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Systemic inflammatory markers predict mortality in autoimmune thyroiditis: threshold-driven risk stratification and prognostic insights from a nationwide cohort

Hormones (Athens). 2025 Sep 16. doi: 10.1007/s42000-025-00718-3. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic inflammation plays a pivotal role in autoimmune thyroiditis (AT), yet traditional biomarkers fail to predict systemic complications. The systemic immune-inflammation Index (SII) and the systemic inflammation response index (SIRI), which integrate multiple immune cell counts, may serve as novel prognostic tools for assessing AT-related mortality.

METHODS: This study analyzed data from 1053 AT patients in the 2007-2012 NHANES cycles. SII and SIRI were calculated using standardized complete blood count parameters. All-cause mortality was assessed through linkage with the National Death Index. Cox proportional hazard models with sequential adjustments evaluated the associations between inflammatory indices and mortality. Nonlinear relationships and critical thresholds were examined using restricted cubic splines.

RESULTS: Elevated SII and SIRI were significantly associated with increased mortality risk. After full adjustment, each log-unit increase in SII (HR = 1.819, 95% CI:1.347-2.457) and each unit increase in SIRI (HR = 1.314, 95% CI:1.124-1.537) independently predicted higher mortality. Threshold analysis identified critical inflection points at ln-SII ≥ 6.18 (HR = 2.629, 95% CI:1.431-4.831) and SIRI ≥ 1.01 (HR = 1.257, 95% CI:1.030-1.535), beyond which mortality risk escalated sharply. Kaplan-Meier curves confirmed significant survival disparities across tertiles (log-rank p < 0.001). Stratified analyses showed consistent associations across demographic and clinical subgroups.

CONCLUSION: SII and SIRI are robust, cost-effective biomarkers for predicting mortality in AT, with defined thresholds marking transitions from compensatory to pathological inflammation. These indices provide a comprehensive reflection of systemic immune dysregulation, offering actionable insights for risk stratification and targeted interventions. Future studies should validate these findings in diverse populations and explore anti-inflammatory therapies to improve outcomes in AT patients.

PMID:40956512 | DOI:10.1007/s42000-025-00718-3

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