Hypercalcaemia ✅

Related Subjects: | Familial Hypocalciuric Hypercalcaemia (FHH) | Primary Hyperparathyroidism | Lung Cancer | Hypercalcaemia | Multiple Myeloma | Oncological Emergencies | Bisphosphonates

🚑 Hypercalcaemia Emergency Management – Ward Algorithm

Hypercalcaemia severity (albumin-adjusted calcium):

• 🟢 Mild: 2.6–3.0 mmol/L
• 🟠 Moderate: 3.0–3.5 mmol/L
• 🔴 Severe: >3.5 mmol/L (medical emergency)

1️⃣ Immediate Clinical Assessment

• Perform ABCDE assessment. Assess hydration status and fluid balance.
• Check for neurological symptoms: Confusion, Lethargy, Delirium, Reduced GCS
• Look for dehydration signs: Dry mucous membranes, Tachycardia, Postural hypotension
• Record baseline observations and urine output.
• Perform ECG monitoring. Look for Short QT interval, Occasionally heart block or ventricular arrhythmias

2️⃣ Confirm the Diagnosis

• Check albumin-adjusted serum calcium.
• Repeat calcium if unexpected or borderline.
• Assess severity category to guide urgency of treatment.

3️⃣ First-Line Treatment – Volume Expansion

• 💧 Start IV 0.9% saline. Typical replacement: 2–4 litres within the first 24 hours
• Adjust according to age, renal function, and heart failure risk
• Aim to restore intravascular volume and promote renal calcium excretion.
• Monitor: Fluid balance, Urine output, Daily weights if needed
• Loop diuretics should NOT be used routinely but may be useful if fluid overload develops.

4️⃣ Investigate the Underlying Cause

🧪 The most important early branching test in hypercalcaemia is parathyroid hormone (PTH). If PTH is high or inappropriately normal, think primary/tertiary hyperparathyroidism. If PTH is suppressed, think malignancy, myeloma, vitamin D excess, granulomatous disease, drugs or other endocrine causes.

NICE NG132 says that to differentiate primary hyperparathyroidism from familial hypocalciuric hypercalcaemia (FHH), measure urine calcium excretion using one of: 24-hour urinary calcium excretion, random renal calcium:creatinine excretion ratio, or random calcium:creatinine clearance ratio.

• 🧪 Confirm and assess severity:
  • Repeat corrected calcium or ionised calcium if available
  • Albumin, Urea & electrolytes, TFTs, eGFR, Phosphate, Magnesium, Glucose
  • ECG if moderate/severe hypercalcaemia or cardiac symptoms
  • PTH, Vitamin D ALP , FBC , ESR or CRP, LFTs
  • Myeloma / malignancy screen: Serum protein electrophoresis and Serum free light chains. Urine Bence Jones protein / urine electrophoresis where used locally.
  • Consider CXR, CT imaging or cancer-specific tests depending on symptoms and examination
• 💊 Medication and supplement review:
  • Thiazide diuretics, Lithium, Calcium supplements
  • Vitamin D or vitamin A excess
  • Antacids / calcium carbonate preparations
• 🦴 If PTH is high or inappropriately normal:
  • Consider primary hyperparathyroidism
  • Consider tertiary hyperparathyroidism in advanced CKD
  • Check urinary Ca excretion / calcium-creatinine clearance ratio if familial hypocalciuric hypercalcaemia is possible
  • Consider bone density assessment, renal stones history and renal tract imaging depending on context
  • Check PTHrP when hypercalcaemia looks PTH-independent, especially when malignancy is suspected.
• 🌫️ If PTH is suppressed:
  • Consider malignancy, myeloma, bone metastases or PTHrP-mediated hypercalcaemia
  • Consider granulomatous disease such as sarcoidosis or TB
  • Consider thyrotoxicosis, adrenal insufficiency, immobilisation or vitamin D toxicity
  • Additional tests may include PTHrP, 1,25-dihydroxyvitamin D, ACE level, TFTs, cortisol or imaging, guided by clinical suspicion
• 🫁 Imaging if malignancy suspected: Chest X-ray, CT scan where indicated

🧠 Teaching point: PTH should be suppressed when calcium is high. A “normal” PTH in hypercalcaemia is therefore abnormal, because it is inappropriately normal and suggests PTH-driven disease.

PTH interpretation:

• ⬆️ Calcium + ⬆️ or normal PTH → Primary hyperparathyroidism
• ⬆️ Calcium + ⬇️ PTH → Malignancy, vitamin D excess, granulomatous disease

5️⃣ Second-Line Treatment – Anti-resorptive Therapy

• 💉 Give an IV bisphosphonate once the patient is adequately hydrated.
• Zoledronic acid 4 mg IV over ~15 minutes
• Pamidronate 60–90 mg IV over 2–4 hours
• Effects: Onset: 24–48 hours Peak calcium reduction: 4–7 days
• Use with caution in renal impairment.

6️⃣ Additional Therapies (Selected Cases)

• Calcitonin Produces rapid calcium reduction. Effect begins within hours. Short-lived (tachyphylaxis occurs)
• Glucocorticoids: Useful in: Sarcoidosis, Lymphoma, Vitamin D intoxication
• Denosumab: Used in bisphosphonate-resistant malignancy-associated hypercalcaemia. Also useful in severe renal impairment

7️⃣ Management of Severe or Refractory Hypercalcaemia

• Consider dialysis if: Severe hypercalcaemia (>3.5–4 mmol/L), Renal failure, Fluid overload preventing hydration
• Seek urgent specialist input: Endocrinology, Oncology, Renal team

8️⃣ Definitive Treatment

• Management ultimately depends on the underlying cause.
• Common treatments include:
  • Parathyroidectomy for primary hyperparathyroidism
  • Oncological therapy for malignancy
  • Steroids for granulomatous disease
  • Stopping causative drugs (e.g. thiazides, vitamin D excess)

🚑 Hypercalcaemia Emergency Algorithm (Ward Management)

🎓 Exam Tips – Hypercalcaemia

• 👉 Primary hyperparathyroidism is the most common cause of hypercalcaemia in the community.
• 👉 Malignancy is the most common cause of severe hypercalcaemia in hospital.
• 👉 Always check PTH first when investigating hypercalcaemia.
• 👉 The ECG change classically associated with hypercalcaemia is short QT interval.
• 👉 IV saline hydration is the first-line treatment before giving bisphosphonates.
• 👉 Hypercalcaemia symptoms are remembered by the phrase: "Bones, Stones, Groans, and Psychiatric Overtones".