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Hypercalcaemia - Management
How do I determine the underlying cause?

  • Do not routinely investigate people with hypercalcaemia that is severe (adjusted serum calcium concentration greater than 3.40 mmol/L) or symptomatic. These people should be admitted to hospital for urgent treatment and investigation.
  • Hypercalcaemia may develop in the context of known disease (for example cancer) where the cause is apparent.
  • For people with unexplained hypercalcaemia that is mild or moderate (adjusted serum calcium concentration 3.40 mmol/L or less) and asymptomatic, look for the underlying cause. There may be more than one cause.
    • Review the medical history and look for clinical features of:
      • Cancer (especially breast, lung, and haematological cancers).
      • Renal failure, dialysis, or transplantation.
      • Renal impairment or kidney stones (suggesting primary hyperparathyroidism).
      • Osteoporotic fracture (this can occur in people with primary hyperparathyroidism that has been present for many years).
      • Sarcoidosis or tuberculosis.
      • Paget's disease of bone (only causes hypercalcaemia if the person is immobilized).
      • Thyrotoxicosis or other endocrine diseases.
      • Dehydration (may be a cause of transient hypercalcaemia, or a symptom).
    • Determine if the person is taking any drugs or vitamin supplements that can cause hypercalcaemia. These include calcium supplements, thiazide diuretics, vitamin D or vitamin D analogues (oral or topical), vitamin A, lithium, or calcium-containing antacids (or calcium supplements co-prescribed with antacids) which can cause milk-alkali syndrome.
    • Ask about any family history of primary hyperparathyroidism, familial hypocalciuric hypercalcaemia, or other endocrine tumours (that is, pituitary, adrenal, pancreatic, or thyroid tumours suggesting multiple endocrine neoplasia).
    • Check for any previous increased or high-normal serum calcium concentrations. In primary hyperparathyroidism, the increase in serum calcium level is usually mild and stable, or is slowly progressive over a period of years.
    • Take a blood sample to test parathyroid hormone (PTH) levels or refer the person to an endocrinologist for investigation.
      • Testing for PTH is not always available in primary care. If this is the case, refer the person to an endocrinologist (urgently if necessary).
      • Check with the local biochemistry laboratory regarding whether PTH testing is available, any specific collection tube is needed, or the sample needs to be transported rapidly or taken close to the laboratory.
      • See Interpreting PTH levels.
    • Consider doing the following additional investigations, but do not delay urgently referring the person to secondary care if cancer is suspected:
      • Chest X-ray (for lung cancer or metastases, sarcoidosis, or tuberculosis).
      • Renal function and serum electrolytes (for renal failure, milk-alkali syndrome, or renal impairment in primary hyperparathyroidism or myeloma).
      • Full blood count (for anaemia of chronic disease).
      • Erythrocyte sedimentation rate or C-reactive protein (may be increased in cancer).
      • Serum and urine protein electrophoresis, including testing for urine Bence–Jones protein (for myeloma).
      • Serum alkaline phosphatase (may be increased in primary hyperparathyroidism, Paget's disease with immobilization, myeloma, or bone metastases) and other liver function tests (for liver metastases; chronic liver failure is also a rare cause of hypercalcaemia).
      • Serum phosphate (may be low in primary hyperparathyroidism) and chloride (may be increased in primary hyperparathyroidism). These tests are often done automatically when serum calcium is requested; there is little value in requesting them if they are not.
      • Thyroid function tests (for thyrotoxicosis).
      • Serum cortisol (morning sample, at 8–9 a.m. — Addison's disease is a rare cause).
      • Urinalysis for urine protein (for renal disease).

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