Approach to Hypercalcemia


In morning report we discussed a perplexing case of a patient who presented with new onset hypercalcemia. Let’s Review an approach to hypercalcemia.


  1. Symptoms
  2. Differential Diagnosis
  3. Investigations
  4. Treatment


“Groans, Stones, Bones, Psychiatric Overtones, Thrones”

  • abdominal pain, nausea, vomiting, pancreatitis
  • kidney stones
  • bony pain, fractures
  • confusion, delirium, coma
  • constipation/polyuria

Differential Diagnosis:



  • CBC, lytes (can get contraction alkalosis à so high bicarb), creatinine
  • PTH, 25-OH-Vit D 
  • Depending on above and clinical picture consider:
    • 24 hour urine calcium
    • Malignancy work up as needed: CXR/CT, SPEP/UPEP, imaging etc
    • ECG (short QT)
    • 1,25-VitD, PTHrP, TSH, Vitamin A level


  • Goals: lower calcium, treat underlying cause
  • Fluids, fluids, fluids for everyone: increases urinary calcium excretion. Onset in hours. Typically NS (normal saline) 150-200cc/hr to target a urine output of 100cc/hr.  Monitor for volume overload.
  • Furosemide is not a maintstay of treatment. Give only if patient is now fluid overloaded from all the fluids you gave
  • Specific treatments that you tailor to your patient:
    • Bisphosphonates: Inhibit bone resorption via interference with osteoclast recruitment and function. Most benefit is in patients with malignancy as their underlying cause
      •  Zoledronic Acid: 4 mg IV (preferred)  (vs Pamidronate: 60-90 mg IV or lower if renal impairment).  Works in 2-3 days.
  • If hypercalcemia is severe, can consider calcitonin: Also interferes with osteoclast function and inhibits bone resorption but also promotes urinary calcium excretion. Onset in 4-6 hours but you get tachyphylaxis at ~48h. 
    • 4 IU/kg Subcut or IM.  Repeat serum calcium in a few hours. Calcitonin can be repeated and increased to 4-8 IU/kg sc q6-12h.
  • Denosumab: RANK-L inhibitor.  Used typically in patients with severe, symptomatic hypercalcemia of malignancy not responsive to bisphosphonates or in whom bisphophonate use is contraindicated due to renal failure (GFR is not a limiting factor for its use like bisphosphonates).
  • Steroids: usually only for granulomatous disaese or lymphoma.
    • Decreases intestinal calcium absorption and decreases 1, 25-OH-VitD. HOWEVER, not to be started overnight, as biopsy may need to be done before initiation of steroids.
  • Hemodialysis: if the patient is anuric.

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