What laboratory tests are used to diagnose Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)?

Laboratory Tests for Diagnosing SIADH

The diagnosis of SIADH requires specific laboratory findings including 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 the absence of hypothyroidism, adrenal insufficiency, or volume depletion. 1

Essential Diagnostic Criteria

Required Laboratory Tests:

1. Serum Measurements:

   • Serum sodium (decreased: <134 mEq/L)
   • Serum osmolality (decreased: <275 mosm/kg)
   • Blood urea nitrogen (typically low in SIADH)
   • Serum creatinine (to assess renal function)
   • Serum uric acid (typically low in SIADH, seen in 70% of cases) 2
   • Serum potassium (usually normal despite dilution)
   • Anion gap (typically lower in SIADH)

2. Urine Measurements:

   • Urine osmolality (inappropriately elevated: >500 mosm/kg relative to serum osmolality)
   • Urine sodium concentration (elevated: >20 mEq/L)
   • Fractional excretion of sodium (often >0.5% in 70% of cases) 2

3. Exclusion Tests:

   • Thyroid function tests (TSH, free T4) to rule out hypothyroidism
   • Morning cortisol or ACTH stimulation test to exclude adrenal insufficiency
   • Clinical assessment of volume status to confirm euvolemia

Clinical Assessment Algorithm

Step 1: Confirm Hyponatremia and Hypoosmolality

• Measure serum sodium (<134 mEq/L)
• Measure serum osmolality (<275 mosm/kg)
• Rule out pseudohyponatremia (occurs with hyperlipidemia or hyperproteinemia) 3

Step 2: Assess Volume Status

• Clinical examination to confirm euvolemic state (absence of edema, normal blood pressure, no orthostatic changes)
• Distinguish from hypovolemic and hypervolemic states

Step 3: Measure Urine Parameters

• Urine osmolality (>500 mosm/kg indicates inappropriate ADH action)
• Urine sodium (>20 mEq/L in SIADH)
• Calculate fractional excretion of sodium if needed

Step 4: Rule Out Other Causes

• Check thyroid function
• Assess adrenal function
• Review medication history for drugs that can cause SIADH
• Consider other conditions that can mimic SIADH (cerebral salt wasting, reset osmostat) 4

Interpretation of Results

SIADH is confirmed when all of the following criteria are met:

1. Hyponatremia with decreased serum osmolality
2. Inappropriately concentrated urine (urine osmolality >100 mosm/kg, typically >500 mosm/kg)
3. Elevated urinary sodium excretion (>20-30 mEq/L) with normal salt and water intake
4. Absence of clinical evidence of volume depletion
5. Normal renal, adrenal, and thyroid function
6. No recent use of diuretic agents 5, 4

Common Pitfalls and Caveats

• Medication review is crucial: Many medications can cause SIADH, including certain antidepressants, antipsychotics, anticonvulsants, and chemotherapeutic agents
• Low urine sodium doesn't rule out SIADH: In patients with poor salt intake, urine sodium may be lower despite SIADH 2
• Uric acid levels: Low serum uric acid is more specific for SIADH than low urea, especially in elderly patients 2
• Cerebral salt wasting mimics SIADH: Both present with hyponatremia and high urine sodium, but volume status differs (hypovolemic in cerebral salt wasting vs. euvolemic in SIADH) 4
• Reset osmostat: A variant of SIADH where the osmotic threshold for ADH release is reset to a lower level, resulting in stable hyponatremia that doesn't worsen with fluid administration 4

By systematically applying these laboratory tests and clinical assessments, clinicians can accurately diagnose SIADH and distinguish it from other causes of hyponatremia, leading to appropriate treatment decisions that improve patient outcomes.