Laboratory Workup for Suspected Hypocalcemia
For any patient with suspected hypocalcemia, immediately order: ionized calcium (or corrected total calcium), magnesium, parathyroid hormone (PTH), phosphorus, creatinine, and 25-hydroxyvitamin D levels to determine both the severity and underlying etiology. 1
Essential Initial Laboratory Panel
The core diagnostic workup must include:
Ionized calcium or pH-corrected ionized calcium – This 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 – Critical to check early, as hypomagnesemia impairs PTH secretion and must be corrected before calcium management will be effective 1, 2
Parathyroid hormone (PTH) – Distinguishes PTH-deficient hypoparathyroidism (low or inappropriately normal PTH) from other causes; elevated PTH suggests pseudohypoparathyroidism or secondary hyperparathyroidism 2, 3
Serum phosphorus – Helps categorize hypocalcemia: low phosphate suggests vitamin D deficiency or malabsorption, while high phosphate points toward hypoparathyroidism or renal failure 3, 4
Serum creatinine – Essential to identify chronic kidney disease as a cause and guide treatment decisions 1
25-hydroxyvitamin D – Identifies vitamin D deficiency (levels <30 ng/mL require supplementation) 1
Additional Recommended Tests
Beyond the core panel, the American College of Cardiology recommends including in the initial evaluation 5:
- Complete blood count 5
- Urinalysis 5
- Blood urea nitrogen 5
- Fasting blood glucose or glycohemoglobin 5
- Liver function tests 5
- Thyroid-stimulating hormone – Particularly important as thyroid disease is common in conditions associated with hypocalcemia, such as 22q11.2 deletion syndrome 5
Cardiac Evaluation
Obtain a 12-lead electrocardiogram to assess for prolonged QT interval, as hypocalcemia can cause cardiac arrhythmias and impair cardiac contractility 5, 1. This is particularly critical when ionized calcium is below 0.8 mmol/L or total calcium is approximately 7.5 mg/dL 6.
Algorithmic Approach Based on Initial Results
If PTH is Low or Inappropriately Normal with Hypocalcemia:
This indicates PTH-deficient hypoparathyroidism 2, 3. Consider:
- Surgical history (most common cause is iatrogenic from anterior neck surgery) 2
- Autoimmune workup if no surgical history 3
- Genetic testing if congenital causes suspected 3
If PTH is Elevated with Hypocalcemia:
This suggests either pseudohypoparathyroidism (PTH resistance) or secondary hyperparathyroidism 2. The phosphorus level helps distinguish:
- High phosphorus → pseudohypoparathyroidism or chronic kidney disease 3
- Low phosphorus → vitamin D deficiency, malabsorption, or renal calcium wasting 3
If Phosphorus is Low:
Consider vitamin D deficiency, malabsorption syndromes, or renal calcium losses 3, 4
If Phosphorus is High:
Consider chronic renal failure or hypoparathyroidism 3
Monitoring During Treatment
Once treatment is initiated 1, 6:
- Check serum calcium and phosphorus within 1 week after starting treatment or adjusting doses 1
- Monitor every 3 months during chronic management 1, 6
- Keep calcium-phosphorus product below 55 mg²/dL² to prevent soft tissue calcification 1
Critical Pitfalls to Avoid
Never overlook magnesium levels – Hypomagnesemia will prevent successful calcium correction regardless of calcium supplementation 1, 2
Do not assume secondary hyperparathyroidism in CKD patients with elevated PTH – Primary hyperparathyroidism with concomitant vitamin D deficiency can present with hypocalcemia and elevated PTH 7
Always check for hypocalcemia during biological stress – Surgery, fracture, injury, childbirth, or infection can precipitate hypocalcemia even in previously stable patients, particularly those with 22q11.2 deletion syndrome 5
Monitor for over-correction – Iatrogenic hypercalcemia from excessive supplementation can cause renal calculi, nephrocalcinosis, and renal failure 5, 1