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Journal of Pediatric Endocrinology and Metabolism

Editor-in-Chief: Kiess, Wieland

Ed. by Bereket, Abdullah / Darendeliler, Feyza / Dattani, Mehul / Gustafsson, Jan / Luo, Fei Hong / Mericq, Veronica / Toppari, Jorma

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Volume 29, Issue 1


Diabetes insipidus in children

Vandana Jain
  • Corresponding author
  • Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Aathira Ravindranath
  • Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2015-09-03 | DOI: https://doi.org/10.1515/jpem-2014-0518


Diabetes insipidus (DI) is one of the common disorders affecting sodium and water homeostasis, and results when ADH is either inadequately produced, or unable to negotiate its actions on the renal collecting tubules through aquaporins. The diagnostic algorithm starts with exclusion of other causes of polyuria and establishing low urine osmolality in the presence of high serum osmolality. In this paper, we have reviewed the diagnosis, etiology and management of DI in children, with special emphasis on recent advances in the field.

Keywords: antidiuretic hormone; apelin; aquaporin; diabetes insipidus; hypernatremia; polyuria; water deprivation test


  • 1.

    Lindholm J. Diabetes insipidus: historical aspects. Pituitary 2004;7:33–8.CrossrefGoogle Scholar

  • 2.

    Kaplan LJ, Kellum JA. Fluids, pH, ions and electrolytes. Curr Opin Crit Care 2010;16:323–31.CrossrefWeb of ScienceGoogle Scholar

  • 3.

    Fitzsimons JT. Physiology and pathophysiology of thirst and sodium appetite. In: Seldin DW, Giebisch G, editors. The kidney. Physiology and Pathophysiology. New York: Raven Press, 1992:1615–48.Google Scholar

  • 4.

    Thompson CJ, Bland J, Burd J, Baylis PH. The osmotic thresholds for thirst and vasopressin release are similar in healthy man. Clin Sci (Lond) 1986;71:651–6.Google Scholar

  • 5.

    Barat C, Simpson L, Breslow E. Properties of human vasopressin precursor constructs: inefficient monomer folding in the absence of copeptin as a potential contributor to diabetes insipidus. Biochemistry 2004;43:8191–203.CrossrefGoogle Scholar

  • 6.

    Stricker EM, Verbalis JG. Water and salt intake and body fluid homeostasis. In: Squire LR, Berg D, Bloom FE, du Lac S, Ghosh A, et al. editors. Fundamental neuroscience, 4th ed. Waltham, MA: Academic Press, 2013:783–97.Google Scholar

  • 7.

    Robertson GL. The regulation of vasopressin function in health and disease. Recent Prog Horm Res 1976;33:333–85.Google Scholar

  • 8.

    De Mota N, Reaux-Le Goazigo A, El Messari S, Chartrel N, Roesch D, et al. Apelin, a potent diuretic neuropeptide counteracting vasopressin actions through inhibition of vasopressin neuron activity and vasopressin release. Proc Natl Acad Sci USA 2004;101:10464–9.Google Scholar

  • 9.

    Hus-Citharel A, Bodineau L, Frugière A, Joubert F, Bouby N, et al. Apelin counteracts vasopressin-induced water reabsorption via cross talk between apelin and vasopressin receptor signaling pathways in the rat collecting duct. Endocrinology 2014;155:4483−93.Web of ScienceGoogle Scholar

  • 10.

    Bodineau L, Hus-Citharel A, Llorens-Cortes C. Contribution of apelin to water balance, blood glucose control, and cardiovascular functions. Ann Endocrinol (Paris) 2010;71:249−56.Web of ScienceGoogle Scholar

  • 11.

    Knepper MA. Molecular physiology of urinary concentrating mechanism: regulation of aquaporin water channels by vasopressin. Am J Physiol 272;1997:F3–12.Google Scholar

  • 12.

