Serum calcium to phosphorous ratio (Ca/P) as a simple, inexpensive screening tool in the diagnosis of primary hyperparathyroidism (PHPT)

Background
PHPT is often overlooked/underdiagnosed. Several strategies (biochemical markers alone or combined in complex algorithms) have been investigated to easily diagnose/screen PHPT, but PHPT diagnosis remains challenging at present, especially in asymptomatic patients. As serum calcium (Ca) and phosphorous (P) are inversely related in PHPT, the Ca/P ratio could be a good candidate tool for PHPT diagnosis. Surprisingly, no literature data on Ca/P ratio are available, despite they are very simple biochemical measurements largely available in any clinical lab setting.
Aim
To investigate the Ca/P ratio diagnostic value in the diagnosis of PHPT. Methods
Data retrospectively obtained from review charts of 97 patients with documented PHPT (69 females; 28 males) [16 (17%) with severe hypercalcemia (O12 mg/dl); 44 (45%) mild hypercalcemia, 36 (38%) normocalcemic PHPT (NCHPT)] were compared with those of 96 controls (C) (44 females; 52 males). Exclusion criteria: age !18 years, severe chronic diseases, cancer, bone metabolic diseases, use of medications affecting serum Ca. Biochemical measurements: PTH, Vitamin D, serum Ca, P, albumin, and creatinine. Normal ranges: PTH (15–88 pg/ml), Ca (8.5–11 mg/dl), P (2.5–5.1 mg/dl). SPSS 19.0 and SigmaPlot 11.0 were used for statistics (group comparisons, ROC curves, cutoffs performance).
Results
Ca and PTH were significantly higher in PHPT [(Ca median:11; min-max:9.4– 15.5); (PTH 135.2; 57.6–1748)] than C [(Ca 9.4; 8.3–10.2); (PTH 32.1; 14–106.1) (P!0.0001). P was significantly lower in PHPT (2.4; 1.4–3.9) than in C (3.5; 2.1– 4.5) (P!0.0001). Ca/P ratio was significantly higher in PHPT than in C. ROC curves analyses identified a cutoff of 3.5 for both Ca/P ratio and Ca/P ratio obtained by using albumin corrected-Ca. The sensitivity and specificity were 86 and 87%, respectively for Ca/P ratio and 89 and 93%, respectively for corrected Ca/P ratio (P!0.0001). The diagnostic value of Ca/P ratio performed better than PTH and Ca used alone or in combination.
Conclusions
Ca/P ratio is a valuable highly sensitive, highly specific tool for the diagnosis of PHPT. Since Ca/P is simple to obtain, easily accessible in every clinical and lab setting worldwide, and inexpensive even when used in large sample size of patients, this diagnostic tool could be useful for screening PHPT, especially in patients accessing emergency rooms or in the general practitioner setting.