What is the best approach to evaluating hyponatremia?

Evaluating Hyponatremia: A Systematic Diagnostic Approach

Initial Laboratory Workup

When serum sodium is <131 mmol/L, obtain serum and urine osmolality, urine sodium, urine electrolytes, and serum uric acid 1, 2. This threshold triggers a comprehensive evaluation, though even mild hyponatremia (130-135 mmol/L) warrants attention given its association with increased falls, fractures, and mortality 2, 3.

Step 1: Confirm True Hypotonic Hyponatremia

• Measure serum osmolality (normal: 275-290 mOsm/kg) to exclude pseudohyponatremia 1, 4
• Normal or high serum osmolality suggests laboratory error, hyperglycemia (add 1.6 mEq/L to sodium for each 100 mg/dL glucose >100 mg/dL), or hypertriglyceridemia 1, 2
• Only proceed with further workup if serum osmolality is low, confirming true hypotonic hyponatremia 5

Step 2: Assess Symptom Severity and Acuity

Determine if hyponatremia is acute (<48 hours) or chronic (>48 hours), as this fundamentally changes correction rates 2, 6.

• Severe symptoms requiring immediate intervention: seizures, coma, somnolence, obtundation, cardiorespiratory distress 2, 3
• Moderate symptoms: nausea, vomiting, headache, confusion 2
• Mild/asymptomatic: weakness, cognitive impairment, gait disturbances 3

Step 3: Measure Urine Studies

Obtain urine osmolality and urine sodium concentration simultaneously 1, 4:

• Urine osmolality <100 mOsm/kg suggests primary polydipsia or reset osmostat 4
• Urine osmolality >100 mOsm/kg indicates inappropriate ADH activity or volume depletion 4
• Urine sodium <30 mmol/L has 71-100% positive predictive value for saline responsiveness (hypovolemic hyponatremia) 1, 4
• Urine sodium >20-40 mEq/L suggests SIADH, cerebral salt wasting, diuretic use, or adrenal insufficiency 4

Step 4: Determine Volume Status

Assess extracellular fluid volume through physical examination, recognizing this has limited accuracy (sensitivity 41.1%, specificity 80%) 1, 4:

Hypovolemic signs (ECF contraction):

• Orthostatic hypotension (systolic BP decrease >10% upright vs. supine) 1
• Orthostatic tachycardia (pulse increase >10% upright vs. supine) 1
• Dry mucous membranes, decreased skin turgor 1, 4
• Flat neck veins 1

Euvolemic signs (normal ECF):

• No edema, no orthostatic hypotension 4
• Normal skin turgor, moist mucous membranes 4
• Normal jugular venous pressure 4

Hypervolemic signs (ECF expansion):

• Peripheral edema, ascites 1, 4
• Jugular venous distention 1, 4
• Pulmonary congestion 4

In neurosurgical patients, central venous pressure measurement improves accuracy: CVP <6 cm H₂O suggests cerebral salt wasting (hypovolemic), while CVP 6-10 cm H₂O suggests SIADH (euvolemic) 4.

Step 5: Additional Diagnostic Tests

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

Rule out endocrine causes:

• TSH to exclude hypothyroidism 2, 4
• Morning cortisol to exclude adrenal insufficiency 2, 5
• Serum creatinine to assess renal function 2, 5

Diagnostic Algorithm by Volume Status

Hypovolemic Hyponatremia (ECF Contraction)

If urine sodium <30 mmol/L: extrarenal losses (GI losses, burns, third-spacing) 1, 4

If urine sodium >20 mmol/L: renal losses 4

• Diuretic use (most common) 1
• Cerebral salt wasting (in neurosurgical patients) 1, 4
• Salt-losing nephropathy 4
• Adrenal insufficiency 1

Euvolemic Hyponatremia (Normal ECF)

If urine osmolality >300 mOsm/kg and urine sodium >40 mEq/L: SIADH 4

Common SIADH causes to investigate 4, 3:

• Malignancy (especially small cell lung cancer)
• CNS disorders (stroke, hemorrhage, infection)
• Pulmonary disease (pneumonia, tuberculosis)
• Medications (SSRIs, carbamazepine, NSAIDs, PPIs)

Must exclude before diagnosing SIADH 1, 4:

• Hypothyroidism (check TSH)
• Adrenal insufficiency (check morning cortisol)
• Primary polydipsia (urine osmolality <100 mOsm/kg)

Hypervolemic Hyponatremia (ECF Expansion)

Characterized by edema, ascites, or pulmonary congestion 4:

• Heart failure (check BNP) 2
• Cirrhosis (check liver function tests, albumin) 2, 5
• Advanced renal failure (check creatinine, GFR) 4

Tests NOT Recommended

Do not obtain ADH or natriuretic peptide levels 1, 2. These have limited diagnostic value, with ADH detectable even in non-SIADH hyponatremia and "appropriate" levels undefined 1. The available data on these hormones are conflicting and do not change management 1.

Critical Pitfalls to Avoid

• Relying solely on physical examination for volume status determination leads to misdiagnosis in 59% of cases 1, 4
• Failing to distinguish SIADH from cerebral salt wasting in neurosurgical patients, as treatments are opposite (fluid restriction vs. volume replacement) 1, 2, 4
• Ignoring mild hyponatremia (130-135 mmol/L) despite its association with falls (23.8% vs. 16.4% in normonatremic patients), fractures, and increased mortality 2, 3
• Ordering ADH levels, which delays treatment without providing actionable information 1, 2
• Assuming hypervolemic patients are always volume overloaded—some may have effective arterial underfilling requiring careful fluid management 5