Risk of hypercalcemia in patients with very high serum 25-OH vitamin D levels

Objective: We aimed to evaluate the risk of hypercalcemia in patients with very high levels of 25-hydroxy vitamin D (25(OH)D).

Methods: The distribution of patients who were screened for 25(OH)D in our hospital between January 2014 and December 2018 was evaluated and patients with serum concentrations of 25(OH)D >88 ng/mL were selected. Then, biochemical parameters of the cases with 25(OH)D >88 ng/mL were compared according to calcium status, vitamin D level (group 1, 88-100 ng/mL; group 2, 100-150 ng/mL, and group 3, >150 ng/mL), and gender.

Results: A total of 282 932 patients who underwent 25(OH)D tests in our hospital were evaluated. A total of 1311 (0.5%) patients had very high 25(OH)D levels (>88 ng/mL). Four hundred and ninety-five patients who met our inclusion criteria and had complete data participated in the study. The median age was 58 years (interquartile range [IQR] = 41-71 years) and the median level of 25(OH)D was 104.6 mg/mL (IQR = 94.9-124.9 ng/mL). Most of the subjects (83.7%) with very high 25(OH)D levels were normocalcemic. A weak inverse correlation was observed between 25(OH)D level and intact parathyroid hormone (iPTH) level (r = -0.118, P = .01), but no correlation between 25(OH)D and calcium levels was observed. Alkaline phosphatase (ALP) levels were significantly higher in males (P = .032), and age and iPTH levels were higher in females (P < .001 and P = .004). ALP, phosphorus levels, and iPTH suppression rates were higher in hypercalcemic patients (P < .001, P < .001, and P < .001, respectively), while the iPTH level was significantly lower in hypercalcemic patients (P < .001) than in normocalcemic patients. Amongst the three groups with different 25(OH)D levels, no difference was found in levels of iPTH, calcium, phosphorus, ALP, or age.

Conclusion: Most patients with very high vitamin D levels were normocalcemic, but severe hypercalcemia was also observed. Vitamin D replacement therapy and follow-up should be performed according to clinical guideline recommendations.