Symptoms and Treatment of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
The symptoms of SIADH primarily depend on the severity of hyponatremia and range from mild symptoms like headache and nausea to severe manifestations including confusion, seizures, and coma, with treatment focused on fluid restriction as first-line therapy and pharmacological interventions for refractory cases. 1
Symptoms of SIADH
Symptoms of SIADH correlate with the degree of hyponatremia and can be classified into three categories:
Mild Hyponatremia (126-135 mEq/L)
- Often asymptomatic or subtle symptoms
- Nausea
- Muscle cramps
- Headache
- Mild neurocognitive deficits 1
Moderate Hyponatremia (120-125 mEq/L)
- Weakness
- Gait instability
- Headache
- Dizziness
- Nausea and vomiting 1
Severe Hyponatremia (<120 mEq/L)
- Confusion
- Delirium
- Lethargy
- Seizures
- Coma
- Brain herniation (rare)
- Death if left untreated 1
Diagnostic Criteria for SIADH
The diagnosis of SIADH relies on established criteria:
- Hyponatremia (serum sodium <134 mEq/L)
- Hypoosmolality (plasma osmolality <275 mOsm/kg)
- Inappropriately high urine osmolality (>500 mOsm/kg) relative to serum osmolality
- Inappropriately high urinary sodium concentration (>20 mEq/L)
- Clinical euvolemia
- Normal renal, adrenal, and thyroid function 1
Treatment Options for SIADH
First-Line Treatment
- Fluid restriction (1,000-1,500 mL/day) - This is the mainstay of therapy for chronic SIADH 1
- Discontinuation of implicated medications if possible 1
- Adequate oral salt intake 1
For Moderate to Severe Symptomatic Hyponatremia
- Hypertonic (3%) saline administration under close monitoring 2, 1
- Correction rate should not exceed 8-10 mmol/L per day to avoid osmotic demyelination syndrome 1
- In susceptible patients (severe malnutrition, alcoholism, advanced liver disease), slower rates of correction are advisable 3
For Refractory Cases
Vasopressin receptor antagonists (vaptans) - Tolvaptan is indicated for clinically significant hypervolemic and euvolemic hyponatremia, including SIADH 3
- Starting dose: 15 mg once daily
- Can be increased to 30 mg after 24 hours, maximum 60 mg daily
- Should be initiated in a hospital setting with close monitoring of serum sodium
- Limited to 30 days of use due to risk of liver injury 3
Demeclocycline - Can be used to induce negative free-water balance if fluid restriction is not tolerated 4
Urea - Can be effective for rapid correction of symptomatic hyponatremia in SIADH 5
- Dosage: 30g orally 2-3 times over 24 hours or 80g IV as a 30% solution over 6 hours
- Works through osmotic diuresis and sodium retention
Important Considerations and Precautions
Too rapid correction of hyponatremia (>12 mEq/L/24 hours) can cause osmotic demyelination syndrome, resulting in serious neurological sequelae 3
Patients with SIADH should be monitored for changes in serum electrolytes and volume status during treatment 3
Tolvaptan is contraindicated in:
- Patients with ADPKD
- Those unable to sense or respond to thirst
- Hypovolemic hyponatremia
- Patients taking strong CYP3A inhibitors
- Anuria
- Hypersensitivity to tolvaptan 3
SIADH is often associated with underlying conditions that should be identified and treated, including:
- Malignancies (especially small cell lung cancer)
- CNS disorders
- Pulmonary diseases
- Medications
- Post-surgical states 1
Treatment Algorithm
- Confirm SIADH diagnosis using established criteria
- Assess symptom severity:
- For mild symptoms: Fluid restriction (1,000-1,500 mL/day) + salt intake
- For moderate to severe symptoms: Consider hypertonic saline under close monitoring
- If first-line treatment fails:
- Consider tolvaptan (start at 15 mg daily)
- Alternative options: demeclocycline or urea
- Monitor serum sodium levels to ensure correction rate doesn't exceed 8-10 mmol/L/day
- Address underlying cause if identified
By following this approach and understanding the spectrum of symptoms, clinicians can effectively manage SIADH while minimizing the risk of complications from treatment.