Initial observations regarding free cortisol quantification logistics among critically ill children

• Published in: Intensive care medicine Vol. 36; no. 11; pp. 1914 - 1922
• Main Authors: Zimmerman, Jerry J., Barker, Ruth M., Jack, Rhona
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.11.2010; Springer
• Subjects: ACTH; Adolescent; Adrenal Insufficiency - diagnosis; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anesthesiology; Biological and medical sciences; Child; Child, Preschool; Chromatography; Clinical death. Palliative care. Organ gift and preservation; Clinical Laboratory Techniques; Corticosteroids; Critical Care Medicine; Critical Illness; Emergency Medicine; Female; Humans; Hydrocortisone - blood; Infant; Intensive; Intensive care medicine; Male; Medical sciences; Medicine; Medicine & Public Health; Pain Medicine; Pediatric Original; Pediatrics; Pneumology/Respiratory System; Sensitivity and Specificity; Liquid chromatography/mass spectrometry; Radioimmunoassay; Chemiluminescence immunoassay; Centrifugal ultrafiltration; Relative adrenal insufficiency; Total cortisol; Critical illness related cortisol insufficiency; Equilibrium dialysis; Free cortisol; Endocrinopathy; Intensive care; Hydrocortisone; Glucocorticoid; Ultrafiltration; Adrenal gland diseases; Child; Resuscitation; Human; Corticosteroid; Steroid hormone; Critically ill; Antiinflammatory agent; Chemiluminescence; Liquid chromatography; Adrenal insufficiency; Adrenal hormone; Mass spectrometry; Logistics
• ISSN: 0342-4642; 1432-1238; 1432-1238
• DOI: 10.1007/s00134-010-2007-1

Purpose 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. Methods 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. Results 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. Conclusions 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.