SIADH

Question 1

What is SIADH

Answer 1

syndrome of inappropriate anti-diuretic hormone (SIADH) results from excess ADH secretion.

results in reduced diuresis - water excretion and urinary output are reduced. This leads to an increase in total body water and hyponatraemia.

Question 2

Epidemiology

Answer 2

• Hyponatraemia is the most common electrolyte disorder encountered in clinical practice
• The prevalence of hyponatraemia in the community is around 8% and increases with age (approximately 12% in people aged 75 or older)

Question 3

Neurological aetiology of SIADH

Answer 3

• Meningitis, encephalitis or cerebral abscess
• Intracranial haemorrhage, e.g. subarachnoid or subdural haemorrhage
• Stroke
• Trauma

Question 4

Cancerous aetiology of SIADH

Answer 4

• Small cell carcinoma of the lung most commonly
• Other cancers, e.g. breast cancer, and head and neck tumours, are rarer causes

Question 5

Infectious and Endocrine aetiology of SIADH

Answer 5

• Infections
  
  • Pneumonia
  • Tuberculosis
  • HIV
• Endocrine
  
  • Hypothyroidism
  • Hypopituitarism

Question 6

Pneumonic for drugs that can cause SIADH

Answer 6

CARDISH

Question 7

CARDISH

Answer 7

chemo, antidepressants, recreational drugs, diuretics, inhibitors e.g. ACEI & SSRIs, sulfonylurea, hormones e.g. desmopressin)
PPIs
TCAs

Question 8

RFs

Answer 8

• Age >50
• Pulmonary conditions
• Malignancy
• Medicine associated with SIADH induction
• CNS disorder

Question 9

Pathophysiology of SIADH

Answer 9

Increased ADHresults in increased free water retention, subsequent dilution of the blood and a decrease in solutes in the blood.

Increase in blood volume leads to stretching of heart muscle and release of ANP and BNP (natriuretic peptide) > Inhibits RAAS > promotes natriuresis (excretion of sodium). This leads to sodium and water excretion, which promotes further ADH activity.

Question 10

What happens to the kidney’s in SIADH?

Answer 10

Overtime, the kidneys will adapt.

The number of aquaporin channels will decrease to compensate for the amount of ADH present.

This will now lead to diuresis as well as natriuresis. This is why there is there is a euvolaemic state rather than a hypervolaemic state, coupled with hyponatraemia.

Overall: patients will have high urine Na+ levels and low serum Na+ levels.

Question 11

What do the clinical features in SIADH depend on?

Answer 11

degree of hyponatraemia and the rate of change in serum sodium levels (acute or chronic)

Large proportion asymptomatic

Question 12

Key presentations for SIADH

Answer 12

Hyponatraemic and euvolaemic (no features of hyper- or hypovolaemia)

Question 13

Symptoms of SIADH

Answer 13

Mild(130-135 mmol/L):

• Nausea, vomiting, headache, lethargy, anorexia

Moderate(125-129 mmol/L):

• Weakness, muscle aches, confusion, ataxia, asterixis

Severe(< 125 mmol/L):

• Reduced consciousness, seizures, myoclonus, respiratory arrest

Question 14

Investigations for SIADH

Answer 14

Blood tests

Renal function: gives a serum sodium that confirms hyponatraemia. May also show a low serum urea consistent with mild volume expansion.

Serum osmolality: a low serum osmolality is seen, less than 280 mOsm/kg.

Urinary tests

Urinary osmolality: a high urine osmalality is seen, greater than 100 mOsm/kg.

Urine sodium: typically a high urinary sodium is seen, greater than >40 mmol/L.

Question 15

Diagnostic criteria

Answer 15

• Low plasma osmolality: < 275 mOsm/kg
• High urine osmolality: > 100 mOsm/kg
• High urine sodium: > 30 mmol/L
• Clinical euvolaemia
• Exclusion of glucocorticoid deficiency or hypothyroidism(rare)

Question 16

First line treatment

Answer 16

Fluid restriction

Question 17

Acute management of SIADH <48 hrs onset

Answer 17

Acute hyponatraemia must be treated urgently due to the risk of cerebral oedema and herniation

• Hypertonic (3%) saline is preferred - slow infusion to avoid complications
• Furosemide (diuretic) - in patients who have fluid overload. Causes an increase in water, Na+, Ka+ and Cl- excretion. (Note: KCl should be replaced)

Question 18

Chronic management of SIADH
Mild to moderate asymptomatic cases

Answer 18

• fluid restriction to increase Na+ conc
  
  • Fluid restriction may not be used in SIADH secondary to subarachnoid haemorrhage as it risks lowering blood pressure which may cause cerebral vasospasm and infarction.

Question 19

Management of severe or symptomatic cases

Answer 19

• Demeclocycline, a tetracycline antibiotic, causes an iatrogenic nephrogenic diabetes insipidus through the inhibition of ADH. Though historically popular it is rarely used today.
• A newer class of drugs termedvaptans(e.g. tolvaptan) are now more commonly used. These ADH receptor antagonists are effective but expensive agents.

Question 20

Complications of SIADH

Answer 20

• Cerebral oedema: hyponatraemia lowers the osmolality of the blood causing an osmotic shift of water into brain tissue with subsequent oedema and risk of herniation
• Central pontine myelinolysis:rapid correction of sodium can cause osmotic demyelination, particularly in chronic hyponatraemia (slow correction is vital)
  
  • Manifests as tremors, dysarthria, quadriplegia, ophthalmoplegia, seizures and extrapyramidal symptoms
  • May result in ‘locked-in syndrome’, where patients are awake but unable to verbally communicate or move
  • Diagnosis is confirmed with MRI