How to differentiate between Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), Cerebral Salt Wasting Syndrome (CSWS), and Diabetes Insipidus (DI) in a patient?

Differentiating SIADH, CSWS, and DI

The key to differentiating these three conditions lies in assessing volume status and urine characteristics: SIADH presents with euvolemia and concentrated urine, CSWS with hypovolemia and high urinary sodium despite volume depletion, and DI with polyuria and dilute urine.

Initial Assessment Framework

Step 1: Measure Serum and Urine Osmolality

• Diabetes Insipidus (DI): Serum osmolality >295 mOsm/kg with inappropriately dilute urine (urine osmolality <300 mOsm/kg) 1
• SIADH and CSWS: Both show low serum osmolality (<275 mOsm/kg) with inappropriately concentrated urine (>500 mOsm/kg) 2

If urine is dilute with high serum osmolality, DI is confirmed and you can stop here 1. The challenge lies in distinguishing SIADH from CSWS, which requires careful volume assessment.

Step 2: Assess Volume Status (The Critical Differentiator)

This is where SIADH and CSWS diverge completely, and accurate assessment is essential because their treatments are opposite 3.

Clinical Volume Assessment

SIADH (Euvolemic) 2, 4:

• Normal blood pressure without orthostatic changes
• Moist mucous membranes
• Normal skin turgor
• No edema
• No signs of dehydration
• Central venous pressure (CVP) 6-10 cm H₂O 4, 5

CSWS (Hypovolemic) 6, 3:

• Orthostatic hypotension and tachycardia
• Dry mucous membranes
• Decreased skin turgor
• Flat neck veins
• Signs of volume depletion
• CVP <6 cm H₂O 4, 5
• Unquenchable thirst (a key distinguishing feature) 4

Critical Pitfall: Physical examination alone has poor accuracy (sensitivity 41.1%, specificity 80%) for volume assessment 1. Therefore, additional objective measures are essential.

Step 3: Laboratory Differentiation

Urine Sodium and Osmolality Pattern

Both SIADH and CSWS 2, 3:

• Urine sodium >20-40 mEq/L
• Urine osmolality >500 mOsm/kg
• Serum uric acid <4 mg/dL (73-100% positive predictive value for SIADH, but can also occur in CSWS) 1, 4

The key difference: In CSWS, high urinary sodium persists despite clinical hypovolemia, whereas in SIADH it occurs in a euvolemic state 3, 5.

Fractional Excretion of Urate (FEurate) - A Powerful Discriminator

This is one of the most reliable tests to differentiate these conditions 7:

• Measure FEurate before and after correcting hyponatremia 5
• SIADH: Elevated FEurate that normalizes when hyponatremia is corrected with water restriction 7
• CSWS: Elevated FEurate that persists even after hyponatremia correction 7, 5

The Furosemide Test (Highly Specific)

This test can definitively distinguish between SIADH and CSWS 6:

• Administer furosemide 20 mg IV
• SIADH: Sodium levels normalize after furosemide 6
• CSWS: Sodium remains low despite furosemide, confirming renal salt wasting 6

Isotonic Saline Challenge

A short-term infusion of isotonic saline can help identify the etiology 5:

• SIADH: Minimal improvement or worsening of hyponatremia (dilutional effect)
• CSWS: Improvement in sodium levels with volume repletion 5

Step 4: Context-Specific Risk Factors

CSWS is More Common Than SIADH in Neurosurgical Patients

In patients with CNS pathology, CSWS may actually be more prevalent than SIADH 7, 5:

• Subarachnoid hemorrhage (SAH) - particularly with poor clinical grade, ruptured anterior communicating artery aneurysms, and hydrocephalus 1
• Traumatic brain injury 5, 8
• Post-pituitary surgery (9-35% develop hyponatremia) 6
• Brain tumors 5
• CNS infections 5

SIADH Common Causes 2:

• Malignancy (especially small cell lung cancer)
• Pulmonary diseases
• Medications (SSRIs, carbamazepine, NSAIDs, opioids, chemotherapy)
• Postoperative states
• Pain, nausea, stress 2

Algorithmic Approach Summary

1. Measure serum and urine osmolality

   • If serum osm >295 + urine osm <300 → DI confirmed

2. If serum osm <275 + urine osm >500 → SIADH vs CSWS

3. Assess volume status clinically

   • Euvolemic + no thirst → likely SIADH
   • Hypovolemic + unquenchable thirst → likely CSWS

4. Confirm with objective measures:

   • CVP: <6 cm H₂O = CSWS; 6-10 cm H₂O = SIADH 4, 5
   • Furosemide test: normalizes Na = SIADH; persistent low Na = CSWS 6
   • FEurate after correction: normalizes = SIADH; persists = CSWS 7, 5
   • Isotonic saline trial: improves Na = CSWS; no improvement = SIADH 5

Critical Treatment Implications

The distinction is clinically crucial because treatments are opposite 3:

• SIADH: Fluid restriction to 1 L/day 1, 2
• CSWS: Aggressive volume and sodium replacement with isotonic or hypertonic saline, plus fludrocortisone for severe cases 1, 6
• Using fluid restriction in CSWS can worsen outcomes and is potentially fatal 1, 8

Common Pitfalls to Avoid

• Never rely on physical examination alone - use objective measures like CVP, furosemide test, or FEurate 1, 6
• Never assume SIADH in neurosurgical patients - CSWS is often more common in this population 7, 5
• Never use fluid restriction in subarachnoid hemorrhage patients at risk of vasospasm - this can precipitate cerebral ischemia 1, 2
• Never ignore unquenchable thirst - this strongly suggests CSWS or polydipsia, not SIADH 4