What is the appropriate workup and treatment for a patient presenting with hypocalcemia (low calcium levels), considering potential underlying conditions such as kidney disease, parathyroid disorders, or malabsorption syndromes?

Workup of Hypocalcemia

Initial Laboratory Assessment

Begin by measuring ionized calcium (or corrected total calcium), parathyroid hormone (PTH), magnesium, phosphate, creatinine, and albumin to establish the diagnosis and identify the underlying cause. 1, 2

Essential First-Line Tests

• Ionized calcium or corrected total calcium: Confirms hypocalcemia (ionized <1.15 mmol/L or corrected total <8.4 mg/dL) 1, 2
• Intact PTH: Differentiates hypoparathyroidism (low/inappropriately normal PTH) from other causes (elevated PTH) 1, 3
• Magnesium: Hypomagnesemia is present in 28% of hypocalcemic patients and must be corrected first, as hypocalcemia cannot be adequately treated without correcting magnesium 1, 4
• Phosphate: Elevated in hypoparathyroidism and renal failure; low in vitamin D deficiency 1, 5
• Creatinine and renal function: Identifies chronic kidney disease as a cause 1, 2, 5
• Albumin: Necessary to calculate corrected calcium if only total calcium is measured 1

Second-Line Tests Based on Initial Results

• 25-hydroxyvitamin D: If PTH is elevated, measure to assess for vitamin D deficiency (target >30 ng/mL) 1, 2
• Alkaline phosphatase: Rising levels indicate negative calcium balance and bone disease 1
• ECG: Essential to assess for prolonged QT interval and cardiac arrhythmias, particularly in symptomatic patients 1, 6, 7

Clinical Assessment for Severity

Determine whether hypocalcemia is symptomatic or asymptomatic, as this dictates urgency of treatment. 1, 2

Symptomatic Hypocalcemia (Requires Immediate IV Treatment)

• Neuromuscular irritability: Paresthesias (circumoral, hands, feet), positive Chvostek's or Trousseau's signs 2, 8, 4
• Severe manifestations: Tetany, laryngospasm, bronchospasm, seizures, focal or generalized tonic muscle cramps 1, 2, 8, 4
• Cardiac manifestations: Prolonged QT interval, cardiac arrhythmias, ventricular arrhythmias, myocardial dysfunction 1, 8, 7

Asymptomatic Hypocalcemia

• Mild hypocalcemia: Corrected calcium <8.4 mg/dL without symptoms 2
• Treatment indicated when: PTH is above target range for CKD stage or calcium <8.4 mg/dL with elevated PTH 1, 2

Identifying the Underlying Cause

Use the PTH level as the primary branch point in your diagnostic algorithm. 1, 3

Low or Inappropriately Normal PTH (Hypoparathyroidism)

• Post-surgical hypoparathyroidism: Most common cause, occurs after thyroid or parathyroid surgery 1, 8, 4
• Genetic disorders: 22q11.2 deletion syndrome (80% lifetime history of hypocalcemia) 1
• Autoimmune hypoparathyroidism: Less common 3
• Magnesium disorders: Severe hypomagnesemia impairs PTH secretion 1, 4

Elevated PTH (Secondary Hyperparathyroidism)

• Chronic kidney disease: Defective vitamin D activation leads to hypocalcemia and compensatory PTH elevation 1, 2, 5
• Vitamin D deficiency: Low 25-hydroxyvitamin D (<30 ng/mL) with elevated PTH 1, 2, 3
• Malabsorption syndromes: Impaired calcium and vitamin D absorption 1, 3
• Medications: Bisphosphonates, foscarnet, citrate (in blood products) 1, 4

Special Clinical Contexts

• Massive transfusion: Citrate in blood products binds calcium; monitor ionized calcium continuously 1
• Tumor lysis syndrome: Hyperphosphatemia causes calcium-phosphate precipitation 1
• Critical illness: Hypoperfusion, hypothermia, and hepatic insufficiency impair citrate metabolism 1

Monitoring During Workup

Frequency of calcium monitoring depends on treatment modality and clinical severity. 1, 2

• During IV bolus administration: Monitor vitals and ECG continuously 1, 6
• During intermittent IV infusions: Measure serum calcium every 4-6 hours 1, 6
• During continuous IV infusion: Measure serum calcium every 1-4 hours 1, 6
• Chronic oral supplementation: Measure corrected calcium and phosphorus at least every 3 months 1, 2
• High-risk periods: Targeted monitoring during surgery, childbirth, infection, or severe illness in predisposed patients 1

Critical Pitfalls to Avoid

• Never treat hypocalcemia without checking magnesium first: Hypomagnesemia causes both impaired PTH secretion and end-organ PTH resistance; calcium supplementation alone will fail 1, 4
• Avoid calcium administration with high phosphate: Risk of calcium-phosphate precipitation in tissues, particularly in tumor lysis syndrome 1
• Do not mix calcium with bicarbonate or phosphate-containing fluids: Precipitation will occur 1, 6
• Never administer calcium and ceftriaxone together in neonates: Fatal ceftriaxone-calcium precipitates can form 6
• Avoid over-correction: Can cause iatrogenic hypercalcemia, renal calculi, and renal failure 1, 2