Multifactorial causes of severe persistent hypercalcemia in an immunosuppressed woman with chronic kidney disease

We present the case of a 62-year-old woman with history of chronic kidney disease and birdshot retinochoroidopathy on immune suppression who presented with hypercalcemia, acute kidney injury, and Pneumocystis jirovecii pneumonia (PJP). Despite initial treatment with intravenous (IV) fluids, calcitonin, zoledronic acid, and antimicrobials for her pneumonia, her hypercalcemia persisted. Given her diagnosis of PJP and markedly elevated levels of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and vitamin A, prednisone (40 mg/day) and IV denosumab (120 mg) were added to her regimen; however, there was no significant improvement in calcium levels. On hospital day 27, intermittent hemodialysis was initiated, resulting in a rapid correction of hypercalcemia, improved kidney function, and better volume status. The patient was discharged on prednisone with stable laboratory parameters. This case highlights the complex interplay of factors contributing to treatment-refractory hypercalcemia, including vitamin D toxicity, granulomatous infection-driven 1,25-dihydroxyvitamin D excess, and impaired renal clearance. It underscores the importance of early detection of supplement misuse, multidisciplinary care, and the potential need for hemodialysis when conventional treatments fail.