{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T20:30:32Z","timestamp":1777408232336,"version":"3.51.4"},"reference-count":31,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Euthyroid sick syndrome (ESS), and particularly low T3, have been associated with increased mortality in septic patients, yet the prognostic value of free thyroxine (fT4) remains controversial. This study aims to evaluate the association between fT4 on ICU admission and mortality in septic patients. Methods: We conducted a single-center, retrospective observational study including 149 adult patients with sepsis or septic shock admitted to the Anesthesia and Intensive Care I Department of the Cluj County Emergency Hospital, Cluj-Napoca, Romania, between January 2019 and September 2025. Free T4 and thyroid-stimulating hormone (TSH) levels were measured within 24 h of ICU admission. The primary outcome was 28-day mortality, and the secondary outcome was in-hospital mortality. Demographic data, comorbidities, severity scores (SOFA, APACHE II), laboratory parameters, and outcomes were analyzed. Univariate and multivariate logistic regression analyses were performed, and predictive performance was assessed using area under the receiver operating characteristic curve (AUROC). Results: A total of 149 patients were included. Twenty-eight-day mortality was 29.73%, and 53.57% in patients with sepsis and septic shock, respectively. Serum fT4 was significantly lower in non-survivors, for both primary and secondary outcome (p = 0.01 and p = 0.014, respectively), whereas TSH levels were similar between groups. In the univariate analysis, fT4 showed moderate predictive ability for mortality (AUROC 0.615 and 0.632). Multivariate models, including age, hemoglobin, SOFA score, and fT4, showed a greater discriminative performance (AUROC 0.805 and 0.799). Conclusions: Lower fT4 levels on ICU admission seem to be independently associated with increased mortality in septic patients. Incorporating fT4 into multiparametric prognostic models might improve early risk stratification in sepsis, particularly in settings where other thyroid parameters are not routinely available.<\/jats:p>","DOI":"10.3390\/diagnostics16050680","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T11:23:45Z","timestamp":1772105025000},"page":"680","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Free Thyroxine as a Predictor of Mortality in Critically Ill Septic Patients\u2014A Retrospective Study"],"prefix":"10.3390","volume":"16","author":[{"given":"Matei Florin","family":"Negru\u021b","sequence":"first","affiliation":[{"name":"Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4959-3458","authenticated-orcid":false,"given":"Vlad","family":"Pastor","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7167-1679","authenticated-orcid":false,"given":"Robert","family":"Bolca\u0219","sequence":"additional","affiliation":[{"name":"Anesthesia and Intensive Care II Department, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0183-9815","authenticated-orcid":false,"given":"Oana","family":"Antal","sequence":"additional","affiliation":[{"name":"Anesthesia and Intensive Care II Department, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5033-1009","authenticated-orcid":false,"given":"Robert","family":"Szabo","sequence":"additional","affiliation":[{"name":"Anesthesia and Intensive Care II Department, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Petri\u0219or","sequence":"additional","affiliation":[{"name":"Anesthesia and Intensive Care II Department, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wang, J., Wang, Y., Xu, Z., Chou, C., Xiang, J., Zhang, X., Hou, X., Yue, S., Ye, S., and Chen, F. (2025). Association between Sensitivity to Thyroid Hormone and Prognosis in Septic Patients: A Retrospective Cohort Analysis. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1611963"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, Regional, and National Sepsis Incidence and Mortality, 1990\u20132017: Analysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Mu\u0219at, F., P\u0103duraru, D.N., Bolocan, A., Palc\u0103u, C.-A., Bunea, A.-A., Ion, D., and Andronic, O. (2025). Sepsis Burden in a Major Romanian Emergency Center-An 18-Year Retrospective Analysis of Mortality and Risk Factors. Medicina, 61.","DOI":"10.3390\/medicina61050864"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1186\/s13054-025-05600-7","article-title":"Sepsis Canada Healthcare Costs after Sepsis: A Systematic Review","volume":"29","author":"Chechulina","year":"2025","journal-title":"Crit. Care"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1186\/s13054-020-02950-2","article-title":"Mortality in Sepsis and Septic Shock in Europe, North America and Australia between 2009 and 2019\u2014 Results from a Systematic Review and Meta-Analysis","volume":"24","author":"Bauer","year":"2020","journal-title":"Crit. Care"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1007\/s11739-020-02546-2","article-title":"Thyroid Hormone Disorders: A Predictor of Mortality in Patients with Septic Shock Defined by Sepsis-3?","volume":"16","author":"Liu","year":"2021","journal-title":"Intern. Emerg. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Dai, J.-J., Du, D.-F., Ma, G., and Jiang, M.-J. (2023). Association between Serum-Free Thyroxine Level and All-Cause Mortality in Critically Ill Patients: A Retrospective Study from MIMIC-IV. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1164369"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1002\/j.2040-4603.2016.tb00695.x","article-title":"Euthyroid Sick Syndrome","volume":"6","author":"Lee","year":"2016","journal-title":"Compr. Physiol."},{"key":"ref_10","first-page":"S237","article-title":"Thyroid Hormone Disorders and Sepsis","volume":"28","author":"Luo","year":"2017","journal-title":"Biomed. Mater. Eng."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"14137","DOI":"10.1038\/s41598-018-32543-7","article-title":"The Value of Decreased Thyroid Hormone for Predicting Mortality in Adult Septic Patients: A Systematic Review and Meta-Analysis","volume":"8","author":"Kim","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"387","DOI":"10.4103\/ijem.IJEM_20_18","article-title":"Prognostic Value of Thyroid Profile in Critical Care Condition","volume":"22","author":"Gutch","year":"2018","journal-title":"Indian J. Endocrinol. Metab."