What are the causes of hypocalcemia (low calcium levels)?

Causes of Hypocalcemia

Hypocalcemia is primarily caused by hypoparathyroidism, vitamin D deficiency, chronic kidney disease, and various genetic disorders, with each requiring specific management to prevent serious complications including seizures, cardiac arrhythmias, and movement disorders. 1

Primary Causes of Hypocalcemia

Parathyroid-Related Causes

• Hypoparathyroidism:
  • Postsurgical (75% of cases) - most common overall cause 2
  • Primary/idiopathic (25% of cases)
  • Genetic disorders (e.g., 22q11.2 deletion syndrome) 1
  • Autoimmune disorders affecting parathyroid glands

Vitamin D-Related Causes

• Vitamin D deficiency (nutritional)
• Impaired vitamin D metabolism
• Vitamin D resistance
• Reduced intestinal calcium absorption

Kidney-Related Causes

• Chronic kidney disease (CKD) 1
  • Reduced 1,25(OH)₂D production
  • Phosphate retention
  • Skeletal resistance to PTH

Medication-Induced Hypocalcemia 3

• Bisphosphonates
• Cisplatin
• Anticonvulsants
• Aminoglycosides
• Proton pump inhibitors
• Calcimimetics (e.g., cinacalcet)
• Certain antibiotics (e.g., ceftriaxone in neonates) 4

Other Causes

• Acute pancreatitis - calcium sequestration in fat necrosis
• Hypomagnesemia - impairs PTH secretion and action 1
• Tumor lysis syndrome - phosphate release binds calcium
• Hungry bone syndrome - post-parathyroidectomy
• Critical illness - multiple mechanisms
• Biological stress including:
  • Surgery
  • Fractures
  • Childbirth
  • Severe infections 1

Special Populations and Considerations

22q11.2 Deletion Syndrome

This genetic disorder presents with:

• Hypocalcemia in 80% of adults due to hypoparathyroidism 1
• Increased risk during biological stress (surgery, childbirth, infection)
• Often worsened by alcohol or carbonated beverages 1

Chronic Kidney Disease

In CKD, hypocalcemia results from:

• Phosphate retention leading to decreased ionized calcium
• Decreased 1,25(OH)₂D production
• Skeletal resistance to PTH action 1
• Secondary hyperparathyroidism as a compensatory mechanism

Clinical Implications and Management

The clinical presentation of hypocalcemia varies based on severity and chronicity:

• Acute severe hypocalcemia: neuromuscular irritability, tetany, seizures 5
• Chronic hypocalcemia: fatigue, irritability, abnormal movements, QT prolongation 1

Management depends on the underlying cause:

• Acute symptomatic hypocalcemia: IV calcium gluconate 4
• Chronic hypocalcemia: oral calcium and vitamin D supplementation 1
• Specific causes (e.g., hypomagnesemia): targeted replacement 1

Pitfalls and Caveats

1. Overlooking hypocalcemia in high-risk patients - Always check calcium levels in patients with:

   • Recent neck surgery
   • 22q11.2 deletion syndrome
   • CKD
   • Symptoms of neuromuscular irritability

2. Failure to correct for albumin - Low albumin falsely lowers total calcium; use corrected calcium or ionized calcium 1

3. Ignoring magnesium status - Hypomagnesemia can cause refractory hypocalcemia that won't respond to calcium replacement alone 1

4. Overcorrection risks - Aggressive calcium replacement can lead to hypercalcemia, renal calculi, and renal failure 1

5. Medication interactions - Some medications (e.g., ceftriaxone) can interact with calcium, especially in neonates 4

Proper identification of the underlying cause of hypocalcemia is essential for effective management and prevention of serious complications including seizures, cardiac arrhythmias, and movement disorders.