Syndrome of Inappropriate ADH secretion

Question 1

What are the causes of SIADH?

Answer 1

Neurological:

• Meningitis
• Cerebral abscess
• Head injury
• SAH
• GBS
• MS
• SLE
• AIDS

Pulmonary:

• Various cancers (small-cell lung cancer, mesothelioma)
• Lung diseases (pneumonia, CF, asthma, TB, positive pressure ventilation)

Malignancy:
- Oropharyngeal, stomach, pancreas, leukemia, lymphoma, thymoma, GU cancers

Drugs:

• Thiazide diuretics
• SSRIs
• PPIs
• ACE-Is
• loop diuretics
• Opiates
• Vincristine
• Ciprofloxacin
• Alcohol withdrawal

Misc.

• Sarcoidosis
• Hypothyroidism
• Inherited mutations
• Pain
• Endurance exercise

Question 2

What is the pathophysiology of SIADH?

Answer 2

A condition of abnormal water handling not excessive salt loss:
- Release of ADH not inhibited by falling plasma osmolality

When water ingested, this decreases plasma osmolality which usually feeds back to the hypothalamus (via osmoreceptors) to stop the synthesis of ADH (which is then normally stored in vesicles and released from the posterior pituitary)

Question 3

How does SIADH present?

Answer 3

Dependent on the rate at which hyponatraemia develops:

• Acute = can be mild and still significant symptoms
• Chronic (>48hrs) = can have very low sodium and be completely asymptomatic (due to compensatory process of cerebral adaptation where neurons change metabolism to fit with the abnormal sodium levels)

Mild:
- N+V, vomiting, headache, anorexia, lethargy

Moderate:
- Muscle cramps, weakness, confusion, ataxia

Severe:
- Drowsiness, seizures, coma

Other signs:

• Low GCS
• Cognitive impairment - short term memory loss, disorientaion, confusion
• Focal or generalised seizures
• Brainstem herniation (if severe acute hyponatraemia) - coma, resp arrest
• Hypervolaemia - pulmonary oedema, peripheral oedema, raised JVP, ascites

Question 4

How do you investigate SAIDH?

Answer 4

Fluid status:

• euvolaemic or hypevolaemic
• If dehydrated, then will likely not be SIADH

Blood:

• Na - Low
• K - if raised, consider Addison’s
• osmolality - low (due to low Na)
• TFT - ?hypothyroidism cause of SIADH
• Cortisol - ?Addison’s cause of SIADH

(repeat results to confirm)

Urine:
- Excess ADH results in water NOT salt retention so concentrated urine high in Na should be produced

Imaging:
- CXR/CT - ?lung Ca, atypical pneumonia

Question 5

What is required for a diagnosis of SIADH?

Answer 5

Hyponatraemia 
Low plasma osmolality 
Inappropriately elevated urine osmolality 
High urine Na 
Euvolaemia 
Normal TFT and adrenal function

Question 6

How do you manage SIADH?

Answer 6

Manage the underlying cause:
- e.g. stop any offending medications

Acute, symptomatic hyponatraemia = a medical emergency:

• Administration of hypertonic 3% saline - 150ml IV over 15mins
• Repeat after 20 mins if no clinical improvement
• Recheck serum Na at 6, 12, 24 and 48hrs for over correction

Assess hydration status:
- Euvolaemia = confirm hypotonic hyponatraemia - check urine Na and if high, likely SIADH
- Then calculate electrolyte free water clearance using ‘Furst formula’:
(Urine Na + K)/Serum Na
- Depending on outcome - restrict fluids and reevaluate or consult with specialist
- If fluid restrictions inadequate - consider demeclocycline (ADH blocker)

Question 7

What is important to keep in mind with treating hyponatraemia?

Answer 7

Do not correct too rapidly:
- Ensuring that the sodium level does not rise by more than 6 mmol/L in the first six hours or 10 mmol/L in the first 24 hours

Else you get osmotic demyelination syndrome/central pontine demyelinolysis:

Confusion, delirium, hallucinations.

Balance problems, tremor.

Problem swallowing.

Reduced alertness, drowsiness or sleepiness, lethargy, poor responses.

Slurred speech.

Weakness in the face, arms, or legs, usually affecting both sides of the body

Symptoms occur 2-4 days later

Risk factors:

• F>M
• Hypokalaemia
• Alcoholism
• Liver transplant