Diabetes insipidus is a heterogeneous condition characterized by polyuria and polydipsia caused by a lack of secretion of vasopressin, its physiological suppression following excessive water intake, or kidney resistance to its action. In many patients, it is caused by the destruction or degeneration of the neurons that originate in the supraoptic and paraventricular nuclei of the hypothalamus. Known causes of these lesions include: germinoma or craniopharyngioma; Langerhans cell histiocytosis and sarcoidosis of the central nervous system; local inflammatory, autoimmune or vascular diseases; trauma following surgery or accident; and, rarely, genetic defects in vasopressin biosynthesis inherited as autosomal dominant or X-linked recessive traits. Thirty to fifty percent of cases are considered idiopathic. Magnetic resonance imaging (MRI) allows identification of the posterior pituitary hyperintensity and of hypothalamic-pituitary abnormalities. Thickening of the pituitary stalk is the second most common finding on MRI scans in several local inflammatory pathologies and autoimmune diseases or germinoma, but it is not specific to any single subtype. A progressive increase in the size of the anterior pituitary gland should alert physicians to the possibility that a germinoma is present, whereas a decrease can suggest the presence of an inflammatory or autoimmune process. Most children with acquired central diabetes insipidus and a thickened pituitary stalk have anterior pituitary hormone deficiencies during follow-up. Biopsy of enlarged pituitary stalk should be reserved for patients with a hypothalamic-pituitary mass and progressive thickening of the pituitary stalk, since spontaneous recovery may occur.

1.
Robertson GL: Posterior pituitary; in Felig P, Baxter JD, Frohman LA (eds): Endocrinology and Metabolism, ed 3. New York, McGraw-Hill, 1995, pp 385–432.
2.
Robinson AG: Disorders of antidiuretic hormone secretion. Clin Endocrinol Metab 1985;14:55–88.
3.
King LS, Agre P: Pathophysiology of the aquaporin water channels. Ann Rev Physiol 1996;58:619–648.
4.
Engel A, Fujiyoshi Y, Agre P: The importance of aquaporin water channel protein structures. Embo J 2000;19:800–806.
5.
Deen PM, Verdijk MA, Knoers NV, Wieringa B, Monnens LA, van Os CH, van Oost BA: Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine. Science 1994;264:92–95.
6.
Hochberg Z, Van Lieburg A, Even L, Brenner B, Lanir N, Van Oost BA, Knoers NV: Autosomal recessive nephrogenic diabetes insipidus caused by an aquaporin-2 mutation. J Clin Endocrinol Metab 1997;82:686–689.
7.
Kuwahara M, Iwai K, Ooeda T, Igarashi T, Ogawa E, Katsushima Y, Shinbo I, Uchida S, Terada Y, Arthus MF, Lonergan M, Fujiwara TM, Bichet DG, Marumo F, Sasaki S: Three families with autosomal dominant nephrogenic diabetes insipidus caused by aquaporin-2 mutations in the C-terminus. Am J Hum Genet 2001;69:738–748.
8.
Nijenhuis M, van den Akker EL, Zalm R, Franken AA, Abbes AP, Engel H, de Wied D, Burbach JP: Familial neurohypophysial diabetes insipidus in a large Dutch kindred: effect of the onset of diabetes on growth in children and cell biological defects of the mutant vasopressin prohormone. J Clin Endocrinol Metab 2001;86:3410–3420.
9.
Maghnie M, Cosi G, Genovese E, Manca-Bitti ML, Cohen A, Zecca S, Tinelli C, Gallucci M, Bernasconi S, Boscherini B, Severi F, Aricò M: Central diabetes insipidus in children and young adults. N Engl J Med 2000;343:998–1007.
10.
Mootha SL, Barkovich AJ, Grumbach MM, Edwards MS, Gitelman SE, Kaplan SL, Conte FA: Idiopathic hypothalamic diabetes insipidus, pituitary stalk thickening, and the occult intracranial germinoma in children and adolescents. J Clin Endocrinol Metab 1997;82:1362–1367.
11.
Czernichow P, Pomarede R, Brauner R, Rappaport R: Neurogenic diabetes insipidus in children. Front Horm Res 1985;13:190–209.
12.
Sklar CA, Grumbach MM, Kaplan SL, Conte AF: Hormonal and metabolic abnormalities associated with central nervous system germinoma in children and adolescents and the effect of therapy: report of 10 patients. J Clin Endocrinol Metab 1981;52:9–16.
13.
Maghnie M, Villa A, AricÒ M, Larizza D, Pezzotta S, Beluffi G, Genovese E, Severi F: Correlation between magnetic resonance imaging of posterior pituitary and neurohypophysial function in children with diabetes insipidus. J Clin Endocrinol Metab 1992;74:795–800.
