Laboratory Tests for Hyponatremia Evaluation
The essential laboratory workup for hyponatremia should include serum osmolality, urine sodium, urine osmolality, complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, and cortisol levels to determine the underlying cause and guide appropriate treatment. 1
Initial Laboratory Assessment
When evaluating hyponatremia (serum sodium <135 mmol/L), the following tests should be ordered:
Essential Tests
Serum studies:
- Complete metabolic panel (sodium, potassium, chloride, bicarbonate, BUN, creatinine, glucose)
- Serum osmolality
- Complete blood count
- Liver function tests
- Thyroid-stimulating hormone (TSH)
- Morning cortisol level
Urine studies:
- Urine sodium
- Urine osmolality
- Urine specific gravity
Diagnostic Algorithm Based on Laboratory Results
Step 1: Assess Serum Osmolality
- Hypotonic hyponatremia (serum osmolality <280 mOsm/kg): True hyponatremia
- Isotonic hyponatremia (serum osmolality 280-295 mOsm/kg): Pseudohyponatremia
- Hypertonic hyponatremia (serum osmolality >295 mOsm/kg): Translocational hyponatremia (e.g., hyperglycemia)
Step 2: For Hypotonic Hyponatremia, Assess Volume Status and Urine Studies
Use this diagnostic table to interpret results:
| Volume Status | Urine Sodium | Urine Osmolality | Likely Diagnosis |
|---|---|---|---|
| Hypovolemic | <20 mEq/L | >100 mOsm/kg | Extrarenal losses (GI, skin) |
| Hypovolemic | >20 mEq/L | >100 mOsm/kg | Renal losses (diuretics, adrenal insufficiency) |
| Euvolemic | >20-40 mEq/L | >500 mOsm/kg | SIADH |
| Euvolemic | Variable | Normal | Reset osmostat syndrome |
| Hypervolemic | <20 mEq/L | Elevated | Heart failure, cirrhosis, nephrotic syndrome |
Special Considerations
Adrenal Insufficiency
Cortisol deficiency can present with hyponatremia that mimics SIADH 2. If morning cortisol is low (<104 nmol/L or <3.8 μg/dL), consider:
- ACTH stimulation test (preferably low-dose)
- Additional pituitary hormone testing if central adrenal insufficiency is suspected
Thyroid Function
Hypothyroidism can cause hyponatremia through impaired free water excretion. TSH measurement is essential, particularly in patients with no obvious cause of hyponatremia 1, 3.
Medication Review
Review all medications, particularly:
- Diuretics
- Antidepressants (especially SSRIs)
- Antipsychotics
- Antiepileptic drugs
- NSAIDs
Additional Tests Based on Clinical Suspicion
- For suspected heart failure: BNP or NT-proBNP, echocardiogram
- For suspected cirrhosis: Liver function tests, albumin, coagulation studies
- For suspected malignancy: Appropriate imaging or tumor markers
- For suspected polydipsia: Water loading test (under careful supervision)
Common Pitfalls to Avoid
Failing to measure serum osmolality: Essential to differentiate true hyponatremia from pseudohyponatremia or translocational hyponatremia 3
Overlooking adrenal insufficiency: Can present identically to SIADH but requires glucocorticoid replacement rather than fluid restriction 2
Incomplete urine studies: Both urine sodium and osmolality are necessary to properly categorize hyponatremia 1
Neglecting medication review: Many common medications can cause or contribute to hyponatremia 1
Missing hyperglycemia: High glucose levels can cause translocational hyponatremia; corrected sodium should be calculated 4
By following this systematic approach to laboratory testing for hyponatremia, clinicians can accurately determine the underlying cause and implement appropriate treatment strategies to improve patient outcomes.