SIADH Diagnostic Criteria and Clinical Features
Essential Diagnostic Criteria
The diagnosis of SIADH requires five cardinal criteria to be met simultaneously: hypotonic hyponatremia (serum sodium <135 mEq/L), inappropriately concentrated urine (urine osmolality >500 mOsm/kg), elevated urinary sodium (>20-40 mEq/L), clinical euvolemia (absence of edema or volume depletion), and normal renal, thyroid, and adrenal function 1, 2.
Laboratory Findings
Serum sodium <135 mEq/L with plasma osmolality <275 mOsm/kg defines the hypotonic hyponatremia characteristic of SIADH 1, 2.
Urine osmolality inappropriately elevated (>500 mOsm/kg) relative to the low plasma osmolality, indicating failure of normal ADH suppression 1, 2.
Urine sodium concentration >20-40 mEq/L despite hyponatremia, reflecting physiologic natriuresis as the body attempts to maintain fluid balance at the expense of plasma sodium 1, 2, 3.
Serum uric acid <4 mg/dL has a positive predictive value of 73-100% for SIADH, making it a useful supportive finding 4, 5.
Volume Status Assessment
Clinical euvolemia is mandatory - patients must have no orthostatic hypotension, normal skin turgor, moist mucous membranes, and absence of peripheral edema, ascites, or jugular venous distention 1, 2.
Central venous pressure (CVP) of 6-10 cm H₂O distinguishes SIADH from cerebral salt wasting (CVP <6 cm H₂O), which is critical in neurosurgical patients 5, 3.
Physical examination alone has poor accuracy (sensitivity 41.1%, specificity 80%) for volume assessment, requiring laboratory confirmation 4.
Exclusion Criteria
Normal thyroid function (TSH) must be documented to exclude hypothyroidism as a cause of hyponatremia 4, 3.
Normal adrenal function must be confirmed to rule out adrenal insufficiency 4, 3.
Absence of diuretic use is essential, as diuretics can mimic SIADH laboratory findings 4.
Normal renal function excludes renal causes of impaired water excretion 3.
Clinical Features by Severity
Symptom Severity Related to Sodium Level and Rate of Decline
Symptoms correlate with both absolute serum sodium concentration and rate of fall, particularly when sodium decreases >0.5 mmol/L/hour 2.
Mild symptoms (sodium 126-135 mEq/L) include headache, nausea, and vomiting 5.
Moderate symptoms (sodium 120-125 mEq/L) manifest as confusion, lethargy, and anorexia 6, 2.
Severe symptoms (sodium <120 mEq/L) present with seizures, coma, and risk of death 6, 2.
Neuromuscular Manifestations
Neurological symptoms predominate and include altered mental status, confusion, and decreased level of consciousness 5, 7.
Seizures occur with severe hyponatremia and represent a medical emergency requiring immediate intervention 1, 7.
Osmotic demyelination syndrome can result from overly rapid correction (>12 mEq/L/24 hours), causing dysarthria, mutism, dysphagia, spastic quadriparesis, and potentially death 8.
Gastrointestinal Features
Pathophysiology
Persistent or elevated plasma arginine vasopressin (AVP) occurs despite hyponatremia and low plasma osmolality, the fundamental defect in SIADH 1, 2.
Water retention followed by physiologic natriuresis maintains fluid balance at the expense of plasma sodium, explaining the high urine sodium despite hyponatremia 1, 2, 3.
Osmoregulated inhibition of thirst fails, allowing continued fluid intake that perpetuates the dilutional hyponatremia 2.
Four Patterns of AVP Secretion in SIADH
Type A: Erratic AVP release with no relationship to plasma osmolality 2.
Type B: Reset osmostat where AVP secretion occurs at a lower osmotic threshold 2.
Type C: Persistent AVP release despite low plasma osmolality 2.
Type D: Normal osmoregulated AVP secretion with enhanced renal sensitivity to AVP 2.
Common Etiologies
Malignancy
- Small cell lung cancer is the most common malignancy causing SIADH, with paraneoplastic syndrome affecting 1-5% of patients 4, 1.
Neurological Disorders
- CNS disorders including meningitis, encephalitis, head trauma, and subarachnoid hemorrhage commonly cause SIADH 1, 2.
Pulmonary Diseases
- Pneumonia, tuberculosis, and other lung diseases are frequent pulmonary causes 2.
Medications
High-risk medications include SSRIs, carbamazepine, oxcarbazepine, cyclophosphamide, vincristine, and NSAIDs 1, 6.
Chemotherapeutic agents such as cisplatin and vinca alkaloids frequently induce SIADH 1.
Critical Diagnostic Pitfalls
Distinguishing SIADH from cerebral salt wasting (CSW) is essential in neurosurgical patients, as they require opposite treatments - SIADH needs fluid restriction while CSW requires volume and sodium replacement 4, 1, 5.
Hospital-acquired hyponatremia from hypotonic IV fluids in the setting of elevated AVP affects 15-30% of hospitalized patients and is entirely preventable by using isotonic maintenance fluids 4, 3.
Pseudohyponatremia from hyperglycemia or hyperlipidemia must be excluded by measuring serum osmolality 4.