What is the management plan for Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), including symptoms, tests, medications, and laboratory monitoring?

Management of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

Free water restriction and specific pharmacological therapies are the mainstays of SIADH management, with treatment approach determined by symptom severity and serum sodium levels.

Diagnostic Criteria for SIADH

SIADH manifests as euvolemic hypoosmolar hyponatremia characterized by:

• Hyponatremia (serum sodium < 134 mEq/L) 1
• Hypoosmolality (plasma osmolality < 275 mosm/kg) 1
• Inappropriately high urine osmolality (> 500 mosm/kg) 1
• Inappropriately high urinary sodium concentration (> 20 mEq/L) 1
• Absence of hypothyroidism, adrenal insufficiency, or volume depletion 1

Clinical Presentation

Symptoms correlate with severity and acuity of hyponatremia:

• Mild (Na 125-130 mEq/L): General weakness, confusion, headache, and nausea 1
• Severe (Na < 120 mEq/L): Life-threatening manifestations including seizures, coma, and death 1

Diagnostic Workup

1. Laboratory tests:

   • Serum sodium, osmolality, and uric acid (< 4 mg/dL in SIADH) 1
   • Urine osmolality (> 300 mosm/kg in SIADH) 1
   • Urinary sodium (> 40 mEq/L in SIADH) 1
   • Thyroid function tests and cortisol levels to exclude other causes 1

2. Clinical assessment:

   • Evaluate intravascular volume status 1
   • Calculate fractional excretion of urate (can improve diagnostic accuracy to 95%) 1

3. Differential diagnosis:

   • Exclude other causes of hyponatremia: hypoadrenalism, hypothyroidism, drug nephrotoxicity, iatrogenic hypotonic fluid administration 1
   • Rule out paraneoplastic hyponatremia due to elevated atrial natriuretic peptide 1

Treatment Algorithm Based on Symptom Severity

1. Severe Symptomatic Hyponatremia (Na < 120 mEq/L with seizures, coma)

• First-line: Hypertonic 3% saline IV 1, 2
  • Target correction: 6 mmol/L over 6 hours or until severe symptoms improve 2
  • Maximum correction: 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 2
• Monitoring: Check serum sodium every 4-6 hours during initial correction 2

2. Mild to Moderate Symptomatic Hyponatremia

• First-line: Free water restriction (< 1 L/day) 1
• Second-line options (if water restriction fails):
  • Tolvaptan (vasopressin V2 receptor antagonist) 3
    • Initial dose: 15 mg once daily 3
    • Can be titrated to 30 mg and maximum 60 mg daily 3
    • Must be initiated in hospital setting with close sodium monitoring 3
  • Demeclocycline (tetracycline antibiotic that induces nephrogenic diabetes insipidus) 1, 4
  • Oral sodium supplementation (NaCl 100 mEq orally three times daily) 2
  • Urea (increases solute excretion) 5

Special Considerations

Medication-Induced SIADH

• Common culprits: platinum-based chemotherapy, vinca alkaloids, opioids, NSAIDs, anticonvulsants, antidepressants 1
• Management: Discontinue implicated medications when possible 1

Cancer-Related SIADH

• Most commonly associated with small cell lung cancer 1
• Management: Treating the underlying malignancy is the definitive treatment 1
• Consider multidisciplinary team approach for patients requiring multimodality therapy 1

Rate of Sodium Correction

• Chronic hyponatremia: Never exceed correction of 8 mmol/L in 24 hours 2
• Acute hyponatremia: Rapid correction (>1 mmol/L/hour) only for severely symptomatic cases 1
• Monitor for overcorrection: Risk is higher in severely symptomatic patients 2

Monitoring During Treatment

• Serum sodium levels: Check at 0,6,24, and 48 hours after initiating treatment 4
• Monitor for signs of osmotic demyelination syndrome: dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures 3
• For patients on tolvaptan, monitor for dehydration and hypovolemia 3
• If discontinuing vaptan therapy for longer than 5-6 days, monitor for hyponatremic relapse 4

Long-term Management

• Maintain fluid restriction and/or pharmacological therapy until underlying cause is addressed 4
• Consider tapering vaptan dose rather than abrupt discontinuation 4
• For chronic SIADH where the cause cannot be eliminated, long-term therapy may be necessary 6

Common Pitfalls to Avoid

• Misdiagnosis: Confusing SIADH with cerebral salt wasting (CSW), which requires volume repletion rather than restriction 7
• Overcorrection: Exceeding safe correction rates can lead to osmotic demyelination syndrome 2
• Undertreating severe symptoms: Delaying treatment in life-threatening hyponatremia increases mortality 1
• Inappropriate fluid management: Using hypotonic fluids can worsen hyponatremia 1
• Failure to identify and address underlying causes: Particularly malignancies, pulmonary pathologies, and CNS disorders 5