Highlights & Basics
- Arginine vasopressin deficiency (AVP-D; previously known as central diabetes insipidus) or resistance (AVP-R; previously known as nephrogenic diabetes insipidus) are disorders characterized by polydipsia, polyuria, and formation of inappropriately hypotonic (dilute) urine due to renal water loss.
- AVP-D occurs due to reduced synthesis or release of AVP from the hypothalamo-pituitary axis. AVP-R occurs due to renal insensitivity to AVP.
- Recognized risk factors for AVP-D include pituitary surgery, craniopharyngioma, infiltrative pituitary stalk lesions, traumatic brain injury, subarachnoid hemorrhage, congenital hypothalamo-pituitary defects, autoimmune disorders, and Wolfram syndrome (also called DIDMOAD [diabetes insipidus, diabetes mellitus, optic atrophy, and deafness] syndrome). Risk factors for AVP-R include lithium therapy, chronic kidney disease, and chronic hypercalcemia or hypokalemia. Genetic mutations are responsible for inherited forms of both types.
- Both AVP-D and AVP-R may be associated with hypernatremia, and this may present as a medical emergency. Significant hypernatremia usually only occurs in these conditions in association with adipsia (loss of thirst perception) or impaired access to free water.
- Treatment goals are correction and stabilization of water deficit and electrolyte balance, together with reduction in symptoms of excessive urinary water loss and thirst. In AVP-D, the synthetic AVP analog desmopressin (also known as DDAVP) is the treatment of choice. The mainstay of treatment for AVP-R is adequate fluid intake to match output and insensible losses. Salt restriction and diuretics may help reduce polyuria.
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Citations
Christ-Crain M, Bichet DG, Fenske WK, et al. Diabetes insipidus. Nat Rev Dis Primers. 2019 Aug 8;5(1):54.[Abstract]
Tomkins M, Lawless S, Martin-Grace J, et al. Diagnosis and management of central diabetes insipidus in adults. J Clin Endocrinol Metab. 2022 Sep 28;107(10):2701-15.[Abstract][Full Text]
Kavanagh C, Uy NS. Nephrogenic diabetes insipidus. Pediatr Clin North Am. 2019 Feb;66(1):227-34.[Abstract]
Bockenhauer D, Bichet DG. Pathophysiology, diagnosis and management of nephrogenic diabetes insipidus. Nat Rev Nephrol. 2015 Oct;11(10):576-88.[Abstract]
Knepper MA, Kwon TH, Nielsen S. Molecular physiology of water balance. N Engl J Med. 2015 Apr 2;372(14):1349-58.[Abstract]
1. Christ-Crain M, Bichet DG, Fenske WK, et al. Diabetes insipidus. Nat Rev Dis Primers. 2019 Aug 8;5(1):54.[Abstract]
2. Arima H, Cheetham T, Christ-Crain M, et al. Changing the name of diabetes insipidus: a position statement of the working group for renaming diabetes insipidus. J Clin Endocrinol Metab. 2022 Dec 17;108(1):1-3.[Abstract][Full Text]
3. Tomkins M, Lawless S, Martin-Grace J, et al. Diagnosis and management of central diabetes insipidus in adults. J Clin Endocrinol Metab. 2022 Sep 28;107(10):2701-15.[Abstract][Full Text]
4. Adams NC, Farrell TP, O'Shea A, et al. Neuroimaging of central diabetes insipidus - when, how and findings. Neuroradiology. 2018 Oct;60(10):995-1012.[Abstract]
5. Kavanagh C, Uy NS. Nephrogenic diabetes insipidus. Pediatr Clin North Am. 2019 Feb;66(1):227-34.[Abstract]
6. Aleksandrov N, Audibert F, Bedard MJ, et al. Gestational diabetes insipidus: a review of an underdiagnosed condition. J Obstet Gynaecol Can. 2010 Mar;32(3):225-31.[Abstract]
