Syndrome of Inappropriate ADH Secretion

Last updated 17 August 2026.

Key points

SIADH: inappropriate secretion of ADH causing water retention and euvolaemic hypotonic hyponatraemia, without the oedema of true volume overload or the signs of true volume depletion.
Causes: CNS disease (stroke, SAH, meningitis, trauma), pulmonary disease (pneumonia, small cell lung cancer, TB), drugs (SSRIs are a very common cause, especially in the elderly, also carbamazepine, antipsychotics, PPIs, cytotoxics), post-operative state, pain and nausea.
Diagnosis: hyponatraemia with low plasma osmolality, inappropriately concentrated urine (urine osmolality above 100 mosm/kg), urine sodium usually above 30 mmol/L, and clinical euvolaemia.
Must exclude first: hypothyroidism and adrenal insufficiency, both of which mimic SIADH biochemically and must be ruled out before the diagnosis is made.
Clinical features: mostly reflect the hyponatraemia itself - nausea, headache and confusion, progressing to seizures and reduced consciousness if severe or rapid.
Management: treat the underlying cause; fluid restriction (typically 750-1000 mL/day) is first line. Hypertonic saline is reserved for severe or symptomatic hyponatraemia under specialist guidance.
The critical danger: correcting sodium too fast risks osmotic demyelination syndrome (central pontine myelinolysis). Correction should not exceed 8-10 mmol/L in 24 hours.
Key differential: cerebral salt wasting - also causes hyponatraemia after brain injury, but is hypovolaemic with high urine output, requiring the opposite fluid management.

Introduction

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is caused by ADH being released, or acting, in excess of what plasma osmolality would normally demand.¹ The kidney continues to reabsorb water inappropriately, diluting the plasma and producing hypotonic hyponatraemia.

Crucially, the excess water is distributed across the body rather than confined to the extracellular space, so patients are clinically euvolaemic - there is no oedema (as in heart failure or cirrhosis) and no signs of volume depletion (as in true hypovolaemic hyponatraemia). SIADH is the commonest cause of hyponatraemia in hospital inpatients.

Aetiology

Causes of SIADH.
Category	Causes
CNS	Stroke, subarachnoid haemorrhage, meningitis or encephalitis, head trauma, brain abscess, and other structural or inflammatory brain disease
Pulmonary	Pneumonia, small cell lung cancer (ectopic ADH secretion by the tumour itself), tuberculosis, empyema, and other lung pathology, possibly via vagal afferents or, in malignancy, autonomous hormone production
Drugs	SSRIs - a very common cause, particularly in older patients starting treatment; also carbamazepine, antipsychotics, tricyclic antidepressants, PPIs, cytotoxic chemotherapy (vincristine, cyclophosphamide), opioids and MDMA/ecstasy
Post-operative and other	The post-operative state (a combination of surgical stress, pain and opioid analgesia), pain and nausea in their own right (both are potent non-osmotic stimuli of ADH release), and other malignancies producing ectopic ADH (pancreatic, prostatic)

Diagnosis

SIADH is a diagnosis of exclusion, made on a combination of biochemistry and clinical assessment of volume status.²

Diagnostic criteria for SIADH.
Criterion	Finding
Serum sodium / plasma osmolality	Hyponatraemia with low plasma osmolality (true hypotonic hyponatraemia, not pseudohyponatraemia from hyperlipidaemia or hyperproteinaemia, and not from hyperglycaemia)
Urine osmolality	Inappropriately concentrated, above 100 mosm/kg - the kidney should be producing maximally dilute urine in the face of low plasma osmolality, and failure to do so is the hallmark of the syndrome
Urine sodium	Usually above 30 mmol/L, reflecting a normal or expanded effective circulating volume with normal renal sodium handling
Volume status	Clinically euvolaemic - no oedema, no ascites, no signs of dehydration, normal blood pressure and skin turgor
Thyroid and adrenal function	Must be normal. Both hypothyroidism and, especially, adrenal insufficiency can produce a biochemically identical picture and must be excluded before SIADH is diagnosed
No diuretic use	Thiazide diuretics in particular can produce a very similar picture and should be stopped before the diagnosis is confirmed

Clinical features

SIADH itself is biochemical; the clinical picture comes almost entirely from the degree and rate of onset of the hyponatraemia, plus features of the underlying cause.

Features of hyponatraemia by severity.
Severity	Features
Mild / chronic	Often asymptomatic, or subtle - mild nausea, headache, poor concentration, unsteady gait (an underappreciated cause of falls in older patients)
Moderate	Nausea and vomiting, headache, lethargy, confusion, muscle cramps
Severe or rapidly falling	Seizures, reduced consciousness and coma, from cerebral oedema as water shifts into brain cells along the osmotic gradient - a medical emergency

The rate of fall matters as much as the absolute level: a sodium that has fallen rapidly (e.g. over hours, as can happen post-operatively) is far more dangerous than the same level reached gradually over weeks, because the brain has no time to adapt by extruding intracellular osmoles.

Differential diagnosis

Hyponatraemia is first categorised by clinical volume status, which narrows the differential substantially before biochemistry is even reviewed.

