SAT-346 Hypercalcemia Secondary to Calcitriol and PTHrP Cosecretion Only Responsive to Hydroxychloroquine

Abstract

Background: Hypercalcemia of malignancy mediated by concurrent elevations in both 1,25-dihydroxyvitamin D (calcitriol) and parathyroid hormone (PTH)-related protein (PTHrP) is a rare phenomenon previously only reported with solid tumors. The preferred treatment for calcitriol-mediated hypercalcemia is glucocorticoid therapy and second-line therapy is traditionally ketoconazole. Hydroxychloroquine has previously been reported as efficacious only in cases of calcitriol excess related to sarcoidosis. Clinical case: A sixty-two year-old female with a history of diffuse large B cell lymphoma, complicated by disease progression despite multiple treatment regimens over the preceding five years, developed acute hypercalcemia to a corrected value of 14.7 mg/dL (8.9-10.3). Work-up revealed a suppressed PTH, PTHrP <2.0 pmol/L (0.0-3.4), and calcitriol elevation of 136.0 pg/mL (19.9-79.3). She was treated with zolendronate with rapid normalization of calcium levels. Upon recurrence of hypercalcemia six months later, repeat calcitriol was 176.0 pg/mL with a new PTHrP elevation of 7.0 pmol/L. Repeat dosing of zolendronate was less efficacious. She was prescribed prednisone 60 mg daily with subsequent addition of denosumab 120 mg weekly with continued hypercalcemia. Given rising levels of calcitriol and PTHrP (up to 285.6 pg/mL and 43.5 pmol/L, respectively) and potential drug interactions between ketoconazole and her chemotherapy, she was started on hydroxychloroquine 400 mg daily. Her calcium normalized and calcitriol dropped to 61.1 pg/mL despite imaging evidence of continued lymphoma progression. Three weeks later, she developed septic shock and was transitioned to hospice. Conclusion: In reviewing the literature, this appears to be the first reported case of a hematologic malignancy with pathologic levels of both calcitriol and PTHrP. It is also the first reported efficacy of hydroxychloroquine in malignant hypercalcemia. Interestingly, PTHrP secretion occurred months after the initial development of hypercalcemia. Control of both calcitriol and calcium levels did not occur until initiation of hydroxychloroquine despite preceding use of high-dose glucocorticoids and anti-resorptive therapy. Our case suggests that hydroxychloroquine should be considered in cases of calcitriol-mediated hypercalcemia resistant to glucocorticoids, particularly as it has less drug interactions and a more favorable side effect profile when compared to ketoconazole.