What tests are used to rule out Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)?

Tests to Rule Out SIADH

The essential diagnostic tests to rule out Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) include serum sodium, serum osmolality, urine osmolality, urine sodium, and assessment of volume status, as these directly evaluate the cardinal diagnostic criteria.

Diagnostic Criteria for SIADH

SIADH is a diagnosis of exclusion that requires the following cardinal criteria:

1. Hypotonic hyponatremia (serum sodium <135 mEq/L)
2. Urine osmolality inappropriately concentrated relative to plasma osmolality (typically >100 mOsm/kg)
3. Urinary sodium excretion >30 mEq/L with normal salt and water intake
4. Clinical euvolemia (absence of edema or volume depletion)
5. Normal renal, adrenal, and thyroid function

Essential Laboratory Tests

First-line Tests

• Serum sodium and osmolality - To confirm hypotonic hyponatremia 1
• Urine osmolality - Should be >100 mOsm/kg in SIADH despite hyponatremia 2
• Urine sodium concentration - Typically >30 mEq/L in SIADH 2
• Assessment of volume status - To confirm euvolemia (clinical examination)
• Serum urea and creatinine - To exclude renal dysfunction 1
• Serum uric acid - Typically low in SIADH (present in 70% of cases) 1

Second-line Tests to Rule Out Other Causes

• Thyroid function tests (TSH) - To exclude hypothyroidism 3
• Morning serum cortisol or ACTH stimulation test - To exclude adrenal insufficiency 1, 4
• Serum potassium and anion gap - Patients with SIADH typically show lower anion gap with nearly normal total CO2 and serum potassium 1
• Fractional excretion of sodium - Often >0.5% in SIADH 1

Imaging and Additional Tests

• Chest radiograph - To identify pulmonary pathology (e.g., lung cancer) that may cause SIADH 5
• Brain imaging (CT or MRI) - If neurological causes are suspected 4

Diagnostic Algorithm

1. Confirm hyponatremia: Serum sodium <135 mEq/L
2. Assess plasma osmolality: Should be low (<280 mOsm/kg)
3. Measure urine osmolality: Should be inappropriately high (>100 mOsm/kg) relative to plasma osmolality
4. Measure urine sodium: Should be >30 mEq/L with normal salt intake
5. Assess volume status: Patient should be clinically euvolemic
6. Rule out other causes:
   • Exclude renal, adrenal, and thyroid dysfunction
   • Consider medication review for drugs associated with SIADH (e.g., vincristine, SSRIs) 6

Clinical Pearls and Pitfalls

• Low urea and uric acid are characteristic findings in SIADH but not specific, especially in elderly patients 1
• Urine sodium may be low in patients with SIADH who have poor sodium intake, creating a potential diagnostic pitfall 1
• Medication review is crucial as many drugs can cause SIADH, including vincristine, SSRIs, and certain chemotherapeutic agents 6, 5
• Adrenal insufficiency can mimic SIADH but typically presents with lower total CO2 despite low urea and uric acid levels 1
• Measurement of plasma AVP is not required for diagnosis of SIADH 5

Therapeutic Considerations

For confirmed SIADH, treatment options include:

• Water restriction (first-line for chronic cases) 4
• Tolvaptan (vasopressin V2-receptor antagonist) for clinically significant cases 7
• Treatment of the underlying cause 5

Remember that too rapid correction of hyponatremia (>12 mEq/L/24 hours) can cause osmotic demyelination syndrome 7, so careful monitoring is essential during treatment.