Syndrome of Inappropriate Anti-Diuretic Hormone

• Syndrome of Inappropriate Anti-Diuretic Hormone (SIADH) refers to the increased release of antidiuretic hormone (ADH) from the posterior pituitary, leading to hyponatraemia (low sodium)
• Antidiuretic hormone (ADH)


  Produced in the hypothalamus and secreted by the posterior pituitary gland, also known as vasopressin, stimulates water reabsorption from the collecting ducts in the kidneys
• Potential sources of too much ADH

  • Increased secretion by the posterior pituitary
  • Ectopic ADH, most commonly by small cell lung cancer
• Excessive ADH


  Results in increased water reabsorption in the collecting ducts, diluting the blood and causing hyponatraemia (low sodium)
• SIADH results in euvolaemic hyponatraemia

  Euvolaemic means normal volume of blood. The urine becomes more concentrated as the kidneys excrete less water, leading to high urine osmolality and high urine sodium
• The symptoms of SIADH relate to low sodium (hyponatraemia)
• Urine concentration


  The urine becomes more concentrated as the kidneys excrete less water
• Patients with SIADH


  • Have high urine osmolality and high urine sodium
• Causes of SIADH


  • Post-operative
  • Lung infection (particularly atypical pneumonia and lung abscesses)
  • Brain pathologies (head injury, stroke, intracranial haemorrhage, meningitis)
  • Medications (e.g., SSRIs and carbamazepine)
  • Malignancy (particularly small cell lung cancer)
  • Human immunodeficiency virus (HIV)
• TOM TIP: 'The top three causes of SIADH to remember are post-operative, SSRIs, and small cell lung cancer. SIADH relating to small cell lung cancer is an exam favourite. I have seen several cases of SIADH relating to major surgery and the use of SSRIs.'
• Exclusion criteria for other causes of hyponatraemia


  • Short synacthen test to exclude adrenal insufficiency
  • No history of diuretic use, diarrhoea, vomiting, burns, fistula, or excessive sweating
  • No excessive water intake
  • No chronic kidney disease or acute kidney injury
  • No heart failure or liver disease
• Primary polydipsia


  Involves excessive water consumption with no underlying cause, diluting the blood and urine, causing euvolaemic hyponatraemia. However, there is low urine sodium and urine osmolality
• Establishing the cause of SIADH

  Sometimes the cause will be obvious, for example, in someone that recently started an SSRI, has a chest infection, or recent major surgery. The cause is confirmed if the hyponatraemia resolves when the cause is removed
• Management of SIADH


  Involves admission if symptomatic or severe, treating the underlying cause, fluid restriction, vasopressin receptor antagonists (e.g., tolvaptan). Correcting sodium slowly to prevent osmotic demyelination. Fluid restriction involves limiting the patient’s fluid intake to 750-1000 ml per day. Vasopressin receptor antagonists, such as tolvaptan, work by blocking ADH receptors. They can cause a rapid rise in sodium. They are initiated by an endocrinologist and require close monitoring (e.g., 6 hourly sodium levels)
• Osmotic Demyelination Syndrome
• Tolvaptan


  • Block ADH receptors
  • Can cause a rapid rise in sodium
  • Initiated by an endocrinologist
  • Require close monitoring (e.g., 6 hourly sodium levels)
• Osmotic Demyelination Syndrome


  • Also known as central pontine myelinolysis (CPM)
  • Usually a complication of long-term severe hyponatraemia (e.g., under 120 mmol/L) being treated too quickly (e.g., more than a 10 mmol/L increase per 24 hours)
• Water movement in Osmotic Demyelination Syndrome

  1. As blood sodium concentration drops, water moves by osmosis across the blood-brain barrier into the cells of the brain

  2. Water moves from the area of low concentration of solutes (the blood) to the area of high concentration of solutes (the brain), causing the brain to swell with fluid

  3. The brain adapts by reducing the solutes in the brain cells so that water is balanced across the blood-brain barrier and the brain does not become oedematous

  4. This adaptation takes a few days

  5. Once blood sodium levels rapidly rise, causing water to rapidly shift out of the brain cells and into the blood, two phases of symptoms occur
• First phase of Osmotic Demyelination Syndrome symptoms


  • Due to electrolyte imbalance
  • Patient presents as encephalopathic and confused
  • May have a headache, vomiting, and seizures
• Second phase of Osmotic Demyelination Syndrome symptoms


  • Due to demyelination of the neurones, particularly in the pons
  • Occurs a few days after the rapid correction of sodium
  • May present with spastic quadriparesis, pseudobulbar palsy, cognitive and behavioural changes
  • Significant risk of death
• Prevention is essential as treatment is only supportive once osmotic demyelination occurs
• A proportion of patients make a clinical improvement, but most are left with some neurological deficit