Sepsis has been extensively investigated with increasing evidence of maladaptive homeostasis, functional GC deficiency, and higher mortality in those with very high or very low cortisol levels.27 From studies in adults and mice, greater understanding has emerged for the corticotropin-cortisol dissociation in critical illness.28,29,30,31 Téblick et al31 found high circulating cortisol levels to be associated with central activation of the hypothalamus and increased pro-opiomelanocortin expression in the pituitary. This evidence concerns the gene POMC and Sepsis.