Abstract
Sepsis is frequently complicated by non-thyroidal illness syndrome (NTIS). Although thyroid hormones are essential for cardiovascular and respiratory stability, their supplementation in sepsis remains controversial due to conflicting evidence. This study aimed to evaluate the impact of thyroid hormone supplementation on 28 day mortality, mechanical ventilation, vasopressor use, ICU length of stay, and changes in SOFA scores in patients with sepsis. We analyzed 20,231 septic patients from the Medical Information Mart for Intensive Care Database IV (MIMIC-IV) database, comparing those treated with levothyroxine sodium within seven days to a control group using 1:4 propensity score matching. Early levothyroxine sodium administration was significantly associated with increased 28 day mortality in both the original (HR 2.48, 95% CI 1.96–3.15; P < 0.001) and propensity score matching (PSM) cohorts (HR 2.38, 95% CI 1.75–3.23; P < 0.001). The treatment group required higher cumulative norepinephrine equivalents (P = 0.006) and longer vasoactive support duration. Multistate modeling revealed that the treatment group had fewer days alive without mechanical ventilation (17.8 vs. 21.8 days; P < 0.001) and fewer days discharged alive (11.3 vs. 13.4 days; P = 0.006). In patients with less severe sepsis, levothyroxine sodium administration should be approached with particular caution, as it may be associated with adverse clinical outcomes.
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Data availability
The data that support the findings of this study are available from PhysioNet but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of PhysioNet.
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Acknowledgements
The authors acknowledge the Laboratory for Computational Physiology at MIT for the development and maintenance of the MIMIC-IV (version 3.1) database.
Funding
This study was funded by the Hebei Provincial Health Commission Key Scientific and Technological Research Program [20221205].
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J.C and M.C contributed equally to this work and shared first authorship. J.Y.G was responsible for the study of concepts and design. J.C and M.C were responsible for data extraction and drafting the initial manuscript. Q.W.Y and Z.J.G were responsible for statistical analysis and data interpretation. K.X and S.L were responsible for literature retrieval and data validation. J.Y.G provided critical revision of the manuscript for important intellectual content. All authors had full access to all the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. All authors read and approved of the final manuscript.
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Chu, J., Chen, M., Guo, J. et al. Early levothyroxine sodium administration and clinical outcomes in patients with sepsis: a MIMIC-IV database analysis. Sci Rep (2026). https://doi.org/10.1038/s41598-026-43822-z
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DOI: https://doi.org/10.1038/s41598-026-43822-z
