What are the primary causes of hypocalcemia?

Primary Causes of Hypocalcemia

The primary causes of hypocalcemia include hypoparathyroidism, chronic kidney disease, vitamin D deficiency, and hypomagnesemia, with each having distinct mechanisms that disrupt calcium homeostasis. 1

Major Etiological Categories

Parathyroid Hormone (PTH) Related Causes

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

Kidney-Related Causes

• Chronic Kidney Disease (CKD):
  • Multiple mechanisms involved: 1
    • Phosphate retention
    • Decreased vitamin D activation (reduced 1,25-dihydroxycholecalciferol production)
    • Skeletal resistance to PTH

Vitamin D-Related Causes

• Vitamin D Deficiency or Metabolism Issues: 3
  • Inadequate dietary intake
  • Insufficient sun exposure
  • Malabsorption syndromes
  • Liver disease (impaired 25-hydroxylation)
  • Kidney disease (impaired 1α-hydroxylation)
  • Medication-induced (e.g., phenytoin accelerates vitamin D catabolism) 4

Magnesium-Related Causes

• Hypomagnesemia: 1
  • Impairs PTH secretion
  • Reduces target organ responsiveness to PTH
  • Makes calcium replacement ineffective until corrected

Medication-Induced Hypocalcemia

• Medications:
  • Denosumab (particularly in CKD patients) 5
  • Bisphosphonates
  • Phenytoin (affects vitamin D metabolism) 4
  • Loop diuretics 5

Other Causes

• Acute Pancreatitis
• Tumor Lysis Syndrome
• Hungry Bone Syndrome (post-parathyroidectomy)
• Critical Illness

Clinical Presentation and Diagnosis

Hypocalcemia can present with varying severity of symptoms: 3

• Neuromuscular irritability
• Tetany and paresthesias
• Muscle cramps and tremors
• Seizures (may be the first sign in some conditions)
• Altered mental status
• Cardiac arrhythmias (including prolonged QT interval)

Diagnostic Approach

When evaluating hypocalcemia, assess: 1

• pH-corrected ionized calcium
• Parathyroid hormone levels
• Vitamin D status (25-OH and 1,25-OH)
• Magnesium levels
• Phosphate levels
• Kidney function (creatinine)

Management Considerations

Treatment depends on severity and underlying cause: 3, 6

• Acute symptomatic hypocalcemia: IV calcium gluconate
• Chronic hypocalcemia: Oral calcium and vitamin D supplementation
• Specific causes require targeted treatment:
  • Hypoparathyroidism: Consider recombinant human PTH
  • Hypomagnesemia: Magnesium repletion before calcium
  • CKD: Treatment based on disease stage

Important Caveats

• Hypocalcemia risk increases during biological stress (surgery, childbirth, infection) 7
• Carbonated beverages and alcohol can worsen hypocalcemia 7, 1
• Magnesium deficiency must be corrected before calcium replacement will be effective 1
• Patients with renal impairment require careful monitoring and dose adjustment 8
• Concomitant use of calcium with certain medications (e.g., cardiac glycosides) requires caution 8

Understanding the specific etiology is crucial for effective management of hypocalcemia, as treatment approaches vary significantly depending on the underlying cause.