Diagnostic Workup for Chronic Hyponatremia
The workup for chronic hyponatremia should include assessment of volume status, measurement of serum and urine osmolality, urine electrolytes, uric acid, and evaluation of extracellular fluid volume status to determine the underlying cause and guide appropriate treatment. 1
Initial Laboratory Evaluation
When serum sodium is less than 131 mmol/L, the following tests should be ordered:
- Serum osmolality
- Urine osmolality
- Urine electrolytes (especially sodium)
- Serum uric acid
- Thyroid function tests
- Cortisol levels (to rule out adrenal insufficiency)
A normal or high serum osmolality may indicate pseudohyponatremia from hyperglycemia or hypertriglyceridemia, which requires different management than true hypotonic hyponatremia 2.
Volume Status Assessment
Categorizing patients by volume status is crucial for determining etiology:
Hypovolemic Hyponatremia
- Clinical signs: Orthostatic hypotension, dry mucous membranes, tachycardia
- Urine sodium: Typically <20 mEq/L (unless renal sodium wasting)
- Likely causes: GI losses, diuretics, cerebral salt wasting (CSW), adrenal insufficiency
- Additional test: Central venous pressure (CVP) <6 cm H₂O suggests CSW 2, 1
Euvolemic Hyponatremia
- Clinical signs: No edema, normal vital signs
- Urine sodium: >20-40 mEq/L
- Likely causes: SIADH, hypothyroidism, adrenal insufficiency
- Additional test: CVP 6-10 cm H₂O suggests SIADH 2
Hypervolemic Hyponatremia
- Clinical signs: Edema, ascites, elevated JVP
- Urine sodium: <20 mEq/L
- Likely causes: Heart failure, cirrhosis, renal failure 1
Differentiating SIADH from Other Causes
For suspected SIADH, confirm the following criteria:
- Serum sodium <134 mEq/L
- Plasma osmolality <275 mosm/kg
- Inappropriately high urine osmolality (>500 mosm/kg)
- Inappropriately high urinary sodium (>20 mEq/L)
- Normal thyroid and adrenal function 1
A serum uric acid level <4 mg/dL in the presence of hyponatremia has a positive predictive value for SIADH of 73-100%, though this may also be seen in CSW 2.
Special Considerations
Neurosurgical Patients
In neurosurgical patients, distinguishing between SIADH and CSW is particularly important as treatment approaches differ significantly:
- CVP measurement is valuable: <6 cm H₂O suggests CSW, while 6-10 cm H₂O suggests SIADH 2
- ADH levels have limited diagnostic value and are not recommended for routine workup 2
Liver Disease Patients
For patients with liver cirrhosis:
- Evaluate for systemic vasodilation and decreased effective plasma volume
- Check for activation of renin-angiotensin-aldosterone system
- Monitor for complications including hepatic encephalopathy, hepatorenal syndrome, and spontaneous bacterial peritonitis 1
Common Pitfalls to Avoid
Failure to exclude pseudohyponatremia: Always check serum osmolality to rule out laboratory error or conditions like hyperglycemia.
Misdiagnosing SIADH vs. CSW: These conditions require opposite treatments (fluid restriction vs. fluid replacement), so accurate diagnosis is critical.
Overlooking medication causes: Many medications can cause hyponatremia, including diuretics, antidepressants, and antipsychotics.
Relying on ADH levels: Measuring ADH or natriuretic peptide levels is not supported by evidence and should not be part of routine evaluation 2.
Neglecting to assess volume status accurately: This is the cornerstone of diagnosis and subsequent management.
By following this systematic approach to the workup of chronic hyponatremia, clinicians can accurately determine the underlying cause and implement appropriate treatment strategies to improve patient outcomes and reduce morbidity and mortality.