SIADH- Syndrome of inappropriate ADH secretion

Question 1

Definition

Answer 1

Excess secretion of ADH from posterior pituitary gland resulting in euvolemic hyponatremia.

Question 2

Pathophysiology

Answer 2

Excess 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 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

Causes of SIADH

Answer 3

• Infections of lung: particularly atypical pneumonia & lung abscess, TB
• Meningitis (infection of brain)
• Neoplasms: ectopic ADH secretion from SCLC, prostate cancer, pancreatic cancer, lymphomas, cancers of thymus gland
• Drug induced: SSRIs (Fluoxetine, Citalopram, Sertaline), Carbamazepine (anti-convulsant), Chlorpropamide (sulfonylurea for T2DM), Cyclophosphamide
• Head injury

Question 4

Symptoms of SIADH

Answer 4

Symptoms of hyponatremia (serum sodium < 135mmol/L): mild -> severe
- nausea, VOMITING, headache, lethargy
- weakness & muscle aches, confusion
- reduced consiousness & seizures

Question 5

Investigations & diagnosis

Answer 5

Diagnosis by exclusion:
Serum osmolality - low (increased water reabsorption dilutes blood but isn’t large enough to cause fluid overload, there is euvolemic hyponatremia)
U& E - serum Na+ low < 135mmol/L
Urine osmolality- high
Urine sodium- high

Question 6

Treatment

Answer 6

Immediate management:
1) Treat underlying case
2) Fluid restriction to 500-1000ml/day (although patient is EUVOLEMIC & there isn’t fluid overload, this will concentrate the Na+ & increases serum [Na+] to correct the euvolemic hyponatremia)
3) IV hypertonic 0.9% NaCl - aim for slow increases in serum Na+ (maximum increase of 8mmol/L over 24 hrs as complication of rapid rise in Na+ levels = central pontine myelinolysis

Then management for chronic cases (>48 hrs):
Tolvaptan (V2 receptor antagonist, results in increased water excretion so serum Na+ gets concentrated, universally recommended) + consider Demeclocycline (induces nephrogenic DI so kidneys don’t respond to ADH, guidelines differ)

Question 7

Complications of rapid Na+ replacement & of hyponatremia

Answer 7

Complications of rapid Na+ replacement = central pontine myelinolysis (osmotic shift of water from neurones in pons causes locked in syndrome- patient is consious with COMPLETE paralysis of skeletal muscles)

Complications of hyponatremia = cerebral oedema & brainstem herniation through foramen magnum

Question 8

Which tumours cause SIADH?

Answer 8

Ectopic secertion from:
- small cell lung carcinoma = most common
- prostate cancer
- pancreatic cancer
- lymphomas
- cancers of thymus gland

Question 9

Which drugs cause SIADH?

Answer 9

• cyclophosphamide
• Chlorpropamide (sulfonylurea for T2DM)
• Carbamazepine (anti-convulsant)
• SSRIs

Question 10

Which infections cause SIADH?

Answer 10

Lung- atypical pneumonia & lung abscess, TB
Brain- meningitis