What is the etiology of hypocalcemia?

Etiology of Hypocalcemia

The primary causes of hypocalcemia include hypoparathyroidism (most commonly postsurgical), vitamin D deficiency, chronic kidney disease, hypomagnesemia, and genetic disorders such as 22q11.2 deletion syndrome. 1, 2

Classification of Hypocalcemic Disorders

PTH-Mediated Hypocalcemia

1. Hypoparathyroidism

   • Postsurgical (most common cause of chronic hypocalcemia) 3
   • Autoimmune hypoparathyroidism
   • Genetic causes (22q11.2 deletion syndrome/DiGeorge syndrome) 4, 1
   • Parathyroid agenesis 5

2. Pseudohypoparathyroidism

   • Resistance to PTH action 6

Non-PTH Mediated Hypocalcemia

1. Vitamin D-Related

   • Vitamin D deficiency
   • Disorders of vitamin D metabolism 2

2. Mineral Abnormalities

   • Hypomagnesemia (can make hypocalcemia refractory to treatment) 1
   • Hyperphosphatemia 1

3. Medication-Induced

   • Certain anticonvulsants 4
   • Bisphosphonates
   • Calcitonin

4. Other Causes

   • Chronic kidney disease 1
   • Acute pancreatitis
   • Tumor lysis syndrome
   • Massive blood transfusion 1

Factitious/Physiologic Hypocalcemia

• Hypoalbuminemia (affects total calcium but not ionized calcium) 6
• Laboratory errors

Special Considerations for Specific Populations

Neonatal Hypocalcemia

• Early neonatal hypocalcemia occurs during first 24-48 hours of life due to delayed PTH surge 4
• Generally not associated with obvious clinical problems such as tetany
• Calcium infusion typically prevents or treats this condition 4

22q11.2 Deletion Syndrome

• Hypocalcemia occurs in approximately 80% of patients with this syndrome 4
• May present at any age, especially after puberty
• Typically attributable to hypoparathyroidism
• May be associated with hypothyroidism and hypomagnesemia 4
• Increased risk during biological stress (surgery, childbirth, infection)
• Can be worsened by alcohol or carbonated beverages 4

Clinical Manifestations of Hypocalcemia

Acute Manifestations

• Neuromuscular irritability
• Tetany
• Seizures
• Perioral numbness
• Carpopedal spasms 1

Cardiac Manifestations

• Prolonged QT interval on ECG
• Decreased cardiac contractility (when ionized calcium <1.0 mmol/L)
• Reduced systemic vascular resistance 1

Chronic Manifestations

• Fatigue
• Emotional irritability
• Abnormal involuntary movements
• Predisposition to osteopenia/osteoporosis 4

Precipitating Factors

• Biological stress (surgery, childbirth, infection) 4, 1
• Alcohol consumption
• Carbonated beverages 4
• Decreased oral intake 1
• Puberty 1
• Pregnancy 1

Diagnostic Approach

Essential laboratory tests for diagnosing the cause of hypocalcemia include:

• Ionized calcium (more accurate than total calcium)
• Albumin-corrected total calcium
• Parathyroid hormone (PTH) levels
• Magnesium levels
• Phosphorus levels
• 25-hydroxyvitamin D levels
• Renal function tests 1

Clinical Pearls and Pitfalls

• Hypomagnesemia must be corrected: Untreated hypomagnesemia can make hypocalcemia refractory to treatment 1

• Laboratory reference values: Pay particular attention to phosphate reference values in newborns, especially premature infants. The lower limit is higher in premature infants (1.6 mmol/L) than in adults (1.0 mmol/L) 4

• Monitoring during treatment: Serum calcium should be monitored every 2-4 weeks initially and then every 3-6 months once stable 1

• Dietary considerations: Total elemental calcium intake should not exceed 2,000 mg/day, and patients should avoid alcohol and carbonated beverages 1

• Pregnancy complications: Maternal hypocalcemia increases the risk of spontaneous abortion, premature labor, and preeclampsia 1