    Muglia LJ, Majzoub JA. Disorders of posterior pituitary. In: Sperling MA, editor. Pediatric endocrinology, 3rd ed. Philadelphia: Saunders Elsevier, 2008:335−6.Google Scholar

  • 13.

    Juul KV, Schroeder M, Rittig S, Nørgaard JP. 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;99:2181−7.Google Scholar

  • 14.

    Yadav J, Satapathy A, Jain V. Endocrine causes of disturbed sodium and water homeostasis. In: Jain V, Menon RK, editors. Case based reviews in pediatric endocrinology, 1st ed. New Delhi: Jaypee, 2014:157−68.Google Scholar

  • 15.

    Birk J, Friberg MA, Prescianotto-Baschong C, Spiess M, Rutishauser J. Dominant pro-vasopressin mutants that cause diabetes insipidus form disulfide-linked fibrillar aggregates in the endoplasmic reticulum. J Cell Sci 2009;122:3994–4002.Web of ScienceGoogle Scholar

  • 16.

    Pivonello R, De Bellis A, Faggiano A, Di Salle F, Petretta M, 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;88:1629–36.CrossrefGoogle Scholar

  • 17.

    Maghnie M, Ghirardello S, De Bellis A, di Iorgi N, Ambrosini L, et al. Idiopathic central diabetes insipidus in children and young adults is commonly associated with vasopressin-cell antibodies and markers of autoimmunity. Clin Endocrinol 2006;65:470–8.Web of ScienceGoogle Scholar

  • 18.

    Maghnie M, Altobelli M, Di Iorgi N, Genovese E, Meloni G, et al. Idiopathic central diabetes insipidus is associated with abnormal blood supply to the posterior pituitary gland caused by vascular impairment of the inferior hypophyseal artery system. J Clin Endocrinol Metab 2004;89:1891–6.Google Scholar

  • 19.

    Borenstein-Levin L, Koren I, Kugelman A, Bader D, Toropine A, et al. Post-hemorrhagic hydrocephalus and diabetes insipidus in preterm infants. J Pediatr Endocrinol Metab 2014;27:1261−3.Web of ScienceGoogle Scholar

  • 20.

    Janus DM, Wojcik M, Górska AZ, Wyrobek L, Urbanik A, et al. Adipsic diabetes insipidus in pediatric patients. Indian J Pediatr 2014;81:1307–14.Web of ScienceGoogle Scholar

  • 21.

    Kamsteeg EJ, Wormhoudt TA, Rijss JP, van Os CH, Deen PM. An impaired routing of wild-type aquaporin-2 after tetramerization with an aquaporin-2 mutant explains dominant nephrogenic diabetes insipidus. EMBO J 1999;18:2394−400.CrossrefGoogle Scholar

  • 22.

    Deen PM, Croes H, van Aubel RA, Ginsel LA, van Os CH.Water channels encoded by mutant aquaporin-2 genes in nephrogenic diabetes insipidus are impaired in their cellular routing. J Clin Invest 1995;95:2291−6.Google Scholar

  • 23.

    Sands JM, Blount MA, Klein JD. Regulation of renal urea transport by vasopressin. Trans Am Clin Climatol Assoc 2011;122:82–92.Google Scholar

  • 24.

    Crowley RK, Sherlock M, Agha A, Smith D, Thompson CJ. Clinical insights into adipsic diabetes insipidus: a large case series. Clin Endocrinol (Oxf) 2007;66:475−82.Web of ScienceGoogle Scholar

  • 25.

    Medlej R, Wasson J, Baz P, Azar S, Salti I, et al. Diabetes mellitus and optic atrophy: a study of Wolfram syndrome in the Lebanese population. J Clin Endocrinol Metab 2004;89:1656–61.Google Scholar

  • 26.

    Leger J, Velasquez A, Garel C, Hassan M, Czernichow P. Thickened pituitary stalk on magnetic resonance imaging in children with central diabetes insipidus. J Clin Endocrinol Metab 1999;84:1954–60.Google Scholar

  • 27.

