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

Management of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

The treatment of SIADH should focus on fluid restriction (1,000-1,500 mL/day), discontinuation of implicated medications, and vasopressin receptor antagonists (tolvaptan) for refractory cases, with careful monitoring to prevent overly rapid correction of serum sodium. 1

Diagnosis and Assessment

Before initiating treatment, confirm SIADH diagnosis with these 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)
• Normal adrenal and thyroid function
• Clinical euvolemia 1

Treatment Algorithm Based on Severity

Mild Hyponatremia (126-135 mmol/L)

• Continue diuretic therapy if already prescribed
• No water restriction required
• Monitor serum electrolytes 2
• Address underlying cause if possible 1

Moderate Hyponatremia (121-125 mmol/L)

• With normal renal function: Consider stopping diuretics
• With elevated creatinine: Stop diuretics and provide volume expansion 2
• Fluid restriction (1,000-1,500 mL/day) 1
• Adequate oral salt intake 1

Severe Hyponatremia (<120 mmol/L)

• Stop diuretics immediately
• For symptomatic patients: Consider hypertonic saline (3%) under close monitoring
• Volume expansion with colloid or saline may be necessary
• Limit correction rate to <8-10 mmol/L per 24 hours to prevent osmotic demyelination 1, 3

Pharmacological Interventions

First-line Treatment

• Fluid restriction (1,000-1,500 mL/day) 1, 4
  • Produces modest early rise in serum sodium
  • Well-tolerated but >1/3 of patients fail to reach sodium ≥130 mmol/L after 3 days 4

Second-line Treatment

• 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 hospital setting with close monitoring of serum sodium
  • Do not administer for more than 30 days (risk of liver injury)
  • Avoid fluid restriction during first 24 hours of therapy 5
  • Contraindicated in patients with ADPKD, inability to sense/respond to thirst, hypovolemic hyponatremia, patients taking strong CYP3A inhibitors, anuria, and hypersensitivity to tolvaptan 5

Alternative Options

• Demeclocycline: Can be used if fluid restriction is not tolerated 1, 6
• Urea: Effective for rapid correction of symptomatic hyponatremia 1

Monitoring and Safety Considerations

• Critical safety concern: Correction of serum sodium should not exceed 8-10 mmol/L per 24 hours 1, 3
• For tolvaptan therapy, monitor serum sodium at 0,6,24, and 48 hours after initiation 3
• Patients with severe malnutrition, alcoholism, or advanced liver disease require slower correction rates 5
• When discontinuing tolvaptan after >5-6 days, monitor for hyponatremic relapse; may need to taper dose or restrict fluid 3

Special Considerations

• For patients with severe symptomatic hyponatremia (confusion, seizures), more aggressive intervention with hypertonic saline may be required 1, 7
• In post-surgical states or with meningitis, preventive fluid restriction is vital 7
• After discontinuing tolvaptan, patients should resume fluid restriction and be monitored for changes in serum sodium 5

Treatment Efficacy

Clinical trials have shown that tolvaptan significantly increases serum sodium levels compared to placebo in patients with hyponatremia due to SIADH, with statistically significant improvements seen as early as day 4 of treatment 5.

Remember that the goal of treatment is to address symptoms of hyponatremia while preventing complications from overly rapid correction, which can lead to osmotic demyelination syndrome with serious neurological consequences.