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Difficulty: MediumInterpreting Laboratory Results

A 54-year-old man comes to the clinic for a routine follow-up. He has a history of type 2 diabetes mellitus and familial combined hyperlipidemia. He admits to poor medication adherence over the last year and has not taken his prescribed rosuvastatin or metformin for several months. He has no current symptoms. Vital signs are within normal limits. Physical examination reveals small, yellowish papules on the extensor surfaces of his arms and shoulders. Laboratory studies show the following:

Laboratory TestResult
Sodium125 mEq/L125\text{ mEq/L}
Potassium4.1 mEq/L4.1\text{ mEq/L}
Chloride94 mEq/L94\text{ mEq/L}
Bicarbonate25 mEq/L25\text{ mEq/L}
Blood urea nitrogen12 mg/dL12\text{ mg/dL}
Creatinine0.8 mg/dL0.8\text{ mg/dL}
Glucose150 mg/dL150\text{ mg/dL}

A serum osmolality is subsequently measured and reported as 289 mOsm/kg H2O289\text{ mOsm/kg H}_2\text{O} (reference range: 275−295 mOsm/kg H2O275-295\text{ mOsm/kg H}_2\text{O}). Which of the following is the most likely underlying mechanism for this patient's hyponatremia?

  1. Laboratory measurement artifact due to a decreased plasma water fractionAnswer
  2. B
    Unregulated, nonosmotic secretion of antidiuretic hormone
  3. C
    Osmotically driven shift of intracellular water into the extracellular space
  4. D
    Baroreceptor-mediated antidiuretic hormone release due to decreased effective arterial volume
  5. E
    Excessive intake of free water exceeding the maximal renal excretory capacity

Answer

Laboratory measurement artifact due to a decreased plasma water fraction
The correct underlying mechanism is a laboratory measurement artifact due to a decreased plasma water fraction. This patient has a significantly low serum sodium level (125 mEq/L125\text{ mEq/L}) but a normal measured serum osmolality (289 mOsm/kg H2O289\text{ mOsm/kg H}_2\text{O}). This combination defines isotonic hyponatremia, also known as pseudohyponatremia. The patient's clinical history of familial combined hyperlipidemia, recent medication nonadherence, and the presence of eruptive xanthomas (yellowish papules on the extensor surfaces) strongly point to severe hypertriglyceridemia. In states of marked hyperlipidemia or paraproteinemia (such as multiple myeloma), large lipid or protein molecules occupy an unusually large volume of the total plasma. This decreases the fraction of plasma that is composed of water. When clinical laboratories use indirect ion-selective electrode (ISE) methods, the sample is first diluted, and the sodium concentration is calculated based on the total plasma volume rather than the physiologically relevant plasma water volume. This results in a falsely low reported sodium concentration, despite the actual sodium concentration in the plasma water—and thus the patient's true tonicity—remaining completely normal.

Step-by-Step Solution

1
Interpret the basic metabolic panel.
The patient has marked hyponatremia with a serum sodium level of 125 mEq/L125\text{ mEq/L}.
Identifying the primary electrolyte abnormality directs the subsequent diagnostic workup.
2
Correlate the hyponatremia with the measured serum osmolality.
The measured serum osmolality is 289 mOsm/kg H2O289\text{ mOsm/kg H}_2\text{O}, which is within the normal reference range, indicating isotonic hyponatremia.
Hyponatremia must be classified by tonicity (isotonic, hypotonic, hypertonic) to determine the underlying etiology.
3
Connect the clinical presentation to the laboratory classification.
The patient has a history of familial combined hyperlipidemia, medication nonadherence, and eruptive xanthomas (indicative of severe hypertriglyceridemia). This confirms a diagnosis of pseudohyponatremia.
Severe hyperlipidemia is a classic cause of isotonic hyponatremia (pseudohyponatremia) due to a laboratory measurement artifact.

Key Concept

The initial step in interpreting hyponatremia is evaluating serum osmolality; isotonic hyponatremia (pseudohyponatremia) is a laboratory artifact caused by a decreased plasma water fraction in the setting of severe hypertriglyceridemia or paraproteinemia.
Estimated Time:1m 30s
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Interpreting Laboratory Results

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