SIADH Diagnosis and Management
Diagnostic Criteria
SIADH is diagnosed by the presence of hyponatremia (serum sodium <134 mEq/L), hypoosmolality (plasma osmolality <275 mosm/kg), inappropriately high urine osmolality (>500 mosm/kg), and inappropriately high urinary sodium concentration (>20 mEq/L) in a euvolemic patient, with normal thyroid, adrenal, and renal function. 1
Essential Laboratory Workup
- Serum tests: Sodium, osmolality, glucose, creatinine, TSH, and cortisol to exclude hypothyroidism and adrenal insufficiency 1, 2
- Urine tests: Osmolality (>500 mosm/kg suggests SIADH) and sodium concentration (>20 mEq/L) 1
- Serum uric acid: <4 mg/dL has 73-100% positive predictive value for SIADH 1, 2
Critical Distinction: SIADH vs Cerebral Salt Wasting (CSW)
Volume status assessment is paramount, as treatment approaches are opposite:
- SIADH: Euvolemic (normal skin turgor, moist mucous membranes, no edema, no orthostatic hypotension), CVP 6-10 cm H₂O 1
- CSW: Hypovolemic (orthostatic hypotension, dry mucous membranes, decreased skin turgor), CVP <6 cm H₂O 1
Physical examination alone has poor accuracy (sensitivity 41%, specificity 80%) for volume assessment 2
Management Based on Severity
Severe Symptomatic Hyponatremia (Seizures, Coma, Altered Mental Status)
Immediately transfer to ICU and administer 3% hypertonic saline with a goal to correct 6 mmol/L over 6 hours or until severe symptoms resolve. 1
- Administration: 100 mL boluses of 3% saline over 10 minutes, can repeat up to 3 times at 10-minute intervals 2
- Critical safety limit: Total correction must NOT exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 1, 3
- Monitoring: Check serum sodium every 2 hours during initial correction 1, 2
High-risk patients (malnutrition, alcoholism, advanced liver disease) require even slower correction at 4-6 mmol/L per day. 1, 2, 3
Mild Symptomatic or Asymptomatic Hyponatremia (Sodium <120 mEq/L)
Fluid restriction to 1 L/day is the cornerstone of treatment for SIADH. 1, 2
- Implement fluid restriction to 500-1000 mL/day initially, adjusted based on serum sodium response 1, 4
- Add oral sodium chloride 100 mEq three times daily if no response to fluid restriction alone 2
- Ensure adequate solute intake (salt and protein) alongside fluid restriction 4
Important caveat: Nearly half of SIADH patients do not respond to fluid restriction as first-line therapy 4
Second-Line Pharmacological Options
When fluid restriction fails or is poorly tolerated:
Demeclocycline
- Induces nephrogenic diabetes insipidus, reducing kidney response to ADH 1
- Long history of use in persistent SIADH cases 1
Urea
- Considered very effective and safe in recent literature 1, 4
- Dose: 40 g in 100-150 mL normal saline every 8 hours for neurosurgical patients 2
- Particularly valuable when distinguishing SIADH from CSW is difficult 2
Tolvaptan (Vasopressin Receptor Antagonist)
FDA-approved for clinically significant euvolemic hyponatremia (sodium <125 mEq/L or symptomatic). 2, 3
- Starting dose: 15 mg once daily, can titrate to 30 mg after 24 hours, maximum 60 mg daily 2, 3
- Must initiate in hospital setting with close sodium monitoring 3
- Increases serum sodium significantly more than placebo (3.0 mEq/L/day) 2, 3
- Critical monitoring: Check sodium at 0,6,24, and 48 hours after initiation to prevent overcorrection 5
- Maximum duration: Do not use for more than 30 days due to hepatotoxicity risk 3
- Avoid fluid restriction during first 24 hours of tolvaptan therapy 3
Side effects: Thirst, polydipsia, frequent urination 5
Special Populations and Considerations
Neurosurgical Patients (Subarachnoid Hemorrhage)
- Avoid fluid restriction in patients at risk for vasospasm, as it worsens outcomes 1, 2
- Consider fludrocortisone (0.1-0.2 mg daily) or hydrocortisone to prevent natriuresis 1, 2
- CSW is more common than SIADH in this population and requires volume/sodium replacement, not restriction 1, 2
Cancer Patients (Paraneoplastic SIADH)
- Treatment of underlying malignancy is crucial alongside hyponatremia management 1
- SIADH occurs in 1-5% of lung cancer patients, particularly small cell lung cancer 2
- Hyponatremia usually improves after successful cancer treatment 1
Cirrhotic Patients
- Require more cautious correction (4-6 mmol/L per day) due to higher osmotic demyelination risk 1, 2
- Tolvaptan carries higher risk of GI bleeding in cirrhosis (10% vs 2% placebo) 2
- Consider albumin infusion alongside fluid restriction 2
Management of Overcorrection
If sodium correction exceeds 8 mmol/L in 24 hours, immediately intervene to prevent osmotic demyelination syndrome. 2
- Discontinue current fluids and switch to D5W (5% dextrose in water) 2
- Consider administering desmopressin to slow or reverse the rapid rise 2
- Watch for signs of osmotic demyelination syndrome (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically occurring 2-7 days after rapid correction 1, 2, 3
Common Pitfalls to Avoid
- Never correct chronic hyponatremia faster than 8 mmol/L in 24 hours 1, 3
- Never use fluid restriction in CSW – this worsens outcomes and requires volume replacement instead 1, 2
- Never ignore mild hyponatremia (130-135 mmol/L) – it increases fall risk (21% vs 5%) and mortality (60-fold increase) 2
- Never use tolvaptan in hypovolemic hyponatremia – it is contraindicated 3
- Never fail to identify and treat the underlying cause of SIADH 1
- Never use hypertonic saline in hypervolemic hyponatremia without life-threatening symptoms 2
Discontinuation and Follow-up
After stopping tolvaptan or any SIADH therapy: