What is the workup for hyponatremia (low sodium levels)?

Diagnostic Workup for Hyponatremia

The initial workup for hyponatremia should include assessment of volume status, measurement of serum and urine osmolality, and urine sodium concentration to determine the underlying cause and guide appropriate management. 1

Step 1: Classify Hyponatremia by Plasma Osmolality

• Measure serum osmolality to differentiate between:
  • Hypotonic hyponatremia (low osmolality <275 mOsm/kg) - most common
  • Isotonic hyponatremia (normal osmolality 275-295 mOsm/kg) - pseudohyponatremia
  • Hypertonic hyponatremia (high osmolality >295 mOsm/kg) - typically from hyperglycemia 2, 3

Step 2: Assess Volume Status in Hypotonic Hyponatremia

Categorize the patient into one of three volume states:

Hypovolemic Hyponatremia

• Clinical signs: Orthostatic hypotension, tachycardia, dry mucous membranes, decreased skin turgor
• Laboratory tests:
  • Urine sodium <20 mEq/L (with extrarenal losses)
  • Urine sodium >20 mEq/L (with renal losses - diuretics, salt-wasting nephropathy)
• Common causes: Diuretic excess, vomiting, diarrhea, third-spacing 1, 4

Euvolemic Hyponatremia

• Clinical signs: No edema, no orthostasis
• Laboratory tests:
  • Urine osmolality >100 mOsm/kg
  • Urine sodium >40 mEq/L
• Common causes: SIADH, hypothyroidism, adrenal insufficiency, medications 1
• SIADH diagnostic criteria:
  • Hyponatremia (serum sodium <134 mEq/L)
  • Hypoosmolality (plasma osmolality <275 mOsm/kg)
  • Inappropriately high urine osmolality (>500 mOsm/kg)
  • Inappropriately high urinary sodium (>20 mEq/L)
  • Absence of hypothyroidism, adrenal insufficiency, or volume depletion 1

Hypervolemic Hyponatremia

• Clinical signs: Edema, ascites, elevated jugular venous pressure
• Laboratory tests:
  • Urine sodium <20 mEq/L (typically)
• Common causes: Cirrhosis, heart failure, nephrotic syndrome, advanced kidney disease 1

Step 3: Additional Testing Based on Clinical Context

• Thyroid function tests (TSH, free T4) to rule out hypothyroidism
• Morning cortisol and ACTH to exclude adrenal insufficiency
• Liver function tests and albumin if cirrhosis suspected
• BNP or NT-proBNP if heart failure suspected
• Medication review for drugs associated with hyponatremia (diuretics, antidepressants, antipsychotics, anticonvulsants)
• Serum uric acid (typically <4 mg/dL in SIADH) 1
• Fractional excretion of urate to improve diagnostic accuracy for SIADH 1

Special Considerations in Cirrhosis

In patients with cirrhosis, hyponatremia is often dilutional and defined as serum sodium <130 mmol/L. It significantly increases risk of complications including:

• Spontaneous bacterial peritonitis (OR 3.40)
• Hepatorenal syndrome (OR 3.45)
• Hepatic encephalopathy (OR 2.36) 1

Severity Assessment

Classify hyponatremia severity:

• Mild: 126-135 mEq/L
• Moderate: 120-125 mEq/L
• Severe: <120 mEq/L 1

Assess for symptoms:

• Mild symptoms: Nausea, headache, confusion, muscle cramps
• Severe symptoms: Seizures, coma, respiratory distress 1, 4

Common Pitfalls to Avoid

1. Failure to determine chronicity: Always try to establish if hyponatremia is acute (<48 hours) or chronic (>48 hours) as this affects treatment approach
2. Overlooking pseudohyponatremia: Check for high protein or lipid states
3. Missing medication causes: Review all medications thoroughly
4. Correcting sodium too rapidly: This can lead to osmotic demyelination syndrome
5. Treating laboratory value rather than patient: Treatment urgency should be based on symptoms, not just sodium level
6. Neglecting to reassess: Frequent monitoring of serum sodium during correction is essential

By following this systematic approach to the workup of hyponatremia, clinicians can accurately identify the underlying cause and implement appropriate management strategies to improve patient outcomes and reduce mortality.