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

Treatment for Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

Fluid restriction (<1-1.5 L/day) is the first-line treatment for SIADH, with tolvaptan as an effective second-line therapy for patients who don't respond to fluid restriction. 1

Diagnosis of SIADH

Before initiating treatment, confirm SIADH diagnosis based on:

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

Treatment Algorithm

First-Line Treatment:

1. Fluid Restriction

   • Restrict fluid intake to <1-1.5 L/day 1
   • Nearly 50% of SIADH patients don't respond adequately to fluid restriction alone 2, 3
   • In a randomized controlled trial, fluid restriction (1L/day) increased serum sodium by only 4 mmol/L after 30 days, with >35% of patients failing to reach sodium ≥130 mmol/L after 3 days 3

2. Salt Supplementation

   • Consider oral salt supplementation (3g/day) to augment fluid restriction 1
   • Provides additional solute intake which can help improve serum sodium levels

Second-Line Treatments:

1. Tolvaptan (Vasopressin V2 Receptor Antagonist)

   • Indicated for clinically significant euvolemic hyponatremia, including SIADH, with serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and resistant to fluid restriction 4
   • Dosing:
     • Starting dose: 15 mg once daily
     • May increase to 30 mg once daily after 24 hours
     • Maximum dose: 60 mg once daily 4
   • IMPORTANT SAFETY CONSIDERATIONS:
     • Must be initiated in a hospital setting with close sodium monitoring
     • Avoid rapid correction (>12 mEq/L/24 hours) to prevent osmotic demyelination syndrome
     • Do not use for more than 30 days due to risk of liver injury
     • Contraindicated in patients unable to sense/respond to thirst 4

2. Urea

   • Considered an effective and safe alternative second-line treatment 2
   • Induces osmotic diuresis and increases free water excretion
   • May have better palatability issues but generally well-tolerated

Management of Severe Symptomatic Hyponatremia

For patients with severe symptoms (seizures, coma, cardiorespiratory distress):

• Transfer to ICU with close monitoring
• Administer 3% hypertonic saline
• Target correction of 4-6 mEq/L within 1-2 hours
• Never exceed 8 mEq/L in 24 hours to prevent osmotic demyelination syndrome 1, 5

Monitoring and Follow-up

• Monitor serum sodium every 4-6 hours initially
• For symptomatic patients, check serum sodium every 2-4 hours initially
• Once stabilized, monitor daily until normal, then weekly for 1 month 1
• Track fluid input/output and clinical examination
• Evaluate for symptoms of electrolyte imbalance (weakness, confusion, muscle cramps)

Older Treatments (Less Commonly Used)

Historical treatments with limited current use include:

• Demeclocycline (limited by side effects) 6, 7
• Loop diuretics (may be used in combination with salt supplementation) 7
• Lithium and phenytoin (rarely used due to toxicity concerns) 7

Treatment Pitfalls to Avoid

1. Overly rapid correction of sodium

   • Never exceed 8 mEq/L in 24 hours or 6 mEq/L in 6 hours 1
   • Risk of osmotic demyelination syndrome with rapid correction

2. Inadequate monitoring

   • Failure to monitor serum sodium frequently during initial treatment

3. Inappropriate fluid administration

   • Avoid hypotonic fluids which can worsen hyponatremia
   • Do not restrict fluids in cerebral salt wasting (which can mimic SIADH) 8

4. Medication interactions

   • Strong CYP3A inhibitors (ketoconazole, grapefruit juice, clarithromycin) can increase tolvaptan levels and risk of rapid sodium correction 6

The treatment approach should be guided by symptom severity, chronicity of hyponatremia, and patient response to initial therapy, with careful monitoring to prevent complications from both the hyponatremia itself and its treatment.