What are the diagnostic criteria and treatment options for Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion?

SIADH Diagnosis and Treatment

Diagnostic Criteria

SIADH is diagnosed when five cardinal criteria are met: hypotonic hyponatremia (serum sodium <134 mEq/L), inappropriately elevated urine osmolality (>500 mosm/kg), inappropriately high urinary sodium (>20 mEq/L), euvolemic state (absence of edema or volume depletion), and normal thyroid, adrenal, and renal function. 1, 2

Essential Laboratory Findings

• Serum sodium <134 mEq/L with plasma osmolality <275 mosm/kg 1
• Urine osmolality >500 mosm/kg despite low serum osmolality 1
• Urine sodium >20 mEq/L (typically >30 mEq/L in 70% of cases) 1, 3
• Fractional excretion of sodium >0.5% in 70% of SIADH cases 3

Supporting Laboratory Features

• Serum uric acid <4 mg/dL has 73-100% positive predictive value for SIADH 1, 4
• Low blood urea nitrogen is typical, though less specific in elderly patients 3
• Normal or near-normal total CO2 and potassium despite dilution 3
• Lower anion gap compared to other causes of hyponatremia 3

Critical Exclusions Before Diagnosis

• Rule out hypothyroidism with TSH testing 1, 4
• Rule out adrenal insufficiency with cortisol assessment 1, 4
• Confirm absence of volume depletion through clinical examination (no orthostatic hypotension, dry mucous membranes, or decreased skin turgor) 1, 4
• Exclude thiazide diuretic use as a cause 5

Volume Status Assessment

Euvolemia is essential for SIADH diagnosis—patients should have no edema, no orthostatic hypotension, normal skin turgor, and moist mucous membranes. 4 Physical examination alone has poor sensitivity (41.1%) and specificity (80%) for volume assessment, so laboratory parameters are critical 4.

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Treatment Algorithm Based on Severity

Severe Symptomatic Hyponatremia (Seizures, Coma, Altered Mental Status)

For severe symptoms, immediately transfer to ICU and administer 3% hypertonic saline with a target correction of 6 mmol/L over 6 hours or until symptoms resolve, never exceeding 8 mmol/L total correction in 24 hours. 1, 4

• Administer 3% saline as 100 mL boluses over 10 minutes, repeatable up to three times at 10-minute intervals 4
• Monitor serum sodium every 2 hours during initial correction 1, 4
• Maximum correction: 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 1, 4, 6
• High-risk patients (advanced liver disease, alcoholism, malnutrition) require slower correction at 4-6 mmol/L per day 1, 4

Mild Symptomatic or Asymptomatic Hyponatremia (Sodium <120 mEq/L)

Fluid restriction to 1 L/day is the cornerstone of treatment for chronic SIADH without severe symptoms. 1, 4

• Implement strict fluid restriction to 1000 mL/day 1, 4
• Add oral sodium chloride 100 mEq three times daily if no response to fluid restriction alone 4
• Monitor serum sodium every 24 hours initially, then adjust frequency based on response 4
• Avoid fluid restriction during first 24 hours if using pharmacologic therapy 6

Pharmacological Treatment Options

For chronic SIADH resistant to fluid restriction, demeclocycline or vasopressin receptor antagonists (tolvaptan) are second-line options. 1, 4

Tolvaptan (FDA-Approved)

• Starting dose: 15 mg once daily, titrate to 30 mg after 24 hours, maximum 60 mg daily 6
• Must initiate in hospital setting with close sodium monitoring 6
• Indicated for serum sodium <125 mEq/L or symptomatic hyponatremia resistant to fluid restriction 6
• Limit use to 30 days maximum to minimize hepatotoxicity risk 6
• Contraindicated with strong CYP3A inhibitors 6

Alternative Agents

• Demeclocycline can be considered for chronic SIADH when fluid restriction fails 1
• Urea is effective alongside fluid restriction, particularly in neurosurgical patients 4
• Loop diuretics may be used in select cases 4

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Critical Safety Considerations

Osmotic Demyelination Syndrome Prevention

The single most important safety principle is never exceeding 8 mmol/L sodium correction in 24 hours—overcorrection causes irreversible osmotic demyelination syndrome with dysarthria, dysphagia, quadriparesis, seizures, and death. 1, 4, 6

• For average-risk patients: 4-8 mmol/L per day, not exceeding 10-12 mmol/L in 24 hours 4
• For high-risk patients: 4-6 mmol/L per day, not exceeding 8 mmol/L in 24 hours 1, 4
• If overcorrection occurs, immediately switch to D5W and consider desmopressin to relower sodium 4
• Watch for ODS symptoms 2-7 days post-correction: dysarthria, dysphagia, oculomotor dysfunction, quadriparesis 4

High-Risk Populations Requiring Slower Correction

• Advanced liver disease 1, 4, 6
• Chronic alcoholism 1, 4, 6
• Severe malnutrition 1, 4, 6
• Baseline sodium <120 mEq/L 4
• Prior encephalopathy 4

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Common Pitfalls to Avoid

Never use normal saline (0.9% NaCl) to treat SIADH—it acts as hypotonic fluid in these patients and worsens hyponatremia through paradoxical sodium excretion. 5 The 154 mEq/L sodium in normal saline is less than the combined urine sodium plus potassium concentration in SIADH patients, resulting in net free water retention 5.

• Avoid inadequate monitoring during active correction 1, 4
• Never use fluid restriction in cerebral salt wasting (CSW)—this is a critical differential that requires volume replacement, not restriction 1, 4
• Distinguish SIADH from CSW in neurosurgical patients: CSW shows hypovolemia (CVP <6 cm H₂O) while SIADH shows euvolemia (CVP 6-10 cm H₂O) 1
• Do not ignore mild hyponatremia (130-135 mmol/L)—even mild cases increase fall risk 4-fold and mortality 60-fold 4
• Always identify and treat underlying cause: malignancy, CNS disorders, pulmonary disease, medications (SSRIs, carbamazepine, cyclophosphamide, vincristine) 1, 7