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

Diagnostic Criteria and Management of Syndrome of Inappropriate Antidiuretic Hormone Secretion (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

Essential Criteria

• Hyponatremia (serum sodium < 135 mEq/L) 1
• Decreased serum osmolality (< 275 mOsm/kg) 1
• Inappropriately elevated urine osmolality (> 100 mOsm/kg) relative to serum osmolality 2
• Elevated urinary sodium concentration (> 20-30 mEq/L) with normal salt intake 1, 3
• Clinical euvolemia (absence of edema, ascites, or signs of hypovolemia) 1
• Normal renal, adrenal, and thyroid function 1, 3

Supporting Laboratory Findings

• Serum uric acid < 4 mg/dL (has a positive predictive value of 73-100% for SIADH) 4, 1
• Low blood urea nitrogen (BUN) 5
• Low fractional excretion of urate 1
• Lower anion gap with nearly normal total CO2 and serum potassium 5

Volume Status Assessment

• Clinical determination of volume status using physical examination findings (mucosal hydration, skin turgor, jugular vein distention) 6
• Central venous pressure measurement can help distinguish SIADH (CVP 6-10 cm H₂O) from cerebral salt wasting (CVP <6 cm H₂O) 1

Differential Diagnosis

• Cerebral salt wasting (CSW): presents with hypovolemia despite high urine sodium 1
• Reset osmostat: a variant of SIADH with stable but lower serum sodium setpoint 2
• Hypovolemic hyponatremia: diuretic use, gastrointestinal losses, third spacing 4
• Hypervolemic hyponatremia: heart failure, cirrhosis, nephrotic syndrome 4
• Medication-induced: chlorpropamide, carbamazepine, certain antineoplastics 7
• Endocrine disorders: hypothyroidism, adrenal insufficiency 1

Management Options

General Principles

• Treatment approach depends on symptom severity, acuity of onset, and underlying cause 4
• Maximum correction of serum sodium should not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 4, 1

Treatment Based on Symptom Severity

Severe Symptoms (Seizures, Coma)

• Administer 3% hypertonic saline with an initial goal to correct 6 mmol/L over 6 hours or until severe symptoms resolve 4
• Consider ICU admission for close monitoring during treatment 4
• Monitor serum sodium every 2 hours during initial correction 4

Mild to Moderate Symptoms or Asymptomatic

• Fluid restriction (1-1.5 L/day) is the cornerstone of treatment for chronic SIADH 4, 7
• Add oral sodium chloride supplementation if no response to fluid restriction 4

Pharmacological Options for Refractory Cases

• Vasopressin receptor antagonists (vaptans):
  • Tolvaptan: Initial dose 15 mg once daily, can be titrated up to 60 mg once daily 8
  • Should be initiated in a hospital setting with close monitoring of serum sodium 8
  • Contraindicated in hypovolemic hyponatremia 8
• Demeclocycline: inhibits ADH action at the renal tubule 1, 7
• Urea: increases solute excretion and free water clearance 2
• Loop diuretics with salt supplementation: increases free water excretion 1, 7
• Lithium: reduces renal response to ADH (limited by side effects) 1, 7

Special Considerations

• In neurosurgical patients, distinguish between SIADH and cerebral salt wasting, as CSW requires volume and sodium replacement rather than fluid restriction 4, 1
• Fludrocortisone may be beneficial in neurosurgical patients with hyponatremia 1
• Patients with advanced liver disease, alcoholism, malnutrition, or prior encephalopathy require more cautious correction (4-6 mmol/L per day) due to higher risk of osmotic demyelination syndrome 4

Common Pitfalls to Avoid

• Using fluid restriction in cerebral salt wasting can worsen outcomes 4
• Overly rapid correction of chronic hyponatremia leading to osmotic demyelination syndrome 4, 3
• Inadequate monitoring during active correction 4
• Using 0.9% saline in SIADH treatment can lead to rapid fluctuations in serum sodium levels 2
• Failing to recognize and treat the underlying cause 4
• Measuring ADH levels has limited diagnostic value and is not routinely recommended 6, 1

Monitoring and Follow-up

• For severe symptoms: monitor serum sodium every 2 hours during initial correction 4
• Watch for signs of osmotic demyelination syndrome (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically occurring 2-7 days after rapid correction 4
• If overcorrection occurs, consider relowering with electrolyte-free water or desmopressin 4