How to evaluate and manage hypocalcemia?

Evaluation of Hypocalcemia

Measure pH-corrected ionized calcium as your first and most accurate diagnostic test, then immediately check parathyroid hormone (PTH), magnesium, vitamin D (25-OH), and renal function (creatinine) to determine the underlying cause. 1

Initial Diagnostic Workup

Primary Laboratory Tests

• Ionized calcium (pH-corrected) is the gold standard for diagnosis, as total calcium measurements are unreliable in the presence of hypoalbuminemia or acid-base disturbances 1, 2
• PTH level distinguishes PTH-mediated from non-PTH-mediated causes 1, 3
• Magnesium level must be checked, as hypomagnesemia impairs PTH secretion and causes end-organ PTH resistance, making calcium supplementation alone ineffective 1, 4
• 25-hydroxyvitamin D identifies vitamin D deficiency, a common correctable cause 1
• Creatinine/renal function evaluates for chronic kidney disease, which impairs vitamin D activation and causes phosphate retention 1

Secondary Laboratory Tests

• Phosphorus level helps differentiate causes (elevated in hypoparathyroidism and renal failure, low in vitamin D deficiency) 1
• Thyroid function (TSH) should be assessed, as hypothyroidism may be associated with hypocalcemia 1
• Albumin if only total calcium is available, though ionized calcium is preferred 2

Clinical Assessment

Symptom Severity Evaluation

Assess for life-threatening manifestations first: neuromuscular irritability, tetany, seizures, laryngospasm, bronchospasm, and cardiac arrhythmias with QT prolongation 1, 4. These require immediate intravenous calcium administration 4.

• Neuromuscular symptoms: Paresthesias (hands, feet, perioral region), muscle cramps/spasms, Chvostek's sign, Trousseau's sign 1
• Neurological symptoms: Seizures (may be first presentation), confusion, altered mental status, irritability, anxiety, depression 1
• Cardiovascular symptoms: Prolonged QT interval on ECG, cardiac arrhythmias (ventricular tachycardia/fibrillation), rarely cardiomyopathy 1

Risk Factor Identification

• Biological stressors: Recent surgery (especially thyroid/parathyroid), trauma, childbirth, acute illness, infection 1
• Medication history: Loop diuretics, calcium channel blockers, bisphosphonates, calcimimetics 1
• Transfusion history: Massive transfusion causes citrate-induced hypocalcemia 5, 4
• Genetic conditions: 22q11.2 deletion syndrome has 80% lifetime prevalence of hypocalcemia 1
• Dietary/lifestyle factors: Alcohol consumption, carbonated beverages (especially colas), decreased oral calcium intake 1

Etiologic Classification Based on PTH

Low or Inappropriately Normal PTH (Hypoparathyroidism)

• Postsurgical hypoparathyroidism (75% of cases) - most common cause overall 3
• Primary hypoparathyroidism (25% of cases) including autoimmune, genetic disorders 3
• 22q11.2 deletion syndrome - consider in younger patients with recurrent hypocalcemia 1

High PTH (Secondary Hyperparathyroidism)

• Vitamin D deficiency - check 25-OH vitamin D levels 1
• Chronic kidney disease - phosphate retention and impaired vitamin D activation 1
• Malabsorption syndromes 3

Normal PTH with Hypomagnesemia

• Magnesium depletion impairs PTH secretion and creates PTH resistance; must be corrected before calcium normalizes 1, 4

Special Clinical Contexts

Trauma and Massive Transfusion

Monitor ionized calcium closely during massive transfusion, as citrate in blood products chelates calcium 5, 4. Hypocalcemia below 0.9 mmol/L predicts mortality and transfusion requirements better than fibrinogen, acidosis, or platelet count 5.

Chronic Kidney Disease Patients

Use an individualized approach rather than routine correction in dialysis patients, as the EVOLVE trial showed no adverse outcomes with persistently low calcium in patients receiving calcimimetics 1. However, the 2025 KDIGO Controversies Conference shifted away from permissive hypocalcemia due to risks of severe symptomatic hypocalcemia (7-9% incidence) 4.

Post-Parathyroidectomy

Measure ionized calcium every 4-6 hours for the first 48-72 hours, then twice daily until stable 4. This is a high-risk period for severe "hungry bone syndrome."

Critical Pitfalls to Avoid

• Do not rely on total calcium alone - hypoalbuminemia falsely lowers total calcium while ionized calcium may be normal 2
• Do not supplement calcium without checking magnesium first - hypocalcemia will not correct until hypomagnesemia is treated 1, 4
• Do not overlook acid-base status - a 0.1 unit increase in pH decreases ionized calcium by approximately 0.05 mmol/L 5
• Do not miss concurrent hyperphosphatemia - calcium administration when phosphate is high risks calcium-phosphate precipitation in tissues 4
• Do not assume childhood resolution means permanent cure - in 22q11.2 deletion syndrome, hypocalcemia can recur at any age despite apparent childhood resolution 1, 4