MON-782 - A Case of Hypercalcemia of Malignancy in Adult T Cell Leukemia/Lymphoma

Introduction: Hypercalcemia of malignancy is seen in 20-30% of cancers, and in 50-80% of cases of adult T cell leukemia/lymphoma [ATLL]. Given its prevalence, discussion on etiology and best management strategies is warranted.

Case: A 50-year-old man with sarcoidosis and panhypopituitarism due to a suprasellar mass presented with a serum calcium of 19.2 mg/dL. Prior calcium level was 8.7mg/dL [normal range < 10mg/dL] the year prior. PTH was 5.6 pg/mL [normal range 20.0-80.0pg/mL] when calcium was 16.6 mg/dL. Parathyroid-related peptide (PTH-RP) was 36 pg/mL [normal range 11-20 pg/mL], with creatinine ranging from 1.46-2.61 mg/dL [normal range < 1.30 mg/dL] during the same timeframe. 1-86 PTH-RP measurement was obtained, which returned 2.5 pmol/L [normal range ≤4.2 pmol/L]. 1,25-dihydroxyvitamin D was < 8 pg/mL [normal range 18-72 pg/mL]. Computed tomography of the chest, abdomen, and pelvis revealed multiple enlarged lymph nodes and numerous scattered lytic foci throughout the axial and appendicular skeleton. To evaluate for ATLL, human T-cell lymphotropic virus (HTLV) I/II antibody was checked, and HTLV-I returned positive. Bone marrow biopsy of the right iliac bone revealed ATLL.
The patient received calcitonin, IV fluids, and zoledronic acid 4mg. Following treatment, calcium reached a nadir of 6.6 mg/dL, and calcium/calcitriol supplementation was started. He was discharged, however readmitted two weeks later with calcium of 16.6 mg/dL. He again received calcitonin, IV fluids, and zoledronic acid 4mg. Calcium improved over the following three days before decreasing to 7.3 mg/dL, again requiring calcium/calcitriol supplementation. During the following weeks, calcium supplementation was decreased but calcium rebounded to 13.6 mg/dL and denosumab 60mg was administered. Calcium improved and chemotherapy was initiated. Subsequent calcium levels were persistently low, reaching a nadir of 5.9 mg/dL, and calcium/calcitriol supplementation was resumed.

Conclusion: Hypercalcemia of malignancy in ATLL is driven by PTH-RP, 1,25-dihydroxyvitamin D, osteolytic metastasis, RANK-L, or any combination of these mechanisms. The initially elevated PTH-RP measured the C-terminal peptide, which can accumulate in renal disease even in the absence of malignancy. Given this patient’s concurrent renal impairment, N-terminal 1-86 PTH-RP was measured and was found to be normal, indicating the hypercalcemia was less likely PTH-RP driven. The hypercalcemia in this patient could be a result of lytic lesions but also a result of RANK-L production by neoplastic T-cells in ATLL. Given the only temporary resolution of hypercalcemia following bisphosphonates but the more lasting resolution following denosumab, it is likely that the mechanism of hypercalcemia was primarily RANK-L mediated and that denosumab should be considered as the preferred agent in treating hypercalcemia from ATLL.

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