Prognostic significance of non-thyroidal illness syndrome in sepsis and septic shock cases: a systematic review and meta-analysis

Background: This study aimed to assess non-thyroidal illness syndrome (NTIS) as a prognostic determinant in patients with sepsis, severe sepsis, and septic shock by evaluating thyroid hormone (TH) levels. Methodology: A systematic search was performed through electronic databases including PubMed, Embase, Scopus, and Medline. Following medical subject headings (MeSH) and free-text terms: "euthyroid sick syndrome" or "Euthyroid Sick Syndromes" or "non-thyroidal illness syndrome" or "non-thyroidal illness syndrome" or "sick euthyroid syndrome" or "low T3 syndrome" or "low tri-iodothyronine syndrome" AND "sepsis" or "septic shock" or "systemic inflammatory response syndrome" or "septicemia" or "bacteremia". Boolean operators' combinations were applied to broaden and narrow the search results. Investigators independently reviewed the search results. For the purpose of the meta-analysis each thyroid hormone level was converted into the same unit: nmol/L for T3, T4 and rT3; mu IU/mL for TSH; and pmol/L for fT3 and fT4. Statistical analysis was performed using Stata Statistical Software: Release 16. College Station, TX: StataCorp LLC. Results: A total of 843 patients from 9 studies were included in this analysis. In septic patients, the lowest effect size of thyroid function parameter was TSH (g = 2.05; 95% CI = 1.56-2.54), while T3, fT3, and fT4 had the lowest effect size in severe septic patients (g [95%CI]: 0.83 [0.22-1.44]; 1.92 [0.57-3.27]; 1.00 [0.87-1.13]). Patients with septic shock had the highest effect size of TSH (g = 2.08; 95% CI = 1.54-2.61) and fT4 (g = 9.26; 95% CI = 0.98-17.53). Meanwhile, the lowest was T4 (g = 65.60; 95% CI = 64.63-66.57) and rT3 (g = 0.29; 95% CI = 0.24-0.34). A lower effect size of T3 (g = 0.83; 95% CI = 0.76-0.91), T4 (g = 59.48; 95% CI = 57.92-61.04), fT3 (g = 2.25; 95% CI = 1.83-2.66), and fT4 (g = 9.19; 95% CI = 1.56-16.81) were found in non-survivor groups. Conclusion: Thyroid hormone levels differ according to the severity of sepsis in septic patients. Non-thyroidal illness syndrome is a prognostic factor in septic patients and is associated with the risk of the mortality.