SIADH

Syndrome of inappropriate antidiuretic hormone secretion is characterised by continued release of antidiuretic hormone despite plasma hypo-osmolality, producing water retention, dilutional hyponatraemia and an inappropriately concentrated urine.

Total body sodium remains essentially normal; the problem is retained water rather than lost salt, which is why the patient is clinically euvolaemic and why treatment centres on restricting water rather than replacing sodium.

Common causes include malignancy (small cell lung carcinoma classically), central nervous system disease (stroke, haemorrhage, meningitis, trauma), pulmonary pathology (pneumonia, tuberculosis), and drugs, particularly SSRIs, carbamazepine, thiazides and antipsychotics.

Drug-induced SIADH is under-recognised and reversible, so a careful medication review is one of the highest-yield steps in any new presentation.

Symptoms are those of hyponatraemia and depend far more on the rate of the fall in sodium than on the absolute value; a sodium of 120 mmol/L developing over hours is far more dangerous than the same value reached over weeks.

• Mild or gradual: nausea, headache, lethargy, difficulty concentrating, unsteadiness and falls, often mistaken in older patients for general frailty or a urinary tract infection
• Moderate: confusion, disorientation, muscle cramps, weakness
• Severe or rapid onset: seizures, reduced consciousness, coma, and respiratory arrest from cerebral oedema

Clinically the patient is euvolaemic: no oedema, no raised JVP, no postural drop, normal skin turgor and mucous membranes. This absence of volume signs is the central examination finding and is what separates SIADH from the hypovolaemic and hypervolaemic causes of hyponatraemia.

SIADH is a diagnosis of exclusion and requires all of the following:

• Hyponatraemia with low plasma osmolality (<275 mOsm/kg)
• Inappropriately concentrated urine (urine osmolality >100 mOsm/kg) in the face of plasma hypo-osmolality
• Urine sodium >30 mmol/L with normal salt and water intake
• Clinical euvolaemia
• Normal thyroid, adrenal and renal function, since hypothyroidism and adrenal insufficiency both mimic SIADH closely and are treatable causes that must not be missed
• No recent diuretic use, particularly thiazides

Investigation therefore includes paired serum and urine osmolality, urine sodium, TSH, a morning cortisol or short Synacthen test where adrenal insufficiency is plausible, and renal function. Identifying the underlying cause matters as much as confirming the syndrome: chest imaging and a careful drug history are appropriate in most new cases.

Differentials: hypovolaemic hyponatraemia (urine sodium typically <20 mmol/L if renal handling is intact, with clinical volume depletion), hypervolaemic hyponatraemia (heart failure, cirrhosis, nephrotic syndrome, oedematous), primary polydipsia (dilute urine, osmolality <100 mOsm/kg), pseudohyponatraemia from severe hyperlipidaemia or paraproteinaemia, and hyperglycaemia-induced translocational hyponatraemia.

The correction rate is the single most important safety consideration.

Sodium should not rise by more than 8–10 mmol/L in 24 hours, and more cautiously still in patients at high risk of osmotic demyelination: chronic hyponatraemia, alcohol use disorder, malnutrition, hypokalaemia, advanced liver disease.

Overcorrection causes osmotic demyelination syndrome, which typically becomes apparent days later as dysarthria, dysphagia, quadriparesis or locked-in syndrome, and is frequently irreversible.

Severe symptomatic hyponatraemia (seizures, reduced consciousness):

• Hypertonic 3% saline, typically 100–150 mL as a bolus over 10–20 minutes, repeated once or twice as needed to achieve a rise of about 4–6 mmol/L, which is usually enough to abort seizures and reverse cerebral oedema

• Aim for symptom resolution, not normalisation. Once symptoms settle, stop the hypertonic saline and revert to slower correction

• Check sodium every 1–2 hours during active correction

• If sodium rises too quickly, it can be brought back down with desmopressin and hypotonic fluid, deliberate re-lowering is an accepted rescue strategy and is preferable to accepting an overshoot

Mild to moderate or chronic:

• Fluid restriction is first line, typically 800–1000 mL/day, though it works slowly and fails in patients with very concentrated urine

• Treat the underlying cause: stop the offending drug, treat the infection, investigate for malignancy

• Tolvaptan (a vasopressin receptor antagonist) is an option in resistant cases but requires close monitoring given the risk of rapid overcorrection, and should be started in hospital

• Oral urea or salt tablets with a loop diuretic are alternative approaches where fluid restriction alone is insufficient

• Demeclocycline is now rarely used given slow onset and nephrotoxicity

Referral: nephrology or endocrinology for resistant or unexplained SIADH; oncology if an underlying malignancy is identified; ICU for severe symptomatic hyponatraemia requiring hypertonic saline.