What biochemical tests are needed to support a diagnosis of SIADH in an adult patient?

Biochemical Tests to Support SIADH Diagnosis

The diagnosis of SIADH requires demonstrating hypotonic hyponatremia (serum sodium <135 mmol/L, typically <131 mmol/L for full workup) with inappropriately concentrated urine (>100 mOsm/kg, typically >300-500 mOsm/kg) and elevated urinary sodium (>20-40 mEq/L) in a clinically euvolemic patient. 1, 2, 3

Essential Laboratory Tests

Serum Studies

• Serum sodium: <135 mmol/L defines hyponatremia; values <131 mmol/L warrant comprehensive evaluation 1, 2
• Serum osmolality: Must be low (<275 mOsm/kg) to confirm hypotonic hyponatremia and exclude pseudohyponatremia 2, 3, 4
• Serum uric acid: <4 mg/dL has 73-100% positive predictive value for SIADH, though may also occur in cerebral salt wasting 1, 2, 5
• Blood urea nitrogen (BUN): Typically low in SIADH due to dilution, though less specific in elderly patients 5
• Serum creatinine and electrolytes: To rule out renal causes and assess potassium, calcium, magnesium 1

Urine Studies

• Urine osmolality: >100 mOsm/kg indicates impaired water excretion; >300-500 mOsm/kg is typical for SIADH and represents inappropriately concentrated urine relative to low serum osmolality 2, 3, 5, 4
• Urine sodium concentration: >20-40 mEq/L in SIADH reflects physiologic natriuresis to maintain fluid balance despite hyponatremia 2, 3, 5, 4
• Fractional excretion of sodium: >0.5% in approximately 70% of SIADH cases, though can be lower with poor oral intake 5

Endocrine Exclusion Tests

• Thyroid-stimulating hormone (TSH): Must rule out hypothyroidism as an alternative cause 1, 2
• Cortisol or morning cortisol: Must exclude adrenal insufficiency, as SIADH diagnosis requires normal adrenal function 1, 3, 4

Critical Diagnostic Criteria

SIADH requires ALL five cardinal features: 4

1. Hypotonic hyponatremia (low serum sodium with low serum osmolality)
2. Inappropriately concentrated urine (urine osmolality >100 mOsm/kg, typically >300-500 mOsm/kg)
3. Elevated urinary sodium (>20-40 mEq/L) with normal salt intake
4. Clinical euvolemia (no edema, orthostatic hypotension, or signs of volume depletion)
5. Normal renal, thyroid, and adrenal function

Volume Status Assessment

Physical examination alone is unreliable for determining volume status (sensitivity 41.1%, specificity 80%), so biochemical markers are essential. 1, 2

Euvolemic Features (SIADH)

• No peripheral edema, ascites, or jugular venous distention 1
• No orthostatic hypotension or dry mucous membranes 1
• Normal skin turgor and moist mucous membranes 1

Distinguishing SIADH from Cerebral Salt Wasting (CSW)

• SIADH: Euvolemic, central venous pressure 6-10 cm H₂O, urine sodium >20-40 mEq/L 2
• CSW: Hypovolemic, central venous pressure <6 cm H₂O, urine sodium >20 mEq/L despite volume depletion 2

Tests NOT Recommended

Do not routinely order plasma ADH levels or natriuretic peptide levels—these are not supported by evidence and delay diagnosis. 1, 2

Common Diagnostic Pitfalls

• Ignoring volume status: Misdiagnosing hypervolemic or hypovolemic hyponatremia as SIADH leads to inappropriate treatment 1, 2
• Relying solely on physical examination: Use biochemical markers to confirm clinical assessment 1, 2
• Missing medication causes: Review all medications, particularly SSRIs, carbamazepine, NSAIDs, opioids, chemotherapy agents (platinum-based, vinca alkaloids) 6, 3
• Failing to exclude hypothyroidism and adrenal insufficiency: These must be ruled out before confirming SIADH 6, 1, 3
• Not distinguishing SIADH from CSW in neurosurgical patients: These require opposite treatments (fluid restriction vs. volume replacement) 1, 2, 3