Background: Corticosteroid-binding globulin (CBG) is the principal transport protein for cortisol. High cortisol-binding affinity CBG (haCBG) is cleaved to low affinity CBG (laCBG), liberating cortisol at inflammatory sites. Total CBG and haCBG fall in sepsis and septic shock in relation to sepsis severity . Plasma haCBG concentrations correlate well with sepsis severity, unlike total or free cortisol, hence haCBG measurement may be of prognostic value in sepsis.
Hypothesis: haCBG depletion in sepsis may predict outcomes including vasopressor use and mortality.
Method: An observational cohort study using blood samples collected at 0, 8, 24, 48 and 72 hours from patients admitted to four Dutch Intensive Care Units between 2006 and 2008 . Total and haCBG were assayed in parallel with specific monoclonal antibodies using our novel in-house method [3,4].
Results: A total of 209 results from 4 septic (S), 31 septic shock (SS) and 42 non-septic (NS) patients, were analysed and further categorised according to 28-day mortality (death =D, survival=SU). Total CBG, haCBG and laCBG were lower in the pooled SS and S group (median [range]: 252 nmol/L [4–430]; 174.5 [25–399]; 58 [7–175]) than NS (288 nmol/L [84–615], p<0.0001; 186.5 [67–338], p<0.039; 84.5 [10–395], p<0.0001) and these are both lower than in healthy controls. In sepsis total CBG, laCBG and haCBG did not correlate with admission. haCBG was significantly lower in SS-D compared to SS-SU, S and NS (p=0.016, p=0.006, p=0.006, Tukey’s multiple comparisons test, F=27.3, df=3, p0.002).
Conclusions: This is the first study showing low haCBG levels are associated with death in human sepsis. The results are consistent with an important physiological role for haCBG in cortisol transport in septic shock.