7. Weiner A, Vuguin P. Diabetes Insipidus. Pediatr Rev. 2020 Feb;41(2):96-99.[Abstract][Full Text]
8. Di Iorgi N, Napoli F, Allegri AE, et al. Diabetes insipidus - diagnosis and management. Horm Res Paediatr. 2012;77(2):69-84.[Abstract][Full Text]
9. Grünfeld JP, Rossier BC. Lithium nephrotoxicity revisited. Nat Rev Nephrol. 2009 May;5(5):270-6.[Abstract]
10. Bockenhauer D, Bichet DG. Pathophysiology, diagnosis and management of nephrogenic diabetes insipidus. Nat Rev Nephrol. 2015 Oct;11(10):576-88.[Abstract]
11. Ananthakrishnan S. Diabetes insipidus during pregnancy. Best Pract Res Clin Endocrinol Metab. 2016 Mar;30(2):305-15.[Abstract]
12. Lindsay RS, Seckl JR, Padfield PL. The triple-phase response - problems of water balance after pituitary surgery. Postgrad Med J. 1995 Jul;71(837):439-41.[Abstract][Full Text]
13. Ghirardello S, Hopper N, Albanese A, et al. Diabetes insipidus in craniopharyngioma: postoperative management of water and electrolyte disorders. J Pediatr Endocrinol Metab. 2006 Apr;19 Suppl 1:413-21.[Abstract]
14. Smith D, Finucane F, Phillips J, et al. Abnormal regulation of thirst and vasopressin secretion following surgery for craniopharyngioma. Clin Endocrinol (Oxf). 2004 Aug;61(2):273-9.[Abstract]
15. Agha A, Thornton E, O'Kelly P, et al. Posterior pituitary dysfunction after traumatic brain injury. J Clin Endocrinol Metab. 2004 Dec;89(12):5987-92.[Abstract][Full Text]
16. Agha A, Sherlock M, Phillips J, et al. The natural history of post-traumatic neurohypophysial dysfunction. Eur J Endocrinol. 2005 Mar;152(3):371-7.[Abstract][Full Text]
17. Donadieu J, Rolon MA, Thomas C, et al; French LCH Study Group. Endocrine involvement in pediatric-onset Langerhans' cell histiocytosis: a population-based study. J Pediatr. 2004 Mar;144(3):344-50.[Abstract]
18. Pal R, Rai A, Vaiphei K, et al. Intracranial germinoma masquerading as secondary granulomatous hypophysitis: a case report and review of literature. Neuroendocrinology. 2019 Jul 4 [Epub ahead of print].[Abstract]
19. Sirinvaravong S, Vibhatavata P, Chunharojrith P, et al. Diabetes insipidus and panhypopituitarism as a first presentation of silent adenocarcinoma of lung: a case report and literature review. BMC Endocr Disord. 2019 Oct 29;19(1):114.[Abstract][Full Text]
20. Porter N, Beynon HL, Randeva HS. Endocrine and reproductive manifestations of sarcoidosis. QJM. 2003 Aug;96(8):553-61.[Abstract][Full Text]
21. Santana MF, João GA, Lacerda MV, et al. Diabetes insipidus secondary to tuberculous meningoencephalitis with hypothalamic involvement extending to the hypophysis: a case report. Rev Soc Bras Med Trop. 2018 Nov-Dec;51(6):865-7.[Abstract][Full Text]
22. Domiciano DS, de Carvalho JF, Macedo AR, et al. Central diabetes insipidus induced by tuberculosis in a rheumatoid arthritis patient. Acta Reumatol Port. 2010 Apr-Jun;35(2):232-5.[Abstract][Full Text]
23. Bando H, Iguchi G, Fukuoka H, et al. The prevalence of IgG4-related hypophysitis in 170 consecutive patients with hypopituitarism and/or central diabetes insipidus and review of the literature. Eur J Endocrinol. 2013 Dec 21;170(2):161-72.[Abstract][Full Text]
24. Maghnie M, Cosi G, Genovese E, et al. Central diabetes insipidus in children and young adults. N Engl J Med. 2000 Oct 5;343(14):998-1007.[Abstract][Full Text]
