What is the cause of euvolemic hyponatremia (low sodium level) in a patient with a serum sodium level of 129 mmol/L, high urine osmolality, and high urine sodium level, presenting with no clear signs of volume depletion or overload?

Diagnosis: Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

This patient has euvolemic hyponatremia consistent with SIADH, characterized by low serum sodium (129 mmol/L), low serum osmolality (281 mOsm/kg), inappropriately concentrated urine (osmolality 748 mOsm/kg), and elevated urine sodium (160 mmol/L). 1

Diagnostic Confirmation

The laboratory findings definitively establish SIADH:

• Serum sodium 129 mmol/L represents moderate hyponatremia requiring investigation and treatment 1
• Serum osmolality 281 mOsm/kg (low, <275-290 mOsm/kg normal) confirms hypotonic hyponatremia 1
• Urine osmolality 748 mOsm/kg is inappropriately elevated (>100 mOsm/kg diagnostic threshold), indicating impaired free water excretion despite low plasma osmolality 1, 2
• Urine sodium 160 mmol/L is markedly elevated (>20-40 mmol/L threshold), consistent with physiologic natriuresis that occurs in SIADH 1, 2
• Low uric acid 2.8 mg/dL has 73-100% positive predictive value for SIADH 1
• Normal renal function (creatinine 0.64, eGFR 100) excludes renal causes 1

The euvolemic status is inferred from the clinical presentation showing no clear signs of volume depletion (normal BUN 14, BUN/Cr ratio 22) or volume overload 1, 2.

Pathophysiology

SIADH results from non-osmotic hypersecretion of ADH, causing:

• Excessive water retention leading to dilutional hyponatremia 3
• Physiologic natriuresis to maintain fluid balance at the expense of plasma sodium, explaining the high urine sodium despite euvolemia 2
• Impaired free water excretion manifested by inappropriately concentrated urine 2

Common Etiologies to Investigate

Identify the underlying cause while initiating treatment 1:

• Malignancies - particularly small cell lung cancer (affects 1-5% of lung cancer patients) 1
• CNS disorders - meningitis, encephalitis, head trauma, subarachnoid hemorrhage 1, 3
• Pulmonary diseases - pneumonia, tuberculosis, positive pressure ventilation 1, 3
• Medications - SSRIs, carbamazepine, cyclophosphamide, thiazide diuretics 1, 4
• Postoperative states - pain, nausea, and stress are nonosmotic stimuli for ADH release 1

Treatment Algorithm

For Moderate Asymptomatic SIADH (Sodium 125-129 mmol/L)

Fluid restriction to 1 L/day is the cornerstone of treatment 1, 2:

• Implement strict fluid restriction <1000 mL/day as first-line therapy 1
• Monitor serum sodium every 24 hours initially 1
• Maximum correction must not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 1, 2

If fluid restriction fails after 48-72 hours, add oral sodium chloride 100 mEq (2.3 grams) three times daily 1:

• Total supplementation approximately 7 grams sodium per day 1
• Continue monitoring sodium levels every 24-48 hours 1

For persistent hyponatremia despite fluid restriction and salt supplementation, consider vasopressin receptor antagonists 1, 5:

• Tolvaptan 15 mg once daily, titrate to 30-60 mg based on response 1, 5
• Tolvaptan increases serum sodium significantly more than placebo (4.0 mEq/L vs 0.4 mEq/L at Day 4) 5
• Use with extreme caution and close monitoring to avoid overly rapid correction 1

For Severe Symptomatic Hyponatremia (<125 mmol/L with neurological symptoms)

Administer 3% hypertonic saline immediately 1, 6:

• Target correction of 6 mmol/L over first 6 hours or until symptoms resolve 1
• Total correction must not exceed 8 mmol/L in 24 hours 1, 2
• Check serum sodium every 2 hours during initial correction 1
• Consider ICU admission for close monitoring 1

Critical Safety Considerations

Never exceed 8 mmol/L correction in 24 hours - this causes osmotic demyelination syndrome, a devastating neurological complication 1, 2:

• Symptoms include dysarthria, dysphagia, oculomotor dysfunction, quadriparesis 1
• Typically occurs 2-7 days after rapid correction 1
• High-risk patients (alcoholism, malnutrition, liver disease) require even slower correction at 4-6 mmol/L per day 1

If overcorrection occurs, immediately discontinue current fluids and switch to D5W, consider desmopressin to slow sodium rise 1.

Common Pitfalls to Avoid

• Do not use 0.9% normal saline in SIADH - it acts as a hypotonic solution in these patients, causing rapid fluctuations in serum sodium with risk of both overcorrection during infusion and post-infusion worsening 2
• Do not ignore moderate hyponatremia (130-135 mmol/L) - even mild hyponatremia increases fall risk (21% vs 5%) and mortality (60-fold increase with sodium <130 mmol/L) 1
• Do not delay treatment while pursuing diagnosis - initiate fluid restriction immediately while investigating underlying cause 6
• Do not use fluid restriction in cerebral salt wasting - this mimics SIADH but requires opposite treatment with volume and sodium replacement 1, 2