Causes of Hypomagnesemia
Primary Mechanisms
Hypomagnesemia results from three fundamental mechanisms: inadequate intake, excessive losses (gastrointestinal or renal), or redistribution between body compartments. 1, 2
Gastrointestinal Causes
Gastrointestinal losses represent a major category of hypomagnesemia, particularly in patients with structural or functional bowel disorders.
Malabsorption and Structural Disorders
- Short bowel syndrome causes magnesium deficiency through reduced absorptive surface area and chelation of magnesium with unabsorbed fatty acids in the bowel lumen. 3
- Resection of more than 60–100 cm of terminal ileum leads to fat malabsorption, which directly impairs magnesium absorption through fatty acid chelation. 3
- Chronic diarrhea and high-output stomas result in substantial magnesium losses, with each liter of jejunostomy fluid containing approximately 100 mmol/L sodium and proportional magnesium losses. 3, 4
- Malabsorption syndromes, including inflammatory bowel disease and celiac disease, reduce intestinal magnesium uptake. 4, 2
- Bowel bypass or resection procedures create permanent reductions in absorptive capacity. 2
Acute Gastrointestinal Conditions
- Acute pancreatitis causes redistribution of magnesium. 2
Renal Causes
Renal magnesium wasting occurs when fractional excretion of magnesium exceeds 2% despite hypomagnesemia, indicating the kidney's failure to conserve magnesium appropriately. 1
Medication-Induced Renal Losses
- Loop diuretics (furosemide, bumetanide) and thiazide diuretics inhibit sodium chloride transport in the ascending loop of Henle and distal convoluted tubule, respectively, causing renal magnesium wasting. 4, 1
- Proton pump inhibitors promote renal magnesium loss through mechanisms that remain incompletely understood but are increasingly recognized as a common cause. 5, 6
- Calcineurin inhibitors (tacrolimus, cyclosporine) cause direct renal magnesium wasting, particularly problematic in transplant recipients. 4
- Aminoglycosides (gentamicin), cisplatin, amphotericin B, pentamidine, and foscarnet cause direct nephrotoxic magnesium wasting. 4, 1
Genetic Renal Disorders
- Gitelman syndrome presents with hypokalemia, metabolic alkalosis, renal magnesium wasting, hypomagnesemia, and hypocalciuria (distinguishing feature). 1
- Bartter syndrome presents with hypokalemia, metabolic alkalosis, renal magnesium wasting, hypomagnesemia, and hypercalciuria (distinguishing feature). 1
- Familial renal magnesium wasting is associated with hypercalciuria, nephrocalcinosis, and nephrolithiasis. 1
Metabolic and Endocrine Causes
- Diabetes mellitus causes osmotic diuresis with increased renal magnesium excretion. 2
- Hypercalcemia increases renal magnesium losses through competitive inhibition at renal tubular sites. 2
- Hyperthyroidism and primary aldosteronism increase renal magnesium excretion. 2
- Secondary hyperaldosteronism (from volume depletion) increases renal magnesium and potassium excretion, creating a vicious cycle in patients with gastrointestinal losses. 3, 4
Inadequate Intake
- Starvation or prolonged administration of intravenous fluids without magnesium supplementation. 7, 2
- Alcoholism combines inadequate intake with increased renal losses and malabsorption. 7, 2
- Poor nutrition in vulnerable populations. 2
Increased Requirements
- Pregnancy and lactation increase magnesium requirements beyond typical dietary intake. 7, 2
- Early childhood represents a period of increased magnesium demand for growth. 7
- Excessive lactation can deplete maternal magnesium stores. 2
Redistribution
- Acute stress from serious injury, extensive surgery, or critical illness causes rapid redistribution of magnesium from extracellular to intracellular compartments. 7
- Epinephrine administration and cold stress trigger acute hypomagnesemia through redistribution. 7
- Exchange transfusion causes redistribution of magnesium. 2
Self-Perpetuating Mechanisms
Hypomagnesemia creates a vicious cycle through secondary effects on parathyroid hormone and vitamin D metabolism.
- Magnesium deficiency reduces secretion and function of parathyroid hormone, which directly increases renal magnesium loss. 3
- Reduced parathyroid hormone indirectly decreases manufacture of 1,25-hydroxy-vitamin D, which normally increases jejunal magnesium absorption, further impairing magnesium balance. 3
- Secondary hyperaldosteronism from volume depletion (common in patients with gastrointestinal losses) increases renal magnesium excretion, making repletion impossible until volume status is corrected. 3, 4
Diagnostic Approach
Measure fractional excretion of magnesium and urinary calcium-creatinine ratio to distinguish gastrointestinal from renal causes. 1
- Fractional excretion of magnesium <2% indicates appropriate renal conservation, pointing to gastrointestinal losses or inadequate intake. 1
- Fractional excretion of magnesium >2% in a patient with normal kidney function indicates renal magnesium wasting. 1
- Hypercalciuria suggests Bartter syndrome, loop diuretics, or familial renal magnesium wasting. 1
- Hypocalciuria suggests Gitelman syndrome or thiazide diuretics. 1
Critical Pitfall
In patients with gastrointestinal fluid losses (diarrhea, high-output stomas), failure to correct volume depletion with intravenous saline before starting magnesium supplementation allows secondary hyperaldosteronism to perpetuate renal magnesium wasting, rendering oral magnesium therapy ineffective. 3, 4