25. Liu W, Hou J, Liu X, et al. Causes and follow-up of central diabetes insipidus in children. Int J Endocrinol. 2019 Mar 27;2019:5303765.[Abstract][Full Text]
26. Di Iorgi N, Allegri AE, Napoli F, et al. Central diabetes insipidus in children and young adults: etiological diagnosis and long-term outcome of idiopathic cases. J Clin Endocrinol Metab. 2014 Apr;99(4):1264-72.[Abstract]
27. Schaefers J, Cools M, De Waele K, et al. Clinical presentation and outcome of children with central diabetes insipidus associated with a self-limited or transient pituitary stalk thickening, diagnosed as infundibuloneurohypophysitis. Clin Endocrinol (Oxf). 2017 Aug;87(2):171-6.[Abstract][Full Text]
28. Pivonello R, De Bellis A, Faggiano A, et al. Central diabetes insipidus and autoimmunity: relationship between the occurrence of antibodies to arginine vasopressin-secreting cells and clinical, immunological, and radiological features in a large cohort of patients with central diabetes insipidus of known and unknown etiology. J Clin Endocrinol Metab. 2003 Apr;88(4):1629-36.[Abstract][Full Text]
29. Canton A, Simo R, Mesa J, et al. Central diabetes insipidus: a complication of herpes simplex encephalitis. J Neurol Neurosurg Psychiatry. 1996 Sep;61(3):325-6.[Abstract][Full Text]
30. Franco-Paredes C, Evans J, Jurado R. Diabetes insipidus due to Streptococcus pneumoniae meningitis. Arch Intern Med. 2001 Apr 23;161(8):1114-5.[Abstract]
31. Hannon MJ, Finucane FM, Sherlock M, et al. Clinical review: disorders of water homeostasis in neurosurgical patients. J Clin Endocrinol Metab. 2012 May;97(5):1423-33.[Abstract][Full Text]
32. Liamis G, Milionis HJ, Elisaf M. A review of drug-induced hypernatraemia. NDT Plus. 2009 Oct;2(5):339-46.[Abstract][Full Text]
33. Faje AT, Nachtigall L, Wexler D, et al. Central diabetes insipidus: a previously unreported side effect of temozolomide. J Clin Endocrinol Metab. 2013 Oct;98(10):3926-31.[Abstract][Full Text]
34. Misgar RA, Rasool A, Wani AI, et al. Central diabetes insipidus (Infundibuloneuro hypophysitis): a late complication of COVID-19 infection. J Endocrinol Invest. 2021 Dec;44(12):2855-6.[Full Text]
35. Menotti S, di Filippo L, Terenzi U, et al. Hypophysitis in COVID-19: a systematic review. Pituitary. 2024 Dec;27(6):874-88.[Abstract]
36. Jiao T, Huang Y, Sun H, et al. Research progress of post-acute sequelae after SARS-CoV-2 infection. Cell Death Dis. 2024 Apr 11;15(4):257.[Abstract][Full Text]
37. Taieb A, Nassim BHS, Asma G, et al. The growing understanding of the pituitary implication in the pathogenesis of long COVID-19 syndrome: a narrative review. Adv Respir Med. 2024 Feb 14;92(1):96-109.[Abstract][Full Text]
38. Chang MY, Lin JL. Central diabetes insipidus following carbon monoxide poisoning. Am J Nephrol. 2001 Mar-Apr;21(2):145-9.[Abstract]
39. Fujiwara TM, Bichet DG. Molecular biology of hereditary diabetes insipidus. J Am Soc Nephrol. 2005 Oct;16(10):2836-46.[Abstract]
40. Werny D, Elfers C, Perez FA, et al. Pediatric central diabetes insipidus: brain malformations are common and few patients have idiopathic disease. J Clin Endocrinol Metab. 2015 Aug;100(8):3074-80.[Abstract][Full Text]
41. Rigoli L, Bramanti P, Di Bella C, et al. Genetic and clinical aspects of Wolfram syndrome 1, a severe neurodegenerative disease. Pediatr Res. 2018 May;83(5):921-9.[Abstract][Full Text]
