What are the diagnostic criteria for syndrome of inappropriate antidiuretic hormone secretion (SIADH)?

Diagnostic Criteria for SIADH

The diagnosis of SIADH requires five cardinal criteria: hypotonic hyponatremia (serum sodium <134 mEq/L), plasma hypoosmolality (<275 mosm/kg), inappropriately elevated urine osmolality (>500 mosm/kg), elevated urinary sodium (>20 mEq/L), and euvolemia with normal thyroid, adrenal, and renal function. 1, 2

Essential Diagnostic Criteria

Core Laboratory Requirements

• Serum sodium <134 mEq/L with corresponding plasma osmolality <275 mosm/kg confirms hypotonic hyponatremia 1
• Urine osmolality >500 mosm/kg despite low plasma osmolality indicates inappropriate urinary concentration 1
• Urine sodium concentration >20-40 mEq/L demonstrates continued renal sodium excretion despite hyponatremia 1, 2
• Serum uric acid <4 mg/dL has a positive predictive value of 73-100% for SIADH, though it may also occur in cerebral salt wasting 1, 2

Critical Exclusion Criteria

• Normal thyroid function (TSH) must be documented to exclude hypothyroidism as a cause 2, 3
• Normal adrenal function must be confirmed to rule out adrenal insufficiency 1, 2
• Normal renal function is required, as renal failure can produce a similar biochemical picture 1
• Absence of volume depletion distinguishes SIADH from hypovolemic hyponatremia 1, 2
• Absence of edema or volume overload excludes hypervolemic causes like heart failure or cirrhosis 1, 2

Clinical Assessment of Volume Status

Euvolemia Confirmation

• Euvolemia is characterized by absence of orthostatic hypotension, normal skin turgor, moist mucous membranes, and no peripheral edema 1, 2
• Physical examination alone has poor accuracy (sensitivity 41.1%, specificity 80%) for determining volume status, so clinical judgment must incorporate multiple findings 2, 4
• Central venous pressure of 6-10 cm H₂O supports euvolemia in SIADH, distinguishing it from cerebral salt wasting (CVP <6 cm H₂O) 1

Distinguishing SIADH from Cerebral Salt Wasting

• In neurosurgical patients, differentiating SIADH from cerebral salt wasting is critical because they require opposite treatments—fluid restriction for SIADH versus volume replacement for cerebral salt wasting 1, 2
• Cerebral salt wasting presents with true hypovolemia (orthostatic hypotension, tachycardia, dry mucous membranes, flat neck veins) despite elevated urine sodium >20 mEq/L 1
• SIADH presents with euvolemia and urine sodium >20-40 mEq/L with urine osmolality >300 mOsm/kg 2

Pathophysiologic Understanding

Mechanism of Hyponatremia

• Persistent or elevated plasma arginine vasopressin (AVP) despite hyponatremia and low plasma osmolality leads to water retention 1, 3
• Physiologic natriuresis occurs to maintain fluid balance at the expense of plasma sodium, resulting in concentrated urine with high sodium content 1
• Osmoregulated inhibition of thirst fails to curb fluid intake in SIADH, perpetuating the dilutional hyponatremia 3

Four Patterns of AVP Secretion

• Erratic AVP release, reset osmostat, persistent AVP release at low plasma osmolality, and normal osmoregulated AVP secretion represent the four categories of osmoregulated AVP secretion described in SIADH 3

Common Etiologies to Investigate

Major Diagnostic Categories

• Malignancy (particularly small cell lung cancer, which causes SIADH in 15% of cases), head and neck cancer (3%), and various other tumors 5
• Neurological diseases including CNS disorders, head trauma, and infections 3, 5
• Pulmonary diseases such as pneumonia, tuberculosis, and positive pressure ventilation 3, 5
• Medications including SSRIs, carbamazepine, oxcarbazepine, NSAIDs, tramadol, cyclophosphamide, vincristine, vinblastine, cisplatin, and certain antipsychotics 1, 6, 5

Tests NOT Recommended

• Plasma ADH levels are not supported by evidence and delay diagnosis, so routine ordering is not recommended 2, 4
• Natriuretic peptide levels are not recommended for routine SIADH diagnosis 2
• Bioelectrical impedance for hydration assessment is not recommended in the diagnostic workup 2

Critical Diagnostic Pitfalls

• Failing to assess volume status accurately is the most common diagnostic error, as misclassification leads to inappropriate therapy 1, 2
• Ignoring mild hyponatremia (130-135 mmol/L) as clinically insignificant is a critical mistake, as even mild hyponatremia increases fall risk (21% vs 5%) and mortality 4
• Misdiagnosing cerebral salt wasting as SIADH in neurosurgical patients can be fatal if fluid restriction is applied to a hypovolemic patient 1, 2
• Failing to exclude hypothyroidism and adrenal insufficiency before confirming SIADH diagnosis 2, 7