12th April 2024

Syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Syndrome of inappropriate ADH secretion (SIADH), also known as syndrome of inappropriate antidiuresis (SIAD), is a disorder characterised by the following: 

• Hyponatraemia
• low serum osmolality <270mOsm/kg
• inappropriately high urine osmolality above 100mOsmol/kg. 

Normally, when dehydrated, the high serum osmolality causes increased ADH release to increase water reabsorption. Conversely, with low serum osmolality, e.g. in water intoxication, there is a decrease in ADH release to reduce water retention. However, in SIADH increased ingestion of water does not lead to suppression of ADH, therefore causing concentrated urine, reduced urine volume and the increased water retention dilutes the serum sodium levels. The increase in total body water (TBW) causes increased urinary sodium excretion, worsening the hyponatraemia.(²)

SIADH can be secondary to tumours such as small cell lung cancer, brain disorders (trauma or infection), pneumonia, cytotoxic therapy (chemotherapy or radiotherapy), narcotics, analgesics, hypothyroidism, and hypoadrenalism. Rare mutations in the Type 2 vasopressin receptor (AVPR2) can have the same effect as anti-epileptic drugs such as carbamazepine. The ‘gain in function’ mutation to AVPR2 can increase the expression of Type 2 aquaporin water channels, enhancing the sensitivity to ADH.

Signs and symptoms of SIADH include headache, nausea and vomiting, abnormal neurological signs as well as impaired consciousness. In severe cases, there may be coma or convulsions and death. It is one of the commonest causes of hyponatraemia in hospitals, therefore it is important to identify and treat the underlying cause. Treatment consists of restricting fluid intake of up to 1L per day and replacing the sodium lost in the urine. However, it is important to avoid correcting hyponatraemia too rapidly, as increasing sodium levels more than 10 mmol/L per 24 hrs can lead to irreversible brain damage (central pontine demyelination) and death. Vaptans can be used in chronic SIADH, they antagonise the V2 receptors lowering aquaporin water channels in the collecting ducts, thus reducing water re-absorption. Demeclocycline can also be used as it diminishes the action of ADH in the collecting duct, effectively inducing nephrogenic diabetes insipidus.