Performance of glucagon stimulation test in diagnosing central adrenal insufficiency in children when utilising the Roche Elecsys® cortisol II assay: a pilot study

Abstract

Abstract Objectives The glucagon stimulation test (GST) is used for the simultaneous assessment of central adrenal insufficiency (CAI) and growth hormone deficiency. The new Roche cortisol II (C II) assay was recently introduced, confounding interpretation of the GST. The performance of the GST in diagnosing central adrenal insufficiency (CAI), utilising the C II assay, was therefore compared with that of the overnight metyrapone test (ONMTPT). Methods A diagnostic accuracy study was performed by retrospectively analysing folders and laboratory records of 25 children and adolescents investigated for hypopituitarism with the GST and the ONMTPT between September 2016 and December 2019. The peak serum cortisol (C) of the GST, the post-metyrapone serum 11-deoxycortisol and adrenocorticotropin levels of the ONMTPT were recorded. Diagnostic performance of the GST at a previously suggested cut-off of 374 nmol/L was evaluated. Results Seventeen boys and 8 girls, aged 1.7–16.3 years (median 7.3 years) were identified. The sensitivity of the post-GST C-level at 374 nmol/L was 0.40 (95% confidence interval [CI] 0.17–0.69), specificity 0.64 (95% CI 0.39–0.84), positive predictive value 0.44 (95% CI 0.19–0.73), negative predictive value 0.60 (95% CI 0.36–0.80), accuracy 0.54 (95% CI 0.35–0.72), positive likelihood ratio (+LR) 0.93 (95% CI 0.49–1.77) and negative LR 1.12 (95% CI 0.40–3.15). The area under the receiver of operating characteristics (ROC) curve was 0.379 (95% CI 0.142–0.615). Conclusions This study suggests that the GST at any C II cut-off cannot replace the ONMTPT as a diagnostic test for CAI in children. Findings should be confirmed in a larger study.