SIADH & Diabetes Insipidus

Question 1

Describe the normal physiology of ADH (Vasopressin) secretion.

Answer 1

1. ADH (Vasopressin) is produced by the hypothalamus in response to increased serum osmolality. (serum concentration/low circulatory water)
2. ADH is then transported to the posterior pituitary gland.
3. It is then released into the circulatory system.
4. It travels to the kidneys and binds to ADH receptors (Aquaporin-2 Channels) on the distal convoluted tubules.
5. Water is re-absorbed from the urine.
   
   • Serum osmolality decreases (Serum is more watery)
   • Urine osmolality increases. (Urine more concentrated)
6. The hypothalamus detects this and reduces ADH release.

Question 2

What is SIADH?

Answer 2

Water retention due to inappropriate ADH secretion.

Too much ADH=Watery blood

This leads to hyponatraemia.

Question 3

When starting SSRIs, when does ADH usually occur?

Answer 3

Usually within the first few weeks.

It then stops within 2 weeks of stopping.

If someone is elderly, is on diuretics and an SSRI is started then there is greater chance that they will develop hyponatraemia.

Question 4

What are some of the potential non-pharmacological causes of SIADH?

Answer 4

• Brain damage
  
  • Meningitis/Encephalitis/abscess, SAH, Subdural Haemorrhage, Stroke.
• Malignancy
  
  • Small cell lung cancer, Pancreas and prostate cancer.
• Infections
  
  • TB, Pneumonia
• Drugs (See other card)
• Endocrine- Hypothyroidism
• Other - Porphyrias, Positive end-expiratory pressure (PEEP)

Question 5

What are some of the pharmacological causes of the release of ADH/Vasopression (SIADH and thus hyponatraemia)

Answer 5

• Diuretics (Thiazides especially)
• Antipsyhotics - haloperidol
• Antidepressants - SSRI, TCA
• Sulfonylureas
• Carbamazepine
• Morphine
• NSAIDs

Question 6

How do you manage SIADH?

Answer 6

1. Treat the underlying cause
2. Fluid restriction (1 to 1.5 litres a day)
3. Replacing Sodium - Normal NaCL infusion.
   
   • But done slowly so as to prevent Central Pontine Myelinolysis.
   • No more than 10mmol/24 hours.
4. Demeclocycline - a tetracycline antibiotic that reduces the sensitivity of ADH receptors on the distal tubules of the kidneys. (Creates a partial nehprogenic DI)
5. Vaptans (Vasopressin receptor antagonists) Blocks kidney receptors..

Question 7

How do you diagnose SIADH?

Answer 7

• Low urinary output
• Low Sodium (Euvolaemic hyponatraemia)
  
  • Low plasma osmolality (watery blood)
• Normal to High Urinary Sodium - PCT compensates and dumps sodium in order to dump water.

Question 8

What are some common symptoms of DI?

Answer 8

Signs & Symptoms

• Poluria, Polydipsia, Nocturia, Dehydration.

Question 9

What is Diabetes Insipidus?

Answer 9

Not able to hold onto water (resorption) because of either:

1/ Reduced ADH secretion from the posterior pituitary gland. (Cranial DI)

2/ Impaired response of the kidneys (Nephrogenic DI)

Question 10

In terms of serum/plasma sodium, urinary sodium, Serum osmolality and urinary osmolality…how can you tell the difference between SIADH and DI?

Answer 10

• DI (Concentrated blood - Lots of Watery urine)
  
  • Hypernatraemia
  • Serum/plasma osmolality - High (Concentrated blood)
  • Urinary Sodium - Low/normal
  • Urinary osmolality - Low
  • Urine output - High
• SIADH (Watery blood - concentrated urine)
  
  • Hyponatraemia
  • Serum/plasma osmolality - Low
  • Urinary sodium - High
  • Urinary osmolality - High
  • Urine output - Low

Question 11

How do you diagnose DI?

Answer 11

The 8 Hour Water Deprivation test.

• To see if kidneys produce dilute urine despite restriction
• Stage 1 - to diagnose dilute urine.
• Stage 2 - desmopressin given & water drunk.
  
  • If Urine concentrates then Cranial DI
  • If it doesn’t then nephrogenic DI.

Question 12

What are some causes of cranial/neurogenic DI?

Answer 12

1. Idiopathic (Most common<= 50%)
2. Tumours - tumours (craniopharyngioma, pituitary tumour)
3. Intracranial
4. Trauma
5. Infiltrates- Sarcoidosis, TB, Wegener’s, Histiocytosis.
6. Infections - encephalitis, meningitis, cerebral abscess.
7. Vascular - haemorrhage/thrombosis, aneurysms, Sick cell disease, Sheehan’s syndrome. (postpartum pituitary necrosis)

Inherited - Autosomal recesssive Wolfram syndrome (DIDMOAD gene mutation)

Question 13

What are some causes of nephrogenic DI?

Answer 13

• Inherited
• Aquired
  
  • Drugs - lithium, orlistat.
  • Electrolytes - Hypercalcaemia, Hypokalaemia
  • CKD
  • Renal tubular acidosis
  • Pregnancy.