Preoperative Thyroid Hormone Ratios and Complete Blood Count (CBC)-Derived Biomarkers for Differentiating Benign Thyroid Nodules from Papillary Thyroid Carcinoma: A Retrospective Single-Center Case–Control Study

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Background/Objectives: Preoperative differentiation between benign thyroid nodules and papillary thyroid carcinoma (PTC) remains clinically challenging, particularly after indeterminate cytology. This study evaluated routinely available complete blood count (CBC)-derived indices, erythrocyte parameters, thyroid function tests, and arithmetic thyroid hormone ratios. Methods: This retrospective, single-center case–control study reviewed thyroidectomy records from July 2020 to November 2024. Histopathology was re-adjudicated from the source reports; 158 adults with clearly benign nodules (n = 93) or PTC (n = 65) formed the final analytic cohort. Missing laboratory values were handled by variable-specific complete-case analysis. Benjamini–Hochberg false-discovery-rate (FDR) correction and an exploratory multivariable logistic model were applied. Results: Preoperative TSH and the conventional platelet-to-lymphocyte ratio (PLR) were higher in PTC (p = 0.002, q = 0.013; and p = 0.004, q = 0.023), whereas the fT4/TSH and fT3/TSH ratios were lower (both q = 0.013). The fT3 difference was nominal (p = 0.018, q = 0.076), and MCV was not significant (p = 0.076). In 126 complete cases, each doubling of TSH was associated with higher odds of PTC (adjusted odds ratio [aOR] 1.51, 95% CI 1.08–2.13), whereas higher fT3 was associated with lower odds (aOR 0.41, 95% CI 0.19–0.87). Conclusions: TSH and fT3 were independently associated with PTC in the exploratory model, while the PLR and TSH-normalized hormone ratios differed between groups but lacked validated diagnostic performance. These measures should not be used in isolation; prospective multicenter studies are needed to determine whether they add clinically meaningful information to ultrasonographic, cytological, and molecular assessments.