What is the appropriate diagnostic work‑up and initial management for a patient with euvolemic hyponatraemia, low plasma osmolality, inappropriately concentrated urine and normal renal, adrenal and thyroid function suggestive of syndrome of inappropriate antidiuretic hormone secretion?

Diagnostic Work-Up and Initial Management of SIADH

For a patient with euvolemic hyponatremia, low plasma osmolality, inappropriately concentrated urine, and normal renal/adrenal/thyroid function, the diagnosis is SIADH, and first-line management is fluid restriction to 1 L/day (or 800–1200 mL/day), with 3% hypertonic saline reserved only for severe symptomatic cases. 1, 2, 3

Diagnostic Confirmation

The diagnosis of SIADH requires five cardinal criteria to be met simultaneously 4, 5:

• Hypotonic hyponatremia: serum sodium <135 mmol/L with serum osmolality <275 mOsm/kg 1, 4
• Inappropriately concentrated urine: urine osmolality >100 mOsm/kg (typically >300–500 mOsm/kg) despite low serum osmolality 1, 4, 6
• Elevated urine sodium: typically >20–40 mEq/L (often >40 mEq/L) with normal salt intake 1, 5, 6
• Clinical euvolemia: absence of edema, orthostatic hypotension, dry mucous membranes, or jugular venous distension 1, 4
• Normal renal, adrenal, and thyroid function: confirmed by normal creatinine, TSH, and cortisol levels 1, 4, 6

Essential Laboratory Work-Up

The initial diagnostic panel should include 1:

• Serum sodium, serum osmolality, and urine osmolality
• Urine sodium concentration (spot sample acceptable)
• Serum creatinine and BUN to exclude renal insufficiency
• TSH to rule out hypothyroidism
• Morning cortisol (>18–20 µg/dL excludes adrenal insufficiency in acute illness) 1
• Serum uric acid <4 mg/dL has 73–100% positive predictive value for SIADH 1

Do not order plasma ADH levels—this adds no clinical value, delays diagnosis, and does not alter management. 1

Volume Status Assessment

Physical examination alone is unreliable (sensitivity 41%, specificity 80%) for determining euvolemia 1. Look specifically for:

• Euvolemic signs: normal skin turgor, moist mucous membranes, no orthostatic hypotension, no peripheral edema, no ascites 1, 4
• Absence of hypovolemia: no tachycardia, no flat neck veins, no orthostatic vital sign changes 1
• Absence of hypervolemia: no jugular venous distension, no peripheral edema, no pulmonary congestion 1

Identify the Underlying Cause

Review for common etiologies 4, 5, 2, 3:

• Malignancy: small-cell lung cancer (15% incidence), head/neck cancer (3%), other solid tumors 5
• CNS disorders: meningitis, encephalitis, stroke, subarachnoid hemorrhage, brain tumors 4, 2
• Pulmonary disease: pneumonia, tuberculosis, positive-pressure ventilation 4, 2
• Medications: SSRIs, carbamazepine, NSAIDs, opioids, cyclophosphamide, vincristine, cisplatin, melphalan 1, 5, 3
• Post-operative state: inappropriate hypotonic fluid administration 4

Initial Management Algorithm

For Asymptomatic or Mildly Symptomatic Patients (Sodium 120–134 mmol/L)

Fluid restriction is the cornerstone of chronic SIADH management 1, 4, 2, 3, 6:

• Restrict fluid intake to 800–1200 mL per 24 hours (or ≤1 L/day) 1, 2, 3
• Monitor serum sodium every 24–48 hours initially 1
• If no response to fluid restriction after 48–72 hours, add oral sodium chloride 100 mEq three times daily 1
• Target correction rate: 4–8 mmol/L per day, maximum 8 mmol/L in 24 hours 1, 2

For Severe Symptomatic Patients (Seizures, Altered Mental Status, Coma)

Admit to ICU for immediate hypertonic saline administration 1, 2, 3, 6:

• Administer 3% hypertonic saline with initial goal to correct 6 mmol/L over 6 hours or until severe symptoms resolve 1
• Give 100 mL boluses of 3% NaCl over 10 minutes, repeating up to three times at 10-minute intervals 1
• Combine with intravenous furosemide to produce negative free-water balance 3
• Check serum sodium every 2 hours during initial correction phase 1
• Total correction must not exceed 8 mmol/L in any 24-hour period to prevent osmotic demyelination syndrome 1, 2, 6

Pharmacological Options for Resistant Cases

If fluid restriction fails or is poorly tolerated 1, 3:

• Demeclocycline (induces nephrogenic diabetes insipidus) 4, 3
• Vasopressin receptor antagonists (tolvaptan, conivaptan) for euvolemic hyponatremia 1
• Loop diuretics (furosemide) combined with oral salt supplementation 1, 3
• Urea, lithium, and phenytoin have limited supporting data 3

Critical Safety Considerations

Osmotic Demyelination Syndrome Prevention

Never correct chronic hyponatremia faster than 8 mmol/L in 24 hours 1, 2, 6:

• Standard correction rate: 4–8 mmol/L per day 1
• Maximum limit: 10 mmol/L in 24 hours or 18 mmol/L in 48 hours 2
• High-risk patients (liver disease, alcoholism, malnutrition): 4–6 mmol/L per day maximum 1

If Overcorrection Occurs

• Immediately discontinue hypertonic saline and switch to D5W (5% dextrose in water) 1
• Consider desmopressin to slow or reverse the rapid sodium rise 1
• Monitor for signs of osmotic demyelination syndrome 2–7 days after correction: dysarthria, dysphagia, oculomotor dysfunction, quadriparesis 1

Common Diagnostic Pitfalls

• Failing to exclude hypothyroidism and adrenal insufficiency before confirming SIADH 1
• Not reviewing medications that can induce SIADH (SSRIs, carbamazepine, chemotherapy) 1, 5
• Relying solely on physical examination for volume assessment without laboratory correlation 1
• Ordering ADH levels, which adds no value and delays diagnosis 1
• Misdiagnosing cerebral salt wasting as SIADH in neurosurgical patients—CSW requires volume replacement, not fluid restriction 1

Monitoring During Treatment

• Serum sodium: every 2 hours for severe symptoms, every 4–6 hours for mild symptoms, then daily 1
• Daily weights and strict intake-output monitoring 1
• Electrolytes (potassium, magnesium) and renal function regularly 1
• Watch for neurological deterioration suggesting osmotic demyelination 1, 6