SIADH | Notion

Syndrome of inappropriate ADH secretion

The syndrome of inappropriate ADH secretion (SIADH) is characterised by hyponatraemia secondary to the dilutional effects of excessive water retention. Patients with SIADH are typically euvolemic, i.e. they do not show signs of overt volume depletion or overload.

Pathophysiology

SIADH involves an excessive release of antidiuretic hormone (ADH), also known as vasopressin, which leads to water retention, volume expansion, and dilutional hyponatraemia
ADH is produced by the hypothalamus and stored in the posterior pituitary gland. Its primary function is to regulate the body's water balance
It does this by increasing water reabsorption in the collecting ducts of the kidneys, thereby decreasing the volume of urine produced
In SIADH, there is an inappropriate and continuous release of ADH that is not inhibited by normal physiological mechanisms, such as adequate or excess body fluid levels
As a result, the kidneys reabsorb more water, leading to decreased urine output, and expansion of extracellular fluid volume.
Importantly, this increase in body fluid volume does not lead to the expected signs of fluid overload, such as oedema or hypertension, because the excess fluid is uniformly distributed throughout all body fluid compartments.
However, as water is retained in the body, the concentration of electrolytes in the blood, particularly sodium, becomes diluted, leading to hyponatraemia.

Causes of SIADH

Category	Examples
Malignancy	• small cell lung cancer
• also: pancreas, prostate
Neurological	• stroke
• subarachnoid haemorrhage
• subdural haemorrhage
• meningitis/encephalitis/abscess
Infections	• tuberculosis
• pneumonia
Drugs	• sulfonylureas (glimepiride and glipizide)
• SSRIs, tricyclics
• carbamazepine
• vincristine
• cyclophosphamide
Other causes	• positive end-expiratory pressure (PEEP)
• porphyrias

Investigations

Urine osmolality: Urine osmolality is inappropriately high (>100 mOsm/kg) in relation to serum osmolality, as the kidneys should normally dilute urine in the setting of low serum osmolality.
Urine sodium concentration: Urine sodium concentration is typically high (>40 mmol/L) due to the action of ADH on the renal tubules.

Management

correction must be done slowly to avoid precipitating central pontine myelinolysis
fluid restriction
demeclocycline: reduces the responsiveness of the collecting tubule cells to ADH
ADH (vasopressin) receptor antagonists have been developed