What is the evaluation and treatment approach for a patient with hypocalcemia?

Evaluation of Hypocalcemia

Initial Diagnostic Workup

Measure pH-corrected ionized calcium as the most accurate diagnostic test, followed by parathyroid hormone (PTH), magnesium, phosphate, creatinine, and 25-hydroxyvitamin D levels to determine the underlying etiology. 1

Essential Laboratory Tests

• Ionized calcium (pH-corrected) is the gold standard for diagnosis, as total calcium can be misleading due to albumin binding 1
• PTH level distinguishes hypoparathyroidism (low/inappropriately normal PTH) from other causes (elevated PTH) 1
• Magnesium level must be checked in all hypocalcemic patients, as hypomagnesemia causes hypocalcemia through impaired PTH secretion and end-organ PTH resistance 1, 2
• Serum phosphate helps differentiate causes: elevated in hypoparathyroidism, low in vitamin D deficiency 1
• Renal function (creatinine) evaluates for chronic kidney disease as a contributing factor 1
• 25-hydroxyvitamin D assesses vitamin D stores 1

Additional Diagnostic Studies

• Electrocardiogram to evaluate for QT prolongation, which predicts risk for cardiac arrhythmias including torsades de pointes 1, 2
• Thyroid function tests (TSH) annually in at-risk populations, as hypothyroidism may be associated 1

Clinical Assessment

Symptom Recognition

The severity of symptoms guides urgency of treatment:

• Neuromuscular symptoms: Paresthesias (perioral, hands, feet), muscle cramps/spasms, tetany, Chvostek's and Trousseau's signs 1, 3
• Severe manifestations: Seizures, laryngospasm, bronchospasm, altered mental status 1, 3
• Cardiovascular: QT prolongation, arrhythmias (ventricular tachycardia/fibrillation), rarely cardiomyopathy 1, 2
• Neuropsychiatric: Irritability, anxiety, depression, confusion 1

Risk Factor Identification

• Post-surgical hypoparathyroidism accounts for 75% of all hypoparathyroidism cases (thyroidectomy, parathyroidectomy) 1
• Biological stress periods: Surgery, childbirth, infection, acute illness, puberty, pregnancy 1
• Medications: Loop diuretics, bisphosphonates, denosumab, calcium channel blockers 1
• Chronic kidney disease: Phosphate retention and impaired vitamin D activation 1
• Genetic syndromes: 22q11.2 deletion syndrome has 80% lifetime prevalence of hypocalcemia 1
• Lifestyle factors: Alcohol consumption, carbonated beverages (especially colas) 1

Etiologic Classification

PTH-Mediated Causes (Low/Inappropriately Normal PTH)

• Post-surgical hypoparathyroidism (75% of cases) 1
• Primary hypoparathyroidism (25% of cases): autoimmune, genetic (22q11.2 deletion), infiltrative disorders 1

Non-PTH-Mediated Causes (Elevated PTH)

• Vitamin D deficiency or impaired metabolism 1
• Chronic kidney disease: Reduced 1,25-dihydroxyvitamin D production and phosphate retention 1
• Hypomagnesemia: Present in 28% of hypocalcemic patients 4, 2
• Hungry bone syndrome: Post-parathyroidectomy rapid bone remineralization 1
• Medication-induced: Bisphosphonates, denosumab, foscarnet 1

Special Clinical Contexts

• Massive transfusion: Citrate in blood products chelates calcium; hypocalcemia <0.9 mmol/L predicts mortality better than fibrinogen, acidosis, or platelet count 1, 4
• Tumor lysis syndrome: Phosphate release causes calcium-phosphate precipitation 4

Critical Diagnostic Pitfall

Always check and correct magnesium first—calcium replacement will be completely ineffective without magnesium correction, as hypomagnesemia impairs both PTH secretion and end-organ PTH response. 4, 2 The European Society of Cardiology explicitly emphasizes that calcium administration without magnesium correction is futile. 2

Monitoring During Evaluation

• Continuous cardiac monitoring during acute symptomatic hypocalcemia 4, 2
• Serial ionized calcium measurements every 4-6 hours in acute settings 4
• Post-parathyroidectomy: Measure ionized calcium every 4-6 hours for first 48-72 hours, then twice daily until stable 4

Special Population Considerations

• 22q11.2 deletion syndrome patients require heightened surveillance during stress periods and have 80% lifetime hypocalcemia risk 1
• CKD patients: Individualized approach rather than routine correction; maintain calcium in low-normal range (8.4-9.5 mg/dL) 4
• Patients on calcimimetics: Recent paradigm shift away from permissive hypocalcemia due to 7-9% severe hypocalcemia risk 4