14.
Maghnie M, Aricò M, Villa A, Genovese E, Beluffi G, Severi F: MR of the hypothalamic-pituitary axis in Langerhans cell histiocytosis. Am J Neuroradiol 1992;13:1365–1371.
15.
Maghnie M, Bossi G, Klersy C, Cosi G, Genovese E, Aricò M: Dynamic endocrine testing and magnetic resonance imaging in the long-term follow-up of childhood Langerhans cell histiocytosis. J Clin Endocrinol Metab 1998;83:3089–3094.
16.
Imura H, Nakao K, Shimatsu A, Ogawa Y, Sando T, Fujisawa I, Yamabe H: Lymphocytic infundibuloneurohypophysitis as a cause of central diabetes insipidus. N Engl J Med 1993;329:683–689.
17.
Maghnie M, Genovese E, Sommaruga MG, Aricò M, Locatelli D, Arbustini E, Pezzotta S, Severi F: Evolution of childhood central diabetes insipidus into panhypopituitarism with a large hypothalamic mass: is ‘lymphocytic infundibuloneurohypophysitis’ in children a different entity? Eur J Endocrinol 1998;139:635–640.
18.
Maghnie M, Genovese E, Aricò M, Villa A, Beluffi G, Campani R, Severi F: Evolving pituitary hormone deficiency is associated with pituitary vasculopathy: dynamic MR study in children with hypopituitarism, diabetes insipidus, and Langerhans cell histiocytosis. Radiology 1994;193:493–499.
19.
Verbalis JG, Robinson AG, Moses AM: Postoperative and post-traumatic diabetes insipidus. Front Horm Res 1985;13:247–265.
20.
Traggiai C, Stanhope R: Endocrinopathies associated with midline cerebral and cranial malformations. J Pediatr 2002;140:252–255.
21.
Blotner H: Primary or idiopathic diabetes insipidus: a system disease. Metabolism 1958;3:191–200.
22.
Bode HH: Disorders of posterior pituitary; in Kaplan SA (ed): Clinical Pediatric Endocrinology. Philadelphia, Saunders, 1990, pp 63–86.
23.
Pomarede R, Czernichow P, Rappaport R, Royer P: ADH-deficient diabetes insipidus in children. A study of 93 cases (in French). Arch Fr Pédiatr 1980;37:37–44.
24.
Greger NG, Kirkland RT, Clayton GW, Kirkland JL: Central diabetes insipidus: 22 years’ experience. Am J Dis Child 1986;140:551–554.
25.
Wang LC, Cohen ME, Duffner PK: Etiologies of central diabetes insipidus in children. Pediatr Neurol 1994;11:273–277.
26.
Maghnie M, Sommaruga MG, Beluffi G, Severi F: Role of MR imaging in the evaluation of the functional status of the posterior pituitary gland: the view of a pediatric endocrinologist. Am J Neuroradiol 1993;14:1443–1445.
27.
Brooks BS, El Gammal T, Allison JD, Hoffmann WH: Frequency and variation of the posterior pituitary bright signal on MR images. Am J Neuroradiol 1989;153:1033–1038.
28.
Fujisawa I, Asato R, Okumura R, Nakano Y, Shibata T, Hamanaka D, Hashimoto T, Konishi J: Magnetic resonance imaging of neurohypophysial germinomas. Cancer 1991;68:1009–1014.
29.
Léger 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;84:1954–1960.
30.
Thodou E, Asa SL, Kontogeorgos G, Kovacs K, Horvath E, Ezzat S: Clinical case seminar. Lymphocytic hypophysitis: clinicopathological findings. J Clin Endocrinol Metab 1995;80:2302–2311.
31.
Ahmed SR, Aiello DP, Page R, Hopper K, Towfighi J, Santen RJ: Necrotizing infundibulo-hypophysitis: a unique syndrome of diabetes insipidus and hypopituitarism. J Clin Endocrinol Metab 1993;76:1499–1504.
32.
Scherbaum WA, Bottazzo GF: Autoantibodies to vasopressin cells in idiopathic diabetes insipidus: evidence for an autoimmune variant. Lancet 1983;1:897–901.
33.
De Bellis A, Colao A, Di Salle F, Muccitelli VI, Iorio S, Perrino S, Pivonello R, Coronella C, Bizzarro A, Lombardi G, Bellastella A: A longitudinal study of vasopressin cell antibodies, posterior pituitary function, and magnetic resonance imaging evaluations in subclinical autoimmune central diabetes insipidus. J Clin Endocrinol Metab 1999;84:3047–3051.
