Corticotropin-stimulated steroid profiles to predict shock development and mortality in sepsis: From the HYPRESS study

TY - JOUR

T1 - Corticotropin-stimulated steroid profiles to predict shock development and mortality in sepsis: From the HYPRESS study

AU - Briegel, Josef

AU - Möhnle, Patrick

AU - Keh, Didier

AU - Lindner, Johanna M

AU - Vetter, Anna C

AU - Bogatsch, Holger

AU - Lange, Dorothea

AU - Frank, Sandra

AU - Hinske, Ludwig C

AU - Annane, Djillali

AU - Vogeser, Michael

AU - SepNet Critical Care Trials Group

AU - Kluge, Stefan

N1 - © 2022. The Author(s).

PY - 2022/11/7

Y1 - 2022/11/7

N2 - RATIONALE: Steroid profiles in combination with a corticotropin stimulation test provide information about steroidogenesis and its functional reserves in critically ill patients.OBJECTIVES: We investigated whether steroid profiles before and after corticotropin stimulation can predict the risk of in-hospital death in sepsis.METHODS: An exploratory data analysis of a double blind, randomized trial in sepsis (HYPRESS [HYdrocortisone for PRevention of Septic Shock]) was performed. The trial included adult patients with sepsis who were not in shock and were randomly assigned to placebo or hydrocortisone treatment. Corticotropin tests were performed in patients prior to randomization and in healthy subjects. Cortisol and precursors of glucocorticoids (17-OH-progesterone, 11-desoxycortisol) and mineralocorticoids (11-desoxycorticosterone, corticosterone) were analyzed using the multi-analyte stable isotope dilution method (LC-MS/MS). Measurement results from healthy subjects were used to determine reference ranges, and those from placebo patients to predict in-hospital mortality.MEASUREMENTS AND MAIN RESULTS: Corticotropin tests from 180 patients and 20 volunteers were included. Compared to healthy subjects, patients with sepsis had elevated levels of 11-desoxycorticosterone and 11-desoxycortisol, consistent with activation of both glucocorticoid and mineralocorticoid pathways. After stimulation with corticotropin, the cortisol response was subnormal in 12% and the corticosterone response in 50% of sepsis patients. In placebo patients (n = 90), a corticotropin-stimulated cortisol-to-corticosterone ratio > 32.2 predicted in-hospital mortality (AUC 0.8 CI 0.70-0.88; sensitivity 83%; and specificity 78%). This ratio also predicted risk of shock development and 90-day mortality.CONCLUSIONS: In this exploratory analysis, we found that in sepsis mineralocorticoid steroidogenesis was more frequently impaired than glucocorticoid steroidogenesis. The corticotropin-stimulated cortisol-to-corticosterone ratio predicts the risk of in-hospital death. Trial registration Clinical trial registered with www.CLINICALTRIALS: gov Identifier: NCT00670254. Registered 1 May 2008, https://clinicaltrials.gov/ct2/show/NCT00670254 .

AB - RATIONALE: Steroid profiles in combination with a corticotropin stimulation test provide information about steroidogenesis and its functional reserves in critically ill patients.OBJECTIVES: We investigated whether steroid profiles before and after corticotropin stimulation can predict the risk of in-hospital death in sepsis.METHODS: An exploratory data analysis of a double blind, randomized trial in sepsis (HYPRESS [HYdrocortisone for PRevention of Septic Shock]) was performed. The trial included adult patients with sepsis who were not in shock and were randomly assigned to placebo or hydrocortisone treatment. Corticotropin tests were performed in patients prior to randomization and in healthy subjects. Cortisol and precursors of glucocorticoids (17-OH-progesterone, 11-desoxycortisol) and mineralocorticoids (11-desoxycorticosterone, corticosterone) were analyzed using the multi-analyte stable isotope dilution method (LC-MS/MS). Measurement results from healthy subjects were used to determine reference ranges, and those from placebo patients to predict in-hospital mortality.MEASUREMENTS AND MAIN RESULTS: Corticotropin tests from 180 patients and 20 volunteers were included. Compared to healthy subjects, patients with sepsis had elevated levels of 11-desoxycorticosterone and 11-desoxycortisol, consistent with activation of both glucocorticoid and mineralocorticoid pathways. After stimulation with corticotropin, the cortisol response was subnormal in 12% and the corticosterone response in 50% of sepsis patients. In placebo patients (n = 90), a corticotropin-stimulated cortisol-to-corticosterone ratio > 32.2 predicted in-hospital mortality (AUC 0.8 CI 0.70-0.88; sensitivity 83%; and specificity 78%). This ratio also predicted risk of shock development and 90-day mortality.CONCLUSIONS: In this exploratory analysis, we found that in sepsis mineralocorticoid steroidogenesis was more frequently impaired than glucocorticoid steroidogenesis. The corticotropin-stimulated cortisol-to-corticosterone ratio predicts the risk of in-hospital death. Trial registration Clinical trial registered with www.CLINICALTRIALS: gov Identifier: NCT00670254. Registered 1 May 2008, https://clinicaltrials.gov/ct2/show/NCT00670254 .

KW - Adult

KW - Humans

KW - Adrenocorticotropic Hormone

KW - Hydrocortisone/therapeutic use

KW - Hospital Mortality

KW - Glucocorticoids/pharmacology

KW - Mineralocorticoids/pharmacology

KW - Corticosterone

KW - Cortodoxone

KW - Chromatography, Liquid

KW - Tandem Mass Spectrometry

KW - Sepsis/drug therapy

KW - Shock, Septic

KW - Desoxycorticosterone/therapeutic use

U2 - 10.1186/s13054-022-04224-5

DO - 10.1186/s13054-022-04224-5

M3 - SCORING: Journal article

C2 - 36345013

VL - 26

JO - CRIT CARE

JF - CRIT CARE

SN - 1364-8535

IS - 1

M1 - 343

ER -