    Maghnie M, Cosi G, Genovese E, Manca-Bitti ML, Cohen A, et al. Central diabetes insipidus in children and young adults. N Engl J Med 2000;343:998–1007.Google Scholar

  • 28.

    Di Iorgi N, Allegri AE, Napoli F, Calcagno A, Calandra E, et al. Central diabetes insipidus in children and young adults: etiological diagnosis and long-term outcome of idiopathic cases. J Clin Endocrinol Metab 2014;99:1264−72.Web of ScienceGoogle Scholar

  • 29.

    Leger J, Velasquez A, Garel C, Hassan M, Czernichow P. Thickened pituitary stalk on magnetic resonance imaging in children with central diabetes insipidus. J Clin Endocrinol Metab 1999;84:1954−60.Google Scholar

  • 30.

    Di Iorgi N, Napoli F, Allegri AE, Olivieri I, Bertelli E, et al. Diabetes insipidus–diagnosis and management. Horm Res Paediatr 2012;77:69−84.CrossrefGoogle Scholar

  • 31.

    Babey M, Kopp P, Robertson GL. Familial forms of diabetes insipidus: clinical and molecular characteristics. Nat Rev Endocrinol 2011;7:701−14.CrossrefWeb of ScienceGoogle Scholar

  • 32.

    Srivatsa A, Majzoub JA. Disorders of water homeostasis. In: Lifshitz F, editor. Pediatric endocrinology, 5th ed. New York: Informa Healthcare, 2007:651−92.Google Scholar

  • 33.

    Vande Walle J, Stockner M, Raes A, Norgaard JP. Desmopressin 30 years in clinical use: a safety review. Curr Drug Saf 2007;2:232–8.Google Scholar

  • 34.

    Jakobsson B, Berg U. Effect of hydrochlorothiazide and indomethacin treatment on renal function in nephrogenic diabetes insipidus. Acta Paediatr 1994;83:522−5.CrossrefGoogle Scholar

  • 35.

    Seckl JR, Dunger DB. Diabetes insipidus. Current treatment recommendations. Drugs 1992;44:216–24.Google Scholar

  • 36.

    Mishra G, Chandrashekhar SR. Management of diabetes insipidus in children. Indian J Endocrinol Metab 2011;15:S180−7.Google Scholar

  • 37.

    Los EL, Deen PM, Robben JH. Potential of nonpeptide (ant)agonists to rescue vasopressin V2 receptor mutants for the treatment of X-linked nephrogenic diabetes insipidus. J Neuroendocrinol 2010;22:393−9.CrossrefGoogle Scholar

  • 38.

    Sanches TR, Volpini RA, Massola Shimizu MH, Bragança AC, Oshiro-Monreal F, et al. Sildenafil reduces polyuria in rats with lithium-induced NDI. Am J Physiol Renal Physiol 2012;302:F216−25.Web of ScienceGoogle Scholar

  • 39.

    Féraille E, Dizin E, Roth I, Derouette JP, Szanto I, et al. NADPH oxidase 4 deficiency reduces aquaporin-2 mRNA expression in cultured renal collecting duct principal cells via increased PDE3 and PDE4 activity. PLoS One 2014;9:e87239.Google Scholar

  • 40.

    Wade JB. Statins affect AQP2 traffic. Am J Physiol Renal Physiol 2011;301:F308.Google Scholar

About the article

Corresponding author: Vandana Jain, Additional Professor, Division of Pediatric Endocrinology, Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India, Phone: +91 9810167265, E-mail:

Received: 2015-01-29

Accepted: 2015-07-27

Published Online: 2015-09-03

Published in Print: 2016-01-01

Citation Information: Journal of Pediatric Endocrinology and Metabolism, Volume 29, Issue 1, Pages 39–45, ISSN (Online) 2191-0251, ISSN (Print) 0334-018X, DOI: https://doi.org/10.1515/jpem-2014-0518.

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