Non-thyroidal Illness Syndrome and Clinical Outcomes in Critically Ill ICU Patients: A Prospective Cohort Study

Background Non-thyroidal illness syndrome (NTIS) is a common condition in critically ill patients, yet its prognostic value remains unclear. This study aimed to assess the incidence of NTIS among critically ill patients and evaluate its association with clinical outcomes and mortality. Methods A prospective cohort study was conducted in a tertiary hospital between 2019 and 2025. Adult intensive care unit (ICU) patients without known thyroid disease were included. Thyroid function tests, including thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3), were measured within 24 hours of admission. Clinical data, comorbidities, and outcomes were recorded. Patients were classified as having low FT3 (<3.0 nmol/L) or normal FT3 (≥3.0 nmol/L). Logistic regression and receiver operating characteristic (ROC) analysis were used to evaluate the prognostic performance of thyroid hormones, with survival used as the reference outcome. Results Among 180 patients (mean age = 57.7 ± 18 years; 111/180 (62%) male), 93/180 (52%) had NTIS. Patients with low FT3 were older and had higher rates of diabetes, cardiovascular, and pulmonary diseases (p < 0.05). They more frequently developed shock, respiratory failure, and required mechanical ventilation. ICU mortality was significantly higher among the low FT3 group (37/93 (43%) vs. 7/85 (7.5%), p < 0.001). After adjustment for age, comorbidities, and illness severity, both low FT3 (OR = 0.23, 95% CI = 0.07-0.79; p = 0.007) and low FT4 (OR = 0.80, 95% CI = 0.65-0.99; p = 0.03) remained independently associated with mortality, whereas TSH showed no significant association. ROC analysis demonstrated that FT3 had the strongest association with survival (area under the curve = 0.208, p < 0.001), reflecting an inverse relationship when survival was used as the reference outcome. Conclusion NTIS is highly prevalent in critically ill patients and is associated with increased mortality and adverse outcomes. Low FT3, in particular, is associated with disease severity and may serve as a prognostic marker in the ICU; however, these findings reflect association rather than causation.