SAT-262 - Lipoprotein X as A Rare Cause of Pseudohyponatremia: A Case Series

Lipoprotein X (LpX) is a rare, abnormal, cholesterol-rich lipoprotein that accumulates in cholestatic liver disease and can cause extreme hypercholesterolemia. LpX interferes with indirect ion-selective electrode sodium measurements, leading to pseudohyponatremia. This phenomenon has been mostly described in primary biliary cirrhosis and primary sclerosing cholangitis, but this case series demonstrates a wider variety of potential causes of LpX. Given the rarity of LpX, there is a need for greater awareness of this entity in cases of pseudohyponatremia and cholestasis.

We describe three hospitalized patients identified between 2022 and 2025 presenting with pseudohyponatremia and severe hypercholesterolemia ultimately attributed to LpX. All patients had concurrent liver disease from distinct etiologies.

Case 1 is a 72-year-old woman with obstructive jaundice from intrahepatic cholangiocarcinoma who presented with a serum sodium of 117 mmol/L, total cholesterol of 1,750 mg/dL, and low-density lipoprotein (LDL) exceeding 2,000 mg/dL. Case 2 is a 62-year-old woman with metastatic renal cell carcinoma and Stauffer’s syndrome who presented with dizziness and a serum sodium of 109 mmol/L, total cholesterol exceeding 2,100 mg/dL, and LDL exceeding 2,000 mg/dL. Case 3 is a 36-year-old man with type 1 diabetes and end-stage renal disease who developed cholestasis from sepsis with underlying steatotic liver disease, with serum sodium of 130 mmol/L, total cholesterol of 812 mg/dL, and LDL of 915 mg/dL.

In all cases, measured serum osmolality was normal or elevated despite low laboratory sodium values, and point-of-care sodium testing (when obtained) confirmed pseudohyponatremia. Lipid profiles demonstrated disproportionately high total cholesterol and calculated LDL with relatively modest apolipoprotein B elevations, consistent with LpX rather than atherogenic LDL excess. Management focused on treating the underlying hepatobiliary pathology. One patient developed symptomatic hyperviscosity and required plasma exchange, resulting in biochemical and symptomatic improvement.

LpX should be considered in patients with hyponatremia, cholestasis, and extreme hypercholesterolemia. While drastically elevated lipid profile measurements are not reflective of atherogenic LDL, LpX confers a risk of hyperviscosity syndrome, and patients should be counseled about these signs. Recognition of LpX-induced pseudohyponatremia is critical to avoid inappropriate sodium correction and to guide management toward the underlying cause, with plasma exchange reserved for symptomatic hyperviscosity.

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