Serum Calcium/Phosphorus Ratio in Biochemical Screening of Primary Hyperparathyroidism

Bestepe, Nagihan; Cuhaci, Fatma Neslihan; Polat, Burcak; Ogmen, Berna Evranos; Ozdemir, Didem; Ersoy, Reyhan; Cakir, Bekir

doi:10.1590/1806-9282.20220645

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Revista da Associação Médica Brasileira

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Original Article • Rev. Assoc. Med. Bras. 68 (12) • 2022 • https://doi.org/10.1590/1806-9282.20220645 copy

Serum Calcium/Phosphorus Ratio in Biochemical Screening of Primary Hyperparathyroidism

Authorship SCIMAGO INSTITUTIONS RANKINGS

SUMMARY

OBJECTIVE:

Primary hyperparathyroidism is a common endocrine disease and most cases are asymptomatic. Currently, in a hypercalcemic patient, the first laboratory investigation is serum primary hyperparathyroidism measurement. However, the primary hyperparathyroidism level cannot be measured in many primary healthcare centers in our country. In addition, serum calcium levels are normal in normocalcemic primary hyperparathyroidism patients, even if most centers have serum calcium levels measured. Therefore, a simple and inexpensive laboratory biochemical marker is required for the diagnosis of primary hyperparathyroidism. Recently, the calcium/phosphorus ratio has been proposed as a suitable tool for diagnosing primary hyperparathyroidism. This study aimed to investigate the diagnostic value of serum calcium/phosphorus ratio in primary hyperparathyroidism screening.

METHODS:

A total of 462 patients followed in our clinic with a diagnosis of primary hyperparathyroidism were reviewed in this retrospective study. Out of these patients, 148 with normal levels of serum parathyroid hormone, calcium, and phosphorus were selected as the control group. Serum calcium, corrected calcium, phosphorus, albumin, parathyroid hormone, 25-hydroxyvitamin D, and creatinine were evaluated. The diagnostic accuracy of the calcium/phosphorus ratio was investigated using receiver operating characteristic curve analysis.

RESULTS:

There were 404 (87.4%) females and 58 (12.6%) males in the primary hyperparathyroidism group. Calcium, parathyroid hormone, and calcium/phosphorus ratio were significantly higher in primary hyperparathyroidism than in controls (p<0.001 for each). Receiver operating characteristic curve analyses identified a cutoff value of 2.59 (3.35 if calcium and phosphorus are measured in mg/dL) for the calcium/phosphorus ratio, with a sensitivity of 90.5% and specificity of 93.2% (p<0.001).

CONCLUSION:

The calcium/phosphorus ratio is a simple and inexpensive method for primary hyperparathyroidism screening when a cutoff value of 2.59 is used.

Keywords
Calcium; Hyperparathyroidism; Hypercalcemia; Hypophosphatemia; Parathyroid hormone

	All patients PHPT (n=462)	Hypercalcemic PHPT (n=328)	Normocalcemic PHPT (n=134)	Control (n=148)	p¹1. Bilezikian JP. Primary hyperparathyroidism. J Clin Endocrinol Metab. 2018;103(11):3993-4004. https://doi.org/10.1210/jc.2018-01225 https://doi.org/10.1210/jc.2018-01225...	p²2. Bilezikian JP, Bandeira L, Khan A, Cusano NE. Hyperparathyroidism. Lancet. 2018;391(10116):168-78. https://doi.org/10.1016/S0140-6736(17)31430-7 https://doi.org/10.1016/S0140-6736(17)31...	p³
Age (years)	55 (20–82)	55 (20–82)	54 (27–77)	51 (19–76)	0.059	0.062	0.079
Sex, n (%)
Female	404 (87.4)	283 (86.3)	121 (90.3)	96 (64.9)	<0.001	<0.001	<0.001
Male	58 (12.6)	45 (13.7)	13 (9.7)	52 (35.1)	<0.001	<0.001	<0.001
Ca (2.12–2.62 mmol/L)	2.80 (2.30–4.02)	2.85 (2.6–4.02)	2.67 (2.30–2.82)	2.34 (2.17–2.62)	<0.001	<0.001	<0.001
P (0.81–1.45 mmol/L)	0.84 (0.36–1.42)	0.82 (0.36–1.26)	0.91 (0.55–1.42)	1.13 (0.81–1.45)	<0.001	<0.001	<0.001
Ca/P ratio	3.32 (1.84–8.61)	3.51 (2.26–8.61)	2.94 (1.84–4.55)	2.10 (1.53–2.91)	<0.001	<0.001	<0.001
Corrected Ca (2.12–2.62 mmol/L)	2.68 (2.19–4.12)	2.75 (2.62–4.12)	2.56 (2.19–2.62)	2.24 (2.10–2.43)	<0.001	<0.001	<0.001
Corrected Ca/P ratio	3.20 (1.71–7.85)	3.39 (2.10–7.85)	2.79 (1.71–4.65)	1.94 (1.47–2.77)	<0.001	<0.001	<0.001
PTH (15–60 pg/mL)	132 (7.60–1210)	144 (7.60–1210)	97 (30.17–494)	54 (21–60)	<0.001	<0.001	<0.001
Creatinine (0.5–1.1 mg/dL)	0.69 (0.30–1.1)	0.69 (0.30–1.1)	0.68 (0.33–0.99)	0.67 (0.41–1.11)	0.007	0.031	0.007
Albumin (3.5–5.2g/dL)	4.56 (3.49–5.78)	4.52 (3.49–5.78)	4.62 (3.70–5.10)	4.50 (4.0–5.20)	0.035	0.001	0.459
25-Hydroxyvitamin D (20–80 μg/L)	16.10 (2–121)	14.70 (2–121)	18.79 (3–67)	23 (8–53)	0.058	0.061	0.053

	Cutoff	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	Accuracy (%)
All patients
Ca/P ratio	2.59 (3.35 CU)	90.5	93.2	97.7	75.8	91.2
Corrected Ca/P	2.46 (3.18 CU)	91.8	92.6	97.5	78.3	92.0
Serum PTH	60	89.0	100	100	74.4	91.6
Hypercalcemic PHPT
Ca/P ratio	2.59 (3.35 CU)	95.1	93.2	96.9	89.6	94.5
Corrected Ca/P	2.46 (3.18 CU)	97.0	92.6	96.7	93.2	95.6
Serum PTH	60	93.0	100	100	86.6	95.2
Normocalcemic PHPT
Ca/P ratio	2.59 (3.35 CU)	79.1	93.2	91.4	83.1	86.5
Corrected Ca/P	2.46 (3.18 CU)	79.0	92.6	90.5	83.0	86.1
Serum PTH	60	79.1	100	100	84.1	90.1

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[1] *Corresponding author: nagihanbestepe@gmail.com