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Diabetes insipidus (DI) is characterized by the decreased ability of the kidneys to concentrate urine.


  • Antidiuretic hormone (ADH) is the primary determinant of free water balance
  • ADH is produced in posterior pituitary and acts on the V2 receptors of the collecting tubules of the kidney
  • ADH alters the permeability of the collecting tubes to control the free water excretion


DI can be due to different distinct mechanisms (Figure 117-1).

Figure 117-1. Mechanisms of Diabetes Insipidus
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  • Rare disease with prevalence of 3 per 100,000 population
  • No significant sex gender difference

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Clinical Presentation
SymptomsClinical findings
  • Adults—Polyuria, polydipsia, nocturia, and craving for ice water
  • Children—Anorexia, growth defects, enuresis, sleep disturbance, fatigue, difficulty at school
  • Infants—Irritability, chronic dehydration, growth retardation, neurologic disturbance, and hyperthermia
  • If thirst mechanism is intact—
  • Hydronephrosis and distended bladder due to excessive urinary volume
  • If no access to free water or damage to hypothalamic thirst center then—
  • Hypernatremia, dehydration, hypertonic encephalopathy, obtundation, coma, seizure, subarachnoid hemorrhage, and intracerebral hemorrhage

Differential Diagnosis


  • Diabetes mellitus
  • Cushing syndrome
  • Lithium
  • Psychogenic polydipsia


Diagnosis (Figure 117-2)


  • No single diagnostic laboratory test
  • 24-hour urine output of less than 2 liters rules out DI
  • Hyperuricemia can be seen as urate clearance is reduced due to reduced V1 stimulation
  • MRI of the pituitary and hypothalamus should be done to rule out mass lesions
    • In T1-weighted MRI, the normally present bright spot in the sella is lost in most DI patients
  • Water deprivation test is the gold standard for diagnosing DI (see Figure 117-2)
    • Check baseline Na+; do not permit oral intake, measure volume and osmolality of each voided urine sample; weigh patient
    • When two consecutive urine osmolality do not vary by more than 10% and the patient has lost 2% of weight, check Na+, urine osmolality and serum vasopressin levels. Then give 2 mg of desmopressin if needed




  • Goal: to prevent nocturnal enuresis and to control polydipsia
  • General: Avoid dehydration by drinking fluids to match the urine output and by providing intravenous fluid replacement with hypo-osmolar fluid

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Treatment of Diabetes Insipidus
VasopressinDesmopressinDiureticsOther agents
  • Has antidiuretic and vasopressor activity
  • Continuous low-dose infusion preserves organs after brain death
  • Antivasopressin antibodies can be formed
  • Caution: can cause myocardial ischemia, therefore concurrent use of nitrates is advisable in susceptible patients
  • Synthetic analog of vasopressin
  • Has markedly reduced pressor activity and is 2000 times more specific for antidiuresis
  • ...

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