Reliabilty of serum Calcium to Phosphorus (Ca/P) ratio as an accurate and inexpensive tool to define disorders of Ca-P metabolism: preliminary data

Background: Primary hyperparathyroidism (PHPT) is the third most common endocrine disorder. The Ca/P ratio is an accurate tool to differentiate patients with PHPT (>3.5 if Ca and P are expressed in mg/dl) from healthy subjects [1]. The reliability of this index is based on the fact that serum Ca and P are inversely related together. However, other disorders of the Ca-P metabolism, such as hypophosphoremia (HypoP), might impair the Ca/P ratio.

Aim: To validate the accuracy of Ca/P ratio in the diagnosis of Ca-P metabolism disorders, including also patients with documented HypoP.

Methods: A single-center, retrospective, case-control study was carried out, including 130 patients with documented PHPT and 300 patients with HypoP, compared with 120 controls. HypoP patients were enrolled among HIV-infected patients on HAART treatment from the large Modena cohort. The main outcome measures were: serum Ca, P, parathyroid hormone (PTH), 25-OH vitamin D, albumin and creatinine.

Statistical analysis: Comparisons among groups were performed by the nonparametric Kruskal-Wallis, followed by the Dunn’s post hoc test. The diagnostic accuracy of Ca/P ratio was investigated by receiver operator characteristics (ROC) curves in order to define cut-off points (with the highest sensitivity and specificity).

Results: The Ca/P ratio was significantly higher in the group of PHPT together with HypoP, compared to controls (P<0.0001). Also Ca and PTH were significantly different among groups, in particular they were higher (P<0.0001) in PHPT than both controls and HypoP, as expected. At ROC curves analysis, the cut-off of 3.6 for Ca/P ratio was able to identify patients with PHPT and HypoP (sensitivity 91%; specificity 93%). Among patients with Ca/P ratio above 3.6, the thresholds of 10.2 mg/dl for serum Ca (sensitivity 91%; specificity 98%) and of 83.6 pg/ml for PTH (sensitivity 92%; specificity 93%) were defined for the specific diagnosis of PHPT.

Conclusions: In this study we confirm the role of serum Ca/P ratio as a reliable index to diagnose a Ca-P metabolism disorder, especially PHPT and HypoP. In clinical practice, when a Ca/P ratio above 3.6 is found, the presence of serum Ca>10.2 mg/dl or PTH>83.6 pg/ml is able to discriminate patients with PHPT from those with HypoP.

Reference: 1. Madeo et al, Serum Calcium to Phosphorous (Ca/P) Ratio Is a Simple, Inexpensive and Accurate Tool in the Diagnosis of Primary Hyperparathyroidism. JRBM Plus, 2017. DOI: 10.1002/jbm4.10019.