MON-335 Bisphosphonate and Denosumab Refractory Hypercalcemia of Malignancy: What Else Is at Play?
Abstract Hypercalcemia of Malignancy has been historically responsive to anti-resorptive agents. However, when multiple mechanisms contribute, it may be difficult to treat with one modality. This case highlights the importance of the work up in treatment of hypercalcemia in a low PTH state. A 44 yo M with h/o high grade metastatic spindle cell neoplasm with skeletal metastasis was admitted with hypercalcemia. He reported some constipation prior to presentation, however denied confusion. His vital signs were notable for HR of 86 bpm and BP of 112/75 mmHg. Labs at admission were remarkable for an uncorrected Ca of 16.1 (8.8-10.3 ng/mL), a phosphorus (Phos) level of 3.3 mg/dL (2.5-4.5 mg/dL), a PTH level of 11 pg/mL (15-65 pg/mL), PTHrP level of 134 pg/mL (14-27 pg/mL), a 25 OH vit D level of 11 ng/mL (30-100 ng/mL), and a BUN/Cr and GFR of 34/2.38 (8-22 mg/dL/0.5-1.3 mg/dL) and 32 ml/min/m2. He was given intranasal calcitonin and ergocalciferol, then received 2mg IV of zolendronic acid, which reduced the patient’s Ca level to a nadir of 6.6 ng/mL in 5 days. On the next admission serum Ca was elevated to 15.7 ng/dL, which did not respond to zolendronic acid. Given that patient’s Ca was refractory to zolendronic acid, denosumab was given but had no response. He then underwent surgery for cord compression and was given dexamethasone (dex) 4mg IV Q6h post-op. His Ca responded quickly to dex, with a nadir to 9.2 ng/dL, however his Ca became elevated after cessation. Given response to dex, vit D 1,25 OH level was sent and was elevated at 94 pg/mL (18-72 pg/mL). In addition, given his inappropriately normal Phos level in the setting of low PTH, FGF23 was sent and came back elevated at 473 RU/mL (<180 RU/mL). This was likely due to increased bone turnover and release of FGF23. He was discharged with a Ca level of 12.5 ng/mL, however was found to have an elevated Ca to 14.9 ng/mL on presentation to clinic. Given concern that Vit D 1,25 OH, PTHrP and direct bony involvement were all contributing to his hypercalcemia, patient was started on IVF and dex IV. His calcium responded 11.5 ng/mL and was then transitioned to PO dexamethasone and plaquenil. The most likely explanation for this phenomenon is malignancy induced cytokine/PAMP release, which stimulates 1-alpha hydroxylase in tumor macrophages to convert 25 OH D to 1,25 OH D. This was supported by his elevated 1,25 OH D level and a decreased 25 OH D, which suggests that 25 OH D was used as substrate by activated macrophages. This case highlights the importance of ancillary work up of hypercalcemia when a patient’s calcium is refractory to standard anti-resorptive therapy. Moreover, it shows the need for a systematic approach when treating hypercalcemia.
