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Diabetes insipidus

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Diabetes insipidus

Anti-diuretic hormone

Secretion increased by:

  • hyperosmolality or hypotension
  • stress, emotional stimuli
  • trauma, surgery, pain
  • exercise, increased temperature
  • positive pressure ventilation
  • cholinergic and beta agonist drugs
  • nicotine
  • angiotensin II
  • barbiturates
  • chlorpropamide

Secretion decreased by:

  • phenytoin
  • opioid antagonists
  • causes of neurogenic DI

ADH action potentiated by:

  • chlorpamide
  • carbamazepine
  • clofibrate
  • thiazide diuretics
  • prostaglandin synthetase inhibitors

Antagonized by:

  • hypokalaemia
  • hypercalcaemia
  • PGE2
  • drugs which cause nephrogenic DI
  • excess vasopressinase


  • antidiuresis
    - due to action on V2 receptors in distal renal tubule, mainly in collecting duct
    - stimulates adenyl cyclase to produce cAMP which allows a protein kinase to open microtubular passages for water ingress from the renal filtrate
    - up to 12% of glomerular filtrate may be reabsorbed
  • cardiovascular effects (V2): tachycardia, facial flushing, hypotension, increased plasma renin
    - increased PGE2 synthesis resulting in inhibition of ADH-induced cAMP generation
  • vasoconstriction
    - due to V1a stimulation
    - occurs at higher concentrations of ADH
    - clinically significant in hypotensive states
    - skin, mesenteric and coronary vessels particularly sensitive. Action not antagonized by alpha blockade or by vascular denervation
  • other V1a effects: glycogenolysis, stimulation of renal PG synthesis, inhibition of renal renin secretion. Also affects learning, memory and water permeability of brain
  • haemostatic effects: see DDAVP. V2 mediated
  • V1b receptors found in pituitary. Activation leads to corticotrophin secretion
  • some preliminary evidence that vasopressin may be more effective than epinephrine in out of hospital VF arrest.


Neurogenic diabetes insipidus

  • Brain trauma: occasionally may be very mild
  • Iatrogenic: pituitary surgery, radiotherapy to pituitary
  • Tumours: particularly primary pituitary tumours and secondary carcinoma
  • Shock: hypovolaemic or septic. Pregnant women appear to be more susceptible to pituitary apoplexy
  • Electric burns
  • Meningitis
  • Other less common causes include other tumours, granulomata, other infections and thrombosis

Nephrogenic diabetes insipidus



  • Chronic hypercalcaemia
  • Chronic hypokalaemia
  • Drugs:
    - lithium
    – amphotericin B
    – demeclocycline
    – glibenclamide
    – gentamicin
  • Renal disease:
    - post-obstruction
    – pyelonephritis
    – in recovery phase following acute tubular necrosis
    – post transplantation
  • Systemic disorders:
    - polycystic disease
    – sickle cell
    – Sjogren’s syndrome
    – myeloma
    – amyloid
  • Pregnancy:
    - excessive vasopressinase secretion
    – transient DI of pregnancy

Clinical features

  • Polyuria and polydipsia
  • Hyperosmolality only develops if thirst mechanisms or water intake is impaired (eg inadequate fluid replacement in ICU)
  • ± signs of underlying disease


  • plasma and urine osmolalities. Failure of ADH secretion is often partial rather than complete and in this situation there may be a rise in urine osmolality to above plasma osmolality but not to the degree seen in normals. Normal plasma/urine osmolality relationship:

Plasma (mOsm/kg)

Urine (mOsm/kg)

> 288

> 125

> 290

> 200

> 292

> 400

> 294

> 600

  • Failure to concentrate urine adequately suggests either central or nephrogenic DI provided solute diuresis has been excluded and assuming blood urea and glucose are normal. When urea is elevated a corrected osmolality can be calculated substituting a urea measurement of 5 mmol/L. Corrections for hyperglycaemia are less helpful. NB HPA responds to tonicity rather than osmolality.
  • During pregnancy there is a resetting so that plasma sodium and osmolality tend to be lower for any given urine osmolality
  • MRI may help to distinguish primary polydipsia from central DI: presence of hyperintense signal in pituitary consistent with former, absent in latter.
  • response to DDAVP can be used to differentiate neurogenic from nephrogenic DI when neurogenic DI is severe and the patient is dehydrated. Partial forms are difficult to distinguish and the test is unreliable in patients who are able to concentrate their urine to >300 mosmol/kg
  • ADH assay. Concentrations are high/normal in patients with nephrogenic DI and low in those with the neurogenic form


  • major problems in ICU are hypovolaemia and hyperosmolality
  • rapid return to normal osmolality is not always desirable, particularly in patients with cerebral oedema

Mild polyuria (» 3ml/kg/h)

  • probably best to simply replace output with appropriate fluid (usually 5% glucose or water if patient is able to drink) and monitor plasma and urine osmolality
  • consider drug therapy if persistent (>24 h). ADH replacement for patients with neurogenic form.

Severe polyuria (>7 ml/kg/h for 4-6 h)

  • resuscitation with initial aim being to correct intravascular fluid depletion rather than correction of hyperosmolality
  • drug therapy. ADH replacement for patients with neurogenic form.

Drug therapy

ADH therapy

  • aqueous (arginine) vasopressin 5-10 IU SC/IM or by continuous IV infusion (1-2 U/day) Short duration of action decreases risk of cerebral oedema in an unconscious patient in whom recovery of ADH secretion is expected. Although it is a V1 and V2 agonist it is not associated with undesirable V1 effects (eg. coronary vasoconstriction, abdominal and uterine cramps) when given in small IV doses
  • desmopressin (DDAVP). Has specific V2 effects. Parenteral dose: 1-4 m g. Duration of action 8-20 h but there is considerable inter-patient variability. However in individuals the duration of effect is relatively constant. Larger doses are sometimes required in the very early phases of neurogenic DI.

Other drugs

  • thiazides, chlorpropamide, clofibrate and carbamazepine may be useful, particularly in partial neurogenic DI
  • indomethacin and other prostaglandin synthetase inhibitors also reduce polyuria
  • non-hormonal treatment is no suitable for emergency management

Post operative care of patient with DI

  • drink only when thirsty
  • DDAVP 4 mcg IM 12 hourly
  • 3l N/saline per day = 900 mOsm. At urinary osmolality of 750 mOsm/kg NaCl will "occupy" 1250 ml, urea and other solutes will "occupy" 750 ml, leaving 1000 ml available for insensible loss.
  • measure daily plasma osmolality

Transient DI of pregnancy

  • vasopressin resistant DI of pregnancy
  • transient condition caused by excessive placental generated vasopressinase: metabolizes ADH
    - brisk response to DDAVP which is not metabolized by vasopressinase
    +/- associated acute fatty liver and liver failure
  • transient nephrogenic DI of pregnancy also recognized
  • unresponsive to DDAVP
  • normal pregnancy induced elevation of vasopressinase may unmask partial central or nephrogenic DI
    - vasopressinase levels decrease rapidly post partum

Further reading

Vedig AE. Diabetes insipidus. In Oh TE (ed). Intensive Care Manual, 4th ed. Oxford: Butterworth-Heinemann, 1997, p451-459

© Charles Gomersall December 1999


©Charles Gomersall, April, 2014 unless otherwise stated. The author, editor and The Chinese University of Hong Kong take no responsibility for any adverse event resulting from the use of this webpage.
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