Hypercalcemia

Hypercalcaemia is the most common life threatening metabolic disorder encountered in patients with cancer. The incidence varies with the underlying malignancy, being most common in multiple myeloma and breast cancer (40–50%), less so in non-small cell lung cancer, and rare in small cell lung cancer and colorectal cancer.

It is important to remember the existence of non-malignant causes of hypercalcaemia—particularly primary hyperparathyroidism, which is prevalent in the general population.

The pathology of hypercalcaemia is mediated by factors such as parathyroid related protein, prostaglandins, and local interaction by cytokines such as interleukin 1 and tumour necrosis factor. Bone metastases are commonly but not invariably present.

Management

Mild hypercalcaemia (corrected serum calcium concentration ≤3.00 mmol/1) is usually asymptomatic, and treatment is required only if a patient has symptoms. For more severe hypercalcaemia, however, treatment can markedly improve symptoms even when a patient has advanced disease and limited life expectancy to make the end stages less traumatic for the patient and carers.

Treatment with bisphosphonate normalises the serum calcium concentration in 80% of patients within a week. Treatment with calcitonin or mithramycin is now largely obsolete. Corticosteroids are probably useful only when the underlying tumour is responsive to this cytostatic agent—such as myeloma, lymphoma, and some carcinomas of the breast.

Some symptoms, particularly confusion, may be slow to improve after treatment, despite normalisation of the serum calcium concentration. Always consider treating the underlying malignancy to prevent recurrence of symptoms as the median duration of normocalcaemia after bisphosphonate infusion is only three weeks. If effective systemic therapy has been exhausted, or is deemed inappropriate, however, oral bisphosphonates (such as clodronate 800 mg twice daily) or parenteral infusions (every three to four weeks) should be

Major emergencies in palliative care

Hypercalcaemia
Obstruction of superior vena cava
Spinal cord compression
Bone fractures
Other emergencies, such as haemorrhage and acute anxiety and depression, are discussed elsewhere in this series

Questions to ask when considering management of emergencies in patients with advanced disease

What is the problem?
Can it be reversed?
What effect will reversal of the symptom have on a patient’s overall condition?
What is your medical judgment?
What does the patient want?
What do the carers want?
Could active treatment maintain or improve this patient’s quality of life?

Presenting features of hypercalcaemia

Mild symptoms	Severe symptoms and signs
Nausea Anorexia and vomiting Constipation Thirst and polyuria	Gross dehydration Drowsiness Confusion and coma Abnormal neurology Cardiac arrhythmias

Management of hypercalcaemia

Check serum concentration of urea, electrolytes, albumin, and calcium
Calculate corrected calcium concentration
Corrected Ca = measured Ca+ (40–albumin) × 0.02 mmol/1
Corrected calcium value is used for decisions about treatment
Rehydrate with intravenous fluid (0.9% saline)
Amount and rate depends on clinical and cardiovascular status and concentrations of urea and electrolytes
After a minimum of 2 L of intravenous fluids give bisphosphonate infusion
Disodium pamidronate 90 mg over 2 hours or Sodium clodronate 1500 mg over 4 hours or Zoledronic acid 4 mg over 15 minutes
Measure concentrations of urea and electrolytes at daily intervals and give intravenous fluids as necessary
Normalisation of serum calcium takes 3–5 days
Do not measure serum calcium for at least 48 hours after
rehydration as it may rise transiently immediately after treatment
Prevent recurrence of symptoms
Treat underlying malignancy if possible or
Consider maintenance treatment with bisphosphonates and monitor serum calcium every three weeks or
Monitor serum calcium every three weeks or less if the patient
has symptoms, and repeat bisphosphonate infusion asappropriate considered.

Maintenance intravenous bisphosphonates may be administered at a day centre or outpatient department. Oral preparations have the disadvantages of being poorly absorbed and have to be taken at least an hour before or after food. A recent systematic review suggests there is more evidence to support the intravenous route.

Obstruction of superior vena cava

This may arise from occlusion by extrinsic pressure, intraluminal thrombosis, or direct invasion of the vessel wall. Most cases are due to tumour within the mediastinum, of which up to 75% will be primary bronchial carcinomas. About 3% of patients with carcinoma of the bronchus and 8% of those with lymphoma will develop obstruction.

Aetiology of obstruction of superior vena cava

Carcinoma of the bronchus	65–80%
Lymphoma	2–10%
Other cancers	3–13%
Benign causes (now rare)	Benign goiter, aortic aneurysm (syphilis), thrombotic syndromes, idiopathic sclerosing mediastinitis
Unknown or undiagnosed	5%