What labs should be ordered for a patient presenting with hyponatremia?

Laboratory Workup for Hyponatremia

For a patient presenting with hyponatremia, order serum osmolality, urine osmolality, urine sodium, and assess volume status clinically—these four elements form the diagnostic foundation. 1

Essential Initial Laboratory Tests

Serum Studies (First Priority)

• Serum osmolality to exclude pseudohyponatremia (normal: 275-290 mOsm/kg) 1, 2
• Serum sodium to confirm hyponatremia (<135 mmol/L) and determine severity 3, 4
• Serum glucose because hyperglycemia causes 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 calculate effective osmolality 1, 5
• Serum uric acid because levels <4 mg/dL have 73-100% positive predictive value for SIADH 1, 2

Urine Studies (Critical for Diagnosis)

• Urine osmolality to determine if ADH is appropriately suppressed (<100 mOsm/kg indicates appropriate suppression; >100 mOsm/kg suggests impaired water excretion) 1, 5
• Urine sodium concentration to differentiate causes:
  • <30 mmol/L suggests hypovolemic hyponatremia with 71-100% positive predictive value for saline responsiveness 1, 2

  • 20-40 mmol/L with high urine osmolality (>300-500 mOsm/kg) suggests SIADH 2, 5

  • 20 mmol/L despite volume depletion suggests cerebral salt wasting or renal losses 2

Additional Serum Tests Based on Clinical Context

• Thyroid-stimulating hormone (TSH) to exclude hypothyroidism as a cause 1, 5
• Morning cortisol to rule out adrenal insufficiency in difficult cases 1, 5
• Lipid profile if pseudohyponatremia from severe hypertriglyceridemia is suspected 1
• Liver function tests (albumin, bilirubin, transaminases) if cirrhosis is suspected 1

Tests That Should NOT Be Routinely Ordered

Do not obtain ADH levels or natriuretic peptide levels—these are not supported by evidence and should not delay treatment. 1, 2 The American Academy of Neurology explicitly states this is Class III evidence (not recommended). 1

Clinical Assessment (Non-Laboratory but Essential)

While not laboratory tests, volume status assessment is mandatory and guides interpretation of lab results 1, 2:

• Hypovolemic signs: orthostatic hypotension, dry mucous membranes, decreased skin turgor, flat neck veins 1, 2
• Hypervolemic signs: peripheral edema, ascites, jugular venous distention, pulmonary congestion 1, 2
• Euvolemic: absence of both hypovolemic and hypervolemic signs 2

Important caveat: Physical examination alone has poor accuracy (sensitivity 41.1%, specificity 80%) for determining volume status, so laboratory correlation is essential. 1, 2

Diagnostic Algorithm Using Laboratory Results

1. Confirm true hyponatremia: Check serum osmolality to exclude pseudohyponatremia 1, 5
2. Assess urine osmolality:
   • <100 mOsm/kg = appropriate ADH suppression (primary polydipsia, beer potomania) 1, 5

   • 100 mOsm/kg = impaired water excretion, proceed to step 3 1, 5

3. Check urine sodium:
   • <30 mmol/L = extrarenal losses (GI losses, third-spacing) 1, 2

   • 20-40 mmol/L = renal losses or SIADH 2, 5

4. Correlate with volume status to finalize diagnosis 1, 2

Special Populations Requiring Additional Tests

Neurosurgical Patients

• Central venous pressure (CVP) may help distinguish SIADH (CVP 6-10 cm H₂O) from cerebral salt wasting (CVP <6 cm H₂O) 1, 2

Cirrhotic Patients

• Complete liver function panel including albumin 1
• 24-hour urine sodium collection or spot urine sodium/potassium ratio to guide diuretic therapy 1

Cancer Patients

• Consider paraneoplastic workup if SIADH is suspected, particularly in lung cancer 1

Monitoring During Treatment

• Serum sodium every 2 hours during initial correction for severe symptomatic hyponatremia 1
• Serum sodium every 4 hours after resolution of severe symptoms 1
• Daily sodium checks for chronic asymptomatic hyponatremia 1
• Maximum correction limit: 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 1, 3, 4