Laboratory Workup for Hypocalcemia
The initial laboratory workup for hypocalcemia should include ionized calcium (or corrected total calcium), parathyroid hormone (PTH), phosphorus, magnesium, creatinine, and 25-hydroxyvitamin D levels to determine both severity and underlying etiology. 1
Essential Initial Laboratory Panel
The following tests form the core diagnostic workup and should be ordered simultaneously:
- Ionized calcium or pH-corrected ionized calcium is the most accurate measure of biologically active calcium, with levels below 0.8 mmol/L indicating urgent need for correction due to cardiac dysrhythmia risk 1
- Serum magnesium is critical because hypomagnesemia will prevent successful calcium correction regardless of calcium supplementation 1, 2
- Parathyroid hormone (PTH) distinguishes PTH-deficient hypoparathyroidism (low/inappropriately normal PTH) from secondary hyperparathyroidism (elevated PTH) and pseudohypoparathyroidism (elevated PTH with resistance) 3, 4
- Serum phosphorus helps differentiate causes: low phosphorus suggests vitamin D deficiency or malabsorption, while high phosphorus suggests hypoparathyroidism or renal failure 3, 4
- Serum creatinine identifies chronic kidney disease as a cause and guides treatment decisions 1
- 25-hydroxyvitamin D identifies vitamin D deficiency, with levels <30 ng/mL requiring supplementation 1
Additional Recommended Tests
The American College of Cardiology/American Heart Association guidelines recommend a broader initial panel: 5
- Complete blood count 5
- Urinalysis 5
- Blood urea nitrogen 5
- Fasting blood glucose or glycohemoglobin 5
- Liver function tests (important because impaired liver function affects citrate metabolism and calcium gluconate conversion) 5
- Thyroid-stimulating hormone is particularly important as thyroid disease commonly coexists with conditions associated with hypocalcemia 1
Cardiac Evaluation
- 12-lead electrocardiogram should be obtained to assess for prolonged QT interval, as hypocalcemia can cause cardiac arrhythmias and impair cardiac contractility 1
- This is particularly critical when ionized calcium is below 0.8 mmol/L or total calcium is approximately 7.5 mg/dL 5
Context-Specific Additional Testing
When Caustic Ingestion is Suspected
- Serum sodium, potassium, chlorine levels (strong acids/alkalis can cause hyponatremia and hypokalemia) 5
- pH and serum lactate 5
- Blood alcohol levels 5
- β-HCG in young women 5
When Evaluating for Specific Etiologies
The diagnostic approach branches based on PTH and phosphorus levels: 4
If PTH is low/inappropriately normal with high phosphorus:
- Consider genetic testing for hypoparathyroidism syndromes
- Parathyroid autoantibodies
- History of neck surgery or radiation
If PTH is elevated with high phosphorus:
- Evaluate for pseudohypoparathyroidism
- Urinary cyclic AMP response to PTH can distinguish end-organ resistance 2
If phosphorus is low:
- Focus on vitamin D metabolism disorders
- Consider malabsorption workup
- Evaluate for medications affecting vitamin D metabolism 6
Critical Pitfalls to Avoid
- Never overlook magnesium levels – Magnesium deficiency causes both impaired PTH secretion and end-organ resistance to PTH through defective cyclic AMP generation 2. Even with adequate calcium supplementation, hypocalcemia will persist until magnesium is corrected 1
- Do not rely on total calcium alone – Ionized calcium is the biologically active form and should be measured or corrected for albumin and pH 1
- Check for hypocalcemia during biological stress – Surgery, fracture, injury, childbirth, or infection can precipitate hypocalcemia even in previously stable patients 1
Monitoring During Treatment
- Check serum calcium and phosphorus within 1 week after starting treatment or adjusting doses 1
- Monitor every 3 months during chronic management 1
- During acute IV calcium administration, measure serum calcium every 4 to 6 hours for intermittent infusions and every 1 to 4 hours for continuous infusion 7
- Keep calcium-phosphorus product below 55 mg²/dL² to prevent soft tissue calcification 1