Initial observations regarding free cortisol quantification logistics among critically ill children

Abstract

Corticosteroid insufficiency may occur among critically ill patients, but the diagnosis remains controversial. Historically assessment of free cortisol (FC) by means of equilibrium dialysis (ED) has required large blood volumes and prolonged fractionation time preceding analysis. We hypothesized that temperature-controlled centrifugal ultrafiltration with chemiluminescence immunoassay (CU/CI) would provide real-time FC data that highly correlated with ED/radioimmunoassay (ED/RI) or liquid chromatography/mass spectrometry (LC/MS) techniques. We quantified and correlated baseline and corticotropin-stimulated TC and FC by means of CU/CI, ED/RI, and LC/MS among healthy adults and 37 critically ill children. Among critically ill children, FC was three- to fivefold higher than the healthy adults at baseline and increased another five- to eightfold following corticotropin administration. While TC increased approximately twofold following corticotropin administration, FC increased on average more than eightfold. Serum FC per CU/CI highly correlated with FC per ED/RI or LC/MS, but results were available in a fraction of the time. Children failing to increase TC by >9.0 μg/dL (248 nM) following corticotropin demonstrated an appropriate FC increase. Nearly 50% of critically ill children exhibited FC <2.0 μg/dL (55 nM). Neither FC nor TC concentrations correlated significantly with measures of illness severity. Quantification of FC utilizing CU/CI was fast (1-2 h) and results correlated highly with ED/RI or LC/MS methodologies. These data require validation with larger cohorts of healthy and critically ill children but indicate that real-time FC quantification is available to guide cortisol replacement therapy.