PTH-to-tumor-volume ratio as a potential exploratory marker in parathyroid carcinoma: a retrospective cohort study

BACKGROUND: Parathyroid carcinoma is a rare endocrine malignancy that remains difficult to distinguish preoperatively from benign causes of primary hyperparathyroidism due to overlapping clinical and biochemical features. This study evaluates the serum parathyroid hormone (PTH)-to-tumor volume ratio as a potential parameter for differentiating parathyroid carcinoma from benign parathyroid lesions. METHODS: A retrospective analysis was conducted on 344 patients who underwent surgery for primary hyperparathyroidism between 2017 and 2024. Patients were divided into carcinoma (n = 8) and benign lesion groups (n = 336). Clinical, biochemical, and ultrasound-derived tumor volume data were analyzed and compared between groups. RESULTS: Patients with parathyroid carcinoma had significantly higher PTH levels than those with benign lesions (median, 659 vs. 136.4 pg/mL; p = 0.002) and markedly larger tumor volumes (median, 10.14 vs. 0.69 ml; p < 0.001). Despite higher absolute PTH concentrations, the PTH-to-tumor volume ratio was significantly lower in the carcinoma group (median 89.7 vs. 214.56; p = 0.011). In logistic regression analysis, a lower PTH-to-tumor volume ratio was associated with an increased likelihood of parathyroid carcinoma (OR, 0.990; 95% CI: 0.896-0.993; p = 0.04). CONCLUSIONS: In this cohort, parathyroid carcinoma was characterized by a substantially greater tumor burden and higher circulating PTH concentrations, while the PTH-to-tumor-volume ratio was lower than in benign parathyroid lesions. The observed difference in the ratio is hypothesis-generating and warrants confirmation in larger, multicenter studies. Given the limited number of carcinoma cases, its role in clinical decision-making remains to be established.