HemeOnc

Hypercalcemia of Malignancy

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Hypercalcemia of Malignancy, Malignant Hypercalcemia, Humoral Hypercalcemia of Malignancy

  • Epidemiology
  1. Incidence: 10-30% of cancer patients
  • Pathophysiology
  1. Paraneoplastic syndrome (most common, 80% of cases)
    1. Tumor secretes Parathyroid Hormone related peptide (PTHrP)
    2. Results in increased calcium reabsorption in Kidney
  2. Other mechanisms
    1. Bone Metastases release calcium
    2. Local osteolysis by cytokines
    3. Cancer may release circulating bone-resorbing cytokines, calcitriol (Vitamin D)
  3. Rare mechanisms
    1. Immobilization
    2. Medications
    3. Parathyroid carcinoma
  • Labs
  1. Serum Calcium >10.5 mg/dl
    1. Adjust for albumin, as Malnutrition is common (obtain Ionized Calcium if available)
  • Management
  1. See Hypercalcemia for other management
  2. Consult Oncology, Endocrinology, Nephrology
  3. Acute Management
    1. Initial Management (typically in emergency department)
      1. Aggressive rehydration (up to 4 liters Lactated Ringers or Normal Saline per 24 hours)
    2. Next Management (typically after admission)
      1. Furosemide 10-20 mg IV q6-12 hours after rehydration
    3. Acute Renal Failure Management
      1. Consider Dialysis
  4. Monitor serum electrolytes
    1. Serum Calcium (may start as high as 14 mg/dl)
  5. Hypophosphatemia specific management
    1. Indication for Phosphorus Replacement: Serum Phosphate <3 mg/dl
    2. Neutro-Phos 250 mg Phosphorous PO or NG daily
  6. Hypercalcemia specific management
    1. Indications
      1. Serum Calcium >14 mg/dl if asymptomatic
      2. Serum Calcium >12 mg/dl if symptomatic
    2. Methods
      1. Glucocorticoids
        1. Decrease intestinal calcium absorption
      2. Calcitonin
        1. Inhibits Osteoclasts
      3. Bisphosphonates
        1. Inhibit Osteoclast mediated bone resorption (delayed effect over days)
        2. Zoledronic acid: 4 mg IV over 15 min (preferred over Pamidronate)
        3. Pamidronate (Aredia) 60-90 mg IV q4 hours
        4. Major (2001) J Clin Oncol 19:558-67 [PubMed]
      4. Monoclonal antibodies
        1. Denosumab (inhibits Osteoclasts)
  • Prognosis
  1. Hypercalcemia of Malignancy is a poor cancer prognostic sign
  2. Associated with >50% mortality in 30 days