• Clinical science

Diabetes insipidus


Diabetes insipidus (DI) is a condition in which the kidneys are unable to concentrate urine. Central DI, the most common form of diabetes insipidus, is caused by insufficient levels of circulating antidiuretic hormone (ADH); nephrogenic DI, however, is characterized by defective renal ADH receptors in the kidneys. Patients with DI excrete large quantities of diluted urine (polyuria), which causes excessive thirst (polydipsia) in response to fluid loss. Additionally, patients develop the need to urinate at night (nocturia), leading to sleep deprivation and daytime sleepiness. Desmopressin, a synthetic ADH analog, is the treatment of choice in central DI. In nephrogenic DI, hereditary forms are treated with thiazide diuretics or NSAIDs, while acquired forms are first managed by treating the underlying disease.



Epidemiological data refers to the US, unless otherwise specified.




  • ADH enables the integration of aquaporins into the plasma membrane of collecting duct cells → reabsorption of free water
  • Either ADH (central DI) or defective renal ADH receptors (nephrogenic DI) → impaired ability of the kidneys to concentrate urine (hypotonic collecting ducts) → dilute urine (low urine osmolarity)
  • Urine osmolality changes
    • Normal: 500–800 mOsmol/kg
    • Partial DI (300–500 mOsmol/kg)
    • Complete DI (< 300 mOsmol/kg, often < 100 mOsmol/kg)
  • Hyperosmotic volume contraction [12]
    • Loss of fluid with urine increased extracellular fluid osmolarity → passage of fluid from the intracellular to the extracellular space → equalization of the osmolarities of the extracellular and intracellular fluid
    • Due to the loss of fluid, the osmolarities of intracellular and extracellular compartments are now higher (hyperosmotic) than the initial values.
    • The fluid volume is redistributed between the two compartments to equalize the osmolarities and remains lower than the initial values in each of them (volume contraction)

Note that in central DI, ADH levels are decreased, while in nephrogenic DI, they are normal or increased to compensate for the high urine output.References:[1][13]

Clinical features

In the absence of nocturia, diabetes insipidus is very unlikely!



Water deprivation test (confirmatory test)

  • After obtaining baseline lab values, patients stop drinking water for 2–3 hours before the first measurement
  • After 2–3 hours without drinking water
  • Water deprivation continues until one of the following occurs:
    • Urine osmolality rises and reaches a normal value (> 600 mOsmol/kg) → DI ruled out and primary polydipsia confirmed
    • No change in urine osmolality despite a rising plasma osmolality (> 290 mOsmol/kg)
    • Plasma osmolality > 295–300 mOsmol/kg or sodium ≥ 145 meq/L
  • In the latter two situations → administer desmopressin (a synthetic ADH analog)
    • Monitor urine osmolality testing every 30 minutes for 2 hours
      • In CDI: Urine osmolality rises after desmopressin administration (renal ADH receptors are intact).
      • In NDI: Urine osmolality remains low after desmopressin administration (defective renal ADH receptors).
Primary polydipsia (psychogenic polydipsia) Central diabetes insipidus Nephrogenic diabetes insipidus

Lab findings on presentation

ADH levels
  • Normal or decreased
  • Decreased
  • Normal or increased
Plasma osmolality
  • Low-normal (255–280 mOsmol/kg)
  • High-normal or slightly elevated (280–290 mOsmol/kg)
Urine osmolality
  • Very low (< 250 mOsmol/kg)
  • Low
    • Partial DI: 300–500 mOsmol/kg
    • Complete DI: < 300 mOsmol/kg
  • Urine specific gravity < 1.006
Water deprivation test results
  • Plasma osmolality: does not raise above normal level (275–290 mOsmol/kg)
  • Urine osmolality: rises, reaches normal value (> 600 mOsmol/kg)
Desmopressin administration results
  • Plasma osmolality remains elevated
  • Urine osmolality remains low
    • In partial NDI: ∼ 10%
    • In complete NDI: no change


Differential diagnoses


The differential diagnoses listed here are not exhaustive.



last updated 11/04/2020
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