Key Facts

SIADH is the commonest cause of euvolaemic hyponatraemia. It is a diagnosis of exclusion. The rate of sodium correction is critical — too rapid correction causes osmotic demyelination syndrome. Always identify and treat the underlying cause.

Epidemiology

Commonest cause of hyponatraemia in hospitalised patients. Prevalence increases with age. Drug-induced SIADH is very common (especially SSRIs in elderly).

Aetiology

Malignancy: SCLC (~10-15% present with SIADH), head/neck cancers, lymphoma. CNS: meningitis, encephalitis, SAH, stroke, trauma, tumour. Pulmonary: pneumonia (especially Legionella), TB, abscess, COPD. Drugs: SSRIs, carbamazepine, vincristine, cyclophosphamide, PPIs, NSAIDs. Post-operative: pain, nausea, opioids.

Pathophysiology

Inappropriate ADH secretion (or ADH-like activity) → aquaporin-2 insertion in collecting duct → excessive water reabsorption → dilutional hyponatraemia → expansion of ECF (but oedema does not occur due to natriuretic peptide-mediated sodium excretion → euvolaemia). Urine is inappropriately concentrated with high sodium.

Symptoms (Correlate with Severity and Rapidity of Onset)

• Mild (Na⁺ 130-135): often asymptomatic; fatigue, headache
• Moderate (Na⁺ 125-130): nausea, confusion, malaise, gait instability
• Severe (Na⁺ <125): vomiting, drowsiness, seizures, respiratory arrest, coma

Signs

• Euvolaemic: no oedema, no signs of dehydration (key distinction from other causes of hyponatraemia)
• Reduced GCS if severe
• Features of underlying cause (e.g., lung mass, CNS signs)

Red Flags

• Na⁺ <120 mmol/L → medical emergency
• Seizures, coma → immediate hypertonic saline
• Rapidly developing hyponatraemia (hours) → higher risk of cerebral oedema

Diagnostic (All Required)

• Serum Na⁺: <135 mmol/L
• Serum osmolality: <275 mOsm/kg
• Urine osmolality: >100 mOsm/kg (inappropriately concentrated)
• Urine Na⁺: >30 mmol/L
• Clinical euvolaemia: no oedema, no dehydration
• Normal thyroid function: TFTs
• Normal adrenal function: 9am cortisol (or SST)
• No diuretics: drug history

Identify Cause

• CXR: lung pathology (pneumonia, mass)
• CT chest: SCLC (if clinical suspicion)
• CT/MRI brain: CNS cause
• Drug review

Monitoring

• Na⁺: 4-6 hourly during acute management
• Serum osmolality
• Fluid balance: strict I/O

Acute Severe/Symptomatic (Na⁺ <120 or Seizures)

• IV 3% hypertonic saline: 150mL over 20 minutes; recheck Na⁺; can repeat ×2
• Target: raise Na⁺ by 4-6 mmol/L in first 6 hours → symptoms improve
• DO NOT exceed 8-10 mmol/L rise in 24 hours (risk of osmotic demyelination syndrome)
• ITU/HDU monitoring
• If over-corrected: lower Na⁺ with desmopressin 1-2μg IV + 5% dextrose

Chronic/Mild-Moderate

• Fluid restriction: 750-1000mL/day (first-line)
• Treat underlying cause: stop causative drug, treat infection, treat malignancy
• Demeclocycline: 150-300mg BD PO (induces nephrogenic DI; takes 3-5 days to work); SE: photosensitivity, nephrotoxicity
• Tolvaptan: 15mg OD PO (V2 receptor antagonist); potent aquaretic; specialist use (NICE restricts to SCLC-related SIADH); monitor Na⁺ closely (risk of over-rapid correction); avoid fluid restriction when starting
• Salt tablets: NaCl 2-3g TDS (supplementary)

Referral Criteria

• Endocrinology: persistent/complex SIADH
• Oncology: if malignancy identified
• ITU: severe symptomatic hyponatraemia

Prognosis depends on underlying cause. Drug-induced SIADH: resolves on stopping the causative drug. Malignancy-associated: prognosis of underlying cancer. Hyponatraemia itself: associated with increased mortality, falls, fractures (even mild chronic hyponatraemia). Osmotic demyelination syndrome (from over-rapid correction): devastating — locked-in syndrome, quadriplegia, death; largely preventable with careful sodium monitoring.

Causes of Hyponatraemia by Volume Status

SIADH Diagnostic Criteria (Bartter & Schwartz)