Clinical features

Symptoms of hypercalcaemia include:

Diagnosis

The commonest causes of hypercalcaemia are primary hyperparathyroidism and hypercalcaemia of malignancy.

A diagnostic decision chart is shown in Figure 36.1. Primary hyperparathyroidism is most often due to a single parathyroid adenoma, which secretes PTH independently of feedback control by plasma calcium. Hypercalcaemia associated with malignancy is the commonest cause of a high calcium in a hospital population. Some tumours secrete a protein called PTHrP (parathyroid hormone-related protein), which has PTH-like properties.

Rarer causes of hypercalcaemia include:

Treatment

Treatment is urgent if the adjusted serum calcium is greater than 3.5 mmol/L; the priority is to reduce it to a safe level. Intravenous saline is administered first to restore the glomerular filtration rate and promote a diuresis. Although steroids, mithramycin, calcitonin and intravenous phosphate have been used, compounds known as the bisphosphonates have been found to have the best calcium-lowering effects. Bisphosphonates such as pamidronate have become the treatment of choice in patients with hypercalcaemia of malignancy (Fig 36.2). It acts by inhibiting bone resorption.

The cause of the hypercalcaemia should be treated if possible. Surgical removal of a parathyroid adenoma usually provides a complete cure for a patient with primary hyperparathyoidism. Immediately after successful surgery, transient hypocalcaemia may have to be treated with vitamin D metabolites, until the remaining parathyroids begin to operate normally.

Familial hypocalciuric hypercalcaemia

Although a definitive differential diagnosis of hypercalcaemia can often be made, there is one rare condition where a wrong diagnosis can lead to unnecessary surgery. In familial hypocalciuric hypercalcaemia (FHH), a high plasma calcium is sensed by the parathyroids as normal; the patient has normal detectable levels of PTH, despite having hypercalcaemia. There are usually no symptoms of hypercalcaemia, but the patient may be labelled as primary hyperparathyroid, because of the detectable PTH in the face of a high serum calcium. On neck exploration, no parathyroid adenoma is found and it may be discovered subsequently that family members also have asymptomatic hypercalcaemia. Patients with the condition require no treatment; indeed, many would be better off remaining undiagnosed, such is the likelihood of unnecessary surgery.

The hypercalcaemia in FHH may be mild and without symptoms. It is sometimes possible to distinguish this condition from primary hyperparathyroidism on the basis of a urinary calcium excretion, which is inappropriately low for the serum calcium concentration in the patient with FHH. However, in practice, the urinary calcium excretion reference values in both conditions overlap. The possibility of FHH must always be considered when investigating the cause of asymptomatic hypercalcaemia in a relatively young patient.