Hypercalcemia Due to Elevated 1,25-Dihydroxyvitamin D in Severe Tophaceous Gout

Introduction: Granulomatous disorders, like sarcoidosis and tuberculosis, can cause hypercalcemia by increasing production of calcitriol through the activation of extrarenal 1-alpha-hydroxylase by macrophages in granuloma. Patients often are asymptomatic and have low parathyroid hormone (PTH) level and elevated 1,25 dihydroxyvitamin D levels. Severe tophaceous gout can cause granulomatous inflammation and is a rare cause of hypercalcemia. Case Description: A 68-year-old male with severe tophaceous gout and possible seronegative rheumatoid arthritis resulting in extensive deformities presented with asymptomatic hypercalcemia 13.1 mg/dL and worsening kidney function. His laboratory testing notable for creatinine 2.6 mg/dL with baseline chronic kidney disease creatinine 2.0 mg/dL, low PTH, elevated serum 1,25-dihydroxyvitamin D and angiotensin converting enzyme (ACE) levels. Extensive workup ruled out sarcoidosis, malignancy, fungal infections, and tuberculosis. He had resection of his elbow tophi which showed many granulomas. Renal Biopsy consistent with ateriosclerosis disease .Aggressive treatment of his gout with steroids and urate lowering therapy febuxostat improved his hypercalcemia. Discussion: Our patient presented with relatively long-standing hypercalcemia with minor symptoms. This occurred in the setting of severe tophaceous gout and probable seronegative rheumatoid arthritis. In normal states, 25-hydroxyvitamin D is hydroxylated to the active 1,25-dihydroxyvitamin D in renal proximal tubular cells through the enzyme 1α-hydroxylase. In hypercalcemia this conversion is inhibited. Elevated 1,25-dihydroxyvitamin D in the setting of hypercalcemia as seen in this patient points to abnormal unregulated extrarenal conversion, typically found in granulomatous states and lymphomas. Table 2 Review of the 6 cases found in the literature of hypercalcemia associated with tophaceous gout - References Age(Years) Serum Calcium/Uric Acid (mg/dL) Extensive Tophi Granulomas in Tophi Serum1,25-Vitamin D Serum ACE ULT/steroids Reported cause ofhypercalcemia Rodriquez et al [6] 42 14.5/14.0 Yes Yes N ND Yes/Yes Transient increasePTH-RP Sachdeva et al [7] 41 13.5/ND Yes Yes Elevated ND Yes/Yes Increased 1,25-Vitamin D Gallegos-Bayas et al [10] 75 14.0/10.4 Yes Yes N Yes Yes/Yes Increased 1,25-Vitamin D Hasbani et al [11] 62 11.7/11.3 Yes ND ND Yes Yes/Yes PTHindependent Lee et al [12] 49 15.3/11.7 Yes ND N Normal Yes/ No Immobilization Gudlawar, SAmerican Society of Nephrology [13] 40 13.4/11 Yes ND Elevated ND Yes/Yes Increased1,25-Vitamin D ND = No Data; N = Normal; ACE = serum Angiotensin Converting Enzyme; ULT = Urate Lowering Therapy * when measured during hypercalcemia