The glucocorticoid receptor and cortisol levels in pediatric septic shock

Abstract

BackgroundThere is controversy around the prescription of adjunct corticosteroids in patients with fluid-refractory septic shock, and studies provide mixed results, showing benefit, no benefit, and harm. Traditional means for evaluating whether a patient receives corticosteroids relied on anecdotal experience or measurement of serum cortisol production following stimulation. We set out to measure both serum cortisol and the intracellular signaling receptor for cortisol, the glucocorticoid receptor (GCR), in this group of patients.MethodsWe enrolled pediatric patients admitted to the pediatric intensive care unit with a diagnosis of systemic inflammatory response syndrome (SIRS), sepsis, or septic shock as well as healthy controls. We measured serum cortisol concentration and GCR expression by flow cytometry in peripheral blood leukocytes on the day of admission and day 3.ResultsWe enrolled 164 patients for analysis. There was no difference between GCR expression comparing SIRS, sepsis, and septic shock. When all patients with septic shock were compared, those patients with a complicated course, defined as two or more organ failures at day 7 or death by day 28, had lower expression of GCR in all peripheral blood leukocytes. Further analysis suggested that patients with the combination of low GCR and high serum cortisol had higher rates of complicated course (75%) compared with the other three possible combinations of GCR and cortisol levels: low GCR and low cortisol (33%), high GCR and high cortisol (33%), and high GCR and low cortisol (13%; P <0.05).ConclusionsWe show that decreased expression of the GCR correlated with poor outcome from septic shock, particularly in those patients with high serum cortisol. This is consistent with findings from transcriptional studies showing that downregulation of GCR signaling genes portends worse outcome.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-2177-8) contains supplementary material, which is available to authorized users.

The Role of Glucocorticoid Receptor and Oxytocin Receptor in the Septic Heart in a Clinically Relevant, Resuscitated Porcine Model With Underlying Atherosclerosis

“…The GR reduction is in agreement with Jenniskens et al, who reported sepsis-induced organ dysfunction related to a down-regulation of GR in the liver (22). This is in contrast to the ambivalent reports of GR expression in circulating cells (20,21), which may not necessarily represent the role of GR at the organ level during sepsis (35). As reviewed by Cavaillon and Annane (35), in sepsis, organ specific gene expression was determined to share common patterns or show distinctly opposite profiles between different organs (36), whereas circulating cytokines were not reflective of tissue-specific local levels (37).…”

“…Moreover, we have recently demonstrated that impaired GR dimerization aggravated hemodynamic instability and organ dysfunction during LPS-induced circulatory shock (19). Results for GR expression in peripheral blood cells in sepsis are ambivalent (20,21). While a GR down-regulation is associated with organ dysfunction in the septic liver (22), there are no reports of cardiac tissue expression during sepsis.…”

A Comparative Review of Equine SIRS, Sepsis, and Neutrophils

“…Dysregulation of cortisol has already been associated with poorer sepsis outcomes in human patients. In a study on 164 pediatric patients, Alder et al reported that patients with both low glucocorticoid receptor expression and high serum cortisol had higher rates (75%) of multi-organ (>2) failure and death ( 55 ). Taken together, this evidence suggests that previous EMS and/or PPID diagnosis could be a relevant “predisposition” for horses being treated for sepsis, and outcomes in this patient population may warrant further investigation.…”

Expression of Glucocorticoid Receptors in the Early Period After the Return of Spontaneous Circulation Among Patients Who Experienced Cardiac Arrest : A Retrospective Observational Study

“…The a nity of GRs to GC in circulating monocytes is decreased in patients with acquired immunode ciency syndrome [21]. The expression of GR is decreased in critical illness [22], pediatric septic shock, and patients with high serum cortisol [23]. However, hitherto, no study has reported on the GR expression after ROSC in patients who experienced CA.…”