Diagnostic Criteria for Syndrome of Inappropriate Antidiuretic Hormone (SIADH)
The diagnosis of SIADH requires the presence of hypotonic hyponatremia with inappropriate urinary concentration in a euvolemic patient, along with normal renal, adrenal, and thyroid function. 1, 2, 3
Essential Diagnostic Criteria
- Hypotonic hyponatremia (serum sodium <135 mmol/L with decreased serum osmolality) 2, 4
- Urine osmolality inappropriately high relative to plasma osmolality (>100 mOsm/kg, typically >500 mOsm/kg) 3, 5, 4
- Elevated urine sodium concentration (>20-30 mEq/L) with normal salt intake 2, 3, 6
- Euvolemic state (absence of clinical signs of hypovolemia or hypervolemia) 1, 2, 3
- Normal renal, adrenal, and thyroid function 2, 7, 8
- Absence of diuretic use 4
Supporting Laboratory Findings
- Serum uric acid <4 mg/dL (has a positive predictive value of 73-100% for SIADH) 2, 3, 6
- Low blood urea nitrogen 2, 6
- Low anion gap with nearly normal total CO2 and serum potassium 6
- Fractional excretion of sodium >0.5% in approximately 70% of cases 6
Clinical Assessment of Volume Status
Volume status assessment is critical to differentiate SIADH from other causes of hyponatremia:
- Euvolemia in SIADH: No edema, no orthostatic hypotension, normal skin turgor, moist mucous membranes 1, 2, 3
- Central venous pressure measurements: SIADH (CVP 6-10 cm H₂O) vs. Cerebral Salt Wasting (CVP <6 cm H₂O) 3
Important Differential Diagnoses
- Cerebral Salt Wasting (CSW): Characterized by hypovolemia rather than euvolemia 2, 3
- Reset osmostat: A variant of SIADH with stable but lower serum sodium set point 4, 6
- Hypothyroidism: Must be ruled out before diagnosing SIADH 2, 4
- Hypocortisolism: Typically presents with lower total CO2 despite low urea and uric acid levels 6
- Polydipsia: Characterized by excessive fluid intake and low urine osmolality 3, 4
Common Pitfalls in Diagnosis
- Failing to assess volume status accurately, which is essential for differentiating SIADH from other causes of hyponatremia 1, 2
- Not ruling out medication-induced hyponatremia, particularly thiazide diuretics 4
- Confusing SIADH with cerebral salt wasting, especially in neurosurgical patients 2, 3
- Overlooking the need to evaluate adrenal and thyroid function 2, 7
- Misinterpreting urine sodium levels in patients with poor salt intake (may be <30 mEq/L despite SIADH) 6
Classification of SIADH Based on AVP Secretion Patterns
Four categories of osmoregulated AVP secretion in SIADH have been described:
- Erratic AVP release 7
- Reset osmostat 7, 6
- Persistent AVP release at low plasma osmolality 7
- Normal osmoregulated AVP secretion 7
Remember that the severity of symptoms in SIADH is related to both the absolute serum sodium concentration and its rate of fall, particularly if greater than 0.5 mmol/L/h 3, 7.