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Hypercalcaemia of malignancy

Medicine > Endocrine & metabolic

Background knowledge 🧠

Definition

  • Hypercalcaemia of malignancy is a condition characterised by elevated calcium levels in the blood due to cancer.
  • It is often associated with advanced-stage malignancies.
  • Commonly occurs in cancers such as breast, lung, and multiple myeloma.

Epidemiology

  • Occurs in 10-30% of patients with cancer.
  • Most common in patients with breast cancer, lung cancer, and multiple myeloma.
  • Can be a presenting feature of malignancy or occur later in disease progression.

Aetiology and Pathophysiology

  • Tumour secretion of parathyroid hormone-related protein (PTHrP).
  • Osteolytic metastases releasing calcium from bone.
  • Tumour production of calcitriol.
  • Increased bone resorption and decreased renal excretion of calcium.
  • Associated with poor prognosis.

Types

  • PTHrP-mediated hypercalcaemia (most common).
  • Osteolytic hypercalcaemia due to bone metastases.
  • Calcitriol-mediated hypercalcaemia.
  • Ectopic hyperparathyroidism (rare).

Clinical Features 🌡️

Symptoms

  • Nausea and vomiting.
  • Polyuria and polydipsia.
  • Constipation.
  • Muscle weakness.
  • Confusion and lethargy.
  • Bone pain (in cases with bone metastases).

Signs

  • Dehydration.
  • Hypotonia.
  • Hyporeflexia.
  • Arrhythmias on ECG (e.g., shortened QT interval).
  • Altered mental status.
  • Evidence of underlying malignancy.

Investigations 🧪

Tests

  • Serum calcium: elevated total and ionized calcium levels.
  • Serum PTH: usually low or undetectable.
  • Serum PTHrP: elevated in PTHrP-mediated hypercalcaemia.
  • Serum 1,25-dihydroxyvitamin D: elevated in calcitriol-mediated hypercalcaemia.
  • Bone scan or skeletal survey: to detect osteolytic lesions.
  • ECG: to check for arrhythmias.

Management 🥼

Management

  • Aggressive hydration with intravenous normal saline.
  • Bisphosphonates (e.g., zoledronic acid) to inhibit bone resorption.
  • Calcitonin is sometimes used for rapid, short-term reduction in calcium levels.
  • Denosumab for patients refractory to bisphosphonates.
  • Glucocorticoids for calcitriol-mediated hypercalcaemia.
  • Dialysis in severe or refractory cases.
  • Treat underlying malignancy (chemotherapy, radiotherapy).

Complications

  • Kidney injury (acute and chronic).
  • Cardiac arrhythmias.
  • Neurocognitive deficits.
  • Coma.
  • Death if untreated.

Prognosis

  • Depends on the underlying malignancy and response to treatment.
  • Hypercalcaemia of malignancy often indicates advanced disease.
  • Poor prognosis if not promptly managed.
  • Effective management can improve quality of life.
  • Regular monitoring is essential to prevent recurrence.

Key Points

  • Hypercalcaemia of malignancy is common and serious.
  • Early recognition and treatment are crucial.
  • Management includes hydration, bisphosphonates, and treating the underlying cancer.
  • Regular monitoring and follow-up are essential.
  • Multidisciplinary approach improves outcomes.

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Endocrine & metabolic