Emily J Meyer1,2, Marni A Nenke1,2, Wayne Rankin1,2,3, John G Lewis4, Elisabeth Konings5, Maarten Slager5, Tim C Jansen6, Jan Bakker7, Johannes Hofland5, Richard A Feelders5, David J Torpy1,2. 1. Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia. 2. Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia. 3. Chemical Pathology Directorate, SA Pathology, Adelaide, South Australia, Australia. 4. Steroid & Immunobiochemistry Laboratory, Canterbury Health Laboratories, Christchurch, New Zealand. 5. Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands. 6. Department of Intensive Care, Haga Hospital, The Hague, The Netherlands. 7. Department of Intensive Care, Erasmus Medical Center, Rotterdam, The Netherlands.
Abstract
CONTEXT: Corticosteroid-binding globulin (CBG) and albumin transport circulating cortisol. Cleavage of high-affinity CBG (haCBG) by neutrophil elastase at inflammatory sites causes cortisol release into tissues, facilitating immunomodulatory effects. OBJECTIVE: To determine whether depletion of haCBG 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 haCBG, 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, haCBG and low-affinity CBG (laCBG) than controls. Total CBG and haCBG 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 haCBG 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 haCBG concentrations are associated with mortality in septic shock. These results are consistent with an important physiological role for haCBG in cortisol tissue delivery in septic shock.
CONTEXT: Corticosteroid-binding globulin (CBG) and albumin transport circulating cortisol. Cleavage of high-affinity CBG (haCBG) by neutrophil elastase at inflammatory sites causes cortisol release into tissues, facilitating immunomodulatory effects. OBJECTIVE: To determine whether depletion of haCBG 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 haCBG, 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, haCBG and low-affinity CBG (laCBG) than controls. Total CBG and haCBG were significantly lower in septic shockpatients 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 haCBG 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 haCBG concentrations are associated with mortality in septic shock. These results are consistent with an important physiological role for haCBG in cortisol tissue delivery in septic shock.
Authors: Emily J Meyer; David J Torpy; Anastasia Chernykh; Morten Thaysen-Andersen; Marni A Nenke; John G Lewis; Harinda Rajapaksha; Wayne Rankin; Steven W Polyak Journal: Protein Sci Date: 2020-11-04 Impact factor: 6.725
Authors: Zhen Jiang; Selma Z Elsarrag; Qiming Duan; Edward L LaGory; Zhe Wang; Michael Alexanian; Sarah McMahon; Ingrid C Rulifson; Sarah Winchester; Yi Wang; Christian Vaisse; Jonathan D Brown; Mattia Quattrocelli; Charles Y Lin; Saptarsi M Haldar Journal: Sci Adv Date: 2022-03-09 Impact factor: 14.957
Authors: Emily Jane Meyer; Lucía Spangenberg; Maria José Ramírez; Sunita Maria Christina De Sousa; Victor Raggio; David James Torpy Journal: J Endocr Soc Date: 2021-06-22