ArticleFrontiers in endocrinology2026
A novel marker for predicting malignancy in patients with thyroid nodules diagnosed as AUS on initial cytology: thyroid hormone sensitivity.
Article in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Purpose: This study aimed to evaluate the predictive value of thyroid hormone sensitivity indices and hematological inflammatory markers, in addition to ultrasonographic features, for malignancy in thyroid nodules initially classified as atypia of undetermined significance (AUS). Methods: Data from 415 thyroid nodules initially diagnosed as Bethesda category III (AUS) on fine-needle aspiration biopsy (FNAB) were retrospectively analyzed. Nodules with benign histopathology or benign cytology on repeat FNAB were classified as the benign group, whereas those with malignant histopathology were classified as the malignant group. The groups were compared in terms of ultrasonographic features, baseline hematological parameters, and thyroid hormone sensitivity indices. Results: A total of 185 patients with thyroid nodules initially classified as Bethesda category III (AUS) were included, and 30.8% of surgically treated cases were malignant. A family history of thyroid cancer was more frequent in the malignant group (26.3% vs 10.9%, p=0.008). Malignant nodules were more likely to be solid, hypoechoic, and associated with microcalcifications, irregular margins, intranodular vascularity, and higher EU-TIRADS categories (all p<0.05). TSH and thyroid hormone sensitivity indices (TT4RI, TSHI, TFQI) were significantly higher in malignant nodules. In multivariable analysis, suspicious EU-TIRADS classification, family history of thyroid cancer, intranodular vascularity, PLR-to-PDW ratio, and thyroid hormone sensitivity indices remained independent predictors of malignancy. ROC analysis demonstrated moderate diagnostic performance for TSHI and TT4RI. Conclusion: Thyroid hormone sensitivity indices may serve as adjunctive markers for malignancy risk stratification in Bethesda category III thyroid nodules and may complement ultrasonographic assessment in clinical decision-making.
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