Can hypertriglyceridemia cause hyponatremia?

Hypertriglyceridemia and Pseudohyponatremia

Yes, severe hypertriglyceridemia can cause pseudohyponatremia, which is a laboratory artifact rather than true sodium deficiency. This occurs when extremely high levels of triglycerides in the blood interfere with sodium measurement methods.

Mechanism of Pseudohyponatremia in Hypertriglyceridemia

• Severe hypertriglyceridemia (typically >1000 mg/dL) can cause falsely low sodium readings due to laboratory measurement artifacts 1, 2
• In indirect ion-selective electrode (ISE) methods commonly used in laboratories, the plasma sample is diluted before measurement 2
• Excessive lipids dilute the water component of serum, and since sodium is dissolved only in the aqueous phase, the sodium content per unit volume appears reduced 3, 2
• This creates a discrepancy between measured sodium and actual sodium concentration

Clinical Significance and Recognition

• Pseudohyponatremia should be suspected when:

  • Severe hypertriglyceridemia (>1000 mg/dL) is present
  • Patient lacks clinical symptoms of hyponatremia despite very low sodium readings
  • There is a discrepancy between arterial and venous sodium measurements 1
  • Measured serum osmolality is normal despite apparent hyponatremia 3

• Confirming pseudohyponatremia:

  • Measure serum osmolality (will be normal in pseudohyponatremia)
  • Measure serum sodium by direct potentiometry (will be normal) 3
  • Look for discrepancies between different measurement methods

Clinical Dangers and Pitfalls

• CRITICAL WARNING: Treating pseudohyponatremia with hypertonic saline can lead to fatal outcomes due to inadvertent hypernatremia 2
• Case reports document fatal outcomes when pseudohyponatremia was mistakenly treated as true hyponatremia 2
• Always confirm true sodium status before initiating sodium correction therapy in patients with severe hypertriglyceridemia

Management Approach

1. Identify patients at risk:

   • Those with severe hypertriglyceridemia (>1000 mg/dL)
   • Patients with conditions associated with hypertriglyceridemia (diabetes, metabolic syndrome, genetic disorders) 4, 5

2. Confirm true sodium status:

   • Request direct potentiometry sodium measurement
   • Measure serum osmolality
   • Be suspicious of hyponatremia in setting of severe hypertriglyceridemia

3. Treat the underlying hypertriglyceridemia:

   • Lifestyle modifications (alcohol cessation, reduced carbohydrate intake, weight loss) 4, 5
   • Optimize glycemic control in diabetic patients 4
   • Consider fibrates (fenofibrate 54-160 mg daily) for severe hypertriglyceridemia 4
   • Consider plasmapheresis for extreme cases (triglycerides >2000 mg/dL) 1, 3

Associated Conditions

• Severe hypertriglyceridemia is often associated with:
  • Acute pancreatitis 6, 1
  • Uncontrolled diabetes 6, 1
  • Genetic disorders affecting lipid metabolism (LPL gene mutations, APOC2, APOA5) 6
  • Metabolic syndrome 5

By addressing the underlying hypertriglyceridemia, the pseudohyponatremia will resolve as triglyceride levels normalize 1, 3. The key is recognizing this laboratory artifact to avoid inappropriate and potentially dangerous sodium correction.