pseudohyponatraemia

Pseudohyponatraemia is an analytical artifact in which serum sodium concentration is reported as low despite normal circulating sodium content. It occurs when indirect ion-selective electrode methods are used to measure sodium in serum or plasma that contains an abnormally high fraction of non-aqueous material, such as lipids or proteins. Because indirect assays assume a standard aqueous fraction, increased non-water solids lead to a falsely low sodium value while the true osmolality remains normal.

Pathophysiology and laboratory context

Most serum sodium lies in the aqueous extracellular space. Indirect ISE measurements dilute serum samples and assume a constant water fraction. Excess lipids (hyperlipidaemia) or high protein levels (hyperproteinemia, including paraproteinaemias) reduce the serum’s water fraction, producing a spuriously low sodium reading. Direct ISE methods measure sodium in undiluted plasma and usually yield a normal value in pseudohyponatraemia. The serum osmolality is typically normal, so the osmolar gap is not enlarged.

Causes

Severe hyperlipidaemia or hyperproteinaemia (e.g., monoclonal gammopathies such as multiple myeloma or Waldenström macroglobulinaemia), paraproteinemia, high-dose intravenous immunoglobulin therapy, or other conditions increasing non-aqueous serum content.

Clinical assessment and diagnosis

Pseudohyponatraemia should be suspected when hyponatraemia is discordant with clinical status and with a normal measured osmolality. Verification by re-measuring sodium using a direct ISE method or assessing serum osmolality can confirm the artifact.

Management

No specific treatment for hyponatraemia is indicated if pseudohyponatraemia is confirmed. Address the underlying lipid or protein abnormality if clinically relevant. If true hyponatraemia is present, manage according to standard guidelines for the underlying cause and neurologic risk.

See also: hyponatramia, hyperlipidaemia, paraproteinaemia.