How should I diagnose and manage a patient with suspected syndrome of inappropriate antidiuretic hormone secretion (SIADH)?

Diagnosis and Management of SIADH

For suspected SIADH, confirm the diagnosis with simultaneous measurement of serum sodium, plasma osmolality, urine osmolality, and urine sodium, then treat based on symptom severity: severe symptomatic hyponatremia requires ICU admission with 3% hypertonic saline targeting 6 mmol/L correction over 6 hours (never exceeding 8 mmol/L in 24 hours), while chronic or mild cases respond to fluid restriction at 1 L/day as first-line therapy. 1, 2

Diagnostic Confirmation

Essential diagnostic criteria must all be present simultaneously: 1, 2

• Hypotonic hyponatremia: Serum sodium <134 mEq/L with plasma osmolality <275 mosm/kg 1, 2
• Inappropriately concentrated urine: Urine osmolality >500 mosm/kg despite low plasma osmolality 1, 2
• Elevated urinary sodium: Urine sodium >20 mEq/L, indicating continued natriuresis 1, 2
• Clinical euvolemia: No orthostatic hypotension, tachycardia, peripheral edema, ascites, or jugular venous distention 1, 2
• Normal organ function: Exclude hypothyroidism (check TSH), adrenal insufficiency (check cortisol), and volume depletion 1, 2

Volume status assessment is paramount—the single most critical diagnostic step is distinguishing SIADH (euvolemic) from cerebral salt wasting (hypovolemic), as they require opposite treatments. 1, 2 Physical examination alone has poor accuracy; when available in neurosurgical patients, use central venous pressure: SIADH shows CVP 6-10 cm H₂O versus CSW with CVP <6 cm H₂O. 1

Supportive Laboratory Findings

Additional parameters strengthen the diagnosis: 3

• Serum uric acid <4 mg/dL has 73-100% positive predictive value for SIADH 1
• Low blood urea nitrogen (though less specific in elderly patients) 3
• Fractional excretion of sodium >0.5% in 70% of SIADH cases 3
• Lower anion gap with nearly normal total CO2 and potassium despite dilution 3

Identify the Underlying Cause

Search systematically for the etiology, as treating the underlying cause is definitive therapy: 1, 4

• Malignancy: Small cell lung cancer is the most common (1-5% of cases); obtain chest CT 1, 2
• CNS pathology: Infections, abscesses, subarachnoid hemorrhage, head trauma, space-occupying lesions—obtain neuroimaging (CT or MRI) 1, 2, 4
• Medications: SSRIs, carbamazepine, oxcarbazepine, NSAIDs, tramadol, thiazide diuretics, vincristine, cyclophosphamide, cisplatin 1, 5, 6
• Pulmonary disease: Pneumonia, tuberculosis 2, 7

Management Algorithm Based on Severity

Severe Symptomatic Hyponatremia (Neurological Symptoms Present)

Transfer immediately to ICU for close monitoring. 1 Neurological symptoms include confusion, seizures, altered mental status, or coma and typically occur with sodium <120 mEq/L or rapid decline >0.5 mmol/L/hour. 2, 7

Administer 3% hypertonic saline with goal to correct 6 mmol/L over 6 hours or until severe symptoms resolve. 1 Monitor serum sodium every 2 hours initially. 1

Critical safety rule: Total correction must not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome. 1 In patients with malnutrition, alcoholism, or advanced liver disease, use even more cautious correction rates of 4-6 mmol/L per day. 1

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

Implement fluid restriction to 1 L/day as first-line therapy. 1 This produces a correction rate averaging 1.0 mEq/L/day, which is slower but safest for chronic management. 1, 8

Discontinue any offending medications immediately (SSRIs, carbamazepine, thiazides, NSAIDs, tramadol). 1, 6

Consider oral salt supplementation as an adjunctive measure. 1

Chronic SIADH Management (When Underlying Cause Cannot Be Corrected)

Continue fluid restriction to 1 L/day as first-line chronic therapy. 1 This remains the mainstay for patients who can tolerate it. 1, 5, 7

If fluid restriction fails or is poorly tolerated, demeclocycline is the recommended second-line agent. 1, 5 Demeclocycline induces nephrogenic diabetes insipidus, reducing the kidney's response to ADH. 1

Tolvaptan (V2 receptor antagonist) is FDA-approved for clinically significant euvolemic hyponatremia: Start at 15 mg once daily, titrate to 30 mg after 24 hours if needed, maximum 60 mg daily. 1 Tolvaptan produces rapid correction at 3.0 mEq/L/day, equivalent to hypertonic saline. 1, 8

Alternative second-line options include urea (considered very effective and safe in recent literature), though less commonly used. 1

Critical Pitfalls to Avoid

Never use fluid restriction in cerebral salt wasting—this is the opposite of correct treatment. 1, 2 CSW requires volume and sodium replacement, not restriction. In neurosurgical patients, especially those with subarachnoid hemorrhage at risk for vasospasm, fluid restriction worsens outcomes. 1

Never use fludrocortisone for SIADH—it is specifically indicated for CSW and will worsen fluid retention in SIADH. 1

Avoid overly rapid correction leading to osmotic demyelination syndrome. 1 Monitor sodium levels closely during active correction—inadequate monitoring is a common error. 1

Do not discontinue hypotonic fluids like D5W in SIADH patients, as they worsen hyponatremia by providing free water that cannot be properly excreted. 1

Recognize that thiazide diuretics combined with SSRIs or other SIADH-inducing medications substantially increases risk, particularly in older adults. 1 Monitor electrolytes within 4 weeks after starting therapy and after dose increases. 1

In patients with small cell lung cancer and paraneoplastic SIADH, initiate appropriate cancer treatment as soon as the patient is stabilized—effective cancer treatment is often the definitive solution. 1

Special Populations

Older adults, especially women, are at higher risk for medication-induced SIADH. 1 Hyponatremia typically develops within 2 weeks of starting thiazides or SSRIs but can occur at any time. 1

Patients with polypharmacy using two or more hyponatremia-inducing medications have significantly increased risk. 1

In neurosurgical patients with subarachnoid hemorrhage, hyponatremia is associated with higher rates of cerebral ischemia and worse outcomes at 3 months. 1 Avoid fluid restriction in these patients; consider fludrocortisone only if CSW is confirmed, not SIADH. 1