Determining the Cause

After a diagnosis of hypercalcaemia is established, the next step is to determine the cause. Initial testing is directed at malignancy, hyperparathyroidism and hyperthyroidism, the most common causes of hypercalcaemia.

Measurement of circulating PTH in the serum is the most direct and sensitive measure of parathyroid function. A reference range is 10-60 p/ml. A non-suppressed PTH level in the presence of hypercalcaemia suggests a diagnosis of primary hyperparathyroidism. If the PTH level is suppressed in the face of an elevated calcium level, hyperparathyroidism is unlikely.

Parathyroid hormone-related peptide (PTH-rP) is thought to mediate the hypercalcaemia that develops with many malignancies. Assays to measure this peptide are available.

Other electrolytes also may be disturbed in hypercalcaemia. Serum phosphate levels tend to be low or normal in primary hyperparathyroidism and hypercalcaemia of malignancy. Phosphate levels are elevated in hypercalcaemia secondary to vitamin D–related disorders or thyrotoxicosis. Serum chloride levels usually are higher than 102 mEq/L in hyperparathyroidism and less than this value in other forms of hypercalcaemia.

If laboratory evidence of primary hyperparathyroidism is present, CT scan of the head, MRI, ultrasound or nuclear parathyroid scans may be helpful.

Plain x-rays may reveal demineralisation, pathologic fractures, bone cysts and bone metastases. Renal imaging, ultrasound or IVP may show evidence of calcification or stones.