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Practice Rational Testing

Investigation of incidental hypercalcaemia

BMJ 2009; 339 doi: (Published 20 November 2009) Cite this as: BMJ 2009;339:b4613
  1. Devina Joshi, bone and calcium registrar,
  2. Jacqueline R Center, assistant professor,
  3. John A Eisman, professor
  1. 1Osteoporosis and Bone Biology Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia
  1. Correspondence to: J A Eisman j.eisman{at}

    Hypercalcaemia is often asymptomatic, but if it is suspected, various tests can provide guidance to confirm diagnosis and identify the likely cause

    The patient

    A 50 year old woman is found to have hypercalcaemia on routine blood tests. Her corrected calcium concentration was 2.75 (reference range 2.10-2.60) mmol/l, and phosphate 0.7 mmol/l (0.7-1.4) mmol/l. She had no history of abdominal pain, constipation, renal calculi, fractures, or mood disturbances. She was euvolaemic with no signs of chronic renal disease. Routine laboratory tests—including full blood count, serum electrolytes, and renal and liver function—were normal.

    As her hypercalcaemia was mild, she did not require immediate measures to correct this. Investigations to determine the cause of the hypercalcaemia were performed.

    About 40-50% of serum calcium is bound to protein (mostly albumin), and the remaining calcium is free or ionised (the portion under hormonal regulation). Corrected calcium is calculated from total calcium and serum albumin and an accurate reflection of ionised calcium in an individual with a normal serum albumin and normal acid-base balance. Asymptomatic hypercalcaemia (based on corrected or ionised values) is nowadays a common diagnostic and management dilemma, with more patients undergoing routine blood tests for other purposes. However, not all cases require treatment.

    Primary hyperparathyroidism and malignancy together account for 90% of all hypercalcaemic patients.1 Aetiology varies according to the clinical presentation; more indolent cases suggest hyperparathyroidism, and more rapidly developing cases suggest malignancy. About 20-30% of all patients with cancer develop hypercalcaemia at some time as a paraneoplastic phenomenon or as a result of bone metastases.2 Dehydration exacerbates underlying hypercalcaemia by reducing renal calcium excretion, and drugs such as thiazide diuretics4 and lithium may exacerbate the underlying hypercalcaemia of primary hyperparathyroidism. The box outlines other causes of hypercalcaemia.

    Causes of hypercalcaemia

    Most common causes
    • Primary hyperparathyroidism—commonest cause of hypercalcaemia in the community if renal function is …

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