What laboratory tests are recommended for further evaluation of a patient with hyponatremia?

Laboratory Evaluation for Hyponatremia

The initial laboratory workup for hyponatremia should include serum and urine osmolality, urine sodium concentration, and assessment of extracellular fluid volume status to determine the underlying cause. 1

Essential Initial Laboratory Tests

Serum Studies

• Serum osmolality to exclude pseudohyponatremia (normal range: 275-290 mOsm/kg) 1, 2
• Serum sodium (hyponatremia defined as <135 mmol/L, with full workup indicated when <131 mmol/L) 1, 3
• Serum glucose to adjust for pseudohyponatremia (add 1.6 mEq/L to sodium for each 100 mg/dL glucose >100 mg/dL) 1
• Blood urea nitrogen (BUN) and creatinine to assess renal function and volume status 1, 2
• Serum uric acid (<4 mg/dL has 73-100% positive predictive value for SIADH) 1, 3

Urine Studies

• Urine osmolality to determine if water excretion is impaired (>100 mOsm/kg suggests impaired free water excretion) 1, 2
• Urine sodium concentration to differentiate causes:
  • <30 mmol/L suggests hypovolemic hyponatremia (71-100% positive predictive value for saline responsiveness) 1, 4

  • 20-40 mmol/L with euvolemia suggests SIADH 1, 3

  • 20 mmol/L with volume depletion suggests cerebral salt wasting or renal losses 3, 4

Additional Tests Based on Clinical Context

Endocrine Evaluation

• Thyroid-stimulating hormone (TSH) to exclude hypothyroidism 1, 2
• Cortisol level to rule out adrenal insufficiency 1, 2

Volume Status Assessment

• Physical examination for signs of hypovolemia (orthostatic hypotension, dry mucous membranes, decreased skin turgor) or hypervolemia (peripheral edema, ascites, jugular venous distention), though this has limited accuracy (sensitivity 41.1%, specificity 80%) 1, 4

Specialized Tests for Specific Populations

• Liver function tests including albumin for suspected cirrhosis 1
• Brain natriuretic peptide (BNP) to assess for heart failure in hypervolemic hyponatremia 1
• Complete blood count as part of initial workup 1

Tests NOT Recommended

Do not routinely order plasma ADH levels or natriuretic peptide levels, as these are not supported by evidence and delay diagnosis without improving outcomes. 1, 3

Algorithmic Approach to Laboratory Interpretation

1. First, measure serum osmolality to exclude pseudohyponatremia (from hyperglycemia, hyperlipidemia, or hyperproteinemia) 2

2. If serum osmolality is low (<280 mOsm/kg), measure urine osmolality:

   • <100 mOsm/kg indicates appropriate ADH suppression (primary polydipsia) 2

   • 100 mOsm/kg indicates impaired water excretion (proceed to step 3) 1

3. Assess volume status clinically and measure urine sodium:

   • Hypovolemic (urine Na <30 mmol/L): extrarenal losses 1
   • Hypovolemic (urine Na >20 mmol/L): renal losses, diuretics, cerebral salt wasting 3
   • Euvolemic (urine Na >20-40 mmol/L, urine osm >300 mOsm/kg): SIADH 3
   • Hypervolemic (edema, ascites): heart failure, cirrhosis, nephrotic syndrome 1

Critical Pitfalls to Avoid

• Relying solely on physical examination to determine volume status, as it has poor sensitivity and specificity 1, 4
• Failing to distinguish SIADH from cerebral salt wasting in neurosurgical patients, as they require opposite treatments (fluid restriction vs. volume replacement) 1, 4
• Delaying treatment while pursuing extensive diagnostic workup in severely symptomatic patients 5
• Misdiagnosing volume status, which can lead to inappropriate therapy and worsened outcomes 4

Special Considerations for Neurosurgical Patients

In patients with CNS pathology (stroke, subarachnoid hemorrhage, brain injury), distinguishing between SIADH and cerebral salt wasting is critical because treatment approaches differ fundamentally. 1, 4 Consider measuring central venous pressure if available (CVP <6 cm H₂O suggests CSW, while 6-10 cm H₂O suggests SIADH). 1