Author: Martin Crook
Disorders of plasma calcium concentration (Box 87.1) usually result from deranged handling of calcium by the gut, kidneys or bone. Calcium exists in the extracellular fluid in three forms: the physiologically important ionized fraction (50%), the protein-bound fraction (40%) and a small fraction (10%) complexed to anions. Most laboratories measure total calcium, which should be corrected for the plasma albumin concentration (a major determinant of the ionized calcium fraction):
Although primary hyperparathyroidism is the commonest cause of hypercalcaemia, cancer is most often the cause of severe hypercalcaemia requiring inpatient management. Typically this occurs in a patient known to have a cancer involving bone (e.g. carcinoma of the breast, bronchus, renal, thyroid or prostate) or a haematological cancer such as myeloma or lymphoma, but may sometimes be the presenting complaint. Hypercalcaemia in patients with cancer is related to osteolytic metastases in 20% cases and to secretion of parathyroid-hormone-related protein (PTHrP) in 80% cases. A small percentage is due to increased production of 1,25-dihydroxy vitamin D (associated with lymphoma) and ectopic PTH secretion.
Principles of management
Treat the underlying disorder: causes of hypercalcaemia are listed in Table 87.1.
Investigation of the patient with hypercalcaemia is given in Table 87.2.
Correct hypovolaemia and increase the renal excretion of calcium.
Inhibit accelerated bone resorption.
Avoid thiazides and lithium carbonate, which contribute to hypercalcaemia and also patient immobilization.
Moderate or severe hypercalcaemia (total calcium >3 mmol/L)
- The first-line treatment is rehydration. In patients with mild symptoms, oral rehydration (a fluid intake of at least 2–3L/day) may be sufficient. Patients with more severe symptoms should receive normal saline 1L 6–8-hourly IV. The use of furosemide is no longer recommended in the management of hypercalcaemia.
- If plasma calcium remains >3 mmol/L despite rehydration, drug therapy to inhibit osteoclast-mediated bone resorption is indicated. The most commonly used agents are given in Table 87.3.
- Specific treatment will be needed to prevent a recurrence of hypercalcaemia (e.g. chemotherapy for malignancies, surgery for primary hyperparathyroidism).
- For severe refractory hypercalcaemia, haemodialysis may be needed: seek advice from a nephrologist.
Causes of hypocalcaemia are given in Table 87.4. Acute severe hypocalcaemia (with tetany) is most commonly seen in patients with chronic kidney disease after elective subtotal parathyroidectomy or total thyroidectomy.
Be aware that hyperventilation may also cause carpopedal spasm due to reduced ionized calcium, resulting from a respiratory alkalosis.
Acute severe hypocalcaemia, for example with tetany
Give 10 mL of calcium gluconate 10% (2.25 mmol) IV over 5 min, followed by a continuous infusion of calcium gluconate. This can be repeated and, if indicated, followed with infusion of calcium gluconate 10% infusion 40 mL (9 mmol) over 24h.
It is essential to monitor serum calcium concentrations regularly and also exclude and manage concomitant hypomagnesaemia.
If hypocalcaemia is likely to continue, give oral vitamin D with patient follow-up.
Seek expert advice on further management.