What are the diagnostic criteria and treatment options for Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)?

SIADH Diagnosis

SIADH is diagnosed by demonstrating hyponatremia (serum sodium <134 mEq/L), plasma hypoosmolality (<275 mosm/kg), inappropriately concentrated urine (osmolality >500 mosm/kg), and elevated urinary sodium (>20 mEq/L) in a clinically euvolemic patient after excluding hypothyroidism, adrenal insufficiency, and volume depletion. 1

Essential Diagnostic Criteria

The diagnosis requires five cardinal features to be present simultaneously 2:

• Hypotonic hyponatremia: Serum sodium <134 mEq/L with plasma osmolality <275 mosm/kg 1
• 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 (usually >40 mEq/L) 1, 3
• Clinical euvolemia: Absence of edema, orthostatic hypotension, dry mucous membranes, jugular venous distention, or ascites 1, 2
• Normal renal, adrenal, and thyroid function: Must exclude other causes of hyponatremia 2, 3

Clinical Assessment of Volume Status

Euvolemia is confirmed by the absence of specific physical findings 4:

• No peripheral edema or ascites (excludes hypervolemia) 4
• No orthostatic hypotension or tachycardia (excludes hypovolemia) 4
• Normal skin turgor and moist mucous membranes 4
• Normal jugular venous pressure 4

A serum uric acid <4 mg/dL has a positive predictive value of 73-100% for SIADH, though this may include some cerebral salt wasting cases 1, 4

Critical Exclusions Before Diagnosis

SIADH remains a diagnosis of exclusion—you must rule out 3:

• Hypothyroidism: Check TSH 5
• Adrenal insufficiency: Assess cortisol levels 5
• Diuretic use: Particularly thiazides, which commonly cause hyponatremia 6
• Volume depletion: Clinical assessment and potentially CVP measurement 1

Distinguishing SIADH from Cerebral Salt Wasting (CSW)

This distinction is critical in neurosurgical patients, as treatment approaches are opposite 1, 5:

SIADH characteristics:

• Euvolemic on exam 1
• Central venous pressure 6-10 cm H₂O 1
• Treat with fluid restriction 1

CSW characteristics:

• Hypovolemic on exam (hypotension, tachycardia, dry mucous membranes) 4
• Central venous pressure <6 cm H₂O 1
• Treat with volume and sodium replacement 4

A urinary sodium <30 mmol/L has a positive predictive value of 71-100% for response to saline infusion, suggesting hypovolemia rather than SIADH 5

Clinical Symptoms

Symptoms correlate with both the absolute sodium level and the rate of decline 4, 2:

Mild to moderate hyponatremia (126-135 mEq/L):

• Often asymptomatic or subtle symptoms 4
• Headache, nausea, muscle cramps, general weakness 4
• Neurocognitive problems including falls and attention deficits 4

Severe hyponatremia (<120 mEq/L):

• Confusion, seizures, coma 4
• Life-threatening if acute (<48 hours) 2
• Children at particularly high risk due to larger brain/skull ratio 4

Common Diagnostic Pitfalls

• Ignoring mild hyponatremia (130-135 mEq/L): Even mild hyponatremia increases fall risk (21% vs 5% in normonatremic patients) and mortality 5, 4
• Misdiagnosing volume status: Using fluid restriction in CSW worsens outcomes 1, 4
• Overlooking medication causes: Thiazides, SSRIs, carbamazepine, cyclophosphamide, and vincristine commonly cause SIADH 1
• Missing malignancy: SIADH occurs in 1-5% of lung cancer patients, particularly small cell lung cancer 1, 4
• Attributing nonspecific symptoms to other conditions: Delays diagnosis and treatment 4

Laboratory Workup

Initial evaluation should include 5:

• Serum sodium, osmolality, creatinine, BUN 5
• Urine osmolality and sodium concentration 1
• Serum uric acid 1
• TSH and cortisol to exclude endocrine causes 5
• Assessment of volume status (clinical exam, potentially CVP) 1

Do not obtain ADH or natriuretic peptide levels—they are not supported by evidence and delay treatment 5