Syndrome of Inappropriate Antidiuretic Hormone (SIADH)
Definition
Syndrome of inappropriate antidiuretic hormone (SIADH) is defined as euvolaemic, hypotonic hyponatraemia secondary to impaired free water excretion, usually from excessive antidiuretic hormone (ADH) release.
Pseudohyponatraemia due to hyperglycaemia, hyperlipidaemia, or hyperproteinaemia should be ruled out first. Renal failure, adrenal insufficiency, and appropriate release of ADH secondary to extracellular volume depletion (hypovolaemia, due to gastrointestinal or renal loss) or intravascular volume depletion (hypervolaemia due to congestive heart failure, cirrhosis of the liver, or nephrotic syndrome) must be ruled out in order to diagnose SIADH.
Causes
The potential causes of SIADH include increased ADH release or responsiveness. These may be due to:
Malignancy
- Lung, gastrointestinal, or genitourinary cancers
- Lymphomas or sarcomas
- Especially small cell lung cancer
Neurological
- CNS infections, brain trauma, haemorrhage
- Multiple sclerosis, Guillain-Barre syndrome
- Acute intermittent porphyria
Pulmonary
- Pulmonary infections
- Lung cancers
- Respiratory diseases
Drugs
- SSRIs, amiodarone, carbamazepine
- Chlorpromazine, amitriptyline, NSAIDs
- Chemotherapeutic agents
Diagnosis
Laboratory tests are used to confirm the following diagnostic criteria:
Hypotonic hyponatraemia
- Low serum sodium (< 135 mmol/L)
- Low serum osmolality (< 275 mOsmol/kg)
Relatively concentrated urine
- High urine osmolality (> 100 mOsm/kg)
- Indicates raised ADH levels
Euvolaemic hyponatraemia
- High urine sodium (> 30 mmol/L)
- Low serum urea (< 3.6 mmol/L)
- Low serum uric acid (< 238 micromol/L)
Exclusion of endocrinopathy
- Normal serum TSH
- Normal serum cortisol
Further investigations: May include a diagnostic trial with normal saline infusion. This is only performed in patients with suspected volume depletion and should not be used in symptomatic hyponatraemic patients. In SIADH, serum sodium level does not improve after a normal saline infusion (1-2 L of normal saline) is administered.
Management
| Presentation |
Symptoms |
Management |
Monitoring |
| Severe |
Altered mental status, seizures, coma |
3% NaCl infusion, furosemide if needed |
Na+ every 2 hours |
| Moderate |
Nausea, vomiting, headache |
Fluid restriction 1-1.5L/day |
Daily Na+ monitoring |
| Asymptomatic |
No symptoms |
Fluid restriction, treat underlying cause |
Regular Na+ checks |
| Chronic |
Persistent hyponatraemia |
Vaptans, fluid restriction |
Close monitoring first 24h |
Hyponatraemia with severe neurological symptoms
Severe neurological symptoms, such as altered mental status, seizure, and coma, are always treated with hypertonic saline (3% sodium chloride solution), with close monitoring to avoid overcorrection of serum sodium.
- Serum sodium levels should be checked every 2 hours, with a goal of increasing serum sodium by 1 to 2 mmol/L/hour until neurological symptoms resolve.
- Subsequently, correction is slowed to elevate serum sodium by no more than 8 to 10 mmol/L in a 24-hour period.
- Furosemide may be used in addition to hypertonic saline, especially if the patient is at risk for volume overload.
- Central pontine myelinolysis (osmotic demyelination syndrome) may occur with rapid correction of serum sodium in excess of 12 mmol/L/day.
Hyponatraemia with mild to moderate symptoms
Mild to moderate symptoms include nausea, vomiting, or headache.
- In acute SIADH patients, treatment is with fluid restriction of 1 to 1.5 L/day.
- Vasopressin receptor antagonists (vaptans) are used for chronic SIADH patients.
- Investigation and management of any underlying disorder is essential.
- Asymptomatic patients are managed with fluid restriction and investigation of underlying cause.
Complications: Central Pontine Myelinolysis
Central pontine myelinolysis occurs with overcorrection of hyponatraemia where solute-poor cerebral cells are subject to shrinkage. It is characterised by:
- Demyelination of pontine, basal ganglion, and cerebellar regions
- Neurological symptoms including behavior disturbances, lethargy
- Dysarthria, dysphagia, paraparesis or quadriparesis
- Coma and seizures (less common)
Prevention: Avoid correction >12 mmol/L/day