SIADH

Question 1

where is adh produced and released?

what does it do?

Answer 1

Anti-diurectic hormone (ADH) is produced in the hypothalamus and secreted by the posterior pituitary gland.

ADH stimulates water reabsorption from the collecting ducts in the kidneys.

SIADH is a condition where there is inappropriately large amounts of ADH.

Question 2

Pathology

urine Osmolality

Answer 2

The excessive ADH results in excessive water reabsorption in the collecting ducts.

This water dilutes the sodium in the blood so you end up with a low sodium concentration (hyponatraemia).

The excessive water reabsorption is not usually significant enough to cause a fluid overload, therefore you end up with a “euvolaemic hyponatraemia”.

The urine becomes more concentrated as less water is excreted by the kidneys therefore patients with SIADH have a “high urine osmolality” and “high urine sodium”.

Question 3

Clinical Features

Answer 3

Headache
Fatigue
Muscle aches and cramps
Confusion
Severe hyponatraemia can cause seizures and reduced consciousness

Question 4

Causes

Answer 4

Post-operative from major surgery

Infection, particularly atypical pneumonia and lung abscesses

Head injury

Medications (thiazide diuretics, carbamazepine, vincristine, cyclophosphamide, antipsychotics, SSRIs, NSAIDSs,)

Malignancy, particularly small cell lung cancer

Meningitis

Question 5

Diagnosis

Answer 5

In a way, SIADH is a diagnosis of exclusion as we do not have a reliable test to directly measure ADH activity.

Clinical examination will show euvolaemia.

U+Es will show a hyponatraemia.

Urine sodium and osmolality will be high.

Chest xray as a first line investigation for pneumonia, lung abscess and lung cancer ( CT thorax/abodmen/pelvis and MRI brain to find the malignancy)

Other causes of hyponatraemia need to be excluded:

• Negative short synacthen test to exclude adrenal insufficiency
• Burns
• CKD could cause hyponatraemia

Question 6

Management

Answer 6

stop the causative medicationI

correct the sodium slowly to prevent central pontine myelinolysis: aim for a change in sodium of less than 10 mmol/l per 24 hours.

Fluid restriction involves restricting their fluid intake to 500mls – 1litre. This may be enough to correct the hyponatraemia without the need for medications.

Tolvaptan. “Vaptans” are ADH receptor blockers, initiated by a specialist endocrinologist

Demeclocycline is a tetracycline antibiotic that inhibits ADH. It was used prior to the development of vaptans and is now rarely used for this purpose.

Question 7

Central Pontine Myelinolysis

Rate to aim for

Answer 7

Long term severe hyponatraemia (< 120 mmols/l) being treated too quickly (> 10 mmol/l increase over 24 hours).

When this happens water will rapidly shift out of the brain cells and into the blood. This causes two phases of symptoms:

First phase:

• encephalopathic and confused
• nausea and vomiting

These symptoms often resolve prior to the onset of the second phase.

Second phase: this is due to the demyelination of the neurones, particularly in the pons. This occurs a few days after the rapid correction of sodium. 
- spastic quadriparesis
- pseudobulbar palsy  
- cognitive and behavioural changes
There is a significant risk of death.

Prevention is essential as treatment is only supportive once CPM occurs. A proportion of patients make a clinical improvement but most are left with some neurological deficit.