SAT-502 Bisphosphonates for Treatment of Calcitriol-Induced Hypercalcemia

Abstract

Abstract Calcitriol excess is a less common cause of hypercalcemia than hyperparathyroidism. While its primary mechanism is thought to be increased intestinal calcium absorption, accelerated bone resorption contributes as well. The mechanism is presumably through a molecular interaction between the receptor activator of NF-κB ligand/osteoprotegerin ligand on marrow stromal cells and receptor activator of NF-κB on osteoclast precursors. It is this component of increased bone resorprtion that is addressed by bisphosphonates. A 77 year old woman with remote history of non-small cell lung cancer status post left lower lobe lobectomy presented with dry mouth, polyuria, 11 pound weight loss in 6 months, fatigue and calcium of 14.7. Examination was unremarkable. Laboratory evaluation included creatinine of 1.4 mg/dl, parathyroid hormone low at 19 pg/ml, 25 hydroxyvitamin D normal at 47 ng/ml, normal kappa/lambda and serum and urine protein electrophoresis, parathyroid hormone-related protein normal at 15 pg/ml, and 1,25 dihydroxyvitamin D was high at 89 pg/ml. A search commenced for the source, during which time hypercalcemia recurred despite strict low-calcium diet and IVF. PET-CT showed innumerable foci of increased uptake in the skeleton and lymph node biopsy revealed grade 3A follicular lymphoma. She received Zoledronic acid 5 mg IV and normocalcemia was maintained thereafter, without any diagnosis-specific treatment for >3 months. She was subsequently started on Rituxan and Bendamustine.This case demonstrates a patient with calcitriol-induced recurrent hypercalcemia from a follicular lymphoma who achieved normalization and subsequent stabilization of serum calcium levels following administration of bisphosphonate. Hypercalcemia due to calcitriol excess is usually managed acutely with intravenous fluid administration and dietary calcium restriction. Second-line agents such as steroids and ketoconazole can also be used, but these interventions alone have side effects and were contraindicated in our case, while the patient was being evaluated for causes of calcitriol excess which would have been masked by the steroids. There is evidence supporting the role of bone resorption in the genesis of hypercalcaemia in vitamin D intoxication and the rapid response of hypercalcaemia to treatment with bisphosphonates. The first choice for calcitriol-induced hypercalcemia is treating the underlying cause. Bisphosphonates are, however, useful until a diagnosis is made, as they may be safer than steroids and can provide rapid relief even with a single treatment, with minimal side effects.