How do you evaluate the cause of hyponatremia (low sodium levels)?

Evaluating the Cause of Hyponatremia

Begin by measuring serum osmolality, urine osmolality, urine sodium, and assessing volume status—these four parameters will guide you to the underlying cause. 1, 2

Initial Laboratory Workup

When serum sodium is <131 mmol/L (though some define hyponatremia as <135 mmol/L), obtain the following tests immediately 1, 2:

• Serum osmolality (normal: 275-290 mOsm/kg) 1
• Urine osmolality 1, 2
• Urine sodium concentration 1, 2
• Serum uric acid (if <4 mg/dL, has 73-100% positive predictive value for SIADH) 1
• Serum creatinine and BUN 2
• Thyroid-stimulating hormone (TSH) to exclude hypothyroidism 2
• Morning cortisol to exclude adrenal insufficiency 1
• Serum glucose (hyperglycemia causes pseudohyponatremia—add 1.6 mEq/L to sodium for each 100 mg/dL glucose >100 mg/dL) 2

Do not obtain ADH or natriuretic peptide levels—these are not supported by evidence and delay treatment. 1

Step 1: Rule Out Pseudohyponatremia

Check serum osmolality first 1:

• Normal or high serum osmolality (≥275 mOsm/kg): Consider pseudohyponatremia from hyperglycemia, hypertriglyceridemia, or laboratory error 1
• Low serum osmolality (<275 mOsm/kg): True hypotonic hyponatremia—proceed to volume assessment 1

Step 2: Assess Volume Status

Physical examination alone is unreliable (sensitivity 41.1%, specificity 80%), so combine clinical findings with laboratory data. 1, 3

Hypovolemic Signs:

• Orthostatic hypotension 1
• Dry mucous membranes 1
• Decreased skin turgor 1
• Tachycardia 2

Euvolemic Signs:

• No edema 2
• Normal blood pressure 2
• Moist mucous membranes 2

Hypervolemic Signs:

• Peripheral edema 2
• Ascites 2
• Jugular venous distention 2
• Pulmonary congestion 2

Step 3: Interpret Urine Sodium

The urine sodium concentration differentiates renal from extrarenal causes 1, 2:

For Hypovolemic Hyponatremia:

• Urine sodium <30 mmol/L (71-100% positive predictive value for response to saline): Extrarenal losses (GI losses, burns, dehydration) 1, 3
• Urine sodium >20 mmol/L: Renal losses (diuretics, cerebral salt wasting, adrenal insufficiency, salt-losing nephropathy) 1

For Euvolemic Hyponatremia:

• Urine sodium >40 mEq/L + urine osmolality >500 mOsm/kg: SIADH 1
• Urine osmolality <100 mOsm/kg: Primary polydipsia 1

For Hypervolemic Hyponatremia:

• Urine sodium >20 mEq/L: Advanced renal failure 1
• Urine sodium <30 mmol/L: Heart failure, cirrhosis, nephrotic syndrome 2

Step 4: Differential Diagnosis by Category

Hypovolemic Hyponatremia

Characterized by: Volume depletion signs + elevated urinary sodium (>20 mEq/L) OR low urinary sodium (<30 mmol/L) 1

Common causes:

• Cerebral salt wasting (CSW)—especially in neurosurgical patients 1, 3
• Diuretic use 1
• Adrenal insufficiency 1
• GI losses (vomiting, diarrhea) 2
• Salt-losing nephropathy 1

Euvolemic Hyponatremia (SIADH)

Characterized by: Euvolemia + urine osmolality >500 mOsm/kg + urine sodium >40 mEq/L + absence of hypothyroidism/adrenal insufficiency 1

Common causes:

• Neoplasms (especially small cell lung cancer) 1
• CNS disorders (stroke, hemorrhage, trauma) 1, 3
• Medications (SSRIs, carbamazepine, NSAIDs) 1
• Pulmonary disease 2

Hypervolemic Hyponatremia

Characterized by: Volume overload signs + elevated urinary sodium (>20 mEq/L) 1

Common causes:

• Advanced renal failure 1
• Cirrhosis 2
• Heart failure 2

Critical Distinction: SIADH vs. Cerebral Salt Wasting

In neurosurgical patients (stroke, SAH, trauma), distinguishing SIADH from CSW is critical because treatment approaches are opposite. 1, 3

SIADH Features:

• Euvolemia (CVP 6-10 cm H₂O) 1
• Urine sodium >40 mEq/L 1
• Urine osmolality >500 mOsm/kg 1
• Treatment: Fluid restriction 1

Cerebral Salt Wasting Features:

• Hypovolemia (CVP <6 cm H₂O) 1
• Urine sodium >20 mEq/L despite volume depletion 3
• Signs of dehydration 3
• Treatment: Volume and sodium replacement 1, 3

Misdiagnosing CSW as SIADH and restricting fluids can worsen outcomes and increase risk of cerebral ischemia. 1, 3

Common Pitfalls to Avoid

• Relying solely on physical examination for volume status determination—combine with laboratory values 1, 3
• Obtaining ADH levels—not supported by evidence and delays treatment 1
• Ignoring mild hyponatremia (130-135 mmol/L)—even mild hyponatremia increases fall risk (21% vs 5%) and mortality 2, 4
• Failing to check thyroid and adrenal function—these are reversible causes that must be excluded 1, 2
• Using fluid restriction in cerebral salt wasting—this worsens outcomes 1, 3