Diabetes insipidus

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Diabetes insipidus is the less common form of diabetes. It is caused by a failure in the kidney to reabsorb water, or a failure by the pituitary to instruct it to do so. Large volumes of dilute urine are passed, leading to dehydration with hypernatraemia and collapse.



Can be:

Primary polydipsia

Primary polydipsia is due to suppression of AVP secretion by excessive fluid intake (ie normal physiology).

  • This always needs to be eliminated first by history and is treated in effectively the opposite way to default treatment of other causes

Cranial diabetes insipidus

Cranial diabetes insipidus (CDI):

  • Due to loss of ADH production
    • Multiple causes such as tumour, trauma or inflammatory disease such as sarcoid
    • Accordingly treatment is vasopression analogues (response is highly suggestive of diagnosis)
  • The variety stemming from failure of pituitary release of anti-diuretic hormone (ADH) is controlled by intranasal administration of ADH - nowadays synthetic.


Nephrogenic diabetes insipidus

Nephrogenic diabetes insipidus (NDI):

  • Owing to loss of effect of ADH on collecting ducts which can be caused by several mutations in the receptor (V2R, thus some forms X-linked) and effector protein genes (eg in AQP2 or AVPR2).
  • Can be a complication of Conn's syndrome.

Acquired nephrogenic diabetes insipidus

Often caused by disturbance of the aquaporin-2 shuttle. In pregnancy usually transient as often due to increased placental production of vasopressinase that inactivates circulating vasopressin (dDAVP is not degraded by vasopressinase). There are several other possible causes in pregnancy so take care.

Lithium toxicity

Lithium-induced nephrogenic diabetes insipidus has become the commonest cause of acquired nephrogenic diabetes insipidus since the introduction of lithium into treatment of bipolar disorder in the 1950's. Lithium reduces the expression of AQP2.

Treatment is:

  • Stop lithium
  • intravenous rehydration
  • Control sodium intake
    • ie help induce hypovolaemic activation of renin-angiotensin-aldersterone system
  • Thiazide diuretics
    • ie help induce hypovolaemic activation of renin-angiotensin-aldersterone system
  • Amiloride
    • ie inhibits lithium entry into renal collecting duct cells through the epithelial sodium channel
  • Acetazolamide
    • reduces GFR including by decreased renal prostaglandin secretion

Other causes


  • Electrolytes
  • Urine volume and sodium/osmolaity (paired)
  • water-deprivation test - can be dangerous
    • Urinary osmolality of less than 300 mosm/kg H2O despite water deprivation
    • Administration of aqueous vasopressin, patients with nephrogenic diabetes insipidus will show little or no increase in urine osmolality.


Get diagnosis right.

  • Water
  • Desmopressin for cranial diabetes insipidus
  • NSAIDs, thiazides, amiloride and acetazolamide for nephrogenic diabetes insipidus


  • 1794 Johann Peter Frank described polyuric patients excreting nonsaccharine urine and introduced the term of diabetes insipidus.
  • 1913 Farini used posterior pituitary extracts to treat Diabetes Insipidus.
  • 1928 De Lange first describes non central diabetes insipidus as refractory to posterior pituitary extracts
  • 1945 Forssman and Waring describe varieties of nephrogenic diabetes insipidus
  • 1947 Williams and Henry introduced the term nephrogenic diabetes insipidus for the congenital syndrome characterized by polyuria and renal concentrating defect resistant to vasopressin.
  • 1955 du Vigneaud received the Nobel Prize in chemistry for the first synthesis of the hormone vasopressin.
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