Endogenous serum glucocorticoid concentrations, steroidogenic enzyme activity, and 90-day mortality in patients hospitalized with COVID-19: an observational cohort study
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Endogenous serum glucocorticoid concentrations, steroidogenic enzyme activity, and 90-day mortality in patients hospitalized with COVID-19 : an observational cohort study. / Clausen, Clara Lundetoft; Johannsen, Trine Holm; Skakkebæk, Niels Erik; Frederiksen, Hanne; Juul, Anders; Benfield, Thomas.
I: Endocrine Connections, Bind 13, Nr. 8, e240093, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Endogenous serum glucocorticoid concentrations, steroidogenic enzyme activity, and 90-day mortality in patients hospitalized with COVID-19
T2 - an observational cohort study
AU - Clausen, Clara Lundetoft
AU - Johannsen, Trine Holm
AU - Skakkebæk, Niels Erik
AU - Frederiksen, Hanne
AU - Juul, Anders
AU - Benfield, Thomas
N1 - Publisher Copyright: © 2024 the author(s).
PY - 2024
Y1 - 2024
N2 - In the context of severe coronavirus disease 2019 (COVID-19) illness, we examined endogenous glucocorticoid concentrations, steroidogenic enzyme activity, and their correlation with inflammation and patient outcomes. This observational study included 125 hospitalized COVID-19 patients and 101 healthy individuals as a reference group. We utilized LC-MS to assess serum concentrations of 11-deoxycortisol, cortisol, and cortisone, as well as activities of steroidogenic enzymes (11β-hydroxylase and 11β-hydroxysteroid-dehydrogenase type 1). Cox proportional hazards regression analysis and competing risk analysis were employed to analyze associations between glucocorticoid concentrations and outcomes, adjusting for relevant factors. In patients with COVID-19, cortisol concentrations were higher and cortisone concentrations were lower compared to the reference group, while 11-deoxycortisol concentrations were similar. Steroidogenic enzyme activity favored cortisol production. Correlations between glucocorticoid concentrations and inflammatory markers were low. A doubling in concentrations cortisol, was associated with increased 90-day mortality and mechanical ventilation (HR: 2.40 95% CI: (1.03–5.59), P = 0.042 and HR: 3.83 (1.19–12.31), P = 0.024). A doubling in concentrations of 11-deoxycortisol was also associated to mortality (HR: 1.32 (1.05–1.67), P = 0.018), whereas concentrations of cortisone were associated with mechanical ventilation (HR: 5.09 (1.49–17.40), P = 0.009). In conclusion, serum concentrations of glucocorticoid metabolites were altered in patients hospitalized with severe COVID-19, and steroidogenic enzyme activity resulting in the conversion of cortisone to biologically active cortisol was preserved, thus not favoring critical-illness-related corticosteroid insufficiency at the enzymatic level. Glucocorticoid release did not counterbalance the hyperinflammatory state in patients with severe COVID-19. High serum concentrations of 11-deoxycortisol and cortisol were associated with 90-day mortality, and high serum concentrations of cortisol and cortisone were associated with mechanical ventilation.
AB - In the context of severe coronavirus disease 2019 (COVID-19) illness, we examined endogenous glucocorticoid concentrations, steroidogenic enzyme activity, and their correlation with inflammation and patient outcomes. This observational study included 125 hospitalized COVID-19 patients and 101 healthy individuals as a reference group. We utilized LC-MS to assess serum concentrations of 11-deoxycortisol, cortisol, and cortisone, as well as activities of steroidogenic enzymes (11β-hydroxylase and 11β-hydroxysteroid-dehydrogenase type 1). Cox proportional hazards regression analysis and competing risk analysis were employed to analyze associations between glucocorticoid concentrations and outcomes, adjusting for relevant factors. In patients with COVID-19, cortisol concentrations were higher and cortisone concentrations were lower compared to the reference group, while 11-deoxycortisol concentrations were similar. Steroidogenic enzyme activity favored cortisol production. Correlations between glucocorticoid concentrations and inflammatory markers were low. A doubling in concentrations cortisol, was associated with increased 90-day mortality and mechanical ventilation (HR: 2.40 95% CI: (1.03–5.59), P = 0.042 and HR: 3.83 (1.19–12.31), P = 0.024). A doubling in concentrations of 11-deoxycortisol was also associated to mortality (HR: 1.32 (1.05–1.67), P = 0.018), whereas concentrations of cortisone were associated with mechanical ventilation (HR: 5.09 (1.49–17.40), P = 0.009). In conclusion, serum concentrations of glucocorticoid metabolites were altered in patients hospitalized with severe COVID-19, and steroidogenic enzyme activity resulting in the conversion of cortisone to biologically active cortisol was preserved, thus not favoring critical-illness-related corticosteroid insufficiency at the enzymatic level. Glucocorticoid release did not counterbalance the hyperinflammatory state in patients with severe COVID-19. High serum concentrations of 11-deoxycortisol and cortisol were associated with 90-day mortality, and high serum concentrations of cortisol and cortisone were associated with mechanical ventilation.
KW - COVID-19
KW - enzymes
KW - glucocorticoids
KW - inflammation
KW - mortalit
U2 - 10.1530/EC-24-0093
DO - 10.1530/EC-24-0093
M3 - Journal article
C2 - 38904471
AN - SCOPUS:85200734931
VL - 13
JO - Endocrine Connections
JF - Endocrine Connections
SN - 2049-3614
IS - 8
M1 - e240093
ER -
ID: 402065535