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

Treatment of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

The treatment of SIADH should be based on the severity of hyponatremia, with fluid restriction (1,000-1,500 mL/day) as first-line therapy for mild to moderate cases, and vasopressin receptor antagonists like tolvaptan for cases resistant to fluid restriction. 1

Diagnostic Criteria for SIADH

Before initiating treatment, confirm the diagnosis based on established criteria:

• Hyponatremia (serum sodium <134 mEq/L)
• Hypoosmolality (plasma osmolality <275 mOsm/kg)
• Inappropriately high urine osmolality (>500 mOsm/kg)
• Inappropriately high urinary sodium concentration (>20 mEq/L)
• Clinical euvolemia
• Normal renal, adrenal, and thyroid function 1

Treatment Algorithm Based on Severity

Mild Hyponatremia (126-135 mEq/L)

• Continue diuretics if already prescribed
• Monitor electrolytes
• Do not restrict water as this may exacerbate hypovolemia 1
• Ensure adequate oral salt intake 1

Moderate Hyponatremia (120-125 mEq/L)

• Consider stopping diuretics, especially if creatinine is elevated
• Implement fluid restriction (1,000-1,500 mL/day)
• Ensure adequate oral salt intake 1

Severe Hyponatremia (<120 mEq/L)

• Stop diuretics
• Consider volume expansion with colloid or saline
• For symptomatic patients (confusion, seizures):
  • Hypertonic saline may be required for urgent intervention 1, 2
  • Monitor serum sodium closely to prevent too rapid correction 1, 3

Pharmacological Options

First-Line Treatment

• Fluid restriction (1,000-1,500 mL/day) 1, 4
• Discontinue medications that may cause SIADH 1

Second-Line Treatments (if fluid restriction fails)

1. Tolvaptan (vasopressin receptor antagonist):

   • Starting dose: 15 mg once daily
   • Can be titrated to 30 mg, then 60 mg once daily as needed
   • Must be initiated in a hospital setting for close monitoring of serum sodium 1, 5
   • Contraindicated in ADPKD, patients unable to sense/respond to thirst, hypovolemic hyponatremia, patients taking strong CYP3A inhibitors, anuria, and hypersensitivity to tolvaptan 5
   • Should not be administered for more than 30 days to minimize risk of liver injury 5

2. Demeclocycline:

   • Can be used to induce negative free-water balance if fluid restriction is not tolerated 1, 3

3. Urea:

   • Effective for rapid correction of symptomatic hyponatremia in SIADH 1, 4
   • Considered very effective and safe 4

Critical Monitoring Parameters

Prevention of Osmotic Demyelination Syndrome

• Do not exceed correction rate of 8-10 mmol/L per day 1, 3
• For tolvaptan therapy, measure serum sodium at 0,6,24, and 48 hours after initiation 3
• Slower correction rates are advisable in susceptible patients (severe malnutrition, alcoholism, advanced liver disease) 5

Post-Treatment Monitoring

• After discontinuing tolvaptan, resume fluid restriction and monitor serum sodium 1, 5
• For tolvaptan discontinuation longer than 5-6 days, monitor for hyponatremic relapse 3
• May need to taper tolvaptan dose or restrict fluid intake or both 3

Common Pitfalls to Avoid

1. Overly rapid correction of serum sodium (>12 mEq/L/24 hours) can cause osmotic demyelination syndrome, resulting in serious neurological complications 1, 5

2. Water restriction in patients with serum sodium >126 mmol/L is unnecessary and may exacerbate hypovolemia 1

3. Failure to identify and address underlying causes of SIADH, which may include:

   • Malignancies (especially small cell lung cancer)
   • CNS disorders
   • Pulmonary diseases
   • Medications
   • Post-surgical states 1

4. Not recognizing that approximately half of SIADH patients do not respond to fluid restriction as first-line therapy, necessitating consideration of second-line options 4, 6

5. Treating asymptomatic patients too aggressively - mild asymptomatic hyponatremia can be managed with adequate solute intake and careful fluid management 4