SUN-784 Intersecting Malignant And Endocrine Drivers Of Hypercalcemia: A Case-based Analysis

Abstract Disclosure: M. Baksh: None. M. Ramirez: None. B. Kim: None. Introduction: Hypercalcemia of malignancy most often stems from PTHrP excess, osteolytic cytokine release, or tumor overproduction of 1,25-dihydroxy-vitamin-D; while ectopic PTH secretion is rare. [1-2] A prompt work-up—calcium, PTH, followed by PTHrP, vitamin-D metabolites, and serum/urine protein electrophoresis—guides diagnosis and management of severe or symptomatic hypercalcemia in the setting of malignancy. [3-5] Here, we present a challenging case of a 78-year-old female with CLL and marginal zone lymphoma whose severe hypercalcemia evolved into refractory hypocalcemia. Case Presentation:A 78-year-old woman with CLL/marginal-zone lymphoma, HFpEF, stage-III CKD, and hypothyroidism presented with confusion, abdominal pain, and constipation. Labs showed calcium 18.4 mg/dL (ionized 2.41 mmol/L) and creatinine 2.7 mg/dL. Other workup showed an iinappropriately normal PTH 25 pg/ml, normal vitamin D 39 ng/ml, PTHrP 6.1 pmol/L and a monoclonal IgM λ spike on SPEP. A long-standing history of mild hypercalcemia 11.4 mg/dl with mid-normal to high PTH 69 pg/ml and normal 25(OH)D 45 ng/ml; raised possibility of concurrent primary hyperparathyroidism. Initially, she received IV hydration, calcitonin 260 U, one dose IV zoledronic-acid, and cinacalcet 30 mg BID. Serum calcium transiently escalated to 20 mg/dL before declining to 6 mg/dL by day 6, despite oral calcium supplementation; causing hypotension and transient SVT. ICU management with a calcium-gluconate drip and brief vasopressors restored stability. She was discharged on day 10 with oral calcium and scheduled endocrine/hematology follow-up. Discussion: This case underscores the diagnostic challenge posed by hypercalcemia from overlapping endocrine and malignant causes. Hypercalcemia occurs in 20-30 % of malignancies, yet is rare in indolent B-cell neoplasms, with only sporadic PTHrP-mediated cases reported. [3] Our patient had multiple contributors to hypercalcemia: elevated PTHrP, CLL, abnormal SPEP, and an inappropriately normal PTH—raising concern for malignancy-related hypercalcemia with possible primary hyperparathyroidism. This mixed picture illustrates the need for a comprehensive biochemical evaluation when approaching severe hypercalcemia. [6] Additionally, symptomatic hypocalcemia after bisphosphonate therapy highlights the importance of individualized dosing and close monitoring, especially in CKD. [7-8] Conclusion: When evaluating hypercalcemia in the context of hematologic malignancy, clinicians should consider the possibility of overlapping etiologies. This case underscores the importance of a stepwise biochemical workup and highlights the need for vigilant calcium monitoring during treatment, particularly in patients with impaired renal function.References: 8 Presentation: Sunday, July 13, 2025