Serum Biomarker-Based Diagnostic Tools for Primary Hyperparathyroidism: A Systematic Review and Meta-Analysis with Implications for Primary Care.

Background

Hyperparathyroidism is a common endocrine disorder, and its diagnosis can be complex. Various indices based on blood biomarkers have been proposed to improve diagnostic accuracy. The objective of this systematic review was to analyze the diagnostic utility of different indices in primary hyperparathyroidism.

Methods

A systematic review was performed with searches up to January 2026. Risk of bias was assessed, and a meta-analysis was conducted for indices with two or more studies, calculating sensitivity, specificity, and other accuracy measures. The certainty of the evidence was evaluated using the GRADE system.

Results

Twelve studies were included. The calcium-phosphorus ratio demonstrated a sensitivity of 91.6%, specificity of 89.3%, and an area under the curve of 0.957. The parathyroid function index showed a sensitivity of 94.4% and specificity of 94.2%; however, this finding is based on only two studies and requires validation in larger cohorts. The Wisconsin index also showed good performance. Other indices, including the Ca × Cl/P ratio (evaluated in a single study), yielded promising results but with very limited evidence that precludes firm conclusions. All indices performed poorly in cases with normal calcium. Certainty assessment indicated moderate evidence for the main indices and low or very low evidence for the others.

Conclusions

The calcium-phosphorus ratio and the parathyroid function index are valid and useful tools for the diagnosis of primary hyperparathyroidism, with excellent performance. The calcium-phosphorus ratio is especially valuable due to its simplicity and accessibility for screening. No index should be used in isolation; integration with clinical evaluation remains essential.