SIADH (Syndrome of Inappropriate ADH)
Summary
The Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) is the most common cause of euvolaemic hyponatraemia. Excessive ADH release (non-osmotic) leads to water retention in the renal collecting ducts, causing dilutional hyponatraemia. Diagnosis is by exclusion, requiring the patient to be euvolaemic with normal renal, thyroid, and adrenal function. [1,2]
Diagnostic Criteria (Bartter-Schwartz)
- Hyponatraemia (less than 135 mmol/L).
- Low Serum Osmolality (less than 275 mOsm/kg).
- Inappropriately Concentrated Urine (>100 mOsm/kg - usually >300).
- Urine Sodium Elevated (>30 mmol/L) - salt wasting despite low serum sodium.
- Clinical Euvolaemia (No oedema, no dehydration).
- Normal Adrenal and Thyroid Function (Cortisol and TSH normal).
Clinical Pearls
Urine Osmolality Rule: In true hyponatraemia, the kidneys should be trying to excrete maximal water to raise sodium. This means Urine Osmolality should be dilute (less than 100 mOsm/kg). If the Urine Osmolality is >100 in the face of hyponatraemia, ADH is acting inappropriately.
Euvolaemia: SIADH patients are NOT overloaded (no oedema) because the volume expansion triggers ANP (Atrial Natriuretic Peptide), which causes sodium excretion (natriuresis) to maintain volume balance. This explains the High Urine Sodium.
Exclude the "Great Mimics": Severe Hypothyroidism and Adrenal Insufficiency (Addison's) can present with an identical biochemical picture. You MUST check TSH and Cortisol before diagnosing SIADH.
Aetiology (Causes)
- Malignancy (Ectopic ADH):
- Small Cell Lung Cancer (Classic Ca).
- Pancreatic Ca, Lymphoma.
- CNS Disorders:
- Stroke, Subdural, Meningitis, Encephalitis.
- Pulmonary Disorders:
- Pneumonia (Legionella notoriously), TB, Pneumothorax.
- Drugs:
- SSRIs (Citalopram, Sertraline).
- Psychotropics (Carbamazepine, Haloperidol).
- Chemotherapy (Cyclophosphamide, Vincristine).
- Opiates.
- Idiopathic: In elderly.
Mechanism
- High ADH: Acts on V2 receptors in the renal collecting duct.
- Aquaporin-2 Insertion: Water channels insert into the luminal membrane.
- Water Reabsorption: Free water is reabsorbed into the blood.
- Dilution: Serum sodium drops (Dilutional Hyponatraemia).
- Volume expansion: Slight increase in blood volume triggers ANP release.
- Natriuresis: Kidneys dump sodium to fix the volume expansion. (Worsening the hyponatraemia).
Symptoms (Depend on Acuity)
Signs
- Chest: Signs of pneumonia/malignancy?
- Neurology: GCS? Focal signs?
- Hydration: Skin turgor, Cap refill.
Paired Osmolalities
- Serum Osmolality: Low (less than 275).
- Urine Osmolality: High (>100).
Urine Sodium
- Urine Na: High (>30 mmol/L). Note: If less than 20, suspect hypovolaemia/dehydration.
Exclusions
- 9am Cortisol: Exclude Addison's.
- TSH: Exclude Myxoedema.
- Renal/Liver: U&E, LFTs.
Cause Search
- CXR / CT Chest: Lung Ca.
- CT Head: CNS cause.
Management Algorithm
HYPONATRAEMIA (less than 135)
↓
ASSESS SYMPTOMS (Severe?)
┌─────────┴─────────┐
YES NO
↓ ↓
EMERGENCY SIADH CONFIRMED?
(Seizure/Coma) (Euvolaemic + UOsm >100)
↓ ↓
HYPERTONIC SALINE FLUID RESTRICTION
(3% NaCl bolus) (First Line)
↓ ↓
ICU ADMISSION PERSISTENT?
┌───┴───┐
NO YES
↓ ↓
GOOD PHARMACOLOGY
- Demeclocycline
- Tolvaptan (V2 Antag)
- Urea Sachets
1. Fluid Restriction
- Limit oral intake to 500ml - 1000ml / day.
- Often difficult for patients to tolerate (thirst).
- Predictor of failure: If Urine Osmolality > 500 (very concentrated), fluid restriction is unlikely to work alone.
2. Pharmacological (Second Line)
- Tolvaptan: V2-Receptor Antagonist. Blocks ADH effect directly. Careful monitoring needed (risk of rapid correction).
- Demeclocycline: Causes Nephrogenic Diabetes Insipidus (blocks ADH). Slow onset (days).
- Oral Urea: Osmotic diuretic. Palatability issues.
3. Emergency (Symptomatic)
- Hypertonic (2.7% or 3%) Saline: 100ml bolus. Raises Na quickly to stop seizure.
Management Complications
- Osmotic Demyelination Syndrome (ODS): (Formerly Central Pontine Myelinolysis).
- If sodium is corrected too rapidly (>10 mmol/L in 24 hours).
- Water rushes out of brain cells -> shrinkage -> myelin shearing.
- Outcome: Locked-in syndrome (Quadriplegia but aware). Irreversible.
- Prevention: Aim for rise of 4-6 mmol/L per day. Check Na every 4-6 hours.
- Depends on the underlying cause (e.g., SCLC vs Infection).
- Drug-induced SIADH resolves rapidly on stopping the drug.
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Hyponatraemia | European Society of Endocrinology | Detailed algorithm. Prioritises fluid restriction. |
| Tolvaptan | NICE | Approved for failures of fluid restriction. |
Landmark Evidence
1. SALT-1 and SALT-2 Trials (NEJM)
- Demonstrated Tolvaptan significantly increases serum sodium in euvolaemic hyponatraemia compared to placebo.
What is SIADH?
Your body has a hormone (Anti-Diuretic Hormone) that tells kidneys to hold onto water. Normally, this shuts off when you drink enough. In your case, the hormone system is "stuck on", so your kidneys keep hoarding water even though your blood is already too dilute.
Why is my sodium low?
It's not that you lack salt; it's that you have too much water diluting your blood. Imagine checking the saltiness of a soup—if you add too much water, it tastes bland, even if the amount of salt hasn't changed.
Why limit my drinking?
Because your kidneys can't pee out the water fast enough. If you keep drinking normal amounts, the water builds up, dilutes your blood further, and can cause brain swelling.
Can I just eat more salt?
No. Because of the hormone issue, your kidneys will just flush the extra salt out into your urine without fixing the water problem.
Primary Sources
- Spasovski G, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Eur J Endocrinol. 2014.
- Schrier RW, et al. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med. 2006.
Common Exam Questions
- Safety: "Max safe correction rate?"
- Answer: less than 10 mmol/L in first 24 hours (prevents ODS).
- Diagnosis: "Low Na + High Urine Na + Euvolaemia?"
- Answer: SIADH.
- Cause: "Hyponatraemia in a smoker with haemoptysis?"
- Answer: Small Cell Lung Cancer (Ectopic ADH).
- Treatment: "First line treatment?"
- Answer: Fluid Restriction.
Viva Points
- Reset Osmostat: A variant of SIADH (often in pregnancy/malnutrition) where the ADH release curve is normal but shifted to a lower set point. These patients are stable at a lower sodium (e.g., 125) and trying to raise it is futile.
- Urea for SIADH: Why does it work? It creates an osmotic load that must be excreted, dragging water with it (Osmotic diuresis), bypassing the ADH block.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.