1,25-Dihydroxyvitamin D-Mediated Hypercalcemia Due to a Fibrotic Granuloma Lung Disease, Ameliorated By Ketoconazole – a Case Report
Presentation Number: MON 321
Date of Presentation: April 3rd, 2017
Anh-Thu Qui Nguyen* and J Christopher Gallagher
Creighton University Medical Center, Omaha, NE
Introduction: In the absence of malignancy or infectious process, an elevated 1,25-dihydroxyvitamin D [1,25(OH)2D)] is responsible for non-PTH-mediated hypercalcemia in granulomatous lung disease. We report a case of 1,25(OH)2D-mediated hypercalcemia responded to short-term administration of ketoconazole.
Case: A 69 year-old man with history of chronic kidney disease, nephrolithiasis, COPD and type 2 diabetes, who admitted with symptomatic elevated serum calcium at 13.9 mg/dL. He had mild confusion, abdominal pain, constipation and hematuria on admission. Initial aggressive treatment with IV fluids, furosemide and calcitonin did not normalize his hypercalcemia. Work-up revealed ionized calcium of 1.63 mmol/L (ref. 1.13-1.32), parathyroid hormone (PTH) and PTH-related peptide were undetectable. Serum 1,25(OH)2D was elevated at 111 pg/mL (ref. 19.9-79.3) and serum 25(OH)D was 29.7 ng/ml. Serum TSH, FT4, and SPEP/UPEP were normal. A CT chest revealed bilateral enlarged hilar lymph nodes and a 2.8 cm lung mass. Biopsy of lung mass showed lung tissue with fibrotic granulomas, no malignancy, and negative AFB stains. Cultures for fungal and tuberculosis were negative.
Prednisone 40mg/d was initiated, serum total and ionized calcium decreased slightly to 11 mg/dL and 1.55 mmol/L, respectively. He developed delirium within 7 days of prednisone and the dose had to be reduced. Ketoconazole (an 1α-hydroxylase inhibitor) 600mg/d was started and after 3 days serum and ionized calcium normalized to 9.1 mg/dL and 1.18 mmol/L, respectively; serum 1,25(OH)2D decreased to 27.7 pg/mL. Renal function remained stable during ketoconazole therapy. Upon confirmation of granuloma lung disease on biopsy, ketoconazole was discontinued and high-dose prednisone was resumed. Serum total and ionized calcium increased rapidly to 11 mg/dL and 1.51 mmol/L, respectively, and 1,25(OH)2D increased to 59.9 pg/mL after stopping ketoconazole.
Conclusion: Hypercalcemia in granulomatous disease is caused by increased conversion of 25(OH)D to 1,25(OH)2D, via 1α-hydroxylase and in the absence of 24 hydroxylase, a key modulator of 1,25(OH)2D production. Measurement of vitamin D metabolites is key in making a diagnosis 1,25(OH)2D-mediated hypercalcemia. Prednisone 40mg/day is often effective in suppressing 1,25(OH)2D production, and serum calcium may decrease within 3 to 5 days. In this case, no significant improvement of serum or ionized calcium occurred within 7 days of prednisone treatment. Ketoconazole 600mg/day rapidly normalized serum and ionized calcium and 1,25(OH)2D levels. Hypercalcemia recurred after discontinuation of ketoconazole suggesting ketoconazole played a key role in ameliorating hypercalcemia due granulomatous disease. In selected cases, treatment with ketoconazole may offer a temporary relief from hypercalcemia in patient who cannot tolerate high-dose glucocorticoids.
Disclosure: JCG: , Bayer, Inc.. Nothing to Disclose: ATQN