What are the diagnostic considerations for a patient with hyponatremia and suspected SIADH, particularly those with a history of lung disease or neurological disorders?

SIADH Diagnosis

SIADH is diagnosed when a patient presents with hypotonic hyponatremia (serum sodium <135 mmol/L, plasma osmolality <275 mOsm/kg), inappropriately concentrated urine (>500 mOsm/kg), elevated urinary sodium (>20-40 mEq/L), clinical euvolemia, and normal thyroid, adrenal, and renal function. 1

Essential Diagnostic Criteria

The diagnosis requires five cardinal features to be present simultaneously 1, 2:

• Hypotonic hyponatremia: Serum sodium <134-135 mEq/L with plasma osmolality <275 mOsm/kg 1, 2
• Inappropriately concentrated urine: Urine osmolality >500 mOsm/kg despite low plasma osmolality 1, 2
• Elevated urinary sodium: Urine sodium >20-40 mEq/L, reflecting continued sodium excretion despite hyponatremia 1, 2
• Clinical euvolemia: Absence of edema, orthostatic hypotension, dry mucous membranes, jugular venous distention, or ascites 3, 1
• Normal organ function: Exclusion of hypothyroidism, adrenal insufficiency, and significant renal impairment 1, 2

Initial Laboratory Workup

When serum sodium drops below 131 mmol/L, obtain the following tests 3, 2:

• Serum osmolality to confirm hypotonic hyponatremia (normal 275-290 mOsm/kg) and exclude pseudohyponatremia from hyperglycemia or hyperlipidemia 3, 2
• Urine osmolality and urine sodium measured simultaneously with serum tests 3, 2
• Thyroid-stimulating hormone (TSH) to exclude hypothyroidism 3
• Serum cortisol or morning cortisol to rule out adrenal insufficiency 1
• Serum creatinine and electrolytes (including potassium, calcium, magnesium) to assess renal function 3
• Serum uric acid: Levels <4 mg/dL have a 73-100% positive predictive value for SIADH 3, 2

Do NOT order plasma ADH or natriuretic peptide levels—these are not supported by evidence and delay diagnosis 3, 2.

Volume Status Assessment: The Critical Distinction

Physical examination alone is unreliable for determining volume status (sensitivity 41.1%, specificity 80%), so clinical assessment must be combined with laboratory data. 3, 2

Euvolemic (SIADH)

• Clinical signs: Normal skin turgor, moist mucous membranes, no orthostatic hypotension, no edema, no jugular venous distention 3, 1
• Central venous pressure: 6-10 cm H₂O if measured 1
• Urine sodium: >20-40 mEq/L 1, 2
• Treatment: Fluid restriction to 1 L/day 3, 1

Hypovolemic (Cerebral Salt Wasting)

• Clinical signs: Orthostatic hypotension, dry mucous membranes, decreased skin turgor, flat neck veins 3, 2
• Central venous pressure: <6 cm H₂O 1, 2
• Urine sodium: >20 mEq/L despite volume depletion 3, 2
• Treatment: Volume and sodium replacement with isotonic or hypertonic saline, NOT fluid restriction 3, 1

Hypervolemic (Heart Failure, Cirrhosis)

• Clinical signs: Peripheral edema, ascites, jugular venous distention, pulmonary congestion 3, 2
• Urine sodium: >20 mEq/L 2
• Treatment: Fluid restriction to 1-1.5 L/day 3

Special Diagnostic Considerations in Specific Populations

Neurosurgical Patients

Distinguishing SIADH from cerebral salt wasting (CSW) is critical because they require opposite treatments. 3, 1, 2

• CSW is more common than SIADH in patients with subarachnoid hemorrhage, poor clinical grade, ruptured anterior communicating artery aneurysms, and hydrocephalus 3
• CSW presents with true hypovolemia (CVP <6 cm H₂O), high urine sodium >20 mmol/L despite volume depletion, and evidence of extracellular volume depletion 3
• Hyponatremia in subarachnoid hemorrhage patients is associated with higher rates of cerebral ischemia and worse outcomes at 3 months 1

Lung Cancer Patients

• SIADH affects 1-5% of lung cancer patients, particularly those with small cell lung cancer (SCLC) 4, 3
• SCLC cells produce vasopressin (ADH), causing hyponatremia more frequently than Cushing syndrome 4
• ADH levels and hyponatremia usually improve after successful treatment of SCLC 4, 1
• Comprehensive laboratory assessment including urine studies is crucial as paraneoplastic SIADH requires treatment of the underlying malignancy alongside hyponatremia management 3, 1

Medication-Induced SIADH

Review all medications, particularly 3, 1:

• SSRIs and SNRIs (including escitalopram) 1
• Carbamazepine and oxcarbazepine 1
• Chemotherapeutic agents: Cisplatin, vinca alkaloids (vincristine, vinblastine), cyclophosphamide 4, 1
• NSAIDs and tramadol 1
• Opioids 4, 1

Common Diagnostic Pitfalls

• Ignoring mild hyponatremia (130-135 mmol/L): Even mild hyponatremia increases fall risk (21% vs 5% in normonatremic patients) and mortality (60-fold increase with sodium <130 mmol/L) 3
• Relying solely on physical examination: Volume status assessment requires both clinical and laboratory correlation 3, 2
• Failing to assess volume status accurately: Misdiagnosis leads to inappropriate therapy—fluid restriction worsens CSW, while saline worsens SIADH 3, 1
• Ordering unnecessary tests: Plasma ADH and natriuretic peptide levels are not supported by evidence 3, 2
• Missing medication causes: Always review the medication list for SIADH-inducing drugs 1