A Challenging Case of Vitamin D Toxicity Responding to Cinacalcet

Background: Interest in the role of vitamin D in various physiological processes, the prevalence of its deficiency and importance of replacement has increased significantly over the past few decades. However, many formulations of vitamin D are not regulated and are available to the public without clear guidance on safe administration, which has contributed to the uptrend in the incidence and severity of vitamin D toxicity cases. Clinical Case A 57- year-old man with a medical history significant for amyotrophic lateral sclerosis, cervical myelopathy, and oropharyngeal dysphagia presented with weakness, constipation, polydipsia, polyuria and was found to have hypercalcemia with a total Calcium level of 15.5 mg/dL (n 8.6- 10.4), and albumin 4.2 g/dL (n 3.5–5.1). He soon developed acute hypoxic respiratory failure requiring prolonged intubation followed by tracheostomy. Evaluation of the hypercalcemia revealed an elevated 25-hydroxyvitamin D [25(OH)D] > 392 ng/mL (n 30–80), 1,25- dihydroxyvitamin D [1,25(OH)D] >600 pg/mL (n 19.9 - 79.3), PTH 8 pg/mL (n 12–88), and PTHrP 0.7 pmol/L (n< 4.2). The patient had initially stated that he was taking 5000 IU of vitamin D daily but further discussion with his wife revealed that he had been taking 2 teaspoons of a powder cholecalciferol preparation with 125 mcg (5000 IU of vitamin D) per 50 mg, which would be about 800,000 IU/day. He was treated with aggressive IV hydration, calcitonin and received 2 doses of pamidronate with an initial improvement in his Calcium level down to 10 mg/dL followed by recurrence of hypercalcemia. Work up for granulomatous disease and multiple myeloma revealed latent TB. At significantly elevated [25(OH)D] levels, toxicity is partially caused by the direct action of [25(OH)D] on the vitamin D receptor (VDR), and [25(OH)D] can also cross-react with the [1,25(OH)D] assay causing false elevation. Steroids were avoided because of his recent diagnosis of latent TB; hence he was started on Cinacalcet which was gradually increased to 60 mg twice a day with sustained Calcium normalization. Repeat labs showed improvement in [25(OH)D] to 292, and normalization of [1,25(OH)D] at 69.4. He was discharged on Cinacalcet 30 mg twice a day. Conclusion PTH-independent hypercalcemia is usually treated with hydration, anti-resorptive agents including bisphosphonates, denosumab and calcitonin, in addition to steroids in cases of increased 1 αλπηα-hydroxylase activity. Cinacalcet acts on the Calcium sensing receptor (CaSR) in parathyroid tissue, kidneys, bones and the intestine and was recently shown to improve hypercalcemia of malignancy in a report of 2 cases by Sheehan et al. Cinacalcet has helped our patient and might have a potential role for the prompt treatment of vitamin D toxicity, but more data is needed.