The differential diagnosis of hypotonic polyuria is a frequent problem in clinical practice. Three fundamentally different types of defects have to be differentiated: central diabetes insipidus characterized by a lack of the antidiuretic hormone arginine vasopressin; nephrogenic diabetes insipidus characterized by renal insensitivity to arginine vasopressin; and primary polydipsia due to primary excess of fluid intake. The differentiation is crucial as treatment differs substantially and incorrect strategies may lead to severe complications. Since decades the indirect water-deprivation-test is the reference standard for this differentiation. However, it is technically cumbersome and highly vulnerable to false diagnosis. A new test with high diagnostic accuracy is urgently needed. Copeptin is the C-terminal segment of the arginine vasopressin prohormone and is an easy to measure and stable arginine vasopressin surrogate. In patients with hypotonic polyuria, high baseline copeptin levels without prior water deprivation unequivocally identified patients with nephrogenic diabetes insipidus. Conversely, in a large prospective diagnostic study the performance of copeptin after hypertonic saline-infusion was directly compared with that achieved by the water-deprivation-test. Stimulated copeptin levels with a cutoff of 4.9 pmol/L had a high diagnostic accuracy to differentiate between patients with central diabetes insipidus and primary polydipsia, clearly superior to the diagnostic accuracy of the classical water deprivation test. More patients preferred the hypertonic saline plus copeptin test to the water deprivation test, mainly because of its shorter duration. Constant surveillance of plasma sodium levels is important and even simpler test methods should be evaluated. In conclusion, copeptin measured after hypertonic saline infusion has the potential to become the new reference standard in the differential diagnosis of hypotonic polyuria.
18 - 21 May 2019
European Society of Endocrinology