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Hypercalcaemia of Malignancy

Table of Contents

  • Introduction
  • Aetiology
  • Risk Factors
  • Clinical Features
  • Investigations
  • Management
  • Complications
  • References
  • Related Notes
  • Test Yourself

Key Points ⚡

  • Hypercalcaemia: adjusted serum calcium > 2.6 mmol/L.
  • Common causes in malignancy: PTHrP secretion (most frequent, associated with renal, ovarian, endometrial cancers, squamous cell carcinoma), osteolytic metastases (breast cancer, multiple myeloma), calcitriol secretion (lymphomas).
  • Risk factors include multiple myeloma, breast, lung (SCC), renal, thyroid cancers, and lymphomas.
  • Symptoms: confusion, nausea, vomiting, fatigue, thirst, polyuria, constipation, anorexia, bone & abdominal pain, renal colic.
  • Examination: signs of dehydration, hyporeflexia, muscle weakness, abdominal distension, bony tenderness.
  • Investigations: adjusted calcium >2.6 mmol/L; severity: mild (<3.0), moderate (3-3.5), severe (>3.5 mmol/L).
  • Management: IV rehydration, bisphosphonates (zoledronic acid preferred), supportive meds for symptoms, stop contributing drugs.
  • Complications: AKI, pancreatitis, arrhythmias, seizures, coma; poor prognosis (mean survival 2-3 months).

Introduction

  • Hypercalcaemia of malignancy is a common and life-threatening metabolic complication in advanced cancer patients (10-20%).
  • It results from increased calcium due to tumour-related mechanisms.

Aetiology

Mechanisms

  1. PTHrP secretion (most common): from renal, ovarian, endometrial cancers and SCC. Stimulates osteoclastic bone resorption and reduces renal calcium clearance.
  2. Osteolytic metastases: breast cancer and multiple myeloma cause local bone destruction releasing calcium.
  3. Calcitriol secretion: lymphomas overexpress 1-alpha hydroxylase, increasing calcitriol and calcium absorption.

Risk Factors

  • Malignancies: multiple myeloma, breast cancer, lung SCC, renal cancer, thyroid SCC, lymphomas.
  • Medications worsening hypercalcaemia: thiazide diuretics, lithium, calcium/vitamin D supplements.

Clinical Features

History

  • Vague symptoms often present: confusion, nausea, vomiting, fatigue, increased thirst and urination (due to nephrogenic diabetes insipidus), constipation, anorexia, bone and abdominal pain, renal colic.
  • Remember "stones, bones, groans, and psychiatric moans."
  • Mild hypercalcaemia may be asymptomatic.

Examination

  • Dehydration: dry mucosa, sunken eyes, poor skin turgor.
  • Hyporeflexia, muscle weakness, tongue fasciculations.
  • Abdominal distension (constipation), bony tenderness.
  • Usually no lymphadenopathy or hepatosplenomegaly.

Investigations

  • Adjusted serum calcium: >2.6 mmol/L abnormal. Categorise severity:
  • Mild: <3.0 mmol/L
  • Moderate: 3.0–3.5 mmol/L

  • Severe: >3.5 mmol/L

  • Bedside: ECG (bradycardia, shortened QT, heart block).

  • Laboratory:
  • Urea & electrolytes to assess renal function.
  • PTH (usually suppressed in malignancy-related hypercalcaemia).
  • PTHrP (if PTH low).
  • Phosphate (may be low).
  • Calcitriol (in lymphoma cases).
  • Vitamin D levels.

  • Immunoglobulins and electrophoresis (if multiple myeloma suspected).

  • Imaging:

  • Chest X-ray (lung cancer suspicion).
  • CT scan for tumour staging or bone metastases.

Management

  • Supportive care:
  • Treat symptoms (laxatives for constipation, antiemetics, analgesia).
  • Stop exacerbating drugs (thiazides, calcium/vitamin D supplements, lithium).

  • Review meds impairing renal function (NSAIDs, ACE inhibitors).

  • Rehydration:

  • IV fluids to correct dehydration, improve renal calcium clearance.

  • Outpatient management possible for asymptomatic mild cases, but most require admission.

  • Bisphosphonates:

  • IV zoledronic acid preferred (dose adjusted for renal function).
  • Onset delayed; do not repeat before 5 days.
  • Monitor calcium; if persistent hypercalcaemia after 7 days, consider additional doses or denosumab.
Drug Dose (IV) Notes
Zoledronic acid 4 mg Adjust dose per renal function
Disodium pamidronate 30-90 mg (depending on calcium)

Complications

  • Acute kidney injury (AKI)
  • Acute pancreatitis
  • Cardiac arrhythmias
  • Seizures, coma
  • Poor prognosis, mean survival 2-3 months, indicating advanced cancer stage rather than direct calcium toxicity.

References

  • BMJ Best Practice. Hypercalcaemia of malignancy. 2023.
  • Scottish Palliative Care Guidelines. Hypercalcaemia. 2021.
  • RCEM Learning. Hypercalcaemia in malignancy. 2021.
  • NICE CKS. Hypercalcaemia: What is the prognosis? 2019.
  • Anal Cancer and Anal Intraepithelial Neoplasia (AIN)
  • Brain Tumours
  • Breast Cancer
  • Laryngeal Cancer
  • Malignant Spinal Cord Compression (MSCC)

Test Yourself

  • [Link to clinical questions and self-assessment on hypercalcaemia of malignancy]

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