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 meeting specific criteria including hyponatremia, plasma hypoosmolality, inappropriately high urine osmolality, elevated urinary sodium, clinical euvolemia, and normal thyroid and adrenal function, while treatment should be based on symptom severity with fluid restriction as first-line for mild cases and hypertonic saline for severe symptomatic cases. 1

Diagnostic Criteria for SIADH

SIADH diagnosis requires all of the following criteria:

• Serum sodium <134 mEq/L
• Plasma osmolality <275 mOsm/kg
• Inappropriately high urine osmolality (>500 mOsm/kg)
• Elevated urinary sodium concentration (>20 mEq/L)
• Clinical euvolemia (absence of edema and volume depletion)
• Normal adrenal and thyroid function 1

Essential Laboratory Studies

• Serum studies: Sodium, potassium, chloride, bicarbonate, BUN, creatinine, glucose, serum osmolality, liver function tests, calcium
• Urine studies: Urine sodium, urine osmolality
• Additional tests: Thyroid function tests, morning cortisol 1

Differentiating SIADH from Cerebral Salt Wasting (CSW)

This distinction is critical as treatment approaches differ significantly:

Feature	SIADH	CSW
Volume status	Euvolemic	Hypovolemic
Treatment	Fluid restriction	Fluid replacement
Urine output	Normal/low	High
Response to saline	Poor	Good
Central venous pressure	6-10 cm H₂O	<6 cm H₂O

Extracellular fluid (ECF) status is key to distinguishing between SIADH and CSW, though physical examination alone has been shown to be inaccurate (sensitivity 41.1%, specificity 80%) 2, 1

Treatment Algorithm for SIADH

1. For Mild to Moderate Symptomatic Hyponatremia (Na 125-130 mEq/L)

• Discontinue implicated medications if possible
• Fluid restriction (1,000-1,500 mL/day)
• Adequate oral salt intake
• Monitor serum sodium levels daily 1

2. For Severe Symptomatic Hyponatremia (Na <125 mEq/L with neurological symptoms)

• Transfer to ICU
• Monitor sodium every 2 hours
• Administer 3% hypertonic saline
• Calculate sodium deficit
• Correct 6 mEq/L over 6 hours or until severe symptoms resolve
• Do not exceed correction of 8 mmol/L over 24 hours to avoid osmotic demyelination syndrome 2, 1

3. For Chronic or Refractory SIADH

If fluid restriction is not tolerated or ineffective, consider:

• Tolvaptan (vasopressin receptor antagonist): Starting dose 15 mg once daily, titrated to 30 mg, then 60 mg once daily as needed
• Demeclocycline: To induce negative free-water balance
• Urea: Effective for rapid correction of symptomatic hyponatremia 1, 3

Common Causes of SIADH to Investigate

• Malignancy: Especially small cell lung cancer (10-45% of cases)
• CNS disorders: Stroke, hemorrhage, trauma, infection
• Pulmonary diseases: Pneumonia, tuberculosis, asthma, COPD
• Medications:
  • Antidepressants (MAOIs, SNRIs, mirtazapine)
  • Antipsychotics
  • Anticonvulsants (carbamazepine, valproate)
  • Diuretics (especially thiazides)
  • NSAIDs
  • Opioids
  • Chemotherapeutic agents 1

Critical Pitfalls to Avoid

1. Overly rapid correction of sodium (>8 mmol/L/24h) can lead to osmotic demyelination syndrome 1

2. Misdiagnosing CSW as SIADH can worsen outcomes as treatment approaches are opposite:

   • SIADH requires fluid restriction
   • CSW requires fluid replacement 1

3. Fluid restriction in SAH patients at risk of vasospasm can be dangerous and may lead to cerebral infarction 2, 1

4. Using 0.9% saline in SIADH patients can cause rapid fluctuations in serum Na levels 4

5. Inadequate monitoring during treatment can lead to complications 1

Special Considerations in Neurosurgical Patients

Neurosurgical patients have a high prevalence of hyponatremia (up to 50%) and are at increased risk of complications including cerebral edema, mental status changes, seizures, and vasospasm 2

• In SAH patients, consider fludrocortisone rather than fluid restriction, as hyponatremia is significantly associated with poor outcomes (odds ratio 2.7; 95% CI 1.2-6.1) 2, 1

• Central venous pressure (CVP) measurement can help determine volume status:

  • SIADH: CVP 6-10 cm H₂O
  • CSW: CVP <6 cm H₂O 2

By following this structured approach to diagnosis and treatment, clinicians can effectively manage SIADH while minimizing the risk of complications from both the condition itself and its treatment.