An analysis of calcium-to-phosphorus ratio in the diagnosis of normocalcemic primary hyperparathyroidism
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LETTER TO THE EDITOR
An analysis of calcium-to-phosphorus ratio in the diagnosis of normocalcemic primary hyperparathyroidism Pedro Weslley Rosário
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Received: 6 August 2020 / Accepted: 26 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
To the Editor, We read with interest the article by Madeo et al. [1]. recently published in this journal, which proposes the use of the calcium-to-phosphorus (Ca/P) ratio in the diagnosis of parathyroid disorders. We would like to comment specifically on the practical application of this ratio to the diagnosis of normocalcemic primary hyperparathyroidism (NPHPT), which is indeed challenging. According to current guidelines [2, 3], ionized Ca (iCa) should be obtained in patients with normal total Ca and elevated parathyroid hormone (PTH), especially in the absence of an apparent cause of secondary hyperparathyroidism (SHPT). If iCa is elevated, the diagnosis of PTHdependent hypercalcemia is made. Thus, uncertainty regarding the diagnosis of NPHPT persists in patients whose iCa is normal. The authors do not report whether iCa was measured in patients with NPHPT and, if measured, how many patients had normal iCa and, more importantly, what was the sensitivity of Ca/P ratio specifically in these patients. In clinical practice, it is in these patients with normal iCa that the diagnosis of NPHPT would remain doubtful and the Ca/P ratio could be useful. It is reasonable to imagine that a relationship exists among the biochemical alterations in PHPT, i.e., the higher calcemia, the lower phosphatemia and the higher the Ca/P ratio. In fact, the sensitivity of this ratio (cutoff 3.3) was higher in patients with hypercalcemia (96%) than in those with normocalcemia (71%). It is possible that some differences in sensitivity may exist between patients with NPHPT and Ca close to the upper limit of normal (ULN) and the remaining patients, with sensitivity being lower in the latter. In patients with elevated PTH, NPHPT is already very
* Pedro Weslley Rosário [email protected] 1
Santa Casa de Belo Horizonte, Belo Horizonte, Minas Gerais, Brazil
likely when Ca is close to the ULN (for example, >2.5 mmol/l) [4]. A study conducted at another center showed that the sensitivity and specificity of the Ca/P ratio were not superior to the measurement of Ca alone using a cutoff of 2.45 mmol/l [5]. Therefore, exactly in patients in whom greater doubt exists regarding the diagnosis of NPHPT, namely, with Ca that is not close to ULN, may the sensitivity of the Ca/P ratio be lower. In patients with Ca < 2.25 mmol/l, the utility and performance of this ratio are unknown since all patients with PHPT in the study had Ca ≥ 2.25 mmol/l. We recognize the importance of phosphatemia in the differential diagnosis of patients with normal Ca and elevated PTH. Within this context, the finding of hypophosphatemia already favors the diagnosis of NPHPT, and the Ca/P ratio is not necessary because it will always be >3.5. The ratio would be necessary when
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