What is the appropriate work‑up for an asymptomatic patient with hyponatremia?

Workup for Asymptomatic Hyponatremia

For an asymptomatic patient with hyponatremia (serum sodium <135 mmol/L), begin with serum and urine osmolality, urine sodium concentration, urine electrolytes, serum uric acid, and clinical assessment of extracellular fluid volume status to determine the underlying etiology. 1

Initial Laboratory Assessment

Obtain the following tests immediately:

• Serum osmolality to confirm true hypotonic hyponatremia (normal 275-295 mOsm/kg) and exclude pseudohyponatremia from hyperglycemia, hyperlipidemia, or hyperproteinemia 1, 2, 3
• Urine osmolality to assess water excretion capacity: <100 mOsm/kg indicates appropriate ADH suppression (primary polydipsia), while >100 mOsm/kg suggests impaired free water excretion 1, 2
• Urine sodium concentration to differentiate causes: <30 mmol/L suggests extrarenal losses or effective volume depletion, while >20-40 mmol/L indicates renal sodium wasting or SIADH 1, 2, 4
• Serum uric acid: levels <4 mg/dL have 73-100% positive predictive value for SIADH 1
• Serum creatinine and BUN to assess renal function and identify prerenal azotemia (BUN:Cr ratio >20:1 suggests hypovolemia) 1
• Thyroid-stimulating hormone (TSH) to exclude hypothyroidism 1
• Morning cortisol if adrenal insufficiency is suspected 1

Clinical Volume Status Assessment

Perform a focused physical examination to categorize the patient into one of three volume states (though physical exam alone has limited accuracy with 41% sensitivity and 80% specificity): 1

Hypovolemic Signs

• Orthostatic hypotension (>20 mmHg systolic drop or >10 mmHg diastolic drop upon standing) 1
• Dry mucous membranes, decreased skin turgor 1
• Flat neck veins, tachycardia 1

Euvolemic Signs

• Normal blood pressure without orthostasis 1
• Moist mucous membranes, normal skin turgor 1
• No edema, no jugular venous distention 1

Hypervolemic Signs

• Peripheral edema (pedal, sacral) 1
• Ascites 1
• Jugular venous distention 1
• Pulmonary congestion on lung examination 1

Diagnostic Algorithm Based on Initial Results

If Serum Osmolality is Low (<275 mOsm/kg)

Proceed with urine osmolality interpretation:

• Urine osmolality <100 mOsm/kg: Primary polydipsia (excessive water intake with appropriate ADH suppression) 1, 2

• Urine osmolality >100 mOsm/kg: Impaired water excretion; proceed to volume status and urine sodium 1

Hypovolemic Hyponatremia (Volume Depleted)

Urine sodium <30 mmol/L (71-100% positive predictive value for saline responsiveness): 1

• Extrarenal losses: vomiting, diarrhea, third-spacing, burns 1, 2

Urine sodium >20 mmol/L:

• Renal losses: diuretics, salt-wasting nephropathy, mineralocorticoid deficiency, cerebral salt wasting 1, 2

Euvolemic Hyponatremia (Normal Volume Status)

Urine sodium >20-40 mmol/L with urine osmolality >300 mOsm/kg:

• SIADH is the most likely diagnosis 1, 2, 3
• Confirm with serum uric acid <4 mg/dL (73-100% PPV) 1
• Exclude hypothyroidism (check TSH) and adrenal insufficiency (check morning cortisol) 1
• Investigate underlying causes: malignancy (especially small cell lung cancer), CNS disorders, pulmonary disease, medications (SSRIs, carbamazepine, cyclophosphamide, NSAIDs) 1, 2, 3

Hypervolemic Hyponatremia (Volume Overloaded)

Clinical context determines etiology:

• Heart failure: elevated BNP, jugular venous distention, pulmonary edema 1
• Cirrhosis: ascites, liver function test abnormalities, low albumin 1
• Nephrotic syndrome or advanced kidney disease: proteinuria, elevated creatinine 1

Additional Workup Based on Clinical Context

For suspected SIADH, investigate underlying causes:

• Chest X-ray or CT chest to evaluate for pulmonary pathology or malignancy 1
• Brain imaging (CT or MRI) if CNS disorder suspected 1
• Comprehensive medication review for causative agents 1

For neurosurgical patients or those with CNS pathology:

• Distinguish SIADH from cerebral salt wasting (CSW) by assessing central venous pressure if available: CVP <6 cm H₂O suggests CSW, while normal to elevated CVP suggests SIADH 1

For cirrhotic patients:

• Liver function tests, albumin, and assessment for complications (spontaneous bacterial peritonitis, hepatorenal syndrome, hepatic encephalopathy) 1

Common Diagnostic Pitfalls to Avoid

• Do not rely on physical examination alone for volume status assessment—it has poor sensitivity (41%) and specificity (80%) 1
• Do not obtain ADH or natriuretic peptide levels routinely—they are not supported by evidence and delay treatment 1
• Do not ignore mild hyponatremia (130-135 mmol/L)—even mild levels increase fall risk (21% vs 5% in normonatremic patients) and mortality (60-fold increase with sodium <130 mmol/L) 1
• Do not miss medication-induced hyponatremia—review all medications, especially diuretics, SSRIs, carbamazepine, NSAIDs, and chemotherapy agents 1
• In neurosurgical patients, do not assume SIADH—cerebral salt wasting is more common and requires opposite treatment (volume expansion vs. fluid restriction) 1

When to Pursue Full Workup

Investigate thoroughly when serum sodium drops below 131 mmol/L, though even mild hyponatremia (130-135 mmol/L) warrants attention due to increased morbidity and mortality 1, 4