Case Presentation: A 59-year-old female with recently diagnosed perihilar lung mass and liver lesions presented for evaluation of painless jaundice and transaminitis. Initial laboratory studies revealed a sodium of 129 mOsm/kg, elevated bilirubin, alkaline phosphatase, lipase, and liver enzymes. Initial hyponatremia workup showed a serum osmolality of 279 mOsm/kg, urine osmolality of 118 mOsm/kg, and urine sodium of 29 mmol/L. Due to these borderline labs, as well as the patient’s history and presentation, a syndrome of inappropriate antidiuretic hormone secondary to suspected small cell lung cancer was hypothesized. The patient underwent a fluid challenge to clarify the diagnosis further, and hyponatremia was unchanged after receiving 1 L over 10 hours. A bronchial biopsy of the patient’s lung mass returned with non-small cell carcinoma. This finding led to a reconsideration of SIADH as the source of hyponatremia since it is rarely associated with non-small cell carcinoma. Repeat workup revealed an isotonic serum osmolality of 283 mOsm/kg. Serum-free light chains and Serum Protein Electrophoresis revealed no monoclonal gammopathy. The lipid panel was notable for markedly elevated total cholesterol and LDL of 322 mg/dl. These findings were compatible with lipoprotein X accumulation secondary to biliary obstruction causing pseudohyponatremia. ERCP found dilated proximal and mid-CBD with distal CBD stricture, which was treated with the placement of a biliary stent, and the patient was discharged. Hyponatremia resolved upon follow-up.
Discussion: In pseudohyponatremia, sodium concentration is normal in vivo, but appears low in vitro. It is associated with normal serum osmolality and caused by the processing of the sample, which is based on a presupposed relationship between serum and plasma. This relationship is altered when additional non-cellular elements are present, most commonly hypertriglyceridemia. (2) Pseudohyponatremia can occur in patients with biliary obstruction or cholestasis and can have extreme elevations of total serum cholesterol and high levels of lipoprotein-X. Lipoprotein-X is a low-density lipoprotein whose presence in the serum is specific for cholestasis, formed during the re-entry of unesterified cholesterol and phospholipids into the bloodstream. (1) Although in clinical practice, we seldom measured Lipoprotein X, a markedly elevated LDL has been previously reported in these cases and can serve as a proxy. (5) Identifying obstructive biliary cholestasis as a cause of pseudohyponatremia is imperative, as management involves treating the condition causing cholestasis and the physician can easily be led astray looking for other causes. This case also underscores the importance of recognizing cognitive biases, specifically anchoring bias, where excess weight is placed on a single—often initial—piece of information when making clinical decisions without sufficiently adjusting to later information when it becomes available (4). It is essential for physicians to thoroughly investigate etiologies and be ready to reevaluate initial hypotheses as new evidence becomes available.
Conclusions: The presence of lipoprotein-X and hyperlipidemia should be considered in patients with obstructive jaundice and hyponatremia, especially in the presence of conflicting initial workup. As clinicians, we should be aware of the biases that can distort decision-making. Holding our hypotheses lightly allows for the nimble rethinking and reframing necessary for optimal patient care.