Syndrome of inappropriate ADH secretion

Question 1

Define:

Answer 1

Characterised by continued secretion of ADH, despite the absence of normal stimuli for secretion (i.e. increased serum osmolality or decreased blood volume)

Question 2

Aetiology/risk factors:

Answer 2

Increased ADH causes increased water reabsorption, so plasma osmolality falls and there is hyponatremia.

Decrease in urine volume. When VP levels get really high, there is a slight natriuresis (sodium excreted in the urine) – this may be a compensatory mechanism to try to get more fluid excreted.

Question 3

Brain causes:

Answer 3

o	Haemorrhage/thrombosis 
o	Meningitis 
o	Abscess 
o	Trauma
o	Tumour
o	Guillain-Barre syndrome

Question 4

Lung causes:

Answer 4

o Pneumonia
o TB
o Other: abscess, aspergillosis, small cell carcinoma
Klebsiella

Question 5

Tumour causes (ectopic secretion):

Answer 5

o Small cell lung caner
o Lymphoma
o Leukaemia
o Others: pancreatic cancer, prostate cancer, mesothelioma, sarcoma, thymoma

Question 6

Drug causes:

Answer 6

o Vincristine
o Opiates
o Carbamazepine
o Chlorpropamide

Question 7

Metabolic causes:

Answer 7

Alcohol withdrawal

Porphyria

Question 8

Symptoms:

Answer 8

• Decreased urine volume, concentrated urine
• Mild hyponatraemia may be ASYMPTOMATIC
• Headache
• Nausea/vomiting
• Muscle cramp/weakness
• Irritability
• Confusion
• Drowsiness
• Convulsions
• Coma
• Symptoms of underlying cause

Question 9

Epidemiology:

Answer 9

• Hyponatraemia is the MOST COMMON electrolyte imbalance seen in hospital
• < 50% of severe hyponatraemia is caused by SIADH

Question 10

Signs:

Answer 10

•	MILD hyponatraemia - no signs 
•	SEVERE hyponatraemia:
o	Reduced reflexes 
o	Extensor plantar reflexes 
•	Signs of underlying cause 
•	NOTE: the hyponatraemia in SIADH is due to dilution from excessive water reabsorption and not due to a decrease in total body Na+

Question 11

Investigations of other diagnosis:

Answer 11

o Low serum sodium
o Creatinine (check renal function)
o Glucose, serum protein and lipids - to rule out pseudohyponatraemia
• Pseudohyponatraemia = when the sodium concentration is actually normal but is erroneously reported as being low because of the presence of either hyperlipidaemia or hyperproteinaemia
o Free T4 and TSH - hypothyroidism can cause hyponatraemia
o Short synacthen test - adrenal insufficiency can cause hyponatraemia

Question 12

Investigations for diagnosis:

Answer 12

o Low plasma osmolality
o Low serum Na+ concentration
o High urine osmolality
o High urine Na+
o The presence of the above results and the absence of hypovolaemia, oedema, renal failure, adrenal insufficiency and hypothyroidism are required for the diagnosis of SIADH
• Investigations for identifying the cause (e.g. CXR, CT, MRI)

Question 13

Management:

Answer 13

• Fluid restriction – immediate
• Then, give demeclocycline (tetracycline) – if the fluid restriction is insufficient
• Long term: Vasopressin receptor antagonists (VAPTANS) (e.g. tolvaptan)
• In SEVERE cases - slow IV hypertonic saline and furosemide with close monitoring

Question 14

Complications:

Answer 14

•	Convulsions 
•	Coma 
•	Death 
•	Central pontine myelinolysis - occurs with rapid correction of hyponatraemia, dye to damage to myelin of neurones of pons
o	Characterised by:
•	Quadriparesis 
•	Respiratory arrest 
•	Fits

Question 15

Prognosis:

Answer 15

• Depends on the CAUSE
• Na+ < 110 mmol/L is associated with a HIGH MORBIDITY and MORTALITY
• 50% mortality with central pontine myelinolysis