},{"key":"ref_13","first-page":"1161","article-title":"Thyroid Function, Reverse Triiodothyronine, and Mortality in Critically Ill Clinical Patients","volume":"25","author":"Moura","year":"2021","journal-title":"Indian J. Crit. Care Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2479583","DOI":"10.1080\/07853890.2025.2479583","article-title":"Long-Term Prognostic Value of Thyroid Hormone Levels in Chronic Critical Illness Patients","volume":"57","author":"Li","year":"2025","journal-title":"Ann. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.ajem.2021.02.014","article-title":"Thyroid Hormone Levels as a Predictor Marker Predict the Prognosis of Patients with Sepsis","volume":"45","author":"Wang","year":"2021","journal-title":"Am. J. Emerg. Med."},{"key":"ref_16","first-page":"e2023239","article-title":"Association between Severity of Sepsis and Thyroid Function Profile","volume":"94","author":"Siampa","year":"2023","journal-title":"Acta Biomed."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"205","DOI":"10.5114\/ait.2019.86883","article-title":"Thyroid Hormones as Potential Prognostic Factors in Sepsis","volume":"51","author":"Foks","year":"2019","journal-title":"Anaesthesiol. Intensive Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e15335","DOI":"10.7717\/peerj.15335","article-title":"Prognostic Significance of Thyroid Hormone T3 in Patients with Septic Shock: A Retrospective Cohort Study","volume":"11","author":"Sun","year":"2023","journal-title":"PeerJ"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"61","DOI":"10.21037\/jlpm.2018.07.02","article-title":"Endocrine Dysfunction during Sepsis\u2014Are Changes in Hormone Levels a Physiological Adaptation or a Therapeutic Target?","volume":"3","author":"Widmer","year":"2018","journal-title":"J. Lab. Precis. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"96132","DOI":"10.5492\/wjccm.v13.i3.96132","article-title":"Low T3 vs Low T3T4 Euthyroid Sick Syndrome in Septic Shock Patients: A Prospective Observational Cohort Study","volume":"13","author":"Kovacevic","year":"2024","journal-title":"World J. Crit. Care Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zhang, L., Tan, R., Pan, T., and Qu, H. (2024). Impact of Thyroid Hormones on Predicting the Occurrence of Persistent Inflammation, Immunosuppression, and Catabolism Syndrome in Patients with Sepsis. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1417846"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wajner, S.M., and Maia, A.L. (2012). New Insights toward the Acute Non-Thyroidal Illness Syndrome. Front. Endocrinol., 3.","DOI":"10.3389\/fendo.2012.00008"},{"key":"ref_23","first-page":"101336","article-title":"Triiodothyronine Hormone Supplementation Therapy in Septic Shock Patients with Euthyroid Sick Syndrome: Two Pilot, Placebo-Controlled, Randomized Trials","volume":"43","author":"Kovacevic","year":"2024","journal-title":"Anaesth. Crit. Care Pain Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Li, P., Lu, Y., Guo, S.-B., Wang, J.-Y., and Yang, J. (2022). Low Serum Thyroid-Stimulating Hormone Levels May Be an Early Predictor of Sepsis. BMJ Support. Palliat. Care, Epub ahead of print.","DOI":"10.1136\/spcare-2022-004027"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"E2013","DOI":"10.1016\/S2214-109X(25)00356-0","article-title":"Global, Regional, and National Sepsis Incidence and Mortality, 1990\u20132021: A Systematic Analysis for the Global Burden of Disease Study 2021","volume":"13","author":"Gray","year":"2025","journal-title":"Lancet Glob. Health"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"157","DOI":"10.15441\/ceem.23.005","article-title":"Mortality among Adult Patients with Sepsis and Septic Shock in Korea: A Systematic Review and Meta-Analysis","volume":"10","author":"Namgung","year":"2023","journal-title":"Clin. Exp. Emerg. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1097\/JCMA.0000000000000697","article-title":"Association of Thyroid Hormones and Thyroid-Stimulating Hormone with Mortality in Adults Admitted to the Intensive Care Unit: A Systematic Review and Meta-Analysis","volume":"85","author":"Rao","year":"2022","journal-title":"J. Chin. Med. Assoc."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ning, N., Li, J., Sun, W., Ma, C., Li, J., Sheng, H., Chen, Y., Zhao, B., Zhang, J., and Zhu, J. (2023). Different Subtypes of Nonthyroidal Illness Syndrome on the Prognosis of Septic Patients: A Two-Centered Retrospective Cohort Study. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1227530"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Xu, Y., Xu, K., Guo, J., Fang, M., and Wang, Z. (2023). Association between Dynamic Fluctuations in Triiodothyronine Levels and Prognosis among Critically Ill Patients within Comprehensive Intensive Care Units. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1282547"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Krug, N., Bercker, S., Busch, T., Friese, S., Jahn, N., and Voelker, M.T. (2023). Non-Thyroidal Illness Syndrome (NTIS) Is No Independent Predictor for Mortality in ICU Patients. BMC Anesth., 23.","DOI":"10.1186\/s12871-023-02015-1"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Stoian, M., Azamfirei, L., Bandila, S.R., Stoian, A., Bab\u0103, D.-F., and B\u0103nescu, C. (2025). Circulating microRNAs and Plasma Gelsolin as Biomarkers of Sepsis: Molecular Insights and Prospects for Precision Medicine. Biomolecules, 15.","DOI":"10.3390\/biom15111621"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/5\/680\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T11:36:55Z","timestamp":1772105815000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/5\/680"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,26]]},"references-count":31,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["diagnostics16050680"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16050680","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,26]]}}}