Müge Keskin

Background/Objectives: Atypia of undetermined significance (AUS; Bethesda category III) remains a challenging thyroid cytological diagnosis because of its heterogeneous malignancy risk and limited preoperative certainty. Molecular testing can improve risk stratification but is not universally available. This study evaluated the diagnostic and incremental predictive value of preoperative complete blood count-derived systemic inflammatory indices in surgically treated Bethesda III thyroid nodules. Methods: This retrospective cohort included 352 patients who underwent thyroidectomy for Bethesda III thyroid nodules. Preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) were evaluated. Postoperative histopathology served as the reference standard. Receiver operating characteristic analysis and multivariable logistic regression were performed, followed by incremental model assessment, bootstrap internal validation, Hashimoto thyroiditis interaction analysis, and exploratory molecular subgroup analysis. Results: Among 352 patients, 197 (56.0%) had malignant histopathology. Malignant nodules showed higher NLR, PLR, SII, SIRI, and AISI and lower LMR. All six indices remained independently associated with malignancy after multivariable adjustment, with the strongest positive associations observed for SII (adjusted OR, 2.09; 95% CI, 1.60–2.72) and NLR (adjusted OR, 1.96; 95% CI, 1.51–2.54). SII demonstrated the numerically highest individual discrimination (AUC 0.687; 95% CI, 0.631–0.740), followed by NLR (AUC 0.661) and AISI (AUC 0.659); SII and NLR did not differ significantly (DeLong p = 0.182). Addition of SII increased the AUC of the clinico-ultrasonographic model from 0.695 to 0.761, with an optimism-corrected AUC of 0.721. Hashimoto thyroiditis did not significantly modify these associations. In the molecular subgroup, mutation status increased model discrimination from 0.765 to 0.824, whereas no statistically significant additional improvement with SII was detected in the exploratory molecular subgroup. Conclusions: Preoperative systemic inflammatory indices, particularly SII, provide modest but incremental predictive information beyond conventional clinical and ultrasonographic variables in surgically treated Bethesda III thyroid nodules. Their role appears complementary rather than diagnostic when used in isolation, particularly when comprehensive molecular testing is unavailable. Prospective external validation is required before clinical implementation.

Hypertension remains one of the leading causes of global morbidity and mortality and is the leading modifiable risk factor for cardiovascular disease worldwide. The inability of conventional risk factors alone to fully explain the global prevalence of hypertension, together with accumulating evidence implicating endocrine-disrupting chemicals (EDCs) in the pathogenesis of hypertension, has led to growing scientific interest in this field over recent years. EDCs are exogenous environmental chemicals capable of disrupting hormone synthesis, transport, metabolism, and signaling pathways, thereby adversely affecting vascular and metabolic homeostasis. In particular, per- and polyfluoroalkyl substances (PFASs), bisphenol A, phthalates, PCBs, heavy metals, and pesticides have been associated with hypertension and may influence blood pressure regulation through multiple interconnected mechanisms, including oxidative stress, endothelial dysfunction, inflammation, epigenetic modifications, and activation of the renin–angiotensin–aldosterone system. Moreover, prenatal exposure to EDCs has been associated with hypertensive disorders of pregnancy, including gestational hypertension and preeclampsia, with potential implications for long-term maternal cardiovascular health. This review provides a comprehensive overview of the experimental and epidemiological evidence linking endocrine-disrupting chemicals to hypertension, with particular emphasis on the underlying molecular mechanisms, emerging clinical evidence, and future research directions.