A Simple Blood Count Marker for a Complex Diagnosis: Neutrophil-to-Lymphocyte Ratio in Atypical Parathyroid Adenomas

Preoperative differentiation of atypical parathyroid adenomas (APAs) from typical parathyroid adenomas (TPAs) is challenging because of their overlapping histopathological features. Simple biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), have been associated with tumor aggressiveness in various endocrine tumors; however, their role in APA remains unclear.

This retrospective cohort study included 149 patients who underwent parathyroidectomy for primary hyperparathyroidism between July 2020 and May 2024 at our institution. The patients were categorized as having APA (n = 31) or TPA (n = 118). Preoperative NLR and PLR values were compared, and receiver operating characteristic curve analyses were performed to determine the optimal cut-off values. Multivariate logistic regression, effect size calculation, and sensitivity analyses were performed. Biochemical recurrence during follow-up was also assessed.

The Median NLR was significantly higher in patients with APA than in those with TPA (2.88 versus 1.73, P < 0.001), suggesting a stronger systemic inflammatory response in patients with APA. The PLR did not show a significant difference (P = 0.207). NLR demonstrated moderate discriminatory ability, with an area under the receiver operating characteristic curve (area under the curve) of 0.75. An optimal cut-off of 2.36 yielded 67.7% sensitivity and 79.7% specificity in the training cohort. At this threshold, the negative predictive value was 90.4%, indicating that low NLR values reliably excluded APA diagnosis. In the multivariable analysis, NLR remained an independent predictor of APA (adjusted odds ratio = 2.02, 95% confidence interval: 1.31-3.14, P = 0.002). Biochemical recurrence was more frequent in APA (16.1%) than in TPA (1.7%) patients.

NLR is a simple and widely available biomarker with potential utility in distinguishing APA from TPA. Low NLR values may reliably exclude APA, and support clinical risk stratification and postoperative surveillance strategies. External validation in larger, multicenter, and prospective cohorts is required to confirm its diagnostic and prognostic value. This study further investigated the NLR in the broader context of systemic inflammatory biomarkers in endocrine tumors. Building on this premise, the current study explored the diagnostic performance of preoperative NLR in differentiating APA from TPA within a well-defined surgical cohort to address a gap in the existing literature.