SN4 SHORT NOTE 5M

Write a short note on hypercalcaemia.

General Medicine · Final Professional

Definition

Hypercalcaemia is a corrected serum calcium above 10.5 mg/dL (2.6 mmol/L). Because approximately 40% of calcium is albumin-bound, the value must be corrected: add 0.8 mg/dL to the measured calcium for every 1 g/dL that albumin falls below 4 g/dL. Ionised calcium is the physiologically active fraction and is measured directly where available.

Severity: mild (up to 12 mg/dL), moderate (12–14), and severe (> 14 mg/dL — hypercalcaemic crisis).

Causes

Over 90% of cases are due to primary hyperparathyroidism or malignancy — the first step is to separate these two.

Category	Causes	PTH
Primary hyperparathyroidism	Parathyroid adenoma (85%), hyperplasia, carcinoma; MEN 1 and 2A	High or inappropriately normal
Malignancy	PTHrP secretion (squamous cell lung, renal, breast); osteolytic metastases (breast, myeloma, lymphoma); calcitriol production by lymphoma	Suppressed (low)
Granulomatous disease	Sarcoidosis, tuberculosis, histoplasmosis — via extrarenal 1-alpha-hydroxylase producing calcitriol	Low
Drugs	Thiazides, lithium, vitamin D or vitamin A excess, calcium and antacid excess (milk-alkali syndrome)	Variable
Endocrine	Thyrotoxicosis, phaeochromocytoma, adrenal insufficiency	Low
Other	Immobilisation, Paget's disease with immobility, familial hypocalciuric hypercalcaemia, tertiary hyperparathyroidism in CKD	Variable

Clinical Features

"Stones, Bones, Abdominal Groans, Psychic Moans" — plus thirst

Stones = renal calculi, nephrocalcinosis, nephrogenic diabetes insipidus with polyuria and polydipsia, renal impairment

Bones = bone pain, osteitis fibrosa cystica, pathological fracture, brown tumours, osteoporosis

Abdominal groans = anorexia, nausea, vomiting, constipation, peptic ulceration, pancreatitis

Psychic moans = fatigue, depression, poor concentration, confusion, and in severe cases stupor and coma

Cardiac = shortened QT interval, bradycardia, hypertension, and increased sensitivity to digoxin

Dehydration is central to the clinical picture: hypercalcaemia causes nephrogenic diabetes insipidus, and the resulting polyuria worsens volume depletion, which in turn reduces calcium excretion — a vicious cycle that drives the crisis.

Investigations

Corrected calcium (repeat to confirm), phosphate, albumin, alkaline phosphatase, urea and creatinine, magnesium.
Intact PTH — the single most important test. A raised or inappropriately normal PTH indicates hyperparathyroidism; a suppressed PTH directs the search toward malignancy or another cause.
If PTH is suppressed: PTHrP, 25-OH and 1,25-(OH)2 vitamin D, serum and urine protein electrophoresis with free light chains (myeloma), chest X-ray and CT for malignancy and sarcoidosis, and serum ACE.
24-hour urinary calcium — low in familial hypocalciuric hypercalcaemia, distinguishing it from primary hyperparathyroidism and sparing the patient unnecessary surgery.
ECG (short QT), DEXA scan, renal ultrasound for calculi, and sestamibi scan with neck ultrasound to localise a parathyroid adenoma.

Management

Severe or symptomatic hypercalcaemia is a medical emergency.

1. Aggressive intravenous rehydration with isotonic saline — the first and most important step. It restores volume, increases glomerular filtration and promotes calciuresis. Monitor for fluid overload in the elderly and in cardiac or renal disease.

2. Loop diuretics — only after the patient is fully rehydrated, and now used selectively rather than routinely, mainly to manage fluid overload.

3. Bisphosphonates (zoledronic acid, pamidronate) — the mainstay for malignancy-associated hypercalcaemia; inhibit osteoclastic resorption. Onset is delayed 2–4 days, so they do not replace fluids acutely. Adjust for renal function.

4. Calcitonin — rapid but modest and short-lived effect (tachyphylaxis within 48 hours); useful as a bridge while awaiting bisphosphonate action.

5. Corticosteroids — effective in granulomatous disease, vitamin D intoxication and haematological malignancy by reducing calcitriol production.

6. Denosumab — for bisphosphonate-refractory disease or significant renal impairment.

7. Haemodialysis — for severe hypercalcaemia with renal failure or heart failure.

8. Stop contributing drugs — thiazides, lithium, calcium and vitamin D supplements; mobilise the patient.

9. Definitive treatment: parathyroidectomy for primary hyperparathyroidism; treatment of the underlying malignancy.

CLINICAL PEARL

Fluids first, always. The instinct to reach for a bisphosphonate is wrong — these patients are profoundly volume-depleted, and saline rehydration alone often lowers calcium substantially within hours, whereas bisphosphonates take days. Avoid thiazides, which reduce calcium excretion, and avoid immobilisation, which increases bone resorption.

All questions in Fluids & Electrolytes

Every General Medicine chapter →