Diabetes insipidus (DI) is characterized by hypotonic
polyuria greater than 3 liters/24 hours in adults and persisting even during water deprivation. It is mostly due to a defect in arginin-
vasopressin (AVP) synthesis (central DI); other causes are: AVP resistance (nephrogenic DI), abnormal thirst regulation (
primary polydipsia) or early destruction of AVP by placental
enzymes (gestational DI). A thorough medical history is warranted to investigate nocturnal persistence of
polyuria (night waking being a good sign of its organic nature) to specify the onset and duration of the trouble, the medication use and the potential hereditary nature of the disorder. The next step is based on weight and blood pressure measurements and especially the quantification of beverages and diuresis over a 24-hour cycle. Assessment of signs of
dehydration, bladder distention, pituitary
hormone hyper- or hyposecretion,
tumor chiasmatic syndrome, granulomatosis and
cancer is required. The diagnosis is based on
biological assessment, pituitary magnetic resonance imaging (MRI) and results of a
desmopressin test. In severe forms of DI, urine osmolality remains below 250 mOsmol/kg and serum
sodium greater than 145 mmol/L. In partial forms of DI (urine osmolality between 250 and 750), the water deprivation test demonstrating the incapacity to obtain a maximal urine concentration is valuable, together with
vasopressin or copeptin measurement. The pituitary MRI is done to investigate the lack of spontaneous hyperintensity signal in the posterior pituitary, which marks the absence of AVP and supports the diagnosis of central DI rather than
primary polydipsia (although not absolute); it can also recognize lesions of the pituitary gland or pituitary stalk. Acquired central DI of sudden onset should suggest a
craniopharyngioma or
germinoma if it occurs before the age of 30 years, and
metastasis after the age of 50 years. Fifteen to 20% of
head trauma lead to
hypopituitarism, including DI in 2% of cases. Transient or permanent DI is present in 8-9% of endoscopic transphenoidal surgeries. Current advances in DI concern the etiological work-up, with in particular the identification of
IgG4-related hypophysitis or many genetic abnormalities, opening the field of targeted
therapies in the years to come.