Non-thyroidal illness syndrome subtypes and mortality in sepsis: associations with thyroid autoantibodies

Non-thyroidal illness syndrome (NTIS) is frequently observed in patients with sepsis; however, prognostic differences among its subtypes remain poorly defined. This study aimed to evaluate whether different NTIS subtypes and the presence of thyroid autoantibodies are associated with mortality in septic patients.

We conducted a retrospective cohort study including 871 patients with sepsis admitted to a tertiary hospital in Shanghai between 2015 and 2019. Thyroid function tests were performed within 24 hours of sepsis diagnosis. NTIS was categorized into four subtypes according to serum free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) levels: NTIS-1 (isolated low T3), NTIS-2 (combined low T3 and T4), NTIS-3 (low T3 with preserved TSH response), and NTIS-4 (near-normal thyroid hormone levels with mild abnormalities). Thyroid antibodies, including thyroglobulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb), as well as other clinical and laboratory parameters, were measured. The primary outcome was in-hospital mortality. Multivariable logistic regression analyses were performed, adjusting for age, sex, comorbidities, Sequential Organ Failure Assessment (SOFA) score, infection site, and relevant laboratory variables.

NTIS was present in 82% of patients (715/871). Compared with patients without NTIS, those with NTIS were older, had a higher burden of comorbidities, and exhibited more severe organ dysfunction, as reflected by higher SOFA scores (all p < 0.01). After multivariable adjustment, NTIS remained an independent predictor of in-hospital mortality, conferring more than a threefold increased risk (odds ratio [OR] 3.14, 95% confidence interval [CI] 1.52-7.00, p = 0.003). Among NTIS subtypes, both NTIS-1 (OR 4.26, 95% CI 1.33-16.41, p = 0.022) and NTIS-2 (OR 3.99, 95% CI 1.31-14.88, p = 0.024) were associated with approximately a fourfold higher risk of death. TGAb positivity emerged as the strongest prognostic factor, doubling the risk of mortality in the overall cohort (OR 2.15, 95% CI 1.30-3.60, p < 0.01) as well as in the NTIS subgroup (OR 1.97, 95% CI 1.17-3.33, p = 0.011). TPOAb positivity showed a similar trend toward increased mortality but did not reach statistical significance (OR 1.74, 95% CI 0.96-3.14, p = 0.068).

NTIS is highly prevalent among patients with sepsis and independently predicts in-hospital mortality after adjustment for disease severity. Patients with NTIS-1 and NTIS-2 subtypes are at particularly high risk of death. Moreover, TGAb positivity is a strong and independent predictor of mortality. Incorporating thyroid function tests together with thyroid antibody measurements may enhance risk stratification in patients with sepsis.