Mattel Children's Hospital at UCLA Cortisol Quantification Investigation Study - Background and Objectives __________________________________________________                                                     Background: More than 90% of circulating cortisol in serum is protein-bound. Free cortisol is the biologically active form of the hormone. Changes in the concentration of cortisol binding proteins that commonly occur with        critical illness will alter measured serum total cortisol, without affecting the concentration of free cortisol. Free serum cortisol may provide a better index of adequacy of the cortisol stress response. No information regarding free cortisol kinetics has been compiled for critically ill children. Variability in the cortisol response to critical illness may arise from different levels of illness severity or it may be attributable to genetic differences between patients. A meta-analysis of 5 comparable twin studies indicates that 62% of the individual differences in basal cortisol levels are attributable to genetic effects.   SNPs in genes involved in cortisol synthesis or in regulatory control of cortisol synthesis may be partially responsible for differences in basal cortisol levels.   The role of gene polymorphisms along the cortisol synthetic pathway in relation to relatively impaired cortisol synthesis during stress has not been