What are the diagnostic criteria for Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) in a critically ill patient?

Diagnostic Criteria for SIADH

The diagnosis of SIADH requires five cardinal criteria: hypotonic hyponatremia (serum sodium <135 mmol/L with plasma osmolality <275 mOsm/kg), inappropriately concentrated urine (urine osmolality >100 mOsm/kg, typically >500 mOsm/kg), elevated urinary sodium (>20 mEq/L), euvolemic state (absence of clinical signs of hypovolemia or hypervolemia), and normal renal, adrenal, and thyroid function. 1, 2

Essential Diagnostic Criteria

Serum and Plasma Findings

• Hypotonic hyponatremia with serum sodium <135 mmol/L (though full workup typically warranted when <131 mmol/L) 3, 1
• Plasma osmolality <275 mOsm/kg confirming true hypotonicity and excluding pseudohyponatremia 1, 2
• 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 3, 1

Urine Findings

• Urine osmolality inappropriately elevated (>100 mOsm/kg, typically >300-500 mOsm/kg) relative to low plasma osmolality, indicating impaired free water excretion 3, 1, 2
• Urine sodium concentration >20-40 mEq/L despite hyponatremia, reflecting physiologic natriuresis that occurs to maintain fluid balance at the expense of plasma sodium 3, 1, 4
• Fractional excretion of sodium >0.5% in approximately 70% of SIADH cases, though this can be lower with poor oral intake 4

Volume Status Assessment (Critical Distinguishing Feature)

• Euvolemic state is the defining characteristic that separates SIADH from other causes of hyponatremia 3, 1, 2
• Clinical euvolemia means no edema, no orthostatic hypotension, normal skin turgor, moist mucous membranes, and stable vital signs 3, 5
• Central venous pressure 6-10 cm H₂O if invasive monitoring available (versus <6 cm H₂O in cerebral salt wasting) 1, 5
• Physical examination alone has poor accuracy (sensitivity 41.1%, specificity 80%) for volume assessment, so laboratory parameters are essential 3

Exclusion Criteria (Must Rule Out)

• Normal thyroid function - check TSH to exclude hypothyroidism 3, 6
• Normal adrenal function - exclude adrenal insufficiency which can mimic SIADH 3, 6
• Not on diuretics - thiazide diuretics are a common cause of hyponatremia that must be excluded 6
• Normal renal function - SIADH diagnosis requires adequate kidney function 1, 2

Additional Laboratory Findings Supporting SIADH

• Low blood urea nitrogen (BUN) due to dilution, though less specific in elderly patients 4
• Lower anion gap with nearly normal total CO₂ and serum potassium despite dilution 4
• Low fractional excretion of urea can help distinguish from salt depletion 3

Critical Diagnostic Pitfalls to Avoid

• Failing to assess volume status accurately is the most common diagnostic error - SIADH is euvolemic, cerebral salt wasting is hypovolemic, and cirrhosis/heart failure cause hypervolemic hyponatremia 3, 1
• Not excluding medication causes - SSRIs, carbamazepine, NSAIDs, opioids, chemotherapy agents (cisplatin, vinca alkaloids) commonly cause SIADH 1, 7
• Confusing SIADH with cerebral salt wasting in neurosurgical patients - both have elevated urine sodium, but CSW has true hypovolemia with CVP <6 cm H₂O and requires opposite treatment (volume replacement, not fluid restriction) 3, 1, 5
• Missing reset osmostat - a variant where osmoregulation is intact but set at a lower threshold, requiring different management 2, 4
• Ignoring low urine sodium in poorly nourished SIADH patients - urine sodium can be <30 mEq/L with poor oral intake, but this doesn't exclude SIADH 4

Diagnostic Algorithm in Critically Ill Patients

1. Confirm true hyponatremia - measure serum osmolality to exclude pseudohyponatremia from hyperglycemia or hyperlipidemia 6
2. Assess volume status clinically - look for orthostatic hypotension, dry mucous membranes (hypovolemic), versus edema, ascites, JVD (hypervolemic), versus neither (euvolemic) 3, 5
3. Measure urine osmolality and sodium - SIADH shows urine osmolality >100 mOsm/kg (typically >500) and urine sodium >20 mEq/L 1, 2, 4
4. Check thyroid and adrenal function - TSH and cortisol to exclude endocrine causes 3, 6
5. Review medication list - identify potential causative drugs 1, 7
6. In neurosurgical patients, measure CVP if available - helps distinguish SIADH (CVP 6-10) from cerebral salt wasting (CVP <6) 1, 5

The pathophysiology involves persistent or elevated plasma arginine vasopressin (AVP) despite hyponatremia and low plasma osmolality, leading to water retention followed by physiologic natriuresis where fluid balance is maintained at the expense of plasma sodium 2, 6. This explains why SIADH patients are euvolemic despite significant hyponatremia - they retain water but excrete sodium to maintain volume homeostasis 2.