Hypomagnesemia: Symptoms and Causes
Low magnesium (hypomagnesemia, defined as serum magnesium <1.3 mEq/L) most critically manifests as life-threatening cardiac arrhythmias, particularly torsades de pointes, which can progress to cardiac arrest, and requires immediate recognition and treatment. 1, 2
Clinical Symptoms
Cardiac Manifestations (Most Life-Threatening)
- Torsades de pointes (polymorphic ventricular tachycardia) represents the most dangerous cardiac complication and can progress to pulseless cardiac arrest 2
- Ventricular arrhythmias including premature ventricular contractions (PVCs), ventricular tachycardia, and ventricular fibrillation 1
- ECG changes: QT interval prolongation, prolonged PR interval, and widened QRS complex 1, 2
- Increased sensitivity to digoxin toxicity 3
- Poor prognosis in cardiac arrest patients with low plasma magnesium 2
Neuromuscular and Neurological Symptoms
- Seizures (may be the presenting symptom, especially when magnesium falls below 1.2 mg/dL) 1, 4, 5
- Muscle irritability, clonic twitching, and tremors 4, 3
- Tetany similar to hypocalcemia (despite normal or elevated calcium levels) 4
- Abnormal involuntary movements 1, 2
Neuropsychiatric Manifestations
Associated Electrolyte Abnormalities
- Refractory hypokalemia (potassium supplements are ineffective until magnesium is corrected first) 2, 3
- Hypocalcemia (secondary to hypomagnesemia) 1, 3, 6
Important caveat: Most patients remain asymptomatic until serum magnesium falls below 1.2 mg/dL, and serum magnesium can be normal despite significant intracellular depletion. 5, 3
Common Causes
Gastrointestinal Losses (Most Common Non-Renal Cause)
- Chronic diarrhea and steatorrhea 2, 5, 3
- Short bowel syndrome 3, 6
- Continuous nasogastric suctioning 3
- Bowel fistula 3
- Protein-calorie malnutrition 3
- Proton pump inhibitors (PPIs) causing decreased intestinal absorption 6
Renal Losses (Medication-Induced)
- Loop diuretics (furosemide) and thiazide diuretics are the most common medication causes 1, 2, 5
- Chlorthalidone carries higher risk than hydrochlorothiazide (adjusted HR 1.57) with dose-dependent magnesium reduction 2
- Aminoglycosides 2, 3
- Cisplatin (causes direct renal tubular magnesium wasting) 2, 3
- Pentamidine 2, 3
- Epidermal growth factor receptor inhibitors (cetuximab) 2
- Foscarnet 3
Renal Losses (Genetic/Acquired Disorders)
- Gitelman syndrome: associated with hypokalemia, metabolic alkalosis, renal magnesium wasting, and hypocalciuria 5
- Bartter syndrome: associated with hypokalemia, metabolic alkalosis, renal magnesium wasting, and hypercalciuria 5
- Familial renal magnesium wasting with hypercalciuria and nephrocalcinosis 5
- Post-obstructive diuresis and post-acute tubular necrosis 3
- Renal transplantation 3
High-Risk Populations
- Alcoholics (combination of poor intake, gastrointestinal losses, and renal wasting) 3
- Diabetic patients (multiple contributing factors including osmotic diuresis) 3, 7
- Hospitalized patients, especially in intensive care units 3
- Patients receiving total parenteral nutrition without adequate magnesium supplementation 4, 3
- Patients with 22q11.2 deletion syndrome (80% lifetime prevalence of hypocalcemia with associated hypomagnesemia) 1
Endocrine and Metabolic Factors
- Alterations in thyroid hormone function 2
- Sepsis (associated with increased renal magnesium wasting) 7
Diagnostic Approach
To determine the cause, measure fractional excretion of magnesium (FEMg) and urinary calcium-creatinine ratio: 5
- FEMg <2% indicates appropriate renal conservation (gastrointestinal losses or inadequate intake)
- FEMg >2% with normal kidney function indicates renal magnesium wasting
- Hypercalciuria suggests Bartter syndrome, loop diuretics, or familial renal magnesium wasting
- Hypocalciuria suggests Gitelman syndrome or thiazide diuretics
Critical monitoring consideration: Avoid drugs that prolong QT interval or exacerbate hypomagnesemia (macrolides, fluoroquinolones, gentamicin, antivirals) in patients with known hypomagnesemia. 2