Biochemical Ratios for Predicting Primary Hyperparathyroidism: Revisiting Simple yet Powerful Diagnostic Tools

Differentiating primary hyperparathyroidism (PHPT), normocalcemic PHPT (NPHPT), and vitamin D deficiency-related secondary hyperparathyroidism (VDSHPT) remains a diagnostic challenge. This study evaluated the utility of biochemical markers in distinguishing these conditions.

In this cross-sectional study, 437 participants were categorised into PHPT (n = 161), NPHPT (n = 97), VDSHPT (n = 89), and control (n = 90) groups. Serum calcium, phosphate, chloride, PTH, and vitamin D levels were analysed, along with indices such as Ca/P, Cl/P, Ca × Cl/P, and the PF Index (Ca × PTH/P).

Calcium levels were highest in PHPT (2.73 ± 0.17 mmol/L), while phosphate levels were lowest (0.70 ± 0.19 mmol/L) both p < 0.001. PTH levels were significantly elevated in PHPT, NPHPT, and VDSHPT versus controls (p < 0.001). Ca/P ratio was significantly higher in PHPT (4.17 ± 1.21, p < 0.001), as was the Ca × Cl/P ratio (448.5 ± 133.6, p < 0.001). No significant difference was found between NPHPT and VDSHPT groups in Ca/P (p = 0.63) and Ca × Cl/P (p = 0.74) ratios. Ca × Cl/P ratio exhibited the highest diagnostic accuracy for PHPT with a specificity of 89.2% and PPV of 82.2%. Ca/P ratio had the highest sensitivity (77.6%) and an NPV of 86.6%. PF Index (AUC: 0.851, 95% CI: 0.816-0.886) and Cl/P ratio (0.766, 95% CI: 0.711-0.820) showed moderate accuracy. In NPHPT, all markers had high sensitivity but poor specificity (1.6%-23.2%).

The Ca × Cl/P and Ca/P ratios demonstrate substantial diagnostic value for PHPT, while biochemical markers exhibited limited specificity in NPHPT. These findings highlight their role in screening but emphasize the need for additional diagnostic approaches.