Hypercalcaemia of Malignancy

Related Subjects: |Hypercalcaemia of Malignancy

🧪 Hypercalcaemia of malignancy is the most common paraneoplastic endocrine emergency, affecting 10–30% of patients with advanced cancer. It is usually a late manifestation, associated with poor prognosis (median survival ≈ 1–3 months). ⚠️ If untreated, it can rapidly lead to dehydration, renal failure, arrhythmias, coma, and death.

📊 Calcium Conversion

To convert US units (mg/dL) ➝ UK units (mmol/L), multiply by 0.25

📖 Pathophysiology - Four Main Mechanisms

• 🧬 Humoral hypercalcaemia of malignancy (HHM) - Most common (~80%). Caused by tumour secretion of PTH-related peptide (PTHrP), mimicking PTH → ↑ bone resorption & renal Ca²⁺ reabsorption (classically squamous cell lung carcinoma, renal, bladder cancers).
• 🦴 Local osteolytic hypercalcaemia - Direct bone invasion/osteolysis from metastases (e.g. breast cancer, multiple myeloma).
• ☀️ Excess calcitriol production - Certain lymphomas secrete excess 1,25(OH)₂ vitamin D → ↑ gut calcium absorption.
• ⚡ Ectopic PTH secretion - Rare, but causes genuine PTH-driven hypercalcaemia.

👩‍⚕️ Clinical Features - “Stones, Bones, Groans, Moans, & Cardiac Tones”

• 💧 Stones: Polyuria, polydipsia, dehydration, renal calculi.
• 🦴 Bones: Bone pain, pathological fractures.
• 🤢 Groans: Nausea, vomiting, constipation, abdominal pain, pancreatitis.
• 🧠 Moans: Fatigue, confusion, drowsiness, coma.
• ⚡ Cardiac: Shortened QT interval, arrhythmias.

🔎 Diagnosis

• 🩸 Corrected serum calcium: Adjust for albumin. Hypercalcaemia >2.62 mmol/L.
• 🔬 Ionised calcium: >1.32 mmol/L (more accurate in critical illness).
• 📊 U&E, creatinine - assess renal function (often impaired).
• 🧪 PTH (suppressed in malignancy-associated cases).
• Special tests: PTHrP, calcitriol (lymphoma).
• 📸 Imaging (X-ray/CT/MRI) - look for lytic lesions or primary tumour.

💊 Emergency Management

• 💧 Aggressive IV hydration: 0.9% NaCl (3–4 L/24 h if tolerated) to restore intravascular volume & enhance renal calcium excretion.
• ⚡ IV bisphosphonates: Zoledronic acid (first-line), pamidronate. Inhibit osteoclasts; onset 48–72 h.
• 🧪 Calcitonin: Rapid but short-lived calcium reduction - useful as bridging therapy.
• 🦴 Denosumab: Effective in refractory cases or renal impairment (anti-RANKL antibody).
• 💊 Glucocorticoids: In lymphoma/myeloma to suppress calcitriol production.
• 🧾 Dialysis: Reserved for severe/refractory hypercalcaemia with renal failure.
• 🎯 Definitive: Treat underlying cancer (chemo, radiotherapy, surgery) if appropriate.

⚠️ Prognosis

• Late feature in cancer trajectory; median survival ≈ 1–3 months.
• Often heralds incurable disease; emphasis may shift to palliative care after stabilisation.

🧑‍⚕️ Case Examples

• Case 1: 👩 65F with metastatic breast cancer presents with confusion & constipation. Corrected Ca²⁺ = 3.5 mmol/L, suppressed PTH. Managed with IV saline & zoledronic acid → improved in 72 h.
• Case 2: 👨 58M with squamous cell lung carcinoma, bone pain, polyuria, dehydration. Ca²⁺ 3.2 mmol/L, low PTH, ↑ PTHrP. Treated with fluids + calcitonin + denosumab (renal impairment). Prognosis poor → referred to palliative oncology.
• Case 3: 🫁 65M smoker, fatigue, constipation, confusion. Ca²⁺ 3.2 mmol/L, low PTH, hilar lung mass. Diagnosis: PTHrP-mediated hypercalcaemia. Managed with IV fluids, bisphosphonates, and oncology referral.
• Case 4: 🦴 70F with bone pain, anaemia, recurrent infections. Ca²⁺ 3.0 mmol/L, paraprotein, multiple lytic lesions. Diagnosis: Myeloma-related hypercalcaemia. Managed with fluids, bisphosphonates, systemic myeloma therapy.