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Case history

image A 75-year-old man presented to the acute medical unit with a 2 day history of worsening fatigue and confusion on a background of declining health with weight loss and anorexia. On examination he appeared dry with loss of skin turgor and cachexia. He was disorientated in time and place and a mass was felt in his left flank. Biochemistry revealed urea 12.4 mmol/l, creatinine 198 mmol/l and corrected calcium 3.4 mmol/l. A chest X-ray revealed cannonball metastases.

What is the likely diagnosis?

How might a patient with hypercalcaemia present and what is the differential diagnosis?

How should this patient be managed?

What are the recent developments in the management of hypercalcaemia?

What is the likely diagnosis?

The estimated annual prevalence of hypercalcaemia in cancer patients is around 2%.1 Breast carcinoma, renal carcinoma, squamous cell carcinoma, multiple myeloma and lymphomas are the most common malignancies associated with hypercalcaemia. Patients usually have disseminated disease and a poor prognosis with a median length of survival of 3–4 months.

The pathophysiology of hypercalcaemia in malignancy involves an interplay of factors that disrupt normal calcium homeostasis. In many cases, hypercalcaemia may be a consequence of both humoral and tumour-directed osteolytic effects on the bone. In humoral hypercalcaemia of malignancy, the hypercalcaemia is mediated by the tumoral secretion of parathyroid hormone-related protein (PTHrP) that mimics the actions of parathyroid hormone on calcium metabolism. Other mechanisms include overproduction of vitamin D, as seen in haematological cancers such as lymphoma.2 It is important to remember that patients can develop hypercalcaemia without bone involvement.3

How might a patient with hypercalcaemia present and what is the differential diagnosis?

Clinical manifestations are non-specific with a variety of systemic symptoms (Table 32.1); hypercalcaemia is often discovered on a routine blood screen. As the calcium is circulated bound to albumin, the total serum calcium levels could be affected by changes in plasma albumin; therefore, calcium levels need to be corrected for albumin levels. Hypercalcaemia may coexist secondary to primary hyperparathyroidism; hence, levels of calcium and parathyroid hormone should be measured at baseline. A normal or raised level of parathyroid hormone in the presence of a raised calcium level is abnormal and suggests that hyperparathyroidism (primary or tertiary) is the cause of the raised calcium. If the parathyroid hormone level is suppressed, it suggests another cause (such as PTHrP).4 Differential diagnosis includes thiazide diuretics, calcium and vitamin D supplements, granulomatous diseases and lymphoma.

Table 32.1Clinical features of hypercalcaemia.

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