Non-thyroidal illness syndrome and isolated low triiodothyronine as prognostic markers in acute illness: a systematic review and meta-analysis.

PURPOSE: To evaluate the association between thyroid hormone alterations and mortality in critically ill and cardiovascular patients, and to compare the prognostic performance of non-thyroidal illness syndrome and isolated low triiodothyronine. METHODS: PubMed/MEDLINE, Scopus, and Web of Science were systematically searched for studies published between 2014 and 2026 evaluating thyroid dysfunction and mortality in acute or critical illness. Studies assessing non-thyroidal illness syndrome or isolated low triiodothyronine were included. Random-effects meta-analyses were performed using odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Twenty-two studies were included. Fifteen studies evaluating non-thyroidal illness syndrome (5,230 patients) showed a significant association with mortality (OR 3.19, 95% CI 2.10-4.85), although heterogeneity was substantial (I²=67.5%, p<0.0001). Nine studies evaluating isolated low triiodothyronine (6,282 patients) also demonstrated a significant association with mortality (OR 2.93, 95% CI: 2.04-4.20), with substantial heterogeneity (I²=63.8%, p = 0.0048). Subgroup comparison and exploratory meta-regression showed no significant differences in effect size between the two definitions of thyroid dysfunction. CONCLUSIONS: Both non-thyroidal illness syndrome and isolated low triiodothyronine are associated with increased mortality in critically ill and cardiovascular patients. Although current aggregate data do not demonstrate a clear quantitative superiority of one definition over the other, non-thyroidal illness syndrome may provide a more integrated biological framework for interpreting thyroid dysfunction during acute illness.