Primary hyperparathyroidism and malignancy account for approximately 90% of all hypercalcaemia. The clinical distinction is critical because management differs fundamentally. PTH level is the key discriminator: PTH elevated or inappropriately normal = primary hyperparathyroidism; PTH suppressed (low) = malignancy or other non-PTH cause. Always send PTH, PTHrP, 25-OH vitamin D, and 1,25-dihydroxyvitamin D together.

Hypercalcaemia causes a vicious cycle of dehydration: (1) Calcium impairs renal concentrating ability (nephrogenic diabetes insipidus), causing polyuria. (2) Hypercalcaemia causes nausea and vomiting, reducing fluid intake. (3) Dehydration reduces GFR, decreasing renal calcium excretion. (4) Higher serum calcium worsens symptoms further. Aggressive IV saline hydration breaks this cycle by restoring GFR and promoting calciuresis. This is always Step 1, regardless of severity.

Zoledronic acid (Zometa) 4 mg IV over 15 minutes is the most potent bisphosphonate available. It inhibits osteoclast-mediated bone resorption. However, its onset is 2 to 4 days (peak effect at 4 to 7 days). This is why calcitonin is used as a bridge (onset 4 to 6 hours) while waiting for bisphosphonate effect. Duration: 2 to 4 weeks per dose.

Alternative: Pamidronate 60 to 90 mg IV over 2 to 4 hours. Slightly less potent but available at lower cost in Indian hospitals.

The classic mnemonic for hypercalcaemia symptoms: Stones (nephrolithiasis, nephrocalcinosis) · Bones (bone pain, osteitis fibrosa cystica, pathological fractures) · Groans (abdominal pain, constipation, nausea, pancreatitis, peptic ulcer disease) · Psychiatric overtones (anxiety, depression, confusion, psychosis, coma). Also: polyuria, polydipsia, shortened QT, band keratopathy.

In Indian hospitals, tuberculosis is an important and often overlooked cause of hypercalcaemia. Activated macrophages in granulomata express 1-alpha hydroxylase, converting 25-OH vitamin D to active 1,25-dihydroxyvitamin D independently of PTH regulation. The result: unregulated calcium absorption. Check 1,25-dihydroxyvitamin D (will be high) and PTH (will be suppressed). Treatment: corticosteroids (Prednisolone 20 to 40 mg/day) rapidly reduce 1,25-D production and lower calcium. Also seen in sarcoidosis, Wegener granulomatosis, and fungal infections.