What blood tests are necessary to diagnose SIADH in a patient with hyponatremia and potential underlying malignancy?

Blood Tests to Diagnose SIADH

To prove SIADH, you need simultaneous serum and urine studies demonstrating hypotonic hyponatremia with inappropriately concentrated urine in a euvolemic patient, along with exclusion of other causes.

Essential Blood Tests

The core diagnostic panel includes:

• Serum sodium - must be <135 mmol/L (typically <134 mEq/L for SIADH diagnosis) 1, 2
• Serum osmolality - must be low (<275 mOsm/kg) to confirm hypotonic hyponatremia and exclude pseudohyponatremia 2, 3
• Serum uric acid - a level <4 mg/dL has a 73-100% positive predictive value for SIADH, though it may also occur in cerebral salt wasting 1, 2

Essential Urine Tests (Simultaneous Collection)

These must be obtained at the same time as serum studies:

• Urine osmolality - must be inappropriately elevated (>100 mOsm/kg, typically >300-500 mOsm/kg) relative to low serum osmolality 2, 3
• Urine sodium - must be elevated (>20-40 mEq/L) despite hyponatremia, indicating natriuresis 2, 3

Tests to Exclude Other Causes

SIADH is a diagnosis of exclusion, requiring:

• Thyroid-stimulating hormone (TSH) - to rule out hypothyroidism 1, 4
• Serum creatinine and BUN - to exclude renal insufficiency 1, 4
• Serum cortisol or ACTH stimulation test - to rule out adrenal insufficiency 1, 4
• Serum glucose - hyperglycemia causes pseudohyponatremia (add 1.6 mEq/L to sodium for each 100 mg/dL glucose >100 mg/dL) 1

Clinical Assessment Requirements

Laboratory findings must be correlated with clinical euvolemia:

• Physical examination should show absence of volume depletion (no orthostatic hypotension, dry mucous membranes, or decreased skin turgor) and absence of volume overload (no edema, ascites, or jugular venous distention) 2, 5
• Note that physical examination alone has poor accuracy (sensitivity 41.1%, specificity 80%) for volume assessment 1, 2

Diagnostic Criteria Summary

All five cardinal criteria must be present:

1. Hypotonic hyponatremia (low serum sodium and osmolality) 5, 4
2. Inappropriately concentrated urine (urine osmolality >100 mOsm/kg, typically >300-500 mOsm/kg) 2, 5
3. Elevated urinary sodium (>20-40 mEq/L) indicating natriuresis 2, 5
4. Clinical euvolemia (absence of edema and volume depletion) 5, 4
5. Normal renal, thyroid, and adrenal function 5, 4

Tests NOT Recommended

Do not routinely order:

• Plasma ADH levels - not supported by evidence, delays diagnosis, and is not necessary for diagnosis (class III evidence) 1, 2
• Natriuretic peptide levels - not supported by evidence for SIADH diagnosis 1, 2

Special Considerations in Malignancy Context

When underlying malignancy is suspected:

• Screen for paraneoplastic syndromes including SIADH, particularly in lung cancer patients 1
• Small cell lung cancer is the most common malignancy associated with SIADH 3, 6
• Treatment of the underlying malignancy often leads to resolution of SIADH 3

Critical Pitfall to Avoid

Distinguishing SIADH from cerebral salt wasting (CSW) is crucial in patients with CNS pathology, as they require opposite treatments - SIADH requires fluid restriction while CSW requires volume and sodium replacement 1, 2. CSW is characterized by true hypovolemia with low central venous pressure (<6 cm H₂O), while SIADH shows euvolemia with normal CVP (6-10 cm H₂O) 2, 3.