What are the causes of hypomagnesemia?

Causes of Hypomagnesemia

Hypomagnesemia, defined as a serum magnesium concentration <1.3 mEq/L, is far more common than hypermagnesemia and usually results from decreased absorption or increased loss of magnesium from either the kidneys or intestines (diarrhea). 1 This electrolyte disturbance can lead to serious clinical consequences including cardiovascular and neurological complications.

Major Causes of Hypomagnesemia

Gastrointestinal Causes

• Decreased intestinal absorption:
  • Malabsorption syndromes
  • Chronic diarrhea
  • Short bowel syndrome 1
  • Malnutrition 1

Renal Causes

• Increased renal magnesium wasting:
  • Medications:
    • Diuretics (loop diuretics, thiazides) 1
    • Proton pump inhibitors 2
    • Certain antibiotics (aminoglycosides, amphotericin B) 3
    • Cisplatin 3
    • Pentamidine 1
  • Genetic disorders:
    • Bartter syndrome 1
    • Gitelman syndrome 4
  • Alcohol use/abuse 1
  • Kidney replacement therapy (KRT) 1
    • Especially with intensive dialysis strategy and phosphate-free KRT solutions
    • Regional citrate anticoagulation during continuous KRT can worsen magnesium loss 1

Other Causes

• Alterations in thyroid hormone function 1
• Redistribution from extracellular to intracellular space 4
• Critical illness (up to 60-65% of critically ill patients) 1

Clinical Manifestations of Hypomagnesemia

Symptoms typically don't appear until serum magnesium falls below 1.2 mg/dL 4 and may include:

• Neuromuscular: muscle irritability, clonic twitching, tremors 5
• Cardiovascular: arrhythmias, especially polymorphic ventricular tachycardia (torsades de pointes) 1
• Electrolyte disturbances: hypocalcemia and hypokalemia often follow hypomagnesemia 5

Diagnostic Approach

When hypomagnesemia is detected, the first step should be to measure:

• Fractional excretion of magnesium
• Urinary calcium-creatinine ratio 4

Interpretation:

• Fractional excretion <2%: suggests gastrointestinal loss
• Fractional excretion >2% with normal kidney function: indicates renal magnesium wasting 4

Management Considerations

• Asymptomatic patients: oral magnesium supplements 4
• Symptomatic patients with severe deficiency (<1.2 mg/dL): parenteral magnesium (IV magnesium sulfate) 4
• For cardiotoxicity and cardiac arrest: IV magnesium 1-2 g of MgSO4 bolus IV push (Class I recommendation) 1

Prevention in Special Situations

• In patients undergoing kidney replacement therapy: use dialysis solutions containing magnesium to prevent electrolyte disorders 1
• In short bowel syndrome: correct water and sodium depletion first (to address secondary hyperaldosteronism), then consider oral magnesium preparations (e.g., 12 mmol magnesium oxide at night) 1

Important Clinical Pitfalls

1. Hypomagnesemia often coexists with other electrolyte abnormalities, particularly hypokalemia and hypocalcemia, which may not resolve until magnesium is repleted 5

2. Serum magnesium is a poor proxy for total body stores but correlates with symptom development 3

3. Always verify adequate renal function before aggressive magnesium supplementation to avoid iatrogenic hypermagnesemia 4

4. In patients with Bartter syndrome receiving proton pump inhibitors, there is a risk of worsening hypomagnesemia that could compound renal magnesium wasting 1