Case Reports and Reviews: Open Access

Background: Hypercalcemia of malignancy is an important metabolic complication of cancer that may produce neurologic manifestations and is associated with poor prognosis. Diagnosis and management can be particularly challenging in elderly patients with end-stage renal disease (ESRD), in whom abnormalities of calcium and parathyroid hormone homeostasis may complicate interpretation. 

Case Presentation: An 86-year-old man with ESRD and prostate cancer in remission presented with acute confusion, worsening left hip pain, and abnormal laboratory findings. Nephrology evaluation found a creatinine of 5.9 mg/dL and calcium of 10.8 mg/dL. Hospital studies showed anemia secondary to ESRD, elevated serum calcium at 10.8 mg/dL, ionized calcium at 1.50 mmol/L, intact parathyroid hormone (PTH) at 26.3 pg/mL, elevated parathyroid hormone-related peptide (PTHrP) at 3.0 pmol/L, and a normal PSA of 1.3 ng/mL. Radiographs and CT demonstrated a large destructive lytic lesion involving the left lesser trochanter and proximal femoral shaft, highly suspicious for malignancy of uncertain primary origin. Bone scintigraphy subsequently demonstrated intense tracer uptake spanning approximately 13 cm of the left proximal femur, further supporting an active osseous process. Despite medical management, the patient's hypercalcemia persisted, and his encephalopathy worsened. After multidisciplinary discussions, the family opted for comfort care. 

Discussion: Malignancy-associated hypercalcemia may result from PTHrP secretion or osteolytic bone destruction, while ESRD can complicate the interpretation and management of calcium abnormalities. This case highlights that even mild total hypercalcemia, particularly when accompanied by elevated ionized calcium, new confusion, and progressive focal bone pain, should prompt consideration of an underlying destructive osseous process.

Keywords: Hypercalcemia; End-stage renal disease; PTHrP; Destructive bone lesion; Lytic bone lesion; Malignancy; Prostate cancer; Palliative care.