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. 2018 Sep 29;22(1):244.
doi: 10.1186/s13054-018-2177-8.

The Glucocorticoid Receptor and Cortisol Levels in Pediatric Septic Shock

Free PMC article

The Glucocorticoid Receptor and Cortisol Levels in Pediatric Septic Shock

Matthew N Alder et al. Crit Care. .
Free PMC article


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.

Keywords: Cortisol; Glucocorticoid receptor; Sepsis; Septic shock.

Conflict of interest statement

Ethics approval and consent to participate

The institutional review board at Cincinnati Children’s Hospital reviewed and approved the study protocol. Biological samples and clinical data were gathered after signed informed consent by the parents or legal guardians of the study subjects was obtained.

Consent for publication

We consent for publication in Critical Care.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


Fig. 1
Fig. 1
No correlation between glucocorticoid receptor (GCR) alpha and serum cortisol. Comparison of flow cytometric mean fluorescence intensity (MFI) of all leukocyte GCR alpha expression relative to serum cortisol (R = 0.058, P = 0.532)

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