Utility of the urine calcium-to-creatinine ratio to diagnose primary hyperparathyroidism in asymptomatic hypercalcaemic patients with vitamin D deficiency

Abstract

Primary hyperparathyroidism (PHP) is the most common cause of hypercalcaemia, and often requires surgical treatment. Familial hypocalciuric hypercalcaemia (FHH) has similar biochemical features to PHP, but requires no treatment. The most common biochemical method used to distinguish between PHP and FHH is the urine calcium-to-creatinine ratio (UCCR). Vitamin D deficiency may alter the renal excretion of calcium, but it is unclear how vitamin D deficiency affects the diagnostic performance of UCCR. To examine the reliability of UCCR to detect PHP in patients presenting with asymptomatic hypercalcaemia, in the presence or absence of vitamin D deficiency. One hundred and eighteen UCCR measurements from 97 asymptomatic hypercalcaemic patients diagnosed with PHP presenting to a single specialist endocrine unit were analysed retrospectively. A significantly higher proportion of UCCR measurements were <0.010 in patients with serum vitamin D <25 nmol/L when compared with patients with serum vitamin D >25 nmol/L, thus incorrectly suggesting the presence of FHH (proportion of measurements with UCCR >0.010: 11/48 [22.9%], vitamin D <25 nmol/L; 4/70 [5.7%], vitamin D >25 nmol/L; P < 0.001). Urine calcium concentration was 26% lower and serum parathyroid hormone (PTH) was 27% higher in patients with vitamin D deficiency when compared with patients without vitamin D deficiency. These data suggest that the presence of vitamin D deficiency is associated with worsened PTH hypersecretion, impairment of urinary calcium excretion and reduced sensitivity of UCCR measurement with respect to the detection of PHP. These data have important clinical implications for the investigation and management of patients with asymptomatic hypercalcaemia.