What are the initial investigations for a patient presenting with hyponatremia?

Initial Investigations for Hyponatremia

Immediate Laboratory Assessment

The initial workup for hyponatremia (serum sodium <135 mmol/L) should include serum osmolality, urine osmolality, urine sodium concentration, urine electrolytes, serum uric acid, and clinical assessment of extracellular fluid volume status. 1, 2

Essential First-Line Tests

• Serum osmolality (normal: 275-290 mOsm/kg) to exclude pseudohyponatremia from hyperglycemia, hypertriglyceridemia, or laboratory error 2, 3

• Urine osmolality to assess water excretion capacity:

  • <100 mOsm/kg indicates appropriate ADH suppression 2

  • 100 mOsm/kg suggests impaired water excretion 2

  • 300-500 mOsm/kg with elevated urine sodium suggests SIADH 2

• Urine sodium concentration for differential diagnosis:

  • <30 mmol/L suggests extrarenal losses (positive predictive value 71-100% for saline responsiveness) 1, 2

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

  • 20 mmol/L with hypovolemia suggests renal losses, cerebral salt wasting, or diuretic use 2

• Serum uric acid: <4 mg/dL has 73-100% positive predictive value for SIADH (though may also occur in cerebral salt wasting) 1, 2

Additional Baseline Tests

• Serum creatinine and blood urea nitrogen to assess renal function 1
• Serum glucose (adjust sodium by 1.6 mEq/L for each 100 mg/dL glucose >100 mg/dL) 1
• Thyroid-stimulating hormone (TSH) to exclude hypothyroidism 1
• Serum potassium, calcium, and magnesium 1
• Complete blood count 1
• Liver function tests if cirrhosis suspected 1

Critical Clinical Assessment

Volume Status Determination

Physical examination alone has poor accuracy (sensitivity 41.1%, specificity 80%) for determining volume status, so laboratory parameters are essential. 2

• Hypovolemic signs: orthostatic hypotension, dry mucous membranes, decreased skin turgor, flat neck veins 2

• Euvolemic signs: no edema, no orthostatic hypotension, normal skin turgor, moist mucous membranes 1

• Hypervolemic signs: peripheral edema, ascites, jugular venous distention, pulmonary congestion 1, 2

Symptom Severity Assessment

• Severe symptoms (seizures, coma, altered mental status) require immediate hypertonic saline 1
• Mild symptoms (nausea, headache, confusion) allow for more measured correction 1
• Asymptomatic patients still require investigation when sodium <131 mmol/L 1, 2

Diagnostic Algorithm Based on Initial Results

Step 1: Confirm Hypotonic Hyponatremia

• If serum osmolality is normal or high, consider pseudohyponatremia 2, 3
• If serum osmolality is low (<275 mOsm/kg), proceed to Step 2 2

Step 2: Assess Urine Osmolality

• Urine osmolality <100 mOsm/kg: Consider primary polydipsia, reset osmostat, or beer potomania 2
• Urine osmolality >100 mOsm/kg: Proceed to Step 3 2

Step 3: Determine Volume Status and Urine Sodium

For Hypovolemic Patients:

• Urine sodium <30 mmol/L: extrarenal losses (GI losses, burns, third-spacing) 2
• Urine sodium >20 mmol/L: renal losses (diuretics, cerebral salt wasting, adrenal insufficiency) 2

For Euvolemic Patients:

• Urine sodium >20-40 mmol/L with urine osmolality >300 mOsm/kg: SIADH 2
• Rule out hypothyroidism and adrenal insufficiency 2

For Hypervolemic Patients:

• Consider heart failure, cirrhosis, nephrotic syndrome, or advanced renal failure 1, 2

Special Considerations

Neurosurgical Patients

Distinguishing SIADH from cerebral salt wasting (CSW) is critical, as they require opposite treatments. 1, 2

• SIADH: euvolemic, CVP 6-10 cm H₂O, urine sodium >20-40 mmol/L, treat with fluid restriction 1, 2
• CSW: hypovolemic, CVP <6 cm H₂O, urine sodium >20 mmol/L despite volume depletion, treat with volume replacement 1, 2

Tests NOT Recommended

• ADH levels and natriuretic peptide levels are not supported by evidence and should not be obtained 2
• These tests do not change management and delay appropriate treatment 2

Common Diagnostic Pitfalls

• Relying solely on physical examination for volume status determination (sensitivity only 41.1%) 2
• Diagnosing SIADH before excluding hypothyroidism, adrenal insufficiency, and volume depletion 4
• Ignoring mild hyponatremia (130-135 mmol/L), which increases fall risk and mortality 1
• Failing to assess symptom severity before initiating treatment 1
• Not considering medication history, particularly diuretics, SSRIs, carbamazepine, and antipsychotics 5

Monitoring Parameters

• Serum sodium should be checked every 2 hours during active correction of severe symptomatic hyponatremia 1
• Maximum correction rate must not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 1
• High-risk patients (cirrhosis, alcoholism, malnutrition) require even slower correction at 4-6 mmol/L per day 1