What are the diagnostic criteria and management options for Syndrome of Inappropriate Antidiuretic Hormone (SIADH) diagnosis?

Diagnostic Criteria and Management of Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

SIADH is diagnosed when a patient has euvolemic hypoosmolar hyponatremia with inappropriately high urine osmolality and sodium concentration in the absence of diuretic treatment, adrenal insufficiency, heart failure, cirrhosis, and hypothyroidism. 1

Diagnostic Criteria for SIADH

SIADH manifests as euvolemic hypoosmolar hyponatremia with the following criteria:

• Hyponatremia (serum sodium < 134 mEq/L) 1
• Hypoosmolality (plasma osmolality < 275 mosm/kg) 1
• Inappropriately high urine osmolality (> 500 mosm/kg) 1
• Inappropriately high urinary sodium concentration (> 20 mEq/L) 1
• Absence of hypothyroidism, adrenal insufficiency, or volume depletion 1
• Clinical euvolemia (absence of edema and signs of volume depletion) 2
• Normal renal and adrenal function 2

Laboratory Evaluation

• Serum sodium < 134 mEq/L 1
• Serum osmolality < 275 mosm/kg 1
• Urine osmolality > 500 mosm/kg (inappropriately high relative to serum osmolality) 1
• Urine sodium > 20-40 mEq/L 1, 3
• Serum uric acid < 4 mg/dL (has a positive predictive value for SIADH of 73-100%) 1, 3
• Low serum urea 3
• Fractional excretion of urate assessment can improve diagnostic accuracy to approximately 95% 1

Volume Status Assessment

• Volume status determination is critical to distinguish SIADH (euvolemic) from other causes of hyponatremia 1
• Physical examination findings, laboratory tests, and invasive monitoring when available should be used to determine volume status 1
• Central venous pressure (CVP) measurement can help distinguish SIADH (CVP 6-10 cm H₂O) from cerebral salt wasting (CVP <6 cm H₂O) 1

Management Options for SIADH

Acute Management of Symptomatic Hyponatremia

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

• Hypertonic (3%) saline should be administered for severely symptomatic patients 4, 5
• Target correction: 4-6 mEq/L within 1-2 hours to reverse hyponatremic encephalopathy 4
• Maximum correction should not exceed 8-10 mEq/L in 24 hours to prevent osmotic demyelination syndrome 1, 4
• For acute hyponatremia (<48 hours) with severe symptoms, correction can be more rapid but should still not exceed 12 mEq/L/24 hours 6

Chronic Management

1. Fluid Restriction:

   • First-line therapy for most patients with chronic SIADH 2
   • Typically restrict fluid intake to ≤1.0 liter/day 6
   • Fluid restriction should be avoided in the first 24 hours of therapy to prevent overly rapid correction of serum sodium 6

2. Pharmacologic Options:

   • Tolvaptan (Vasopressin V2 receptor antagonist):

     • Indicated for clinically significant euvolemic hyponatremia 6
     • Initial dose: 15 mg once daily, can be titrated to 30 mg and then 60 mg once daily as needed 6
     • Should be initiated in a hospital setting where serum sodium can be closely monitored 6
     • Not recommended for use beyond 30 days due to risk of liver injury 6
     • Contraindicated in hypovolemic hyponatremia 6

   • Other agents (for refractory cases):

     • Urea 4, 5
     • Demeclocycline 1
     • Lithium 1
     • Loop diuretics with salt supplementation 1

3. Special Considerations:

   • In neurosurgical patients, especially those with subarachnoid hemorrhage at risk for vasospasm, fluid restriction should be avoided 1
   • Fludrocortisone may be beneficial in neurosurgical patients with hyponatremia 1

Monitoring and Prevention of Complications

• Monitor serum sodium levels frequently during correction (every 4-6 hours initially) 6
• Too rapid correction (>12 mEq/L/24 hours) can cause osmotic demyelination syndrome with serious neurologic sequelae 6
• In susceptible patients (severe malnutrition, alcoholism, advanced liver disease), slower correction rates are advisable 6
• Consider simultaneous administration of desmopressin in high-risk patients to prevent overly rapid sodium correction 5

Common Pitfalls and Caveats

• Distinguish SIADH from cerebral salt wasting, which presents with hypovolemia despite high urine sodium 1
• Avoid normal saline (0.9%) in SIADH as it can act as a hypertonic solution and cause rapid fluctuations in serum sodium levels 5
• Always rule out hypothyroidism and adrenal insufficiency before diagnosing SIADH 1, 5
• Measuring ADH levels has limited diagnostic value and is not routinely recommended 1
• In patients with lung cancer, especially small cell lung cancer, SIADH is a common paraneoplastic syndrome and should be considered 1
• Early detection and appropriate management can prevent severe hyponatremia, which can lead to seizures, coma, and death 1