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Depletion of high‐affinity corticosteroid‐binding globulin corresponds to illness severity in sepsis and septic shock; clinical implications
Author(s) -
Nenke M.A.,
Rankin W.,
Chapman M.J.,
Stevens N.E.,
Diener K.R.,
Hayball J. D.,
Lewis J.G.,
Torpy D.J.
Publication year - 2015
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.12680
Subject(s) - transcortin , sepsis , septic shock , medicine , shock (circulatory) , endocrinology , immunology , hydrocortisone , corticosteroid , inflammation , globulin , severity of illness , glucocorticoid
Summary Objective Corticosteroid‐binding globulin ( CBG ) is cleaved by neutrophil elastase converting the high‐affinity (ha CBG ) conformation of CBG to a low‐affinity (la CBG ) conformation with a ninefold reduced cortisol‐binding affinity. These in vitro 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 ha CBG and la CBG in vivo in proportion to sepsis severity. Design Prospective, observational cohort study in an adult tertiary level Intensive Care Unit in Adelaide, Australia. Patients Thirty‐three patients with sepsis or septic shock grouped by illness severity [sepsis, septic shock survivors, septic shock nonsurvivors and other shock]. Measurements Plasma levels of ha CBG and la CBG were assessed using a recently developed in‐house assay in patients. Plasma total and free cortisol levels were also measured. Results Plasma total CBG and ha CBG levels fell significantly, in proportion to disease severity ( P < 0·0001 for both). There was a nonsignificant increase in free and total cortisol as illness severity worsened ( P = 0·19 and P = 0·39, respectively). Illness severity was better correlated with ha CBG levels than either free or total cortisol levels. Conclusions Increasing illness severity in sepsis and septic shock is associated with markedly reduced circulating ha CBG concentrations in vivo . We propose that low levels of ha CBG in chronic inflammation may limit the availability of cortisol to inflammatory sites, perpetuating the inflammatory process.