Syndrome of inappropriate antidiuretic hormone secretion (SIADH)

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Definition
Diagnostic features:
Causes of SIADH

Definition

Syndrome of inappropriate antidiuretic hormone (SIADH) secretion is defined as euvolaemic, hypotonic hyponatraemia secondary to impaired free water excretion typically as a result of excessive antidiuretic hormone secretion.

Excess ADH may be secreted from the posterior pituitary gland or an abnormal non-pituitary source.

Diagnostic features:

Low plasma sodium concentration (<135 mmol/l)
Low serum osmolality (<275 mOsm/kg)
High urine osmolality (>100 mOsm/kg & greater than plasma osmolarity)
Euvolaemia
High urine sodium (>30 mmol/L)
No other cause for hyponatraemia (diuretic use, hypothyroidism, cortisol deficiency, hyperproteinaemia, hyperlipidaemia or hyperglycaemia).

Antidiuretic hormone (ADH) is also known as arginine vasopressin (AVP). It is synthesised in the hypothalamus and secreted from the posterior pituitary. It promotes water and sodium resorption.

As the name suggests the primary action of antidiuretic hormone is to prevent diuresis. It achieves this by increasing sodium and water resorption. Click on image to enlarge

Causes of SIADH

Category	Examples
Malignancy	Small cell lung cancer Stomach cancer Oropharyngeal cancer Pancreatic cancer Prostate cancer Leukaemia Lymphoma Thymoma Genitourinary tract cancers
Neurological	Stroke Subarachnoid haemorrhage Subdural haemorrhage Meningitis/encephalitis/abscess Tumour Guillain-Barre syndrome Multiple sclerosis
Infections	Tuberculosis Pneumonia
Drugs	Thiazide diuretics SSRI's Proton pump inhibitors ACE inhibitors Loop diuretics Tricyclics Sulfonylureas* Carbamazepine Vincristine Cyclophosphamide
Respiratory	Asthma Mesothelioma Cystic fibrosis Positive end-expiratory pressure (PEEP)
Other causes	Systemic lupus erythematosus Porphyrias

*the BNF states this has been reported with glimepiride and glipizide.

Diagnostic features summary

Hyponatraemia.
Low plasma osmolality
Inappropriately elevated urine osmolality (>100 mOsmol/kg commonly and > plasma osmolarity)
Urinary sodium >30 mmol/L
Euvolaemia.
Normal thyroid and adrenal function.

Signs & symptoms of hyponatraemia

Nausea and vomiting.
Headache.
Confusion.
Lethargy and fatigue.
Restlessness and irritability.
Muscle weakness, spasms or cramps.
Drowsniess
Seizures.
Coma.

Management

Correct hyponatreamia slowly to avoid precipitating central pontine myelinolysis
Treat underlying cause where possible e.g. stop causative drugs
Fluid restriction (typically 1000 ml/day for adults)
Intravenous hypertonic saline (3% sodium chloride solution) is typically used in patients with neurological symptoms.
Demeclocycline: blocks ADH receptors & reduces responsiveness of the collecting tubule cells to ADH
ADH receptor antagonists (AKA vaptans or vasopressin receptor antagonists) such as tolvaptan are an option but have limited availability

Central pontine myelinolysis (osmotic demyelination syndrome) may occur with rapid correction of serum sodium in excess of 12 mmol/L/day.

If using hypertonic saline the serum sodium levels must be checked every 2 hours. The goal is to increase serum sodium slowly by up to 1 mmol/L/hour to a maximum of 10-12 mmol/L/day until neurological symptoms resolve.

Osmolality abnormalities & underlying causes

Serum osmolality	Urine osmolality	Causes
Normal or increased	Increased	Dehydration Renal disease and uraemia Congestive heart failure Addison's disease Hypercalcaemia Diabetes mellitus/hyperglycaemia Hypernatraemia Alcohol ingestion Mannitol therapy
Normal or increased	Decreased	Diabetes insipidus
Decreased	Increased	SIADH
Decreased	Decreased (with no increase in fluid intake)	Overhydration Hyponatraemia Adrenocortical insufficiency Sodium loss (diuretic or a low-salt diet)