Introduction to hypercalcaemia
Hypercalcaemia is diagnosed on the basis of an elevated serum total calcium concentration, corrected for albumin (normal range 2.10 to 2.60 mmol/L). If the albumin concentration is significantly abnormal, serum ionised calcium should be measured directly.
Hypercalcaemia may be detected incidentally, or present with a variety of nonspecific symptoms (eg failure to thrive in an infant, abdominal pain, constipation, polyuria, polydipsia). Cardiac rhythm abnormalities can also occur.
Hypercalcaemia has many causes (see Causes of hypercalcaemia), but 80 to 90% of cases in adults result from primary hyperparathyroidism or malignancy (see the Palliative Care guidelines for management of hypercalcaemia of malignancy).
Hypercalcaemia is classified as parathyroid-dependent or parathyroid-independent, by simultaneously measuring serum calcium and parathyroid hormone concentrations. In parathyroid-dependent hypercalcaemia, the parathyroid hormone concentration is usually above or at the upper end of the normal range.
Most common causes
Less common causes
thiazide diuretic drugs [NB1]
sarcoidosis or other granulomatous disorders
severe hyperthyroidism
milk alkali syndrome
renal osteodystrophy with tertiary hyperparathyroidism
primary adrenal insufficiency
familial hypocalciuric hypercalcaemia (familial benign hypercalcaemia)
prolonged immobilisation [NB2]
cytochrome P450 24A1 (CYP24A1) gene mutation
idiopathic hypercalcaemia of infancy
neonatal subcutaneous fat necrosis
neonatal severe hyperparathyroidism
infantile hypophosphatasia
William syndrome
NB1: Patients who develop hypercalcaemia after starting a thiazide diuretic usually have primary hyperparathyroidism, which may have been previously undiagnosed.
NB2: Immobilisation during states of high bone turnover (eg adolescence, Paget disease of bone) can cause hypercalcaemia.