Depletion of high‐affinity corticosteroid‐binding globulin corresponds to illness severity in sepsis and septic shock; clinical implications. (8th January 2015)

• Record Type: Journal Article
• Authors: Nenke, M.A.; Rankin, W.; Chapman, M.J.; Stevens, N.E.; Diener, K.R.; Hayball, J. D.; Lewis, J.G.; Torpy, D.J.
• Is Part Of: Clinical endocrinology. Volume 82:Number 6(2015:Jun.)
• Page Start: 801
• Page End: 807
• Publication Date: 2015-01-08
• Subjects: Endocrinology -- Periodicals; 616.4005
• DOI: 10.1111/cen.12680
• Languages: English
• ISSNs: 0300-0664

Abstract

<abstract abstract-type="main" id="cen12680-abs-0001"> <title>Summary</title> <sec id="cen12680-sec-0001" sec-type="section"> <title>Objective</title> <p>Corticosteroid‐binding globulin (CBG) is cleaved by neutrophil elastase converting the high‐affinity (haCBG) conformation of CBG to a low‐affinity (laCBG) conformation with a ninefold reduced cortisol‐binding affinity. These <italic>in vitro</italic> data suggest that cortisol release by CBG cleavage results in the targeted delivery of cortisol to areas of inflammation. Our objective was to determine whether CBG cleavage alters circulating levels of haCBG and laCBG <italic>in vivo</italic> in proportion to sepsis severity.</p> </sec> <sec id="cen12680-sec-0002" sec-type="section"> <title>Design</title> <p>Prospective, observational cohort study in an adult tertiary level Intensive Care Unit in Adelaide, Australia.</p> </sec> <sec id="cen12680-sec-0003" sec-type="section"> <title>Patients</title> <p>Thirty‐three patients with sepsis or septic shock grouped by illness severity [sepsis, septic shock survivors, septic shock nonsurvivors and other shock].</p> </sec> <sec id="cen12680-sec-0004" sec-type="section"> <title>Measurements</title> <p>Plasma levels of haCBG and laCBG were assessed using a recently developed in‐house assay in patients. Plasma total and free cortisol levels were also measured.</p> </sec> <sec id="cen12680-sec-0005" sec-type="section"> <title>Results</title> <p>Plasma total CBG and haCBG levels fell significantly, in proportion to disease severity (<italic>P </italic>< 0·0001 for both). There was a nonsignificant increase in free and total cortisol as illness severity worsened (<italic>P </italic>= 0·19 and <italic>P </italic>= 0·39, respectively). Illness severity was better correlated with haCBG levels than either free or total cortisol levels.</p> </sec> <sec id="cen12680-sec-0006" sec-type="section"> <title>Conclusions</title> <p>Increasing illness severity in sepsis and septic shock is associated with markedly reduced circulating haCBG concentrations <italic>in vivo</italic>. We propose that low levels of haCBG in chronic inflammation may limit the availability of cortisol to inflammatory sites, perpetuating the inflammatory process.</p> </sec> </abstract>