Hyponatraemia by volume status.
Volume status	Typical causes
Hypovolaemic	Vomiting, diarrhoea, diuretics, cerebral salt wasting, Addison's disease, burns, third-spacing
Euvolaemic	SIADH, hypothyroidism, adrenal insufficiency (can appear euvolaemic clinically), primary polydipsia, low solute intake
Hypervolaemic	Heart failure, liver cirrhosis, nephrotic syndrome, renal failure - all with oedema

SIADH versus cerebral salt wasting

Both occur after brain injury (subarachnoid haemorrhage, trauma, neurosurgery) and both cause hyponatraemia with a high urine sodium, which makes them easy to confuse - but they need opposite treatment.

SIADH - euvolaemic, normal or expanded circulating volume; treated with fluid restriction
Cerebral salt wasting - hypovolaemic, from inappropriate renal sodium and water loss (mechanism poorly understood, possibly involving natriuretic peptides); patients are volume-depleted with a high urine output; treated with generous salt and volume replacement, not restriction
Giving fluid restriction to a patient with cerebral salt wasting worsens their hypovolaemia and can precipitate cerebral ischaemia after subarachnoid haemorrhage - assess volume status carefully before restricting fluids in any patient with recent brain injury

Investigations

U&Es - confirm hyponatraemia and monitor trend
Serum and urine osmolality
Urine sodium
9 am cortisol (or short Synacthen test) and thyroid function - to exclude adrenal insufficiency and hypothyroidism, essential before confirming SIADH
Glucose, lipids and total protein - to exclude hyperglycaemia and pseudohyponatraemia
Clinical assessment of volume status - examination for oedema, postural blood pressure, skin turgor, jugular venous pressure
Chest X-ray and, where indicated, CT chest/abdomen or CT/MRI head - to look for an underlying cause such as pneumonia, malignancy or intracranial pathology

Management

Treat the underlying cause wherever possible - stop an implicated drug, treat the infection, resect or treat the tumour. Specific management of the hyponatraemia depends on severity and rate of onset.³

Management of hyponatraemia due to SIADH.
Severity	Management
Mild to moderate, chronic	Fluid restriction, typically 750-1000 mL per day, is first line. Review and stop causative drugs. Reassess sodium regularly.
Resistant to fluid restriction	Demeclocycline (induces nephrogenic diabetes insipidus by blocking the renal action of ADH) or a vasopressin receptor antagonist ('vaptan') such as tolvaptan, which directly blocks the V2 receptor and causes a selective water diuresis⁴
Severe or symptomatic (seizures, coma, very rapid onset)	Hypertonic (e.g. 3%) saline, under specialist guidance with frequent (e.g. 2-4 hourly) sodium monitoring, aiming for a small, controlled early rise sufficient to relieve symptoms rather than full correction

Never correct sodium too fast

This is the single most important safety point in managing any chronic hyponatraemia, including SIADH. Correcting sodium too rapidly risks osmotic demyelination syndrome (central pontine and extrapontine myelinolysis) - irreversible neurological injury, presenting days later with quadriparesis, dysarthria and a 'locked-in' state.

Do not exceed a rise of 8-10 mmol/L in any 24-hour period (some guidelines are more conservative, e.g. 6 mmol/L, in high-risk patients)
Correct even more slowly in chronic hyponatraemia, alcohol excess, malnutrition, advanced liver disease and hypokalaemia - all increase the risk of osmotic demyelination
If sodium rises too fast, it may need to be actively lowered again with hypotonic fluid or, in specialist settings, desmopressin - do not simply 'let it happen'
Hourly overcorrection is a common iatrogenic complication of treating severe symptomatic hyponatraemia enthusiastically - frequent monitoring during hypertonic saline administration is essential

Complications

Seizures and reduced consciousness from severe or rapidly developing hyponatraemia
Falls and fractures in older patients, even with only mild chronic hyponatraemia
Osmotic demyelination syndrome from over-rapid correction
Cerebral oedema with severe acute hyponatraemia, which can be fatal
Complications of the underlying cause - progression of infection or malignancy

Red flags

Prognosis

Prognosis depends heavily on the underlying cause and how carefully the sodium is corrected. Drug-induced SIADH (e.g. from an SSRI) typically resolves within days to weeks of stopping the culprit, and hyponatraemia from a treatable infection improves as the infection resolves.

Even mild, apparently asymptomatic chronic hyponatraemia is increasingly recognised as not truly benign - it is associated with gait instability, falls, fractures and cognitive impairment, particularly in older adults, and correction (cautiously) often improves these outcomes. SIADH from malignancy (particularly small cell lung cancer) carries the prognosis of the underlying tumour and often recurs or persists despite treatment of the hyponatraemia itself.

References

NICE Clinical Knowledge Summaries. Hyponatraemia. Available here
Spasovski G, Vanholder R, Allolio B et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. European Journal of Endocrinology. 2014. Available here
Society for Endocrinology. Clinical practice guidance - disorders of water balance. Available here
BNF. Tolvaptan. Available here
NHS. Low sodium (hyponatraemia). Available here

This article is written for revision and education. It is not clinical guidance and must not be used to make decisions about the care of a patient. Always check current NICE guidance and local protocols.