Hypocalcemia

Definition

Causes / Etiology

1. PTH Deficiency (Hypoparathyroidism)

• Surgical - commonest acquired cause; post-thyroidectomy or parathyroidectomy
• Autoimmune - autoimmune polyglandular deficiency (with adrenal and ovarian failure)
• Hereditary (Idiopathic) - isolated or as part of DiGeorge syndrome (absent thymus + parathyroids)
• Infiltrative - iron/copper deposition, tumour, granuloma

2. PTH Resistance (Pseudohypoparathyroidism / Albright Hereditary Osteodystrophy)

• Defect in the stimulatory G-protein of adenylate cyclase
• PTH is elevated but end-organ unresponsive
• Features: short stature, round face, brachydactyly, extrapyramidal signs, cataracts, subcutaneous calcifications

3. Defective PTH Secretion

• Hypomagnesemia - most important functional cause; impairs both PTH release and target-organ response
• Hypermagnesemia, activating mutations of the calcium-sensing receptor (CaSR), burn injury

4. Vitamin D Deficiency / Resistance

• Inadequate sunlight/dietary intake, malabsorption (small bowel disease)
• Chronic liver or renal disease (impaired 25- and 1-hydroxylation)
• Vitamin D receptor defects

5. Other Causes

• Chronic renal failure - reduced 1,25(OH)2D synthesis + hyperphosphataemia
• Acute pancreatitis - calcium saponification in retroperitoneum
• Hungry bone syndrome - post-parathyroidectomy rapid calcium uptake into bone
• Drugs - heparin, glucagon, protamine, asparaginase, citrated blood (massive transfusion)
• Sepsis, burns, acute renal failure

Clinical Features

Neuromuscular Irritability (hallmark)

• Tetany - the classic manifestation; carpopedal spasm
• Paraesthesias - perioral and peripheral tingling/numbness
• Muscle spasms and cramps
• Laryngeal spasm - can cause stridor and respiratory arrest
• Convulsions / generalized seizures

Bedside Signs

Trousseau sign is more specific; Chvostek sign can be positive in 10% of normal individuals.

Cardiac Effects

• Prolonged QT interval on ECG (most important)
• Low-voltage T waves
• Life-threatening dysrhythmias and cardiac dysfunction (reversible with calcium normalisation)

Neuropsychiatric

• Anxiety, confusion, dementia, psychosis
• Increased intracranial pressure with papilloedema (in PHP)

Chronic Hypocalcemia

• Cataracts (lenticular)
• Calcification of basal ganglia, extrapyramidal signs (choreoathetosis, dystonia)
• Changes in nails and hair; alopecia; candidiasis (in autoimmune hypoparathyroidism)

Diagnosis

1. Serum calcium (total and ionized) - confirm and correct for albumin: Corrected Ca = Total Ca + 0.8 x (4 - albumin g/dL)
2. PTH level - distinguishes hypoparathyroidism (low/absent PTH) from PTH-resistance (elevated PTH)
3. Serum phosphate - elevated in hypoparathyroidism and renal failure; low in vitamin D deficiency
4. Magnesium, vitamin D (25-OH), renal function - to identify underlying cause
5. ECG - QT prolongation
6. Urinary cAMP and phosphaturia after PTH infusion - subnormal response confirms PHP

Treatment

Acute / Severe Hypocalcemia

• IV Calcium gluconate (10 mL of 10% solution over 10-20 min) - treatment of choice
• Monitor ECG during infusion
• Correct concurrent hyperphosphataemia, alkalosis, and hypomagnesemia (refractory hypocalcaemia will not respond until Mg is repleted)

Chronic / Maintenance

• Oral calcium supplements (calcium carbonate or citrate)
• Vitamin D - ergocalciferol (D2) or cholecalciferol (D3); calcitriol (1,25(OH)2D) preferred in hypoparathyroidism and renal failure
• Thiazide diuretics - can be used as adjunct in hypoparathyroid patients (reduce urinary calcium loss)
• Treat the underlying cause (e.g., magnesium replacement, renal disease management)

Summary Table