Abstract
ABSTRACTPrimary hyperparathyroidism (PHPT) diagnosis is challenging and is based on serum calcium (Ca) and parathyroid hormone (PTH). Because serum Ca and phosphorous (P) are inversely related in PHPT, we investigated the diagnostic value of the serum Ca/P ratio in the diagnosis of PHPT. We report a single‐center, case‐controlled, retrospective study including 97 patients with documented PHPT and compared them with those of 96 controls (C). The main outcome measures were: serum PTH, 25‐OH vitamin D, Ca, P, albumin, and creatinine. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the serum Ca/P ratio were calculated. The results were verified using an independent, anonymous set of data extracted from a laboratory database containing over 900 million entries. A total of 35 (36.1%) PHPT patients had normocalcemic PHPT (NCHPT). Ca and PTH were significantly higher in PHPT than in C (p < 0.0001). P was significantly lower in PHPT than in C (p < 0.0001). The Ca/P ratio was significantly higher in PHPT than in C (p < 0.0001). Receiver‐operating characteristic (ROC) curves analyses identified a cutoff of 2.71 (3.5 if Ca and P are expressed in mg/dL) for Ca/P ratio with a sensitivity and specificity of 86% and 87%, respectively (p < 0.0001), confirmed by the independent, big data approach. In conclusion, Ca/P is a valuable tool for the diagnosis of PHPT and is of superior value compared to serum Ca alone, especially in NCPHT. Because Ca/P is simple, inexpensive, and easily accessible worldwide, this ratio is useful for PHPT diagnosis, especially in laboratory/medical settings relying on limited resources, such as low‐income countries. © 2017 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
Highlights
Primary hyperparathyroidism (PHPT) is the third most common endocrine disorder[1] and is the most common cause of hypercalcemia in the outpatient setting.[2]. PHPT should be considered in any person with elevated serum calcium (Ca) levels and no clear evidence of malignancy.[3]. PHPT should be considered in case of hypophosphatemia because the latter is present in 10% to 20% of patients with PHPT.[4]
The biochemical profile of PHPT is classically characterized by elevated serum intact parathyroid hormone (PTH) levels coupled with hypercalcemia and slight or mild hypophosphatemia.[1,3] the diagnosis of PHPT is based on the combination of hypercalcemia and elevated PTH.[3]
By Receiver-operating characteristic (ROC) curve analysis a threshold of 2.64 (3.4 if Ca and P are measured in mg/dL) for the Ca to P ratio (Ca/P) ratio was indicated by the best pair of values for the sensitivity and specificity (Fig. 5)
Summary
Primary hyperparathyroidism (PHPT) is the third most common endocrine disorder[1] and is the most common cause of hypercalcemia in the outpatient setting.[2]. Even though they are in the normal range in NHPHPT and NCPHPT, serum Ca and phosphorous (P) levels are very close to the highest and lowest limit of the normal range, respectively.[5,6,7] To complicate the picture, clinical signs and symptoms are not always present, as in asymptomatic PHPT.[8]. The diagnosis of PHPT is challenging[1,3] and often delayed[2] because of this wide spectrum of clinical and biochemical manifestations, especially in asymptomatic and NCPHPT patients.[8] For all these reasons, physicians cannot completely rule out the diagnosis of PHPT even in presence of normal PTH or normal serum calcium.[9]. No data on Ca/P ratio are available in literature,(11) despite the fact that they are very simple biochemical measurements largely available in any clinical laboratory setting
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