Diabetes insipidus (DI) is a disorder characterized by a high hypotonic urinary output of more than 50ml per kg body weight per 24 hours, with associated polydipsia of more than 3 liters a day [1Robertson GL. Diabetes insipidus Endocrinol Metab Clin North Am 1995 ;  24 : 549-572 [inter-ref]

Cliccare qui per andare alla sezione Riferimenti,2Miller M, Dalakos T, Moses AM, Fellerman H, Streeten DH. Recognition of partial defects in antidiuretic hormone secretion Ann Intern Med 1970 ;  73 : 721-729 [cross-ref]

Cliccare qui per andare alla sezione Riferimenti]. Central DI results from inadequate secretion and usually deficient synthesis of Arginine vasopressin (AVP) in the hypothalamus or pituitary gland. Besides central DI further underlying etiologies of DI can be due to other primary forms (renal origin) or secondary forms of polyuria (resulting from primary polydipsia). All these forms belong to the Polyuria Polydipsia Syndrom (PPS). In most cases central and nephrogenic DI are acquired, but there are also congenital forms caused by genetic mutations of the AVP gene (central DI) [3Babey M, Kopp P, Robertson GL. Familial forms of diabetes insipidus: clinical and molecular characteristics Nat Rev Endocrinol 2011 ;  7 : 701-714 [cross-ref]

Cliccare qui per andare alla sezione Riferimenti] or by mutations in the gene for the AVP V2R or the AQP2 water channel (nephrogenic DI) [4Bockenhauer D, Bichet DG. Pathophysiology, diagnosis and management of nephrogenic diabetes insipidus Nat Rev Nephrol 2015 ;  11 : 576-588 [cross-ref]

Cliccare qui per andare alla sezione Riferimenti]. Primary polydipsia (PP) as secondary form of polyuria includes an excessive intake of large amounts of fluid leading to polyuria in the presence of intact AVP secretion and appropriate antidiuretic renal response.

Differentiation between the three mentioned entities is difficult [5Carter AC, Robbins J. The use of hypertonic saline infusions in the differential diagnosis of diabetes insipidus and psychogenic polydipsia J Clin Endocrinol Metab 1947 ;  7 : 753-766 [cross-ref]

Cliccare qui per andare alla sezione Riferimenti], especially in patients with Primary polydipsia or partial, mild forms of DI [1Robertson GL. Diabetes insipidus Endocrinol Metab Clin North Am 1995 ;  24 : 549-572 [inter-ref]

Cliccare qui per andare alla sezione Riferimenti,6Fenske W, Quinkler M, Lorenz D, Zopf K, Haagen U, Papassotiriou J, e al. Copeptin in the differential diagnosis of the polydipsia-polyuria syndrome–revisiting the direct and indirect water deprivation tests J Clin Endocrinol Metab 2011 ;  96 : 1506-1515 [cross-ref]

Cliccare qui per andare alla sezione Riferimenti], but different tests for differential diagnosis, most recently based on measurement of copeptin, and a thorough medical history mostly lead to the correct diagnosis. This is important since treatment strategies vary and application of the wrong treatment can be dangerous [7Fenske W, Allolio B. Clinical review: Current state and future perspectives in the diagnosis of diabetes insipidus: a clinical review J Clin Endocrinol Metab 2012 ;  97 : 3426-3437 [cross-ref]

Cliccare qui per andare alla sezione Riferimenti]. Treatment of central DI consists of fluid management and drug therapy with the synthetic AVP analogue Desmopressin (DDAVP), that is used as nasal or oral preparation in most cases. Main side effect can be dilutional hyponatremia [8Sawyer WH, Acosta M, Manning M. Structural changes in the arginine vasopressin molecule that prolong its antidiuretic action Endocrinology 1974 ;  95 : 140-149 [cross-ref]

Cliccare qui per andare alla sezione Riferimenti].

In this review we will focus on central diabetes insipidus and describe the prevalence, the clinical manifestations, the etiology as well as the differential diagnosis and management of central diabetes insipidus in the out- and inpatient setting.