How do I diagnose syndrome of inappropriate antidiuretic hormone secretion (SIADH)?

Diagnosing SIADH

SIADH is diagnosed when five cardinal criteria are simultaneously met: hypotonic hyponatremia (serum sodium <134 mEq/L), plasma osmolality <275 mosm/kg, inappropriately concentrated urine (osmolality >500 mosm/kg), urinary sodium >20 mEq/L, and clinical euvolemia in the absence of hypothyroidism, adrenal insufficiency, or volume depletion. 1

Essential Diagnostic Criteria

The diagnosis requires all five of the following criteria to be present simultaneously 1, 2, 3:

• Hypotonic hyponatremia: Serum sodium <134 mEq/L with plasma osmolality <275 mosm/kg 1, 2
• Inappropriately concentrated urine: Urine osmolality >100 mosm/kg (typically >500 mosm/kg) despite low plasma osmolality 1, 2
• Elevated urinary sodium: Urine sodium concentration >20 mEq/L, indicating continued natriuresis despite hyponatremia 1, 2
• Clinical euvolemia: Absence of signs of volume depletion (no orthostatic hypotension, dry mucous membranes, decreased skin turgor) or volume overload (no peripheral edema, ascites, jugular venous distention) 1, 2, 3
• Normal organ function: Normal renal, adrenal, and thyroid function must be confirmed 1, 2, 3

Laboratory Evaluation Algorithm

Initial Screening Tests

Obtain the following tests simultaneously to establish the diagnosis 2, 4:

• Serum sodium and plasma osmolality to confirm hypotonic hyponatremia 2, 4
• Urine osmolality and urine sodium to demonstrate inappropriate urinary concentration 2, 4
• Serum glucose to exclude pseudohyponatremia (adjust sodium by 1.6 mEq/L for each 100 mg/dL glucose >100 mg/dL) 5, 2

Confirmatory Tests

To exclude differential diagnoses and confirm normal organ function 5, 2, 4:

• Thyroid-stimulating hormone (TSH) to rule out hypothyroidism 1, 5, 2
• Serum cortisol or morning cortisol to rule out adrenal insufficiency 5, 2
• Serum creatinine and blood urea nitrogen to assess renal function 5, 4
• Serum uric acid: A level <4 mg/dL has a 73-100% positive predictive value for SIADH 1, 5, 4

Additional Supportive Laboratory Findings

These findings support the diagnosis but are not required 4:

• Low serum urea: Typically low in SIADH (less specific in elderly patients) 4
• Fractional excretion of sodium >0.5% in 70% of cases, reflecting salt intake 4
• Lower anion gap with nearly normal total CO₂ and serum potassium despite dilution 4

Volume Status Assessment

Volume status assessment is paramount—SIADH patients are euvolemic, not hypovolemic or hypervolemic. 1, 2

Signs of Euvolemia (Present in SIADH)

Look for the following clinical findings 1, 2, 3:

• No orthostatic hypotension or tachycardia 1, 2
• Normal skin turgor and moist mucous membranes 1, 2
• No peripheral edema, ascites, or jugular venous distention 1, 2
• Flat neck veins when supine 5

Distinguishing SIADH from Other Causes

Physical examination alone has poor accuracy (sensitivity 41.1%, specificity 80%) for volume assessment 5, 2. In neurosurgical patients, central venous pressure (CVP) should be used when available: SIADH shows CVP 6-10 cm H₂O, while cerebral salt wasting shows CVP <6 cm H₂O 1, 2.

Etiologic Investigation

Once SIADH is diagnosed, investigate the underlying cause 2, 6:

Malignancy (Most Common)

• Small cell lung cancer is the most common malignant cause, occurring in 1-5% of cases 1, 2
• Obtain chest X-ray or chest CT scan in all newly diagnosed SIADH cases 6

CNS Disorders

• CNS infections, space-occupying lesions, subarachnoid hemorrhage, and head trauma can cause SIADH 2
• Consider brain imaging if CNS pathology is suspected 6

Medications

High-risk medications include 1, 2:

• SSRIs, carbamazepine, oxcarbazepine 1, 2
• Chemotherapeutic agents (cisplatin, vinca alkaloids) 1
• NSAIDs, opioids, antipsychotics 1

Pulmonary Diseases

• Pneumonia, tuberculosis, and other lung diseases can cause SIADH 2, 6

Critical Diagnostic Pitfalls

Confusing SIADH with Cerebral Salt Wasting (CSW)

In neurosurgical patients, distinguishing SIADH from CSW is critical because they require opposite treatments. 1, 2

Feature	SIADH	Cerebral Salt Wasting
Volume status	Euvolemic	Hypovolemic
CVP	6-10 cm H₂O	<6 cm H₂O
Treatment	Fluid restriction	Volume and sodium replacement
Clinical signs	No orthostatic hypotension	Orthostatic hypotension, tachycardia

1, 2

Failing to Exclude Hypothyroidism and Adrenal Insufficiency

These conditions must be ruled out before confirming SIADH, as they can mimic the syndrome 1, 2, 6.

Missing Medication Causes

Review all medications, particularly SSRIs, carbamazepine, NSAIDs, opioids, and chemotherapy agents, to avoid missing medication-induced SIADH 2.

Severity Assessment

Symptoms correlate with both the absolute sodium level and the rate of decline, particularly when falling faster than 0.5 mmol/L/hour 2, 3. Acute hyponatremia (<48 hours) produces more severe symptoms at higher sodium levels than chronic hyponatremia due to inadequate cerebral adaptation 2.