Spurious Hyponatremia: Diagnostic and Management Approach
What is Spurious Hyponatremia?
Spurious hyponatremia (pseudohyponatremia) is a laboratory artifact where measured serum sodium appears falsely low despite normal plasma osmolality, most commonly occurring in patients with severe hypertriglyceridemia or paraproteinemia from multiple myeloma. 1, 2
The key pathophysiologic mechanism involves excessive lipids or proteins occupying plasma volume, which dilutes the aqueous phase where sodium is dissolved. Since most laboratories use indirect ion-selective electrode (ISE) methods that dilute samples before measurement, the sodium concentration per unit volume appears artificially reduced despite normal sodium content in the water phase 3, 2.
Diagnostic Approach
Immediate Recognition Criteria
- Check for clinical-laboratory discordance: An asymptomatic patient with severely low sodium (e.g., <120 mmol/L) should immediately raise suspicion for pseudohyponatremia 2
- Calculate versus measure osmolality: The calculated serum osmolality will be decreased, but the measured osmolality will be normal (275-295 mOsm/kg) 2, 4
- Visual inspection of serum: In hypertriglyceridemia, the serum appears creamy or lipemic; in paraproteinemia, the serum has increased viscosity 2
Laboratory Confirmation
- Direct ISE measurement: Request sodium measurement using a direct ion-selective electrode method, which does not dilute the sample and will reveal the true (normal) sodium level 1, 3
- Serum triglycerides: Extremely elevated triglycerides (often >1000 mg/dL) confirm hypertriglyceridemia as the cause 3
- Serum protein electrophoresis: In multiple myeloma, look for monoclonal protein spike (typically IgG or IgA) and calculate the anion gap, which may be negative or markedly reduced 1
Critical Diagnostic Algorithm
- Measure serum osmolality directly (not calculated)
- If measured osmolality is normal (275-295 mOsm/kg) but sodium is low → pseudohyponatremia 2
- Examine serum appearance and check triglycerides and total protein
- Confirm with direct ISE sodium measurement 1, 3
Management Principles
What NOT to Do
Never treat pseudohyponatremia with hypertonic saline or sodium correction—this can be fatal. 3 A case report documented a 26-year-old patient with familial hypertriglyceridemia who received hypertonic saline for apparent hyponatremia, leading to actual hypernatremia and death after neurologic deterioration 3.
Appropriate Management
- No sodium correction is needed: The patient has normal serum sodium and normal osmolality 2
- Treat the underlying condition:
- For hypertriglyceridemia: Manage acute pancreatitis if present, initiate lipid-lowering therapy, consider plasmapheresis for severe cases (triglycerides >1000 mg/dL) 3
- For multiple myeloma: Initiate chemotherapy for the paraproteinemia; as the monoclonal protein decreases, the measured sodium will normalize 1
Monitoring
- Recheck sodium with direct ISE method to confirm true sodium levels 1, 3
- Serial measurements: As the underlying condition improves (e.g., triglycerides decrease or paraprotein burden reduces), the artifact will resolve and flame photometry measurements will normalize 1
- Document the artifact clearly in the medical record to prevent future mismanagement 3
Common Pitfalls to Avoid
- Assuming all low sodium values represent true hyponatremia: Always consider pseudohyponatremia in asymptomatic patients with severe hyponatremia 2
- Treating based on indirect ISE results alone: Request direct measurement or measured osmolality before initiating sodium correction 3
- Overlooking the clinical context: Patients with known hyperlipidemia, multiple myeloma, or Waldenström macroglobulinemia are at high risk 1, 2
- Failing to recognize the urgency: While pseudohyponatremia itself requires no sodium treatment, the underlying conditions (acute pancreatitis, multiple myeloma) require prompt management 3
Special Consideration: Anion Gap Changes
In multiple myeloma with pseudohyponatremia, the anion gap may be markedly negative (e.g., -8.8 mEq/L) due to the cationic charge of the paraprotein 1. This should prompt investigation for paraproteinemia even if not initially suspected.