Abstract
HIGHLIGHTS: What are the main findings? The calcium–phosphorus ratio (Ca/P) and the Parathyroid Function Index (PFindex) showed the highest diagnostic accuracy for identifying primary hyperparathyroidism, with pooled sensitivities and specificities above 90% in the meta-analysis. Among the evaluated tools, the Ca/P ratio emerged as the most widely studied and accessible screening index, while PFindex demonstrated the best discriminatory capacity when directly compared with other indices. What are the implications of the main findings? Simple biochemical indices derived from routine laboratory tests may facilitate earlier detection of primary hyperparathyroidism, particularly in primary care or resource-limited settings. These indices should complement rather than replace clinical assessment and standard biochemical evaluation, and further prospective studies are needed to validate emerging indices such as Ca × Cl/P and dynamic tests. ABSTRACT: 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.