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Depletion of high-affinity corticosteroid-binding globulin corresponds to illness severity in sepsis and septic shock; clinical implications.
Nenke, M A; Rankin, W; Chapman, M J; Stevens, N E; Diener, K R; Hayball, J D; Lewis, J G; Torpy, D J.
Afiliación
  • Nenke MA; Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA, Australia.
  • Rankin W; School of Medicine, University of Adelaide, Adelaide, SA, Australia.
  • Chapman MJ; Chemical Pathology Directorate, SA Pathology, Adelaide, SA, Australia.
  • Stevens NE; Intensive Care Unit, Royal Adelaide Hospital, Adelaide, SA, Australia.
  • Diener KR; Experimental Therapeutics Laboratory, Hanson Institute and Sansom Institute, University of South Australia, Adelaide, SA, Australia.
  • Hayball JD; Experimental Therapeutics Laboratory, Hanson Institute and Sansom Institute, University of South Australia, Adelaide, SA, Australia.
  • Lewis JG; Robinson Research Institute and School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia.
  • Torpy DJ; School of Medicine, University of Adelaide, Adelaide, SA, Australia.
Clin Endocrinol (Oxf) ; 82(6): 801-7, 2015 Jun.
Article en En | MEDLINE | ID: mdl-25409953
OBJECTIVE: 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 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 haCBG and laCBG 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 haCBG and laCBG 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 haCBG 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 haCBG levels than either free or total cortisol levels. CONCLUSIONS: Increasing illness severity in sepsis and septic shock is associated with markedly reduced circulating haCBG concentrations in vivo. We propose that low levels of haCBG in chronic inflammation may limit the availability of cortisol to inflammatory sites, perpetuating the inflammatory process.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Choque Séptico / Transcortina / Hidrocortisona / Sepsis / Inflamación Tipo de estudio: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Endocrinol (Oxf) Año: 2015 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Choque Séptico / Transcortina / Hidrocortisona / Sepsis / Inflamación Tipo de estudio: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Endocrinol (Oxf) Año: 2015 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido