Hypercalcemia of malignancy

Thanks to John for presenting the case of a middle-aged woman with metastatic renal cell carcinoma who presented with subacute diffuse weakness and constipation, found to have symptomatic hypercalcemia, treated with IV fluids and zoledronic acid.


Clinical Pearls

  • A third of patients with malignancy develop hypercalcemia in their disease course.  Hypercalcemia of malignancy is associated with very poor prognosis (~50% 30 day mortality).
  • Constipation plus polyuria is the most specific symptom combination for hypercalcemia
  • Denosumab is superior to zoledronic acid in treating hypercalcemia of malignancy and is safe to use in renal failure.
  • One way to quickly determine the etiology of hypercalcemia from your chemistry panel is to look at the chloride to phosphate ratio.  A ratio > 33 is highly suggestive of a PTH or PTHrP mediated process.

Hypercalcemia ddx:

Hypercalcemia algorithm

** Primary hyperPTH is the most common cause of hypercalcemia in the outpatient setting.  Malignancy is the most common cause of hypercalcemia in the inpatient setting.

Treatment of hypercalcemia:

Ca <12

  • No treatment if asymptomatic
  • Avoid exacerbating factors

Ca 12-14

  • If chronic/asymptomatic ⇒ same tx as Ca <12
  • If acute/symptomatic ⇒ same tx as Ca 14-18

Ca 14-18

  • IVF – lots!
  • Lasix only if concurrent renal/heart failure
  • Calcitonin
  • Bisphosphonate (zoledronic acid >>pamidronate if malignancy. Denosumab if refractory to ZA or severe renal impairment)

Ca >18

  • Above PLUS
  • Hemodialysis

Hypercalcemia treatment chart

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