Corticotroph response to acute stress after ICU admissionTotal selleck chemicals cortisol baseline is clearly elevated in critical illness, but its outcome value is confusing [23-29]. In this study, higher cortisol baseline was observed in non-survivors, especially septic patients, as observed in large cohort studies [30,31]. The dynamic response of cortisol to corticotropin was not predictive of the outcome in our and other hands [23,27], in contradiction with the findings of Annane et al [5]. From these viewpoints, it appears imperative to thoroughly define study populations (that is, proper matching for period on inclusion, gender and age), sample timing, as well as to standardize methods of cortisol measurement, all being critical factors for comparisons.

Free cortisol index (FCI) has been advocated as a better determinant of the HPA status than cortisol in stressed patients [32], although not recommended for routine use by a recent international task force [4]. However, FCI requires cortisol binding globulin (CBG) measurement and total cortisol-to-albumin ratio can be an efficient and simplest surrogate marker [26,29,32-34]. In our study, total cortisol-to-albumin ratio was very high during acute sepsis and presented the best on admission outcome predictor.Differential dissociation of ACTH and cortisol in acute stress after ICU admissionACTH-to-cortisol ratio dissociation, with low ACTH and high cortisol levels, is particularly observed during the chronic phase of critical illness [22], whereas high cortisol and ACTH have been observed during the initial phase [35,36].

Indeed, time-course and specificity of ACTH-to-cortisol dissociation are essential issues. In a small study [35], blood ACTH dramatically dropped in critically ill patients from Day 3 to 4, whereas cortisol remained high. An earlier dissociation was, however, observed on the first to second day in postoperative non-septic cancerous patients [37]. Furthermore, although ACTH-to-cortisol baseline ratio was reported decreased in critically ill non-survivors [23,25], it was either found unchanged in septic non-survivors [24] or lowered in septic patients [26]. In this study, we found a decrease in ACTH-to-cortisol baseline ratio distinctive of sepsis among critically ill patients, as a result of both blunted ACTH content and elevated cortisol.

This suggests non-pituitary-driven sources and non-ACTH regulators of cortisol release during acute sepsis or HPA axis alteration inducing secondary adrenal dysfunction with sustained increased blood cortisol as a result of tissue resistance or impaired clearance [38]. Moreover, systemically or locally released neurotransmitters (catecholamines, Dacomitinib AVP), neuropeptides, inflammatory cytokines (including IL-1, IL-6, MIF) and growth factors have been committed in this respect [38,39].