42. Pallotta MT, Tascini G, Crispoldi R, et al. Wolfram syndrome, a rare neurodegenerative disease: from pathogenesis to future treatment perspectives. J Transl Med. 2019 Jul 23;17(1):238.[Abstract][Full Text]
43. Ott M, Forssén B, Werneke U. Lithium treatment, nephrogenic diabetes insipidus and the risk of hypernatraemia: a retrospective cohort study. Ther Adv Psychopharmacol. 2019;9:2045125319836563.[Abstract][Full Text]
44. Jacob AT, Kumar AH, Halivana G, et al. Bioinformatics-guided disproportionality analysis of sevoflurane-induced nephrogenic diabetes insipidus using the FDA adverse event reporting system database. Br J Clin Pharmacol. 2024 Aug;90(8):1804-10.[Abstract][Full Text]
45. Milano S, Carmosino M, Gerbino A, et al. Hereditary nephrogenic diabetes insipidus: pathophysiology and possible treatment. An update. Int J Mol Sci. 2017 Nov 10;18(11):E2385.[Abstract][Full Text]
46. Lindheimer MD, Davison JM. Osmoregulation, the secretion of arginine vasopressin and its metabolism during pregnancy. Eur J Endocrinol. 1995 Feb;132(2):133-43.[Abstract]
47. Ananthakrishnan S. Gestational diabetes insipidus: Diagnosis and management. Best Pract Res Clin Endocrinol Metab. 2020 Sep;34(5):101384.[Abstract][Full Text]
48. Knepper MA, Kwon TH, Nielsen S. Molecular physiology of water balance. N Engl J Med. 2015 Apr 2;372(14):1349-58.[Abstract]
49. Verbalis JG. Disorders of body water homeostasis. Best Pract Res Clin Endocrinol Metab. 2003 Dec;17(4):471-503.[Abstract]
50. Christ-Crain M. Vasopressin and copeptin in health and disease. Rev Endocr Metab Disord. 2019 Sep;20(3):283-94.[Abstract]
51. Brooks EK, Inder WJ. Disorders of salt and water balance after pituitary surgery. J Clin Endocrinol Metab. 2022 Dec 17;108(1):198-208.[Abstract][Full Text]
52. Yamamoto M, Iguchi G, Bando H, et al. Autoimmune pituitary disease: new concepts with clinical implications. Endocr Rev. 2020 Apr 1;41(2):bnz003.[Abstract][Full Text]
53. Mishra G, Chandrashekhar SR. Management of diabetes insipidus in children. Indian J Endocrinol Metab. 2011 Sep;15 Suppl 3(suppl3):S180-7.[Abstract][Full Text]
54. Baldeweg SE, Ball S, Brooke A, et al; Society for Endocrinology Clinical Committee. Society for Endocrinology clinical guidance: inpatient management of cranial diabetes insipidus. Endocr Connect. 2018 Jul;7(7):G8-11.[Abstract][Full Text]
55. Adrogué HJ, Madias NE. Hypernatremia. N Engl J Med. 2000 May 18;342(20):1493-9.[Abstract]
56. Fleseriu M, Christ-Crain M, Langlois F, et al. Hypopituitarism. Lancet. 2024 Jun 15;403(10444):2632-48.[Abstract]
57. Fenske W, Quinkler M, Lorenz D, et al. Copeptin in the differential diagnosis of the polydipsia-polyuria syndrome - revisiting the direct and indirect water deprivation tests. J Clin Endocrinol Metab. 2011 May;96(5):1506-15.[Abstract][Full Text]
58. Fenske W, Refardt J, Chifu I, et al. A copeptin-based approach in the diagnosis of diabetes insipidus. N Engl J Med. 2018 Aug 2;379(5):428-39.[Abstract][Full Text]
59. Timper K, Fenske W, Kühn F, et al. Diagnostic accuracy of copeptin in the differential diagnosis of the polyuria-polydipsia syndrome: a prospective multicenter study. J Clin Endocrinol Metab. 2015 Jun;100(6):2268-74.[Abstract][Full Text]
60. Refardt J, Vogt DR, Christ-Crain M. Arginine or hypertonic saline-stimulated copeptin to diagnose AVP deficiency. Reply. N Engl J Med. 2024 Jan 18;390(3):289-90.
