What initial laboratory tests should be ordered for a patient presenting with hyponatremia to assess severity, chronicity, and underlying cause?

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Laboratory Workup for Hyponatremia

Order serum osmolality, urine osmolality, urine sodium, serum creatinine, and assess volume status clinically to determine the underlying cause of hyponatremia. 1

Essential Initial Laboratory Tests

Serum Studies

  • Serum sodium confirms hyponatremia (<135 mmol/L); values <131 mmol/L warrant comprehensive workup 1, 2
  • Serum osmolality (normal 275-290 mOsm/kg) distinguishes true hyponatremia from pseudohyponatremia caused by hyperglycemia or hyperlipidemia 1, 3
  • Serum creatinine and BUN assess renal function and help identify prerenal causes 1, 2
  • Serum glucose because hyperglycemia causes pseudohyponatremia (add 1.6 mEq/L to sodium for each 100 mg/dL glucose >100 mg/dL) 1
  • Serum uric acid <4 mg/dL has 73-100% positive predictive value for SIADH, though also seen in cerebral salt wasting 1, 2, 4

Urine Studies

  • Urine osmolality distinguishes appropriate ADH suppression (<100 mOsm/kg) from inappropriate concentration (>100 mOsm/kg, typically >300-500 mOsm/kg in SIADH) 1, 2
  • Urine sodium concentration is the single most useful test for differential diagnosis 1, 2, 3:
    • <30 mmol/L suggests hypovolemic hyponatremia from extrarenal losses (71-100% positive predictive value for saline responsiveness) 1, 4

    • 20-40 mmol/L with euvolemia suggests SIADH 2, 3

    • 20 mmol/L with hypovolemia suggests cerebral salt wasting, diuretic use, or adrenal insufficiency 2, 4

Hormone Studies to Exclude Mimics

  • Thyroid-stimulating hormone (TSH) to rule out hypothyroidism, which can mimic SIADH 1, 2
  • Morning cortisol or ACTH stimulation test to exclude adrenal insufficiency 1, 2

Tests NOT Recommended

Do not order plasma ADH or natriuretic peptide levels—these are not supported by evidence, delay diagnosis, and do not alter management. 1, 2

Volume Status Assessment

Physical examination alone has poor accuracy (sensitivity 41%, specificity 80%) for determining volume status 1, 2, 4. Look for specific findings:

Hypovolemic Signs

  • Orthostatic hypotension, tachycardia 1, 4
  • Dry mucous membranes, decreased skin turgor 1, 2
  • Flat neck veins 1

Euvolemic Signs

  • No edema, no orthostatic hypotension 1
  • Normal skin turgor, moist mucous membranes 1

Hypervolemic Signs

  • Peripheral edema, ascites 1, 2
  • Jugular venous distention 1, 3
  • Pulmonary congestion 1

Diagnostic Algorithm Based on Laboratory Results

Step 1: Confirm True Hyponatremia

  • If serum osmolality is normal or high, consider pseudohyponatremia from hyperglycemia, hyperlipidemia, or hyperproteinemia 1, 3

Step 2: Assess Urine Osmolality

  • <100 mOsm/kg indicates appropriate ADH suppression (primary polydipsia, reset osmostat) 1, 2

  • 100 mOsm/kg indicates impaired water excretion; proceed to urine sodium 1, 2

Step 3: Interpret Urine Sodium with Volume Status

Urine Na <30 mmol/L:

  • Hypovolemic: extrarenal losses (GI losses, burns, third-spacing) 1, 3
  • Hypervolemic: heart failure, cirrhosis, nephrotic syndrome 1, 3

Urine Na >20-40 mmol/L:

  • Hypovolemic: renal losses (diuretics, cerebral salt wasting, adrenal insufficiency, salt-losing nephropathy) 2, 4
  • Euvolemic: SIADH (most common), hypothyroidism, medications 2, 3
  • Hypervolemic: advanced renal failure 2

Special Considerations in Neurosurgical Patients

In patients with stroke, subarachnoid hemorrhage, or brain injury, distinguish SIADH from cerebral salt wasting because they require opposite treatments. 1, 4

SIADH Characteristics

  • Euvolemic on exam 1, 4
  • Urine Na >20-40 mEq/L 2, 4
  • Urine osmolality >300 mOsm/kg 2, 4
  • Central venous pressure 6-10 cm H₂O if measured 1
  • Treatment: fluid restriction 1, 4

Cerebral Salt Wasting Characteristics

  • Hypovolemic on exam (orthostatic changes, tachycardia) 1, 4
  • Urine Na >20 mEq/L despite volume depletion 2, 4
  • Central venous pressure <6 cm H₂O if measured 1
  • Treatment: volume and sodium replacement; never fluid restriction 1, 4

Common Pitfalls to Avoid

  • Relying solely on physical examination for volume status determination—sensitivity is only 41% 1, 2, 4
  • Ordering ADH levels—not evidence-based and delays treatment 1, 2
  • Misdiagnosing cerebral salt wasting as SIADH in neurosurgical patients leads to inappropriate fluid restriction and worsened outcomes 1, 4
  • Failing to check medications that cause SIADH (SSRIs, carbamazepine, NSAIDs, opioids, chemotherapy) 1, 5
  • Not excluding hypothyroidism and adrenal insufficiency before confirming SIADH 1, 2

References

1
Guideline

Management of Sodium Imbalance

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

2
Guideline

Diagnosis and Management of Hyponatremia with Elevated Urinary Sodium

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

3
Research

Management of hyponatremia.

American family physician, 2004

4
Guideline

Determining the Cause of Hyponatremia in Post-Stroke Patients

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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