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Total and high‐affinity corticosteroid‐binding globulin depletion in septic shock is associated with mortality
Author(s) -
Meyer Emily J.,
Nenke Marni A.,
Rankin Wayne,
Lewis John G.,
Konings Elisabeth,
Slager Maarten,
Jansen Tim C.,
Bakker Jan,
Hofland Johannes,
Feelders Richard A.,
Torpy David J.
Publication year - 2019
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.13844
Subject(s) - septic shock , transcortin , sepsis , medicine , globulin , shock (circulatory) , albumin , glucocorticoid , hydrocortisone , endocrinology , intensive care unit , corticosteroid , immunology
Summary Context Corticosteroid‐binding globulin ( CBG ) and albumin transport circulating cortisol. Cleavage of high‐affinity CBG (ha CBG ) by neutrophil elastase at inflammatory sites causes cortisol release into tissues, facilitating immunomodulatory effects. Objective To determine whether depletion of ha CBG is related to mortality in septic shock. Design A single‐center prospective observational cohort study of patients recruited with critical illness or septic shock, using serum samples collected at 0, 8, 24, 48 and 72 hours. Serum total and ha CBG , and total and free cortisol were assayed directly. Glucocorticoid treatment was an exclusion criterion. Mortality was assessed at 28 days from Intensive Care Unit admission. Results Thirty septic shock ( SS ) and 42 nonseptic critical illness ( CI ) patients provided 195 serum samples. SS / CI patients had lower total CBG , ha CBG and low‐affinity CBG (la CBG ) than controls. Total CBG and ha CBG were significantly lower in septic shock patients who died than in those that survived ( P < 0.009, P = 0.021, respectively). Total and free cortisol were higher in septic than nonseptic individuals. Free/total cortisol fractions were higher in those with low ha CBG as observed in septic shock. However, cortisol levels were not associated with mortality. Albumin levels fell in sepsis but were not related to mortality. Conclusions Low circulating ha CBG concentrations are associated with mortality in septic shock. These results are consistent with an important physiological role for ha CBG in cortisol tissue delivery in septic shock.