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Case History

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Image not available. A 73-year-old man with a renal cell carcinoma and pulmonary metastases has been under surveillance for three years. He is referred to the surgical assessment unit with a three-day history of abdominal pains associated with constipation, nausea and profound fatigue. On examination the patient appears dry with loss of skin turgor, and he appears to be disorientated in time and place. His biochemistry reveals a urea of 24 mmol/l, creatinine 363 mmol/l and a corrected calcium of 3.4 mmol/l.

What are the causes of hypercalcaemia?

What is the differential diagnosis?

How would you manage this patient?

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Background

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What are the causes of hypercalcaemia?

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Image not available. Around 30% of patients with known malignancy will develop hypercalcaemia at some stage of the disease.1 Breast, lung and renal carcinomas, multiple myeloma and lymphomas are the most common malignancies associated with hypercalcaemia. Patients usually have disseminated disease and this portends a poor prognosis with a median survival of 3–4 months.

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The pathophysiology of hypercalcaemia in malignancy involves an interplay of factors that disrupt the 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 tumor secreting parathyroid hormone-related protein (PTHrP), which 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

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What is the differential diagnosis?

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Clinical manifestations are non-specific with a variety of systemic symptoms (Table 39.1) and hypercalcaemia is often discovered on a routine blood screen. As circulating calcium is bound to albumin the total serum calcium levels can be affected by changes in plasma albumin; therefore, calcium levels need to be corrected for albumin levels. Hypercalcaemia may be secondary to primary hyperparathyroidism, hence, calcium and PTH should be measured at baseline. A normal or raised PTH in the presence of a raised calcium is abnormal and suggests hyperparathyroidism (primary or tertiary) as the cause of the raised calcium. If PTH is suppressed then it suggests another cause, such as PTHrP.4 Other differential diagnoses include thiazide diuretics, granulomatous diseases and lymphoma.

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Table Graphic Jump Location
Table 39.1Clinical features of hypercalcaemia
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How would you manage this patient?

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Withdraw thiazide diuretics and sources of vitamin A and vitamin D. The majority of patients with significant hypercalcaemia have ...

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