What causes pseudo hyponatremia (false low sodium levels)?

Causes of Pseudo Hyponatremia

Pseudo hyponatremia is primarily caused by high levels of triglycerides, uric acid (>20 mg/dL), or bilirubin, which can falsely lower measured sodium levels without true sodium deficiency. 1

Definition and Mechanism

Pseudo hyponatremia represents a laboratory artifact rather than a true electrolyte disorder. It occurs when serum sodium concentration appears falsely low despite normal sodium levels in the plasma water. This happens due to:

• Measurement method interference: Certain laboratory methods for measuring serum sodium are susceptible to interference from substances that occupy plasma volume
• Normal plasma water sodium: The actual sodium concentration in plasma water remains normal, but the measurement is diluted by non-aqueous components

Common Causes

1. Lipid Abnormalities

• Severe hyperlipidemia: High levels of triglycerides in the blood occupy plasma volume, causing falsely low sodium readings 1
• This is particularly common in conditions like hypertriglyceridemia, poorly controlled diabetes, and certain genetic disorders

2. Protein Abnormalities

• Hyperproteinemia: Conditions with elevated protein levels such as:
  • Multiple myeloma
  • Waldenstrom's macroglobulinemia
  • Intravenous immunoglobulin therapy

3. Other Substances

• Elevated uric acid levels (>20 mg/dL) can cause pseudohypoglycemia and pseudo hyponatremia 1
• Elevated bilirubin levels can interfere with sodium measurements 1

4. Medication-Related Causes

• High acetaminophen plasma levels (>8 mg/dL) may interfere with laboratory measurements 1
• Icodextrin in peritoneal dialysis solutions can cause measurement interference, especially with glucose dehydrogenase-pyrroloquinoline-quinone (GDH-PQQ) based methods 1
• Maltose/galactose/xylose solutions and certain immunoglobulins can interfere with measurements 1

Laboratory Methods and Interference

Different laboratory methods have varying susceptibility to pseudo hyponatremia:

• Flame photometry and indirect ion-selective electrode methods: More susceptible to pseudo hyponatremia
• Direct ion-selective electrode methods: Less affected by non-aqueous components in plasma

Distinguishing from True Hyponatremia

To differentiate pseudo hyponatremia from true hyponatremia:

1. Measure serum osmolality: Normal in pseudo hyponatremia (275-295 mOsm/kg) but low in true hyponatremia
2. Calculate osmolar gap: Difference between measured and calculated osmolality
3. Check for symptoms: Patients with pseudo hyponatremia typically lack neurological symptoms associated with true hyponatremia

Clinical Significance

Recognizing pseudo hyponatremia is crucial because:

• It prevents unnecessary and potentially harmful treatment for hyponatremia
• Treating pseudo hyponatremia as true hyponatremia can lead to dangerous hypernatremia
• Identifying the underlying cause (hyperlipidemia, hyperproteinemia) may reveal important clinical conditions requiring treatment

Prevention of Misdiagnosis

• Be aware of laboratory methods used at your institution
• Consider pseudo hyponatremia in patients with known hyperlipidemia or hyperproteinemia
• Request direct ion-selective electrode measurement when pseudo hyponatremia is suspected
• Correlate sodium levels with clinical presentation and other laboratory values

Proper identification of pseudo hyponatremia prevents inappropriate treatment and focuses attention on addressing the underlying cause of laboratory interference.