 9 48 HPAS 6 3 1 10 Total 20 28 10 58 Total No HPAS 32 57 18 107 HPAS 8 9 3 20 Total 40 66 21 127§

* PMTP ACTH<106pg/ml AND 11DOC<208nmol/l AND 11DOC+C<400nmol/l

§ Number of patients who had DHEAS levels measured

Table 2: HPAS* by age group and gender

• Fig. 1: Predicted ROC curves of DHEAS versus HPAS* by age

from a ROC regression model.

.25 .5 .75 1 .25 .5 .75 1 1-Specificity DHEAS 5-9 years 10-14 years 15-18 years

• Fig. 2: ROC curve of DHEAS versus HPAS for 5-9 yr age group

0.00 0.25 0.50 0.75 1.00 0.00 0.25 0.50 0.75 1.00 1 - Specificity

Area under ROC curve = 0.6935

(0.4716-0.9155)

Table 3: Diagnostic performance of DHEAS at 0.2 µmol/l for 5-9 year old age group

Index of test validity Value 95% Confidence interval Sensitivity Specificity Positive predictive value Negative predictive value Accuracy Positive likelihood ratio Negative likelihood ratio 0.87 0.61 0.37 0.95 0.58 2.26 0.20 0.47-1.00 0.42-0.78 0.16-0.62 0.75-1.00 0.55-0.81 1.35-3.78 0.03-1.30

Conclusions & Recommendations

• No clinical or static biochemical parameter is useful as a

universal screening test for HPAS in asthmatic children.

• Basal adrenal function tests are not suitable for research studies.
• DHEAS may be useful to rule out HPAS in children prior to

adrenarche.

• The utility of DHEAS as a screening tool needs to be confirmed

in a larger study.

Acknowledgements

Financial support: Medical Research Council University of Stellenbosch SA Thoracic Society Harry Crossley Foundation Red Cross Children’s Hospital Recruitment: Sisters Hill, Poggenpoel, Pontac, Steyn, All paediatricians & MOs Lab support: GSH & TBH NHLS, BARC, Roche, B. Fenemore

The authors have nothing to declare.

Disclosure Statement

Assays

• Serum total C & UFC were measured with the ADVIA Centaur

automated chemiluminescent assay.

• 11-desoxycortisol (11DOC) levels were established by a

competitive RIA (Biosource).

• ACTH was measured by an automated sequential immunometric

assay (Immulite 2000).

• DHEAS levels were determined by an electrochemiluminescence

immunoassay (Modular Analytics E170).

Statistical Analysis

• Spearman correlations (r) between the post-metyrapone

(PMTP) ACTH, 11DOC, 11DOC+C and each screening variable were determined.

• A ROC regression model for DHEAS was used to look at

association of age & sex.

• A receiver operating characteristics (ROC) curve was drawn

for the most promising test.

• Diagnostic statistics and their 95% confidence intervals were

calculated.