61. Shin JH, Lee HK, Choi CG, et al. MR imaging of central diabetes insipidus: a pictorial essay. Korean J Radiol. 2001 Oct-Dec;2(4):222-30.[Abstract]
62. Tudor RM, Thompson CJ. Posterior pituitary dysfunction following traumatic brain injury: review. Pituitary. 2019 Jun;22(3):296-304.[Abstract]
63. Garrahy A, Moran C, Thompson CJ. Diagnosis and management of central diabetes insipidus in adults. Clin Endocrinol (Oxf). 2019 Jan;90(1):23-30.[Abstract][Full Text]
64. Expert Panel on Neurologic Imaging; Burns J, Policeni B, et al. ACR appropriateness criteria(®) neuroendocrine imaging. J Am Coll Radiol. 2019 May;16(5s):S161-73.[Abstract][Full Text]
65. American College of Radiology. ACR appropriateness criteria: neuroendocrine imaging. 2018 [internet publication].[Full Text]
66. The Royal Children's Hospital Melbourne. Diabetes insipidus. Mar 2011 [internet publication].[Full Text]
67. Baylis PH, Cheetham T. Diabetes insipidus. Arch Dis Child. 1998 Jul;79(1):84-9.[Abstract][Full Text]
68. Robinson AG. DDAVP in the treatment of central diabetes insipidus. N Engl J Med. 1976 Mar 4;294(10):507-11.[Abstract][Full Text]
69. Toumba M, Stanhope R. Morbidity and mortality associated with vasopressin analogue treatment. J Pediatr Endocrinol Metab. 2006 Mar;19(3):197-201.[Abstract]
70. Bendz H, Aurell M. Drug-induced diabetes insipidus: incidence, prevention and management. Drug Saf. 1999 Dec;21(6):449-56.[Abstract]
71. Fleseriu M, Hashim IA, Karavitaki N, et al. Hormonal replacement in hypopituitarism in adults: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016 Nov;101(11):3888-921.[Abstract][Full Text]
72. Sharma S, Ashton E, Iancu D, et al. Long-term outcome in inherited nephrogenic diabetes insipidus. Clin Kidney J. 2019 Apr;12(2):180-7.[Abstract][Full Text]
73. Shalev H, Romanovsky I, Knoers NV, et al. Bladder function impairment in aquaporin-2 defective nephrogenic diabetes insipidus. Nephrol Dial Transplant. 2004 Mar;19(3):608-13.[Abstract][Full Text]
74. Crowley RK, Sherlock M, Agha A, et al. Clinical insights into adipsic diabetes insipidus: a large case series. Clin Endocrinol (Oxf). 2007 Apr;66(4):475-82.[Abstract]
75. Grant PJ, Tate GM, Hughes JR, et al. Does hypernatremia promote thrombosis? Thromb Res. 1985 Nov 1;40(3):393-9.[Abstract]
76. Juul KV, Schroeder M, Rittig S, et al. National Surveillance of Central Diabetes Insipidus (CDI) in Denmark: results from 5 years registration of 9309 prescriptions of desmopressin to 1285 CDI patients. J Clin Endocrinol Metab. 2014 Jun;99(6):2181-7.[Abstract][Full Text]
77. National Organization for Rare Disorders. Nephrogenic diabetes insipidus. Jun 2023 [internet publication].[Full Text]
78. Barbot M, Ceccato F, Zilio M, et al. Cardiovascular autonomic dysfunction in patients with idiopathic diabetes insipidus. Pituitary. 2018 Feb;21(1):50-5.[Abstract]