34.
Maghnie M, Genovese E, Bernasconi S, Binda S, Aricò M: Persistent high MR signal of the posterior pituitary gland in central diabetes insipidus. Am J Neuroradiol 1997;18:1749–1752.
35.
Willcuts MD, Felner E, White PC: Autosomal recessive familial neurohypophysial diabetes insipidus with continued secretion of mutant weakly active vasopressin. Hum Mol Genet 1999;8:1303–1307.
36.
Grant F, Ahmadi A, Hosley CM, Majzoub JA: Two novel mutations of the vasopressin gene associated with familial diabetes insipidus and identification of an asymptomatic carrier infant. J Clin Endocrinol Metab 1998;83:3958–3964.
37.
Browntein MJ, Russell JT, Gainer H: Synthesis, transport and release of posterior pituitary hormones. Science 1980;207:373–378.
38.
Land H, Schütz G, Schmale H, Richter D: Nucleotide sequence of cloned cDNA encoding bovine arginine vasopressin-neurophysin II precursor. Nature 1982;295:299–303.
39.
Land H, Grez M, Ruppert S, Schmale H, Rehbein M, Richter D, Schutz G: Deduced amino acid sequence from the bovine oxytocin-neurophysin I precursor cDNA. Nature 1983;302:342–344.
40.
Braverman LE, Mancini JP, McGoldrick DM: Hereditary and idiopathic diabetes insipidus. A case report with autopsy findings. Ann Intern Med 1965;63:503–508.
41.
Green JR, Buchan GC, Alvord EC, Swanson AG: Hereditary and idiopathic types of diabetes insipidus. Brain 1967;90:707–714.
42.
Ito M, Jameson JL, Ito M: Molecular basis of autosomal dominant neurohypophyseal diabetes insipidus. Cellular toxicity caused by the accumulation of mutant vasopressin precursors within the endoplasmic reticulum. J Clin Invest 1997;99:1897–1905.
43.
Strom TM, Hortnagel K, Hofmann S, Gekeler F, Scharfe C, Rabl W, Gerbitz KD, Meitinger T: Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein. Hum Mol Genet 1998;7:2021–2028.
44.
Morello JP, Bichet DG: Nephrogenic diabetes insipidus. Ann Rev Physiol 2001;63:607–630.
45.
King LS, Choi M, Fernandez PC, Cartron J-P, Agre P: Defective urinary concentrating ability due to a complete deficiency of aquaporin-1. N Engl J Med 2001;345:175–179.
46.
Salvatoni A, Maghnie M, Lorini R, Marni E: Hyponatremia and seizures during desmopressin acetate treatment in hypothyroidism. J Pediatr 1990;5:835–836.
47.
Baylis PH, Cheetham T: Diabetes insipidus. Arch Dis Child 1998;79:84–89.
48.
Kanno K, Sasaki S, Hirata Y, Ishikawa S, Fushimi K, Nakanishi S, Bichet DG, Marumo F: Urinary excretion of aquaporin-2 in patients with diabetes insipidus. N Engl J Med 1995;332:1540–1545.
49.
Boulgourdjian EM, Martinez AS, Ropelato MG, Heinrich JJ, Bergada C: Oral desmopressin treatment of central diabetes insipidus in children. Acta Paediatr 1997;86;1261–1262.
50.
Fjellestad-Paulson A, Laborde K, Czernichow P: Water balance hormones during long-term follow-up of oral DDAVP treatment in diabetes insipidus. Acta Paediatr 1993;82:752–757.
51.
Kauli R, Galatzer A, Laron Z: Treatment of diabetes insipidus in children and adolescents; in Czernichow P, Robinson AG (eds): Diabetes Insipidus in Man. Front Horm Res 1985;13:304–313.
52.
Maghnie M, Genovese E, Lundin S, Bonetti F, Aricò M: Iatrogenic extrapontine myelinolysis in central diabetes insipidus: are cyclosporine and 1-desamino-8-D-arginine vasopressin harmful in association? J Clin Endocrinol Metab 1997;82:1749–1751.
53.
Ball SG, Vaidja B, Baylis PH: Hypothalamic adipsic syndrome: diagnosis and management. Clin Endocrinol 1997;47:405–409.
54.
Knoers N, Monnens AH: Amiloride-hydrochlorothiazide versus indomethacin-hydrochlorothiazide in the treatment of nephrogenic diabetes insipidus. J Pediatr 1990;117:499–502.
55.
Kirchlechner V, Koller DY, Seidl R, Waldhauser E: Treatment of nephrogenic diabetes insipidus with hydrochlorothiazide and amiloride. Arch Dis Child 1999;80:548–552.
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