What are the causes of hypomagnesemia?

Causes of Hypomagnesemia

Hypomagnesemia can result from inadequate magnesium intake, increased gastrointestinal or renal losses, or redistribution from extracellular to intracellular space, with renal magnesium wasting being a particularly common cause in hospitalized and critically ill patients. 1

Classification of Causes

Inadequate Intake

• Starvation or malnutrition
• Increased requirements (pregnancy, lactation, early childhood) 2
• Total parenteral nutrition (TPN) without adequate magnesium supplementation 3

Increased Gastrointestinal Losses

• Malabsorption syndromes
• Short bowel syndrome 4
• Chronic diarrhea
• Alcoholism (combined mechanism with poor intake) 2

Increased Renal Losses

Medication-Induced

• Diuretics:
  • Thiazide diuretics (e.g., hydrochlorothiazide) - cause hypokalemia, metabolic alkalosis, renal magnesium wasting, and hypocalciuria 1, 5
  • Loop diuretics - cause hypokalemia, metabolic alkalosis, renal magnesium wasting, and hypercalciuria 1
• Proton pump inhibitors (PPIs) - increasingly recognized cause 6, 4
• Chemotherapeutic agents:
  • Cisplatin 3
  • Cetuximab 3
• Antimicrobials:
  • Aminoglycosides 7
• Other medications:
  • Calcineurin inhibitors
  • Amphotericin B

Genetic Disorders

• Gitelman syndrome - associated with hypokalemia, metabolic alkalosis, renal magnesium wasting, and hypocalciuria 1
• Bartter syndrome - associated with hypokalemia, metabolic alkalosis, renal magnesium wasting, and hypercalciuria 1
• Familial renal magnesium wasting - associated with hypercalciuria, nephrocalcinosis, and nephrolithiasis 1

Other Renal Causes

• Volume depletion with secondary hyperaldosteronism 3
• Post-obstructive diuresis
• Recovery phase of acute tubular necrosis
• Hypercalcemia
• Renal tubular acidosis

Redistribution from Extracellular to Intracellular Space

• Acute stress responses:
  • Epinephrine administration
  • Cold stress
  • Serious injury
  • Extensive surgery 2
• Refeeding syndrome
• Hungry bone syndrome
• Acute pancreatitis

Diagnostic Approach

To determine the cause of hypomagnesemia:

1. Measure fractional excretion of magnesium (FEMg) and urinary calcium-creatinine ratio 1

   • FEMg < 2% suggests gastrointestinal loss
   • FEMg > 2% indicates renal magnesium wasting

2. Evaluate for associated electrolyte abnormalities:

   • Hypokalemia - common with diuretic use and genetic disorders 5, 1
   • Hypocalcemia - often resistant to correction until magnesium is repleted 2
   • Metabolic alkalosis - seen with diuretic-induced magnesium wasting 1

Clinical Implications and Management

Hypomagnesemia can cause serious complications:

• Neuromuscular manifestations (tremor, myoclonic jerks, convulsions)
• Cardiovascular effects (ventricular arrhythmias, increased risk of sudden death)
• Metabolic consequences (secondary hypokalemia and hypocalcemia)
• Increased mortality in critically ill patients 8

Treatment should be guided by severity:

• Asymptomatic patients: oral magnesium supplements
• Symptomatic patients or severe deficiency (<1.2 mg/dL): parenteral magnesium 1
• Verify adequate renal function before aggressive supplementation 2

Common Pitfalls and Caveats

1. Serum magnesium levels may not accurately reflect total body magnesium stores, as only 1% of total body magnesium is in the extracellular fluid 8

2. Multiple causes of hypomagnesemia may coexist, particularly in critically ill patients 8

3. Hypomagnesemia can persist despite treatment if the underlying cause is not addressed (e.g., discontinuing PPIs in PPI-induced hypomagnesemia) 4

4. Secondary electrolyte abnormalities (hypokalemia, hypocalcemia) may be resistant to correction until magnesium is repleted 2

5. Magnesium supplementation requires caution in patients with renal impairment to prevent hypermagnesemia 3, 2