Aetiology of hypercalcaemia

The common causes of hypercalcaemia which accounts for about 90% of cases are due to primary hyperparathyroidism and malignancy:

• primary hyperparathyroidism – commonest cause in the community (1), accounts for 80% of cases and is more important in the young
• malignancy accounts for 20-30% of cases (1) and is frequently accompanied by hypoalbuminaemia:
  • suggested by rapidly increasing hypercalcaemia (1)
  • metastases with osteolytic deposits e.g. breast
  • osteoclast activating factors e.g. multiple myeloma
  • ectopic parathyroid hormone like peptide e.g. hypernephroma, ovarian tumour, bronchial carcinoma
  • 10-15% of hypercalcaemia caused by malignancy have associated hyperparathyroidism (2)

Rarer causes of hypercalcaemia include:

• increased extrarenal synthesis of calcitriol in chronic granulomatous disease:
  • sarcoidosis
  • pulmonary tuberculosis
  • berylliosis
• Addison's disease
• Paget's disease with bed rest
• immobilisation - especially in adolescence when bone turnover is increased
• vitamin A and/or D toxicity
• drugs:
  • thiazide diuretics
  • lithium
• thyrotoxicosis:
  • usually mild and accompanied by hypercalciuria
  • due to increased bone turnover
• familial hypocalciuric hypercalcaemia
• tertiary hyperparathyroidism
• milk alkali syndrome
• multiple endocrine neoplasia (MEN) (2,3)

Reference:

• (1) Joshi D, Center JR, Eisman JA. Investigation of incidental hypercalcaemia. BMJ. 2009;339:b4613
• (2) Barth, J.H., Butler, G.E. and Hammond, P.J. 2008. Hypercalcaemia. Biochemical Investigations in Laboratory Medicine. Leeds Teaching Hospitals.
• (3) Carroll MF, Schade DS. A practical approach to hypercalcemia. Am Fam Physician. 2003;67(9):1959-66