Apparent vitamin D intoxication due to paraprotein interference

A 76-year-old man presented shortly after knee arthroplasty with malaise, nausea, and severe parathyroid hormone-independent hypercalcemia. Initial laboratory evaluation demonstrated a markedly elevated 25-hydroxyvitamin D concentration (>250 nmol/L [>100 ng/mL]; reference >50 nmol/L [>20 ng/mL]), suggestive of vitamin D intoxication. However, this diagnosis appeared implausible because the patient used only 400 IU cholecalciferol daily, serum phosphate remained normal, and several Calcium elevation, Renal dysfunction, Anemia and Bone disease features suggested an underlying plasma cell disorder. Further evaluation confirmed symptomatic immunoglobulin A kappa (IgA-κ) multiple myeloma. Repeat measurement of 25-hydroxyvitamin D by liquid chromatography-tandem mass spectrometry (LC-MS/MS) demonstrated a normal concentration (92 nmol/L [36.8 ng/mL]), confirming analytical interference. The falsely elevated result was reproduced in an independent reference laboratory, and 25-hydroxyvitamin D normalized following successful antimyeloma therapy in parallel with a marked reduction in paraprotein concentration. This case highlights the importance of integrating laboratory findings with clinical reasoning and confirms the value of LC-MS/MS in patients with clinically implausible vitamin D concentrations.