Appropriate Workup for Hyponatremia
The appropriate workup for hyponatremia should include assessment of volume status, measurement of serum and urine osmolality, urine sodium concentration, and evaluation of acid-base status to determine the underlying cause and guide treatment. 1, 2
Initial Assessment
1. Laboratory Evaluation
- Serum sodium concentration (define severity):
- Serum osmolality (to differentiate between hypotonic, isotonic, and hypertonic hyponatremia)
- Urine osmolality (to assess ADH activity)
- Urine sodium concentration (to help determine volume status)
- Blood urea nitrogen and creatinine
- Serum potassium, chloride, and bicarbonate
- Hematocrit (to assess for hemoconcentration)
- Acid-base status 4
2. Clinical Assessment of Volume Status
Categorize the patient into one of three volume states:
Hypovolemic Hyponatremia
- Clinical signs: Orthostatic hypotension, tachycardia, dry mucous membranes
- Laboratory: Urine sodium typically <20 mmol/L (unless renal sodium wasting)
- Common causes: Diuretic use, vomiting, diarrhea, third-spacing 3, 5
Euvolemic Hyponatremia
- Clinical signs: No edema, no signs of volume depletion
- Laboratory: Urine sodium typically >40 mmol/L
- Common causes: SIADH, hypothyroidism, adrenal insufficiency, drugs 2, 5
Hypervolemic Hyponatremia
- Clinical signs: Edema, ascites, elevated jugular venous pressure
- Laboratory: Urine sodium typically <20 mmol/L (unless renal failure)
- Common causes: Heart failure, cirrhosis, nephrotic syndrome 1, 3
Specific Diagnostic Tests
For Euvolemic Hyponatremia
- Thyroid function tests (TSH, free T4)
- Morning cortisol level or ACTH stimulation test
- Chest radiograph (to screen for occult malignancy in suspected SIADH)
- Review of medications that can cause SIADH 2, 6
For Hypovolemic Hyponatremia
- Spot urine sodium:potassium ratio (ratio between 1.8 and 2.5 predicts adequate sodium excretion) 1
- Assessment of fluid balance (intake vs. output)
For Hypervolemic Hyponatremia
- Liver function tests (if cirrhosis suspected)
- Brain natriuretic peptide (if heart failure suspected)
- Urinalysis and urine protein (if renal disease suspected)
Monitoring During Workup and Treatment
- Serial serum sodium measurements (every 4-6 hours during active correction)
- Neurological assessment for symptoms of hyponatremia or rapid correction
- Fluid balance monitoring
- Weight measurements 1, 7
Important Diagnostic Pitfalls to Avoid
Failure to recognize pseudohyponatremia: Check serum osmolality to rule out non-hypotonic hyponatremia caused by hyperlipidemia or hyperproteinemia 5
Overlooking medication causes: Many medications can cause hyponatremia, including diuretics, antidepressants, antipsychotics, and anticonvulsants 2
Missing reset osmostat: Consider this diagnosis when sodium levels stabilize at a lower-than-normal level despite appropriate therapy 6
Neglecting to check for adrenal insufficiency: This can be a life-threatening cause of hyponatremia that requires specific treatment 5
Confusing cerebral salt wasting with SIADH: Both present with euvolemic or hypovolemic hyponatremia and elevated urine sodium, but treatment approaches differ significantly 6
Treatment Considerations Based on Diagnostic Findings
For severe symptomatic hyponatremia (seizures, coma): 3% hypertonic saline boluses to raise sodium by 4-6 mEq/L in the first 1-2 hours 2, 7
For chronic hyponatremia: Correct at a rate not exceeding 8 mEq/L in 24 hours to avoid osmotic demyelination syndrome 1, 8
For SIADH: Consider fluid restriction, urea, or tolvaptan depending on severity and response 8, 7
For hypovolemic hyponatremia: Normal saline infusion 3
For hypervolemic hyponatremia: Fluid restriction and treatment of underlying condition 1, 3
By following this systematic approach to the workup of hyponatremia, clinicians can accurately diagnose the underlying cause and implement appropriate treatment strategies while avoiding complications from overly rapid correction.