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CDHB

Hypercalcaemia

If marked (>3.5 mmol/L), this requires urgent attention - usually symptomatic if calcium is >3 mmol/L.

Causes

• Malignant disease - myeloma, carcinoma (e.g., breast, lung, kidney).
• Primary hyperparathyroidism.
• Sarcoidosis.
• Vitamin D intoxication.
• Lithium treatment.
• Thiazide diuretics.
• Milk-alkali syndrome.
• Thyrotoxicosis.
• Bed rest in patients with active Paget's disease.
• Cortisol deficiency.
• Immobilization (ICU).

Symptoms

May be none. Nausea, vomiting, constipation, abdominal pain, thirst, polyuria, confusion, coma.

Investigations

• In all cases of uncertain aetiology, request Na, K, Ca, Mg, PO₄, ALP, alb, creatinine, and PTH level - before giving hypocalcaemic drugs.
• If PTH level is suppressed, consider the tests listed below and Endocrinology consult, depending on the clinical context:
  • 25-hydroxy vitamin D.
  • CXR (lung cancer, lymphoma, sarcoidosis).
  • CBC + diff and ESR.
  • Thyroid function tests.
  • Serum protein electrophoresis, immunoglobulin levels, and serum free light chain analysis (myeloma).
  • X-ray painful bones (metastases, myeloma), consider radionuclide bone scan.
  • Urine calcium to creatinine ratio (preferably fasting).
  • 1,25 dihydroxy vitamin D and parathyroid hormone related peptide assay may be helpful, the latter if malignancy suspected. Recommend consultation with Endocrinology who can authorize these infrequently performed tests.

    Note: Observed calcium levels will need to be corrected if there are major alterations in plasma albumin levels.

Calcium Correction Formula

Management

• This will depend on the severity and clinical context. Minor elevations of serum calcium will usually not require additional therapy apart from ensuring adequate hydration, monitoring, and establishing its cause. A marked elevation is a medical emergency especially if nausea and vomiting, and/or patient is volume depleted. If hypercalcaemia is causing significant symptoms and active treatment is appropriate then the following is recommended.
• Rehydration - this is the cornerstone of management:
  • Correct dehydration with 4-5 L in 24 hours orally and IV. Monitor closely to avoid fluid overload. Start with 1-2 L sodium chloride 0.9% over 2 hours then 1 L sodium chloride 0.9% 6-8 hourly and reassess at regular intervals. Potassium supplements 10-20 mmol potassium chloride per 500 mL may be required, but use premix bags of potassium chloride 30 mmol/L in sodium chloride 0.9% if possible.
• Bisphosphonates
  • Zoledronic acid 4 mg in 100 mL sodium chloride 0.9% IV over 15 minutes, provided eGFR is >35 mL/min, or pamidronate 90 mg in 0.5 L sodium chloride 0.9% IV over 2 hours.
    • Ensure no extravasation occurs (irritant to tissues). Fever and aching may occur for 2-3 days and can be lessened with regular paracetamol.
    • Plasma calcium falls progressively with nadir at 3-5 days.
    • Ongoing monitoring of calcium is necessary as hypercalcaemia is likely to recur if the underlying cause is not identified and treated.
• Prednisone - if sarcoidosis or vitamin D toxicity is proven, prednisone in a dose of 20-40 mg daily may be effective.
• Stop thiazides. Frusemide may be useful by increasing urine calcium excretion, but give only when volume replete.
• Hypercalcaemic patients who have or may have an underlying malignancy, such as myeloma, should be referred to a Haematologist or Oncologist as soon as possible.
• Parathyroid surgery may be indicated in primary hyperparathyroidism. Consider if calcium >2.9 mmol/L, renal calculi, renal impairment, osteoporosis, or age <50 years. Consult Endocrinology.

Topic Code: 1386