Evaluation of adrenal function using the human corticotrophin-releasing hormone test, low dose Synacthen test and 9am cortisol level in children and adolescents with central adrenal insufficiency

Background The insulin tolerance test (ITT) has become less popular in paediatrics because of the risks associated with hypoglycaemia. Human corticotrophin-releasing hormone (hCRH) test results correlate with the ITT and may be an acceptable method to test for central adrenal insufficiency (CAI). Simpler tests, such as the low dose Synacthen test (LDST) and 9am cortisol, have also been proposed. Objective To compare the ability of the hCRH test, LDST, 9am cortisol level and 24-h cortisol profiles to diagnose CAI in a paediatric population. Design and setting A cross-sectional study in a tertiary paediatric endocrine clinic. participants Thirty-one children and adolescents (aged 2.3-18.3 years) with CAI risk factors had an hCRH test, LDST, 9am cortisol and 24-h cortisol profile performed. Results Of 23 patients with confirmed CAI (hCRH peak cortisol < 400 nmol/), 19 failed the LDST (peak cortisol < 267 nmol/l, i.e. 10th percentile for controls). Nineteen would have failed based on the 10th percentile cut point for 9am cortisol (< 140 nmol/l). Using receiver operating characteristic (ROC) curve coordinates, a 9am cortisol < 108 nmol/l was sensitive (83%) and specific (99%) for CAI. The 9am cortisol levels measured on two occasions were repeatable (94%) and correlated (r = 0.83, P = 0.01). All eight adrenally sufficient patients (hCRH peak cortisol >= 400 nmol/l) passed the LDST. Seven had normal 9am cortisol (>= 140 nmol/l). The 24-h cortisol area under the curve (AUC) for these patients was within the 10th-90th percentiles for control subjects' AUC. The peak cortisol to hCRH and LDST were correlated (r = 0.88, P = 0.01), with no difference between the peaks (mean difference -5.3 nmol/l, P = 0.69). Conclusions In children with CAI risk factors, the diagnosis can be made if unstressed 9am cortisol is < 108 nmol/l. As cortisol levels > 381 nmol/l are highly suggestive of normal hypothalamic-pituitary-adrenal (HPA) function, stimulation testing need only be performed if 9am cortisol is 108-381 nmol/l. The LDST should be interpreted cautiously because mild CAI may be missed. When stimulation results are marginal, 24-h cortisol profiles can provide reassurance of normal cortisol status.