What labs should be ordered to diagnose Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) in an adult or elderly patient with impaired renal function?

Laboratory Tests to Diagnose SIADH

Order serum osmolality, urine osmolality, urine sodium, serum sodium, and assess volume status clinically to diagnose SIADH. 1, 2

Essential Laboratory Panel

Serum Tests:

• Serum sodium - will show hyponatremia (<135 mmol/L, typically <134 mEq/L in SIADH) 2, 3
• Serum osmolality (directly measured) - will be low (<275 mOsm/kg) in SIADH 2, 4
• Serum uric acid - typically <4 mg/dL in SIADH (positive predictive value 73-100%, though can overlap with cerebral salt wasting) 1, 2, 5
• Blood urea nitrogen (BUN) - typically low in SIADH, though less specific in elderly patients 5
• Serum creatinine - to confirm normal renal function (required for SIADH diagnosis) 1, 3
• Serum glucose - to rule out pseudohyponatremia from hyperglycemia 1

Urine Tests:

• Urine osmolality - inappropriately elevated (>100 mOsm/kg, typically >300-500 mOsm/kg) relative to low serum osmolality 2, 5, 3
• Urine sodium - elevated (>20-40 mEq/L, often >40 mEq/L) in SIADH 2, 5, 3
• Fractional excretion of sodium - typically >0.5% in 70% of SIADH cases 5

Endocrine Tests to Rule Out Mimics:

• Thyroid-stimulating hormone (TSH) - to exclude hypothyroidism 1, 2
• Morning cortisol - to exclude adrenal insufficiency 1, 3

Diagnostic Criteria for SIADH

The five cardinal criteria must be met: 3, 6

1. Hypotonic hyponatremia (serum Na <135 mmol/L, serum osmolality <275 mOsm/kg) 2, 3
2. Inappropriately concentrated urine (urine osmolality >100 mOsm/kg, typically >500 mOsm/kg) relative to low serum osmolality 2, 3, 6
3. Elevated urine sodium (>20-40 mEq/L) 2, 5, 3
4. Clinical euvolemia (absence of edema, orthostatic hypotension, or signs of volume depletion) 2, 3, 6
5. Normal renal, adrenal, and thyroid function 2, 3, 6

Critical Diagnostic Distinctions in Patients with Impaired Renal Function

In patients with impaired renal function, distinguishing SIADH from other causes becomes more challenging: 1

• Volume status assessment is paramount - physical examination alone has poor accuracy (sensitivity 41.1%, specificity 80%), so correlate clinical findings with laboratory data 1, 2
• Hypovolemic signs include orthostatic hypotension, dry mucous membranes, decreased skin turgor 1, 2
• Hypervolemic signs include peripheral edema, ascites, jugular venous distention 1, 2
• Euvolemic appearance with no edema, normal blood pressure, moist mucous membranes suggests SIADH 1

In elderly patients with impaired renal function specifically: 7

• Serum osmolality >300 mOsm/kg indicates dehydration, not SIADH 7, 4
• BUN may be elevated despite SIADH due to reduced renal clearance 5
• Urine sodium may be lower (<30 mmol/L) in SIADH patients with poor oral intake 5

Tests NOT Recommended

Do not routinely order: 1, 2

• Plasma ADH levels - not supported by evidence and delays diagnosis 1, 2
• Natriuretic peptide levels - not supported by evidence 1, 2
• Bioelectrical impedance for hydration assessment in elderly 7

Common Diagnostic Pitfalls

Never interpret urine values in isolation - always correlate urine osmolality and sodium with serum osmolality and clinical volume status 4

In neurosurgical patients or those with CNS pathology, distinguish SIADH from cerebral salt wasting (CSW): 1, 2

• Both show elevated urine sodium (>20 mEq/L) and concentrated urine 1, 2
• CSW shows true hypovolemia with orthostatic hypotension, low CVP (<6 cm H₂O), dry mucous membranes 1, 2
• SIADH shows euvolemia with normal CVP (6-10 cm H₂O) 1, 2
• This distinction is critical because CSW requires volume replacement while SIADH requires fluid restriction 1, 2

In patients with cirrhosis and impaired renal function: 1

• Hypervolemic hyponatremia is most common (present in ~60% of cirrhotic patients) 1
• Urine sodium may be elevated despite hypervolemia due to diuretic use 1
• Serum uric acid <4 mg/dL is less specific in this population 5