Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

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What is SIADH?

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterised by excessive secretion of antidiuretic hormone (ADH) from the posterior pituitary gland, or another source. ADH controls water reabsorption via its effect on kidney nephrons, causing the retention of water (but not the retention of solutes). By increasing water retention, ADH assists in the dilution of the blood, decreasing the concentration of solutes such as sodium.



1. ADH (also known as vasopressin) is produced by the hypothalamus in response to increased serum osmolality.

2. ADH is transported from the hypothalamus to the posterior pituitary gland.

3. ADH is released into the circulatory system via the posterior pituitary gland.

4. ADH then travels to the kidneys, where it binds to ADH receptors on the distal convoluted tubules.

5. The binding of ADH to these receptors causes aquaporin-2 channels to move from the cytoplasm, into the apical membrane of the tubules:

  • These aquaporin-2 channels allow water to be reabsorbed out of the collecting ducts and back into the bloodstream.
  • This results in both a decrease in volume and an increase in osmolality (concentration) of the urine excreted.

6. The extra water that has been reabsorbed re-enters the circulatory system, reducing the serum osmolality.

7. This reduction in serum osmolality is detected by the hypothalamus and results in decreased production of ADH.

SIADH - normal physiology
An illustration of how serum osmolality is regulated in healthy individuals.


Deranged Physiology in SIADH

The important difference between normal physiology and what occurs in SIADH is the lack of an effective negative feedback mechanism. This results in continual ADH production, independent of serum osmolality. Ultimately this leads to abnormally low levels of serum sodium and relatively high levels of urinary sodium, giving rise to the characteristic symptoms and signs associated with SIADH.

What causes SIADH?

There are lots of potential causes of SIADH including:

  • Primary brain injury (e.g. meningitis. subarachnoid haemorrhage)
  • Malignancy (e.g. small-cell lung cancer)
  • Drugs  (e.g. carbamazepine, SSRIs, amitriptyline)
  • Infectious (e.g. atypical pneumonia, cerebral abscess)
  • Hypothyroidism
Causes of SIADH
Causes of SIADH


Signs and Symptoms


Symptoms of SIADH vary depending on the rate at which hyponatraemia develops. Mild hyponatraemia may cause significant symptoms if the drop in sodium is acute, whereas chronically hyponatraemic patients may have very low serum sodium concentrations and yet be completely asymptomatic. This is thought to be due to a compensatory process known as cerebral adaptation, in which brain cells adapt their metabolism to cope with abnormal sodium levels. Cerebral adaptation can only take place if the change in sodium concentration is gradual, explaining the more severe symptoms seen in acute hyponatraemia and the potentially less severe symptoms seen in patients who are chronically hyponatraemic.

  • Mild – nausea, vomiting, headache, anorexia, lethargy
  • Moderate – muscle cramps, weakness, confusion, ataxia
  • Severe – drowsiness, seizures, coma



The clinical signs of SIADH can also vary significantly, depending on the rate of serum sodium concentration change:

  • Decreased level of consciousness
  • Cognitive impairment – short-term memory loss, disorientation, confusion
  • Focal or generalised seizures
  • Brain stem herniation (severe acute hyponatraemia) – coma, respiratory arrest
  • Hypervolaemia – pulmonary oedema, peripheral oedema, raised jugular venous pressure, ascites


Fluid Status

Is the patient clinically or biochemically dehydrated?

  • In SIADH this will not be the case – the patient is typically either euvolemic or hypervolaemic
  • If dehydration is present, it may suggest an alternative cause of hyponatraemia (e.g. diuretic medication, renal failure)

Blood Tests

Serum sodium:

  • Low in SIADH – <130 mmol/L

Serum potassium:

  • If serum potassium is raised in the presence of hyponatraemia Addison’s disease should be considered

Plasma osmolality

  • Reduced in SIADH (due to the low sodium concentration)


  • Hypothyroidism is a potential cause of SIADH
  • Reduced T3 and raised TSH would suggest this diagnosis

Serum cortisol:

  • Addison’s disease is a cause of hyponatraemia
  • A low serum cortisol would suggest this diagnosis


Urine Tests

Urine osmolality:

  • In healthy individuals, if serum osmolality is low, urine osmolality should be low (as the kidneys should be trying to retain solute).
  • In SIADH, the excess ADH results in water retention, but not solute retention.
  • As a result, concentrated urine relatively high in sodium is produced, despite low serum sodium.

Urine sodium:

  • This will be relatively raised in SIADH, in the context of a decreased serum sodium concentration.



  • Useful in detecting causes of SIADH (e.g. small cell lung cancer, atypical pneumonia)



The following features must be present for a diagnosis of SIADH to be made: ³

  • Hyponatraemia
  • Low plasma osmolality
  • Inappropriately elevated urine osmolality (>plasma osmolality)
  • Urine [Na+] >40 mmol/L with normal salt intake
  • Euvolaemia
  • Normal thyroid and adrenal function


Management of SIADH varies depending on the underlying cause. Definitive management involves treating the underlying cause of SIADH.

Fluid restriction

  • This is a common management strategy used to increase serum sodium concentrations, at least temporarily, whilst the underlying cause is sought and treated.
  • This strategy is greatly dependent on patients co-operating with the treatment plan (fluid restriction is challenging for patients).

The management algorithm below4 provides an overview of the current guidelines on the management of SIADH. You can read the full article here.

Copyright © 2015 The Authors European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.


  1. Craig S; Hyponatremia in Emergency Medicine, Medscape, Published Apr 2010.
  2. Robert D. Zenenberg, Do, et. al (2010-04-27). “Hyponatremia: Evaluation and Management”. Hospital Practice. 38 (1): 89–96
  3. Grant P, Ayuk J, Bouloux PM, et al; The diagnosis and management of inpatient hyponatraemia and SIADH. Eur J Clin Invest. 2015 Aug45(8):888-94. doi: 10.1111/eci.12465. Epub 2015 Jun 28. Available from: [LINK]


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