Diabetes Insipidus

Introduction

Diabetes insipidus is a condition characterised by the passage of large volumes (>3L/day) of dilute urine due to impaired water resorption by the kidney, because of reduced ADH secretion from the posterior pituitary (cranial DI) or impaired response of the kidney to ADH (nephrogenic DI).
 
It is important to distinguish DI from primary polydipsia, which is a psychiatric condition characterised by excessive water consumption. Other causes of polyuria and polydipsia, such as hyperglycaemia, are not to be confused with DI.
 
In health, ADH acts to increase the volume of blood intravascularly, and also to decrease the volume of urine produced. Therefore, a lack of it causes increased urine production and internal volume depletion.

• The most common type of DI in humans is cranial DI, involving a deficiency of ADH.
• DI can also be gestational, or present as an iatrogenic effect of alcohol or some types of drug abuse.
• Despite the name, there is no overlap with the pathophysiology of DM; in DI urine does not contain glucose.
• Incidence in the general population is 3/100,000.

Symptoms

• Polyuria – excessive urination unaffected by reduction of fluid intake.
• Polydipsia – can be uncontrollable and all consuming with patients drinking anything and everything to hand.
• Dehydration since the body cannot conserve much, if any, of the water it takes in.
• Symptoms of hypokalaemia:
  • Muscle weakness
  • Hypotonia
  • Hyporeflexia
  • Cramps
  • Tetany
  • Palpitations
  • Light-headedness (arrhythmias)
• Symptoms of hypernatraemia:
  • Lethargy
  • Thirst
  • Weakness
  • Irritability
  • Confusion
  • Coma
  • Fits
  • Signs of dehydration.

 
N.B.
Other causes of hypernatraemia:
Water loss in excess of sodium loss...

• Fluid loss without water replacement (e.g. diarrhoea, vomit, burns)
• Incorrect IV fluid replacement (Excessive saline)
• Diabetes insipidus – suspect if large urine volume. This may follow head injury or CNS surgery, especially pituitary.
• Osmotic dieresis for diabetic coma
• Primary aldosteronism – suspect if hypertension, hypokalaemia and alkalosis due to high bicarbonate.

Aetiology

 
N.B.
Damage to the hypothalamo-neurohypophysial tract or the posterior pituitary with an intact hypothalamus does not lead to ADH deficiency, and therefore does not cause CDI. This is because ADH is still able to ‘leak’ from the damaged end of the intact neurone.
 
 

Neurogenic Causes

• Cranial/ neurogenic DI is caused by insufficient levels of ADH due to lack of its production in the brain.
• Idiopathic =<50%
• Also due to damage of the hypothalamus, pituitary stalk, posterior pituitary, or head trauma. Vasopressin is released by theposterior pituitary, but unlike most other pituitary hormones, it is produced by the hypothalamus. Cranial DI can therefore be a failure of production at the hypothalamus or a failure of release at the pituitary.
• Congenital: Defects in ADH gene, such as in DIDMOAD. DIDMOAD is a rare autosomal recessive disorder: Diabetes Insipidus,Diabetes Mellitus, Optic Atrophy and Deafness (also known as Wolfram’s syndrome). Familial neurogenic diabetes insipidus is the rarest cause of cranial DI.
• Tumour (may present with DI and hypopituitarism) – craniopharyngioma, metastases, pituitary tumour.
• Trauma: temporary if distal to pituitary stalk as proximal nerve endings frow out to find capillaries in scar tissue and begin direct secretion again.
• Hypophysectomy
• Autoimmune hypophysitis
• Inflammation: histiocytosis, sarcoidosis (suspect neurosarcoidosis if CSF protein high, facial nerve palsy, CSF pleocytosis, DI, hemiparesis, psychosis, papilloedema, ataxia, seizures, optic atrophy, hearing loss or nystagmus)
• Vascular: haemorrhage
• Infection: meningoencephalitis. Sheehan’s syndrome is pituitary infarction from shock, e.g. postpartum haemorrhage. It is rare.

Nephrogenic Causes

• Nephrogenic DI is a form of diabetes insipidus primarily due to pathology of the kidney which results in its improper response to ADH, leading to a decrease in the ability of the kidney to concentrate the urine by removing free water.
• Most common in its acquired forms, meaning that that the defect was not present at birth.
• The most obvious cause is a systemic or renal disorder such as amyloidosis, polycystic kidney disease or electrolyte imbalance.
• There are some inherited causes of nephrogenic DI. These come in the form of type 1, affecting the AVPR2 gene (x-linked defect causing the V2 vasopressin receptor in the kidney to stop functioning prope