Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
Overview Table
Overview of Water Balance Disorders
These 2 tables act as an overview to allow comparison between confusing water balance disorders. They do not contain all the information about these disorders; please review their separate articles for full details.
| Feature | SIADH | Primary Polydipsia | Diabetes Insipidus |
|---|---|---|---|
| Pathophysiology | Excess ADH secretion causes water retention | Excess water intake suppresses ADH secretion | Deficiency (central) or resistance (nephrogenic) to ADH |
| Typical causes | CNS disorder, malignancy, drugs | Psychogenic | Central: brain tumour Nephrogenic: drugs, renal disease |
| Serum sodium (baseline) | Hyponatraemia | Hypernatraemia | |
| Serum osmolality (baseline) | Low (<275 mOsm/kg) | High (>295 mOsm/kg) | |
| Urine osmolality (baseline) | High (concentrated) (>100 mOsm/kg) | Low (diluted) (<100 mOsm/kg) | |
| Diagnosis | Diagnosis by exclusion + supported by:
|
Fluid intake history + water deprivation test:
Paired serum and urine osmolality findings (as above) |
Water deprivation test:
Desmopressin test (central vs nephrogenic):
Paired serum and urine osmolality findings (as above) |
Some key trends, but presented in a different way:
| Disorder | Trends (at baseline) |
|---|---|
| SIADH |
|
| Primary polydipsia |
|
| Diabetes insipidus |
|
Background Information
Definition
SIADH is defined as a disorder characterised by non-physiologic, excess secretion of ADH.
Pathophysiology
Physiology of ADH: [Ref]
- A hormone synthesised in the hypothalamus and secreted from the posterior pituitary gland
- Function: acts on the collecting duct (via vasopressin 2 receptor) to increase expression of aquaporins → increase water reabsorption
- ADH secretion is stimulated by ↑ serum osmolality and ↓ effective arterial blood volume
In SIADH, there is inappropriate excess ADH secretion (in the absence of appropriate stimuli), leading to: [Ref]
- Impaired renal excretion of water (kidney retains more water than needed), and
- Dilutional hyponatraemia
Aetiology
Selected causes of SIADH, this is not an exhaustive list: [Ref]
| Category | Causes |
|---|---|
| Malignancy (~25% cases of SIADH caused by cancer) |
|
| Respiratory |
|
| CNS |
|
| Drugs | Some important and common ones:
|
Clinical Features
Apart from features of the underlying cause, SIADH mainly presents as hyponatraemia [Ref]
- Moderately severe cases: nausea (without vomiting), confusion, headache
- Severe cases: vomiting, abnormal and deep somnolence, cardiorespiratory depression, seizures, coma, hyporeflexia
SIAH is characteristically euvolaemic (in terms of fluid status) [Ref]
- There will be NO features of hypervolaemia (e.g. raised JVP, peripheral oedema, bi-basal crackles) or hypovolaemia (reduced skin turgor, dry mucous membrane, hypotension, tachycardia)
- This is less realistic in real life, but in exams the parameters are typically perfect, and there will be either no mention of hypervolaemic / hypovoalemic features, or denial of them
Diagnosis and Management
Investigation and Diagnosis
SIADH can be diagnosed if ALL the following are present: [Ref]
- Clinical euvolaemia
- Hypotonic hyponatraemia (↓ serum osmolality <275 mmol/kg, serum sodium <135 mmol/L)
- Inappropriately concentrated urine (urine osmolality >100-300 mmol/kg)
- ↑ Urine sodium (>20 mmol/L)
- Adrenal insufficiency and hypothyroidism are excluded
Important differentials of euvolaemic hypotonic hyponatraemia:
- Adrenal insufficiency – can be excluded with a morning cortisol level
- Severe hypothyroidism – can be excluded with TFT
- Primary polydipsia
Primary polydipsia can have similar biochemical findings as SIADH:
- Euvolaemic hypotonic hyponatraemia (same as SIADH)
- Low urine sodium (NB urine sodium is high in SIADH)
- Low urine osmolality (NB urine osmolality is high in SIADH)
- The low urine sodium and osmolality will be corrected after a water deprivation test
- A history of excessive water intake is also suggestive of primary polydipsia
Management
Step 1:
- Identify and treat any reversible causes (e.g. stop causative medications, treatment of malignancy) [Ref]
Step 2: [Ref]
- Fluid restriction (typically 1.0-1.5 L per day)
Step 3 (if refractory to fluid restriction): [Ref]
- Tolvaptan (vasopressin V2 receptor antagonist) – highly effective
- Others with lower efficacy
- Empagliflozin (SGLT-2 inhibitor)
- Oral urea
- Sat tabt tablets +/- loop diuretic
- Increase dietary protein intake
Be aware that severe, symptomatic hyponatraemia (<120 mmol/L) requires emergency treatment with hypertonic saline (3% / 2.7% / 1.8%).