Trusted medical expertise in seconds.

Access 1,000+ clinical and preclinical articles. Find answers fast with the high-powered search feature and clinical tools.

Try free for 5 days
Evidence-based content, created and peer-reviewed by physicians. Read the disclaimer.

Diabetes insipidus

Last updated: March 16, 2021

Summarytoggle arrow icon

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.

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

Epidemiological data refers to the US, unless otherwise specified.

References:[4][5][6][7][8]

  • 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.

Approach

Water deprivation test (confirmatory test) [10]

Primary polydipsia vs. central DI vs. nephrogenic DI
Primary polydipsia (psychogenic polydipsia) Central diabetes insipidus Nephrogenic diabetes insipidus
Cause
  • Primary: idiopathic
  • Secondary: brain lesions (e.g., tumors, hypoxic injury, surgery, etc.)
Mechanism
  • Excessive water intake
  • Decreased ADH release
  • ADH resistance

Lab findings on presentation

Sodium
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.

References:[12][13][14][15]

  1. 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
  2. Kumar, Clark. Kumar and Clark's Clinical Medicine, 9th edition. Elsevier ; 2016
  3. 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
  4. Fujiwara TM, Bichet DG. Molecular biology of hereditary diabetes insipidus. J Am Soc Nephrol. 2005; 16 (10): p.2836-2846. doi: 10.1681/ASN.2005040371 . | Open in Read by QxMD
  5. Maghnie M, Cosi G, Genovese E, et al. Central diabetes insipidus in children and young adults. N Engl J Med. 2000; 343 (14): p.998-1007. doi: 10.1056/NEJM200010053431403 . | Open in Read by QxMD
  6. Mao JF, Zhang JL, Nie M, Lu SH, Wu XY. Diabetes insipidus as the first symptom caused by lung cancer metastasis to the pituitary glands: clinical presentations, diagnosis, and management. J Postgrad Med. 2011; 57 (4): p.302-306. doi: 10.4103/0022-3859.90080 . | Open in Read by QxMD
  7. Kimmel DW, O'neill BP. Systemic cancer presenting as diabetes insipidus. Clinical and radiographic features of 11 patients with a review of metastatic-induced diabetes insipidus. Cancer. 1983; 52 (12): p.2355-2358.
  8. Schrager S, Sabo L. Sheehan syndrome: a rare complication of postpartum hemorrhage. J Am Board Fam Pract. 2001; 14 (5): p.389-391.
  9. Tobias A, Mohiuddin SS. Physiology, Water Balance. StatPearl. 2020 .
  10. Mellinger RC, Zafar MS. Primary polydipsia: Syndrome of inappropriate thirst. Arch Intern Med. 1983; 143 (6): p.1249-1251.
  11. Becker KL, Bilezikian JP, Bremner WJ, et al . Principles and Practice of Endocrinology and Metabolism. Lippincott Williams & Wilkins ; 2001
  12. Miller M, Moses AM. Mechanism of chlorpropamide action in diabetes insipidus. J Clin Endocrinol Metab. 2016; 30 (4): p.488-496. doi: 10.1210/jcem-30-4-488 . | Open in Read by QxMD
  13. Loffing J. Paradoxical antidiuretic effect of thiazides in diabetes insipidus: another piece in the puzzle. J Am Soc Nephrol. 2004; 15 (11): p.2948-2950. doi: 10.1097/01.ASN.0000146568.82353.04 . | Open in Read by QxMD
  14. Magaldi AJ. New insights into the paradoxical effect of thiazides in diabetes insipidus therapy. Nephrol Dial Transplant. 2000; 15 (12): p.1903-1905. doi: 10.1093/ndt/15.12.1903 . | Open in Read by QxMD
  15. Kortenoeven ML, Li Y, Shaw S, et al. Amiloride blocks lithium entry through the sodium channel thereby attenuating the resultant nephrogenic diabetes insipidus. Kidney Int. 2009; 76 (1): p.44-53. doi: 10.1038/ki.2009.91 . | Open in Read by QxMD