Primary polydipsia and Diabetes mellitus (DM), whether central or nephrogenic, must be distinguished. This distinction is essential because improper treatment can have harmful effects. The standard water deprivation test has been the "gold standard" for differential diagnosis for decades. However, this test has a number of limitations that make it less accurate overall for diagnosing problems. Additionally, the test takes 17 hours to complete and is time-consuming for patients. Additionally, patients with primary polydipsia and DI share many of the same clinical signs and symptoms as well as MRI characteristics. Although it was initially demonstrated that direct measurement of arginine vasopressin (AVP) upon osmotic stimulation could circumvent these limitations, the AVP assay's technical limitations prevented it from entering clinical practice. In line with the circulation's AVP concentrations, copeptin secretion is equimolar to AVP. We have demonstrated that patients with nephrogenic DI can be identified using copeptin even without prior fluid deprivation. A copeptin level of 4.9 pmol/L stimulated with hypertonic saline infusion differentiates between central DI and primary polydipsia with high diagnostic accuracy and is superior to the water deprivation test for the more difficult distinction between these two conditions. However, it is essential to note that the hypertonic saline test requires close and consistent sodium monitoring every 30 minutes, which is not always possible in all hospitals. Additionally, side effects are frequent. A non-osmotic stimulation test would therefore be beneficial. Because arginine significantly stimulates copeptin, it is a novel and undiscovered stimulus for this peptide. As a result, an even simpler and well-tolerated test was found to be arginine infusion with copeptin measurement; however, a head-to-head comparison is still lacking.
