What are the causes of hypomagnesemia?

Causes of Hypomagnesemia

Hypomagnesemia is most commonly caused by decreased absorption or increased loss of magnesium from either the kidneys or intestines (diarrhea), with additional factors including certain medications, alcohol use, and malnourishment. 1

Definition and Clinical Significance

Hypomagnesemia is defined as a serum magnesium concentration less than 1.3 mEq/L (normal range: 1.3 to 2.2 mEq/L) 1. It is far more common than hypermagnesemia, with prevalence rates of:

• 2.5-15% in the general population 2
• Up to 12% in hospitalized patients
• 60-65% among critically ill patients 1

Major Causes of Hypomagnesemia

1. Gastrointestinal Causes

• Decreased intake/absorption:
  • Protein-calorie malnutrition
  • Starvation
  • Malabsorption syndromes
  • Short bowel syndrome
  • Chronic diarrhea and steatorrhea
  • Bowel fistulas
  • Continuous nasogastric suctioning 3
  • Intravenous administration of magnesium-free fluids 3

2. Renal Causes

• Increased renal losses:
  • Medications:
    • Loop and thiazide diuretics
    • Proton pump inhibitors (increasingly recognized cause) 2
    • Aminoglycosides
    • Pentamidine
    • Cisplatin
    • Foscarnet 3
  • Genetic disorders:
    • Bartter syndrome (associated with hypercalciuria)
    • Gitelman syndrome (associated with hypocalciuria) 4
  • Other renal conditions:
    • Post-obstructive diuresis
    • Post-acute tubular necrosis
    • Renal transplantation
    • Interstitial nephropathy 3
    • Kidney replacement therapy (KRT) - especially continuous modalities 1

3. Redistribution from Extracellular to Intracellular Space

• Refeeding syndrome (especially with high carbohydrate intake) 1
• Acute stress responses:
  • Epinephrine release
  • Cold stress
  • Serious injury
  • Extensive surgery 5

4. Endocrine and Metabolic Causes

• Diabetes mellitus (multiple contributing factors) 3
• Alcoholism (combination of poor intake, increased GI losses, and renal wasting) 5
• Hyperaldosteronism (secondary) 1
• Hyperthyroidism 4
• Hypercalcemia 1

Diagnostic Approach to Hypomagnesemia

When evaluating hypomagnesemia, the key diagnostic step is to determine if the cause is renal or extrarenal:

1. Measure fractional excretion of magnesium (FEMg):

   • FEMg < 2% indicates extrarenal loss (appropriate renal conservation)
   • FEMg > 2% indicates renal magnesium wasting 4

2. Measure urinary calcium-creatinine ratio:

   • Helps distinguish between different genetic causes:
     • Hypercalciuria suggests Bartter syndrome or familial renal magnesium wasting
     • Hypocalciuria suggests Gitelman syndrome 4

Clinical Manifestations

Most patients with hypomagnesemia are asymptomatic until serum levels fall below 1.2 mg/dL 4. Symptoms include:

• Neuromuscular: Tremor, myoclonic jerks, convulsions, tetany, Chvostek's sign, Trousseau's sign
• Cardiovascular: Arrhythmias (including life-threatening ventricular tachycardia and torsades de pointes)
• Metabolic: Secondary hypokalemia and hypocalcemia resistant to replacement without magnesium correction 5

Treatment Considerations

Treatment depends on severity and symptoms:

• Asymptomatic patients: Oral magnesium supplements
• Symptomatic or severe deficiency (<1.2 mg/dL): Parenteral magnesium (1-2g MgSO₄ IV push for cardiac arrhythmias) 1
• For patients with short bowel syndrome: Magnesium oxide (12-24 mmol daily, preferably at night when intestinal transit is slowest) 1
• If oral supplements ineffective: Consider 1-alpha hydroxy-cholecalciferol (0.25-9.00 mg daily) to improve magnesium balance 1

Important Clinical Pitfalls

1. Serum magnesium may not reflect total body stores - intracellular depletion can occur with normal serum levels 3

2. Refractory hypokalemia or hypocalcemia should prompt evaluation for hypomagnesemia 3

3. Verify renal function before aggressive magnesium replacement - magnesium toxicity can occur in renal insufficiency 5

4. For patients on kidney replacement therapy, use dialysis solutions containing magnesium to prevent depletion rather than relying on supplementation 1