Vitamin D-induced hypercalcemia and nephrolithiasis in a 58-year-old woman with biochemical findings suggestive of 24-hydroxylase deficiency: a case report.

BACKGROUND: Hypercalcemia is most often caused by primary hyperparathyroidism and malignancies. Non-parathyroid hormone (PTH)-dependent hypercalcemia can be caused by abnormal vitamin D metabolism related to excess production from granulomatous disease, excess intake or defects in its degradation. Disturbance in vitamin D metabolism can lead to increased vitamin D sensitivity which can cause hypervitaminosis D at doses otherwise considered safe. Decreased 24-hydroxylase activity due to CYP24A1 mutation leads to increase in 1,25-dihydroxyvitamin D [1,25(OH)2D] and decreases in vitamin D degradation products. Although originally described in infancy and later during pregnancy, this case highlights a postmenopausal woman with no prior history who presented with hypercalcemia and nephrolithiasis after standard dose vitamin D supplementation with biochemical evidence of 24-hydroxylase (CYP24A1) deficiency.

CASE DESCRIPTION: A 58-year-old woman presented with hematuria and abdominal pain secondary to nephrolithiasis. Laboratory studies revealed hypercalcemia, suppressed PTH, and markedly elevated 25-hydroxyvitamin D [25(OH)D] following standard vitamin D supplementation (2,000 international units/day). Her 1,25(OH)2D level was high, and subsequent testing demonstrated an elevated 25(OH)D:24,25-dihydroxyvitamin D [24,25(OH)2D] ratio, as biochemical evidence of CYP24A1 deficiency. Genetic testing was declined. Hypercalcemia improved with discontinuation of vitamin D, intravenous hydration, bisphosphonate therapy, and corticosteroids. The patient remained normocalcemic after stopping supplementation vitamin D until she developed mild recurrence following increased sun exposure seven months later.

CONCLUSIONS: This case highlights hypercalcemia and nephrolithiasis triggered by standard-dose vitamin D supplementation in a previously asymptomatic woman with biochemical findings indicating CYP24A1 deficiency illustrating that the disorder may remain latent until challenged by exogenous or endogenous vitamin D excess. Although genetic testing remains the gold standard for diagnosis, a markedly elevated 25(OH)D:24,25(OH)2D ratio (>80) is a useful biochemical marker for 24-hydroxylase deficiency.