Hypercalcemia in Oncology

Causes in Cancer

PTHrP-mediated (Most common – ~80%)

• Seen in:
  • Squamous cell carcinoma (especially lung)
  • Renal cell carcinoma
  • Head and neck cancer
• Mechanism: Tumor secretes PTH-related peptide (PTHrP)

Osteolytic metastases

• Seen in:
  • Breast cancer
  • Multiple myeloma
  • Mechanism: Bone destruction → calcium release

Vitamin D–mediated

• Seen in:
  • Lymphoma
  • Mechanism: ↑ 1,25-OH vitamin D

Symptoms

• Mild (Ca < 12 mg/dL)
  • Fatigue
  • Constipation
  • Polyuria
  • Polydipsia
• Moderate–Severe (> 14 mg/dL)
  • Nausea/vomiting
  • Dehydration
  • Confusion
  • Delirium
  • Muscle weakness
  • Coma
  • Cardiac:
    • Shortened QT interval
    • Arrhythmias

Diagnosis

• Confirm hypercalcemia
  • Measure total calcium
• Check PTH
  • Result Interpretation
    • ↓ PTH Malignancy likely
    • ↑ PTH Primary hyperparathyroidism
• Further tests
  • PTHrP
  • 1,25-OH Vitamin D
  • Serum protein electrophoresis (if suspecting Multiple myeloma)

Complications

• Acute kidney injury
• Nephrogenic diabetes insipidus
• Cardiac arrhythmias
• Coma
• Death

In cancer patients → indicates poor prognosis

Treatment (Oncologic Emergency)

• Step 1– IV Normal Saline (First line)
  • Correct dehydration
  • Promote calciuresis
• Step 2 – Calcitonin
  • Rapid onset (4–6 hrs)
  • Temporary effect
• Step 3 – IV Bisphosphonates (Main definitive treatment)
  • Zoledronic acid
  • Pamidronate
  • Takes 2–4 days to work
  • Inhibits osteoclasts
• Step 4 – Denosumab
  • For refractory cases
  • Especially useful in renal failure
• Step 5 – Dialysis
  • Severe, life-threatening hypercalcemia
  • Especially if renal failure present

Exam Pearls

• Cancer patient + confusion + dehydration → think hypercalcemia
• First step in treatment → IV fluids
• Most common cause in cancer → PTHrP
• Poor prognostic sign in advanced malignancy