What is the management of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)?

Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

Diagnostic Criteria

SIADH is diagnosed by the presence of hypotonic hyponatremia (serum sodium <135 mEq/L) with inappropriately concentrated urine (>500 mOsm/kg) and elevated urinary sodium (>20 mEq/L) in a euvolemic patient, with normal thyroid, adrenal, and renal function. 1

Key diagnostic features include:

• Euvolemic state - no edema, no orthostatic hypotension, normal skin turgor, moist mucous membranes 1
• Serum osmolality <275 mOsm/kg 1
• Urine osmolality inappropriately high (>500 mOsm/kg) relative to low serum osmolality 1
• Urinary sodium >20 mEq/L despite hyponatremia 1
• Serum uric acid <4 mg/dL has 73-100% positive predictive value for SIADH 2

A common pitfall is failing to accurately assess volume status, which is essential for differentiating SIADH from cerebral salt wasting or other causes of hyponatremia. 1

Common Causes

SIADH results from multiple etiologies:

• Malignancies - particularly small cell lung cancer (affects 1-5% of lung cancer patients) 1
• CNS disorders - meningitis, subarachnoid hemorrhage, head trauma 1, 3
• Pulmonary diseases 4
• Medications - carbamazepine, SSRIs, chlorpropamide, cyclophosphamide, vincristine, cisplatin, NSAIDs, opioids 1, 5
• Postoperative state 3

Management Algorithm

Step 1: Assess Symptom Severity

For severe symptomatic hyponatremia (seizures, coma, altered mental status):

• Transfer to ICU immediately 1
• Administer 3% hypertonic saline with goal to correct 6 mEq/L over 6 hours or until symptoms resolve 2, 1
• Monitor serum sodium every 2 hours initially 1
• Total correction must not exceed 8 mEq/L in 24 hours to prevent osmotic demyelination syndrome 2, 1, 6

For mild symptoms or asymptomatic patients with sodium <120 mEq/L:

• Proceed to chronic management strategies 1

Step 2: Address Underlying Cause

Discontinue offending medications immediately - carbamazepine, SSRIs, chlorpropamide, cyclophosphamide, vincristine 1

Treat underlying malignancy - effective cancer treatment often resolves paraneoplastic SIADH 1

Step 3: Chronic Management (First-Line)

Fluid restriction to 1 L/day is the cornerstone of chronic SIADH treatment. 2, 1, 3

• Avoid fluid restriction during first 24 hours of acute treatment to prevent overly rapid correction 6
• After initial stabilization, implement strict fluid restriction 1
• Patients should be advised they can drink in response to thirst during acute phase 6

Step 4: Pharmacological Options (If Fluid Restriction Fails)

If fluid restriction is ineffective or poorly tolerated:

Oral sodium chloride supplementation:

• Add 100 mEq orally three times daily 2

Demeclocycline (second-line):

• Induces nephrogenic diabetes insipidus 1, 5
• Effective for chronic SIADH when fluid restriction fails 1

Urea:

• Dose: 30 g orally 2-3 times over 24 hours, or 80 g as 30% IV solution over 6 hours 7
• Induces osmotic diuresis and sodium retention 7
• Particularly useful when rapid correction needed alongside fluid restriction 7
• Poor palatability and gastric intolerance limit use 8

Vaptans (vasopressin receptor antagonists):

• Tolvaptan starting dose: 15 mg once daily 6
• Titrate to 30 mg after 24 hours, maximum 60 mg daily as needed 6
• Must initiate and re-initiate in hospital with close sodium monitoring 6
• Increases serum sodium significantly more than placebo (mean increase 4.0 mEq/L at Day 4 vs 0.4 mEq/L with placebo) 6
• Do not use for more than 30 days due to hepatotoxicity risk 6
• Adverse effects include overly rapid correction and increased thirst 8
• Contraindicated with strong CYP3A inhibitors 6

Critical Safety Considerations

Osmotic demyelination syndrome prevention:

• Never exceed 8 mEq/L correction in 24 hours 2, 1, 6
• High-risk patients (advanced liver disease, alcoholism, malnutrition) require slower correction at 4-6 mEq/L per day 2, 1, 6
• Osmotic demyelination causes dysarthria, dysphagia, lethargy, spastic quadriparesis, seizures, coma, or death 6
• Symptoms typically occur 2-7 days after rapid correction 2

Monitoring requirements:

• Severe symptoms: check sodium every 2 hours 1
• Mild symptoms: check sodium every 4 hours initially, then daily 2
• During tolvaptan therapy: frequent monitoring for changes in electrolytes and volume 6

Special Populations

Neurosurgical patients with subarachnoid hemorrhage:

• Avoid fluid restriction in patients at risk for vasospasm 1
• Consider fludrocortisone to prevent vasospasm 1
• Distinguish SIADH from cerebral salt wasting (which requires volume replacement, not restriction) 2, 1

Pediatric patients:

• SIADH most common with meningitis or postoperatively 3
• Fluid restriction vital to prevent symptomatic SIADH 3
• Hypertonic saline reserved only for severely symptomatic patients 3

Cancer patients:

• Treatment of underlying malignancy often resolves SIADH 1
• Hyponatremia usually improves after successful cancer treatment 1

Post-Treatment Management

After discontinuing therapy:

• Resume fluid restriction 6
• Monitor serum sodium and volume status closely 6
• Patients previously on tolvaptan should be advised to resume previous hyponatremia therapies 6