Diabetes insipidus

Last updated: May 11, 2023

Summarytoggle arrow icon

Diabetes insipidus (DI) is a condition in which the kidneys cannot effectively concentrate urine, resulting in hypotonic polyuria. Central DI (CDI), the most common form of DI, is caused by decreased hypothalamic production or pituitary release of antidiuretic hormone (ADH), resulting in insufficient levels of circulating ADH. CDI can be primary (idiopathic) or secondary to brain lesions or injury. Nephrogenic DI (NDI) is characterized by ADH resistance and may be hereditary or acquired. Patients with DI typically develop polydipsia in response to excessive fluid loss. Most patients also experience nocturia, which can lead to sleep deprivation and daytime sleepiness. DI is initially diagnosed based on the presence of hypotonic polyuria on a 24-hour urine collection. Subsequently, confirmatory testing (e.g., water deprivation test) can differentiate between CDI, NDI, and primary polydipsia. Patients with DI should be encouraged to compensate for urinary fluid losses with oral fluids. For CDI, pharmacotherapy with desmopressin (a synthetic ADH analogue) may be used. For acquired NDI, management involves treating the underlying cause (e.g., correcting metabolic derangement, relieving obstructive uropathy, or discontinuing the causative drug); the condition is typically reversible within weeks to months, although lithium-induced NDI may be irreversible. In some cases, pharmacotherapy with thiazide diuretics, NSAIDs, or amiloride may be indicated.

Epidemiologytoggle arrow icon

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

Epidemiological data refers to the US, unless otherwise specified.

Etiologytoggle arrow icon

Central diabetes insipidus (CDI) [2]

DI following neurosurgery (e.g., transsphenoidal surgery) is usually transient.

Nephrogenic diabetes insipidus (NDI) [2]

Pathophysiologytoggle arrow icon

  • 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)
  • Hyperosmotic volume contraction [5]
    • 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.

Clinical featurestoggle arrow icon

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

Diagnosticstoggle arrow icon


Initial laboratory studies [2][6]

Subsequent laboratory studies [2][6][7]

Water deprivation test (indirect assessment of ADH activity)

Urine concentrating capacity is assessed during a period of dehydration; desmopressin is then administered to assess response to a synthetic ADH analogue. [2]

Plasma copeptin (direct assessment of ADH activity) [2][7]

  • Circulating plasma copeptin levels reflect circulating ADH levels.
  • Measure random plasma copeptin levels.
    • ≥ 21.4 pmol/L: NDI is confirmed.
    • < 21.4 pmol/L: Obtain stimulated plasma copeptin testing, e.g., hypertonic saline infusion test.

Plasma ADH measurement is not routinely utilized because results are unreliable, as ADH is unstable and has a short half-life ex vivo.

Brain imaging [6][8]

Differential diagnosestoggle arrow icon

Differential diagnosis of polyuria-polydipsia syndromes

See also “Gestational diabetes insipidus.”

Primary polydipsia vs. central DI vs. nephrogenic DI [2][7]
Central diabetes insipidus Nephrogenic diabetes insipidus Primary polydipsia (psychogenic polydipsia)
  • ADH deficiency
  • Subtypes
    • Partial CDI: partial ADH deficiency
    • Complete CDI: complete ADH deficiency
  • ADH resistance
  • Can be complete or partial
  • Compulsive water intake
  • Decreased
  • Normal or increased
  • Normal or decreased
Initial studies Serum sodium
Plasma osmolality
  • High-normal or high
  • Low
Urine osmolality
  • Very low

Indirect assessment of ADH activity

Water deprivation test
After desmopressin administration
  • Not required

Other causes of polyuria and/or polydipsia

The differential diagnoses listed here are not exhaustive.

Managementtoggle arrow icon

The goals of management are to reduce polyuria and polydipsia to improve the patient's quality of life and maintain eunatremia.

General principles [2]

Hypernatremia is rare in the ambulatory setting but may be present in patients with cognitive impairment, adipsic diabetes insipidus, and those who are hospitalized or cannot access water because of mobility impairment. [10]

Central diabetes insipidus [2]

  • Management should be guided by an endocrinologist.
  • Most patients are able to maintain eunatremia through increased oral fluid intake alone.
  • Initiate pharmacotherapy in patients with either:
  • Agents
    • Desmopressin (preferred): synthetic ADH analogue without vasoconstrictive effects
      • Intranasal administration is preferred.
      • Typically at bedtime to relieve nocturia
      • Start at a low dose to reduce the risk of overcorrection.
    • Chlorpropamide (alternative): enhances the effect of ADH and increases its secretion

Most patients with CDI are able to increase their oral fluid intake to maintain eunatremia without pharmacotherapy. However, desmopressin is typically required to relieve bothersome symptoms of polyuria and polydipsia. [6]

Nephrogenic diabetes insipidus [2]

In patients with renal disease, NSAID treatment must be used with caution because of the potential nephrotoxic effects.

Special patient groupstoggle arrow icon

Gestational diabetes insipidus [11]

Referencestoggle arrow icon

  1. Christ-Crain M, Bichet DG, Fenske WK, et al. Diabetes insipidus. Nat Rev Dis Primers. 2019; 5 (1).doi: 10.1038/s41572-019-0103-2 . | Open in Read by QxMD
  2. Garrahy A, Moran C, Thompson CJ. Diagnosis and management of central diabetes insipidus in adults. Clin Endocrinol (Oxf). 2018; 90 (1): p.23-30.doi: 10.1111/cen.13866 . | Open in Read by QxMD
  3. Christ‐Crain M, Winzeler B, Refardt J. Diagnosis and management of diabetes insipidus for the internist: an update. J Intern Med. 2021.doi: 10.1111/joim.13261 . | Open in Read by QxMD
  4. James Quigley, Cliff Shelton, Basil Issa, Sreebala Sripada. Diabetes insipidus in pregnancy. The Obstetrician & Gynaecologist. 2018; 20 (1): p.41-48.doi: 10.1111/tog.12450 . | Open in Read by QxMD
  5. Saborio P, Tipton GA, Chan JCM. Diabetes Insipidus. Pediatrics in Review. 2000; 21 (4): p.122-129.doi: 10.1542/pir.21-4-122 . | Open in Read by QxMD
  6. Kumar, Clark. Kumar and Clark's Clinical Medicine, 9th edition. Elsevier ; 2016
  7. Di Iorgi N, Napoli F, Allegri AEM, et al. Diabetes Insipidus – Diagnosis and Management. Hormone Research in Paediatrics. 2012; 77 (2): p.69-84.doi: 10.1159/000336333 . | Open in Read by QxMD
  8. Tobias A, Mohiuddin SS. Physiology, Water Balance. StatPearl. 2020.
  9. Gubbi S, Hannah-Shmouni F, Koch CA, et al. Diagnostic Testing for Diabetes Insipidus. Endotext. 2000.
  10. Tomkins M, Lawless S, Martin-Grace J, Sherlock M, Thompson CJ. Diagnosis and Management of Central Diabetes Insipidus in Adults. J Clin Endocrinol Metab. 2022; 107 (10): p.2701-2715.doi: 10.1210/clinem/dgac381 . | Open in Read by QxMD
  11. Becker KL, Bilezikian JP, Bremner WJ, et al . Principles and Practice of Endocrinology and Metabolism. Lippincott Williams & Wilkins ; 2001

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