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Hypercalcaemia

Hypercalcaemia, defined as a corrected calcium >2.6 mmol/L, is the most common form of paraneoplastic syndrome in malignancy and implicated in large numbers of hospital admissions in malignancy. It may be due to ectopic production of parathyroid hormone related peptides or due to direct bone invasion.

It affects around 10% of patients with solid organ cancers and 30% of patients diagnosed with multiple myeloma. It is also a poor prognostic sign with high risk of recurrence, and the average length of survival after the first instance is 3-4 months. Indeed, resistant hypercalcaemia often signifies the terminal phase of illness.

  • Usually patients become symptomatic with corrected calcium levels >2.9mmol/L but those with acute and rapidly rising levels will likely be more symptomatic than those with slow building, chronically raised levels
  • Patients experience any combination of nausea, anorexia, thirst, frequent urination, fatigue, confusion, depression, constipation, and abdominal pain
  • Treat reversible causes/exacerbating factors such as thiazide diuretics and calcium supplements
  • Ensure adequate rehydration with intravenous fluids
  • Corrected calcium <3.0 mmol/L may resolve with rehydration alone but in malignant illness the cause of hypercalcaemia has not been treated, so is likely to recur.
  • If after rehydration corrected calcium remains >2.8 mmol/L or with an initial level >3.0 mmol/L give IV bisphosphonates (see table)
  • Provide medications for alleviation of associated symptoms e.g. laxatives and antiemetics
  • Offer clear explanation and support to patients and those that care for them
  • Once treated recheck calcium after 2-4 days to allow effect to register
  • Consider advance care planning given known prognostic implications
DrugTime to onset of actionDuration of actionComment
Zoledronic Acid 4mg24-48 hours30 daysMore potent than pamidronate
Pamidronate 90mg24 hours7-14 daysDose adjustment in renal impairment
Ibandronate 4mg24-48 hours30 daysOnly bisphosphonate licensed when eGFR<30
Denosumab (monoclonal antibody not bisphosphonate)4 days100 days
  • Given SC so no need for cannulation
  • Licensed for treatment of resistant hypercalcaemia
  • Caution in renal impairment, may cause hypocalcaemia