The syndrome of inappropriate anti-diuretic hormone (SIADH) results from excess ADH secretion.
Osmolality is a measure of osmoles of solute per kilogram of solvent (Osm/kg). In SIADH the release of ADH is inappropriate to the plasma osmolality. This results in a low plasma osmolality and a euvolaemic hyponatraemia.
ADH release is governed by the plasma osmolality.
Antidiuretic hormone (ADH) is produced by the magnocellular neurons in the paraventricular and supraoptic nuclei of the hypothalamus. It is stored and released by the posterior pituitary in response to rising plasma osmolality. It may also be referred to as arginine vasopressin (AVP) or simply vasopressin.
ADH release begins at a plasma osmolality of around 280 mOsm/kg. Thirst is felt at around 290 mOsm/kg. These processes lead to a reduction in the plasma osmolality.
ADH acts on the distal convoluted tubule and collecting duct to increase water reabsorption independent of sodium. ADH stimulates the insertion of aquaporin-2 channels onto the luminal membrane, allowing the free entry of water. ADH also causes vasoconstriction of arterioles.
ADH secretion leads to increased water reabsorption and increasingly concentrated urine. When released in excess it leads to an increase in total body water (TBW), which in turn leads to a dilutional hyponatraemia.
A transient rise in the extracellular volume leads to a natriuresis reducing the TBW but worsening the hyponatraemia.
A variety of conditions may predispose a patient to developing SIADH.
The list below is not exhaustive but illustrates how broad the aetiology can be.
The clinical features associated with SIADH are those of hyponatraemia.
The clinical features of hyponatraemia are largely dependent on the velocity of change in sodium as opposed to the absolute level. Neurological signs will only be seen in severe cases.
SIADH is suspected based on results of clinical chemistry and the patients history.
There is not a single test that conclusively diagnoses SIADH. Instead, diagnosis relies upon biochemistry results and the clinical context.
In euvolaemic hyponatraemia, SIADH should be considered the most likely diagnosis. An inability to dilute urine (raised urine osmolality) and a low plasma osmolality is indicative of SIADH.
Mild disease requires no specific treatment but the underlying cause should be identified and treated. More severe disease requires correction of the hyponatraemia.
Correction of hyponatraemia should not occur rapidly (no faster than 8-10 mmol/L per 24 hours). Rapid increases in plasma sodium may result in osmotic demyelination syndrome.
The typical fluid restriction regime is 500 - 1000mL / 24hrs.
Fluid restriction may not be used in SIADH secondary to subarachnoid haemorrhage as it risks lowering blood pressure which may cause cerebral vasospasm and infarction.
Demeclocycline, a tetracycline antibiotic, causes an iatrogenic nephrogenic diabetes insipidus through the inhibition of ADH. Though historically popular it is rarely used today.
A newer class of drugs termed vaptans (e.g. tolvaptan) are now more commonly used. These vasopressin receptor antagonists are effective but expensive agents.
Those with severe hyponatraemia are at risk of permanent neurological damage due to cerebral oedema, typically seen following a rapid (< 48 hrs) drop in sodium to below 120 mmol/L.
Severe hyponatraemia requires intensive care. Hypertonic saline and furosemide may be utilised. Within the intensive care setting a more rapid increase in serum sodium (4-6 mmol/L in the first hour) may be justified.
In many cases, SIADH is self-limiting or reversible (e.g. post-operative, drugs). In others, it may persist for longer periods and require further fluid restriction and oral salt (causes increased diuresis).
Osmotic demyelination syndrome, also termed cerebral pontine myelinolysis, it is caused by rapid correction of hyponatraemia.
This syndrome occurs due to a rapid increase in extracellular osmolality. It can cause irreversible neurological damage. As such, in the absence of severe neurological features, sodium correction should not exceed 8-10 mmol/L per 24 hours.
Have comments about these notes? Leave us feedback