Makindo Medical Notes

🧪 Hypercalcaemia of Malignancy is the most common paraneoplastic endocrine emergency. It occurs in ~20–30% of patients with advanced cancer and signals a poor prognosis. ⚠️ Untreated, it can rapidly cause dehydration, renal failure, arrhythmias, and coma.

📖 Pathophysiology

• 🦴 Osteolytic metastases (e.g. breast cancer, myeloma) → direct bone resorption by tumour cells.
• 🧬 PTH-related peptide (PTHrP) secretion → mimics PTH, ↑ bone resorption & renal calcium reabsorption (seen in squamous cell carcinoma of lung, renal, bladder cancers).
• ☀️ Excess calcitriol (1,25-dihydroxy-vitamin D) → seen in some lymphomas.
• ⚡ Rarely, ectopic PTH secretion.

👩‍⚕️ Clinical Features ("Stones, Bones, Groans, Moans")

• 💧 Stones: Polyuria, polydipsia, dehydration, renal stones.
• 🦴 Bones: Bone pain, pathological fractures (esp. lytic metastases).
• 🤢 Groans: Nausea, vomiting, constipation, abdominal pain, pancreatitis.
• 🧠 Moans: Fatigue, confusion, drowsiness, coma.
• ⚡ Cardiac: Short QT interval, arrhythmias.

🔎 Investigations

• 🩸 Serum corrected calcium (adjusted for albumin).
• 📊 Renal profile: U&E, creatinine (renal impairment common).
• 🧪 PTH (low in malignancy-related hypercalcaemia).
• 🔬 PTHrP (specialised testing, not routine).
• 📸 Imaging: X-ray/CT/MRI to identify lytic lesions or primary tumour.

💊 Management (Emergency)

• 💧 IV Fluids: Aggressive rehydration with 0.9% NaCl (3–4 L/24 h if tolerated).
• ⚡ IV Bisphosphonates: Zoledronic acid (first-line), pamidronate — inhibit osteoclast activity (take 48–72 h for full effect).
• 🧪 Calcitonin: Rapid but short-acting calcium reduction (used if severe or symptomatic while bisphosphonates take effect).
• 🦴 Denosumab: Useful if refractory to bisphosphonates or renal impairment present.
• 💊 Glucocorticoids: For lymphoma/myeloma (reduce calcitriol production).
• 🎯 Treat the underlying malignancy: chemotherapy, radiotherapy, surgery.

⚠️ Prognosis

• Occurs late in cancer trajectory; median survival ≈ 1–3 months.
• Often a marker of advanced, incurable disease.
• Focus may shift to palliative care once acute management is stabilised.

🧑‍⚕️ Case Examples

Case 1: 👩 A 65-year-old woman with metastatic breast cancer presents with worsening confusion, nausea, and constipation. 🩸 Corrected calcium = 3.5 mmol/L. PTH suppressed. ✅ Managed with IV saline rehydration and zoledronic acid, with symptomatic improvement in 72 h.

Case 2: 👨 A 58-year-old man with squamous cell carcinoma of the lung presents with polyuria, bone pain, and dehydration. 🧪 Calcium = 3.2 mmol/L, low PTH, high PTHrP. ✅ Treated with IV fluids, calcitonin for rapid relief, and denosumab (renal impairment prevented bisphosphonate use). ⚠️ Prognosis poor → referred for palliative oncology input.