What are the diagnostic and treatment approaches for Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)?

Diagnostic and Treatment Approaches for Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

The diagnosis of SIADH requires documenting euvolemic hyponatremia with inappropriately high urine osmolality, reduced effective serum osmolality, and exclusion of other causes of hyponatraemia such as adrenal insufficiency, while treatment should begin with discontinuation of implicated medications, fluid restriction, and adequate oral salt intake. 1

Diagnostic Criteria for SIADH

SIADH diagnosis requires all of the following essential criteria:

1. Hyponatremia (serum sodium <134 mEq/L)
2. Hypoosmolality (plasma osmolality <275 mOsm/kg)
3. Inappropriately high urine osmolality (>500 mOsm/kg) relative to serum osmolality
4. Inappropriately high urinary sodium concentration (>20 mEq/L)
5. Clinical euvolemia (no signs of volume depletion or excess)
6. Normal renal, adrenal, and thyroid function 2

Clinical Assessment

• Evaluate for neurological symptoms based on severity:
  • Mild (126-135 mEq/L): Often asymptomatic or subtle symptoms including nausea, muscle cramps, headache
  • Moderate (120-125 mEq/L): Weakness, gait instability, headache, dizziness, nausea, vomiting
  • Severe (<120 mEq/L): Confusion, delirium, lethargy, seizures, coma 2

Common Etiologies to Investigate

1. Malignancies (especially small cell lung cancer)
2. Pulmonary disorders
3. CNS disorders
4. Medications:
   • Chemotherapeutic agents (platinum-based, vinca alkaloids)
   • Opioids
   • NSAIDs
   • Anticonvulsants
   • Antidepressants 1, 2

Treatment Approach

First-Line Treatment

1. Discontinue implicated medications if possible 1
2. Fluid restriction (1,000-1,500 mL/day) 1, 2, 3
3. Adequate oral salt intake 1

Special Considerations

• For patients with short prognosis: Strict fluid restriction may not be appropriate if not aligned with goals of care 1
• Rate of correction: Limit daily increase of serum sodium to less than 8-10 mmol/L to prevent osmotic demyelination 4

Second-Line Treatments

For cases where fluid restriction is unsuccessful (occurs in approximately 50% of cases) 3:

1. Vasopressin receptor antagonists (vaptans):

   • Tolvaptan: Initial dose 15 mg once daily, can be increased to 30 mg after 24 hours, then to maximum 60 mg daily as needed
   • Monitor serum sodium at 0,6,24, and 48 hours after initiation
   • Avoid fluid restriction during first 24 hours of therapy
   • Treatment should not exceed 30 days to minimize risk of liver injury 5, 3

2. Hypertonic saline:

   • Reserved for symptomatic patients with severe neurological deficits
   • Correction must be slow (<10-12 mmol/L within first 24h, <18 mmol/L within 48h) 6

3. Urea or demeclocycline may be considered when other options fail 3, 6

Monitoring and Follow-up

• For vaptan therapy:

  • Close monitoring of serum sodium during the first 24 hours is critical
  • Discontinuation for >5-6 days should be monitored to prevent hyponatremic relapse
  • Consider tapering the dose or reinstating fluid restriction upon discontinuation 4

• For all treatments:

  • Regular reassessment of clinical status and biochemistry
  • Remain alert to potential underlying etiological factors that may become apparent during treatment 3

Pitfalls and Caveats

1. Avoid overly rapid correction of hyponatremia (>12 mEq/L/24 hours) which can cause osmotic demyelination syndrome resulting in serious neurological sequelae 5

2. Diagnostic accuracy is often poor in clinical practice - ensure all criteria are met before confirming SIADH diagnosis 7

3. Multifactorial etiology is common - continue to evaluate for underlying causes even after treatment has begun 3

4. Patients with malnutrition, alcoholism, or advanced liver disease may require slower rates of sodium correction 5