Diabetes Insipidus: Novel Diagnostic Approaches

Diabetes insipidus (DI) is a water balance disorder characterized by the excretion of a large amount of hypotonic urine associated with a compensatory polydipsia. The polyuria-polydipsia syndrome includes four major entities: central DI (CDI), gestational DI (GDI), nephrogenic DI (NDI), and primary polydipsia (PP). It is essential to differentiate accurately CDI from the other forms, because a wrong diagnosis can have fatal consequences. Clinical manifestations do not differ between DI and PP, even though the underlying mechanism is different. The diagnostic process is often challenging, especially in distinguishing partial CDI from PP. Hyponatremia orientates toward PP, whereas sodium levels at the upper end of the normal reference or hypernatremia are suggestive of DI. However, plasma sodium is normal in the majority of cases; therefore, the differential diagnosis of polyuria requires dynamic testing of the arginine-vasopressin (AVP)-renal axis. The classical water deprivation test (WDT) combined with a desmopressin (DDAVP) test has a poor diagnostic accuracy, is stressful, and requires adherence by patients, adequate supervision by clinicians, and hospitalization. Copeptin and AVP are secreted in equimolar amounts from the neurohypophysis, but the former is more stable and easier to measure. In recent years, the assessment of circulating copeptin levels, especially after stimulation, has replaced the classical test in clinical practice. Arginine-stimulated copeptin seems to be the most convenient, easy, and accurate tool to diagnose DI, even if a confirmation test using hypertonic saline infusion combined with DDAVP is recommended in doubtful cases.