Diabetes insipidus

Last updated: April 27, 2022

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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. 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.

  • Prevalence in the US: 3:100,000 [1]
  • Sex: ♀=♂

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 [9]
    • 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.

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


Water deprivation test (confirmatory test) [10]

Primary polydipsia vs. central DI vs. nephrogenic DI
Primary polydipsia (psychogenic polydipsia) Central diabetes insipidus Nephrogenic diabetes insipidus
  • Excessive water intake
  • Decreased ADH release
  • ADH resistance

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)
Water deprivation test results
Desmopressin administration results

The differential diagnoses listed here are not exhaustive.

Treat the underlying condition, ensure sufficient fluid intake, and initiate a low-sodium, low-protein diet.


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