What is the main cause of hypocalcemia (low calcium levels)?

Main Causes of Hypocalcemia

Hypoparathyroidism is the most common cause of hypocalcemia, with chronic kidney disease (CKD) being another major contributor through multiple mechanisms including phosphate retention, decreased vitamin D activation, and skeletal resistance to parathyroid hormone. 1, 2

Primary Etiologies of Hypocalcemia

1. Parathyroid Hormone (PTH) Related Causes

• Hypoparathyroidism:
  • Post-surgical (75% of hypoparathyroidism cases) 3
  • Primary/idiopathic (25% of hypoparathyroidism cases) 3
  • Genetic disorders (e.g., 22q11.2 deletion syndrome) 1, 2
  • Autoimmune disorders

2. Chronic Kidney Disease Mechanisms

• Phosphate retention leading to calcium-phosphate precipitation 1
• Decreased production of 1,25-dihydroxycholecalciferol (active vitamin D) 1
• Skeletal resistance to PTH action 1
• Development of secondary hyperparathyroidism as a compensatory mechanism 1

3. Vitamin D Deficiency and Disorders

• Inadequate dietary intake
• Malabsorption syndromes
• Liver disease (impaired 25-hydroxylation)
• Kidney disease (impaired 1α-hydroxylation)
• Vitamin D-dependent rickets

4. Electrolyte Abnormalities

• Hypomagnesemia: Impairs PTH secretion and action 2
• Hyperphosphatemia: Forms complexes with calcium 1

5. Medication-Induced

• Glucocorticoids (high-dose therapy) 4
• Bisphosphonates
• Anticonvulsants
• Calcitonin
• Certain chemotherapeutic agents

Pathophysiological Mechanisms

The K/DOQI guidelines explain that hypocalcemia in CKD develops through at least three interrelated mechanisms 1:

1. Phosphate retention: Transient increases in serum phosphorus directly decrease ionized calcium, stimulating PTH release
2. Decreased vitamin D activation: Reduced kidney function impairs conversion of 25(OH)D to active 1,25(OH)₂D
3. Skeletal resistance to PTH: Bones become less responsive to PTH's calcium-mobilizing effects

In patients with 22q11.2 deletion syndrome, hypocalcemia is primarily due to hypoparathyroidism and can be exacerbated by biological stressors such as surgery, fracture, injury, childbirth, or infection 1.

Clinical Implications

Hypocalcemia can present with various symptoms depending on severity:

• Neuromuscular irritability, tetany, paresthesias
• Seizures and altered mental status
• Cardiac arrhythmias and QT prolongation
• Laryngospasm and bronchospasm in severe cases 2, 5

Hypocalcemia can be worsened by:

• Alcohol consumption
• Carbonated beverages (especially colas) 1
• Acute illness or physiological stress 1

Management Considerations

Treatment depends on the underlying cause, severity, and chronicity:

1. Acute symptomatic hypocalcemia: IV calcium gluconate administration 5, 6
2. Chronic hypocalcemia:
   • Daily vitamin D supplementation
   • Calcium supplementation
   • For hypoparathyroidism: Consider recombinant human PTH 7
   • For CKD: Management per K/DOQI guidelines 1

When treating hypocalcemia, always check magnesium levels, as hypomagnesemia can make calcium replacement ineffective until corrected 2.

Caution is needed to avoid overcorrection, which can lead to hypercalcemia, renal calculi, and renal failure 1.

Understanding the underlying cause of hypocalcemia is crucial for appropriate long-term management and prevention of complications.