The glucocorticoid receptor and cortisol levels in pediatric septic shock
Abstract Background There 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...
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doaj-9c87d3c62d2c4ba2a70f8639157667d72020-11-25T02:08:39ZengBMCCritical Care1364-85352018-09-012211710.1186/s13054-018-2177-8The glucocorticoid receptor and cortisol levels in pediatric septic shockMatthew N. Alder0Amy M. Opoka1Hector R. Wong2Division of Critical Care Medicine, Cincinnati Children’s Hospital Medical Center, Children’s Hospital Research FoundationDivision of Critical Care Medicine, Cincinnati Children’s Hospital Medical Center, Children’s Hospital Research FoundationDivision of Critical Care Medicine, Cincinnati Children’s Hospital Medical Center, Children’s Hospital Research FoundationAbstract Background There 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. Methods We 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. Results We 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). Conclusions We 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.http://link.springer.com/article/10.1186/s13054-018-2177-8SepsisSeptic shockGlucocorticoid receptorCortisol |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Matthew N. Alder Amy M. Opoka Hector R. Wong |
spellingShingle |
Matthew N. Alder Amy M. Opoka Hector R. Wong The glucocorticoid receptor and cortisol levels in pediatric septic shock Critical Care Sepsis Septic shock Glucocorticoid receptor Cortisol |
author_facet |
Matthew N. Alder Amy M. Opoka Hector R. Wong |
author_sort |
Matthew N. Alder |
title |
The glucocorticoid receptor and cortisol levels in pediatric septic shock |
title_short |
The glucocorticoid receptor and cortisol levels in pediatric septic shock |
title_full |
The glucocorticoid receptor and cortisol levels in pediatric septic shock |
title_fullStr |
The glucocorticoid receptor and cortisol levels in pediatric septic shock |
title_full_unstemmed |
The glucocorticoid receptor and cortisol levels in pediatric septic shock |
title_sort |
glucocorticoid receptor and cortisol levels in pediatric septic shock |
publisher |
BMC |
series |
Critical Care |
issn |
1364-8535 |
publishDate |
2018-09-01 |
description |
Abstract Background There 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. Methods We 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. Results We 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). Conclusions We 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. |
topic |
Sepsis Septic shock Glucocorticoid receptor Cortisol |
url |
http://link.springer.com/article/10.1186/s13054-018-2177-8 |
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