Arginine vasopressin deficiency: diagnosis, management and the relevance of oxytocin deficiency

Polyuria–polydipsia syndrome can be caused by central diabetes insipidus, nephrogenic diabetes insipidus or primary polydipsia. To avoid confusion with diabetes mellitus, the name ‘central diabetes insipidus’ was changed in 2022 to arginine vasopressin (AVP) deficiency and ‘nephrogenic diabetes insipidus’ was renamed as AVP resistance. To differentiate the three entities, various osmotic and non-osmotic copeptin-based stimulation tests have been introduced in the past decade. The hypertonic saline test plus plasma copeptin measurement emerged as the test with highest diagnostic accuracy, replacing the water deprivation test as the gold standard in differential diagnosis of the polyuria–polydipsia syndrome. The mainstay of treatment for AVP deficiency is AVP replacement with desmopressin, a synthetic analogue of AVP specific for AVP receptor 2 (AVPR2), which usually leads to rapid improvements in polyuria and polydipsia. The main adverse effect of desmopressin is dilutional hyponatraemia, which can be reduced by regularly performing the so-called desmopressin escape method. Evidence from the past few years suggests an additional oxytocin deficiency in patients with AVP deficiency. This potential deficiency should be further evaluated in future studies, including feasible provocation tests for clinical practice and interventional trials with oxytocin substitution. Central diabetes insipidus has been renamed as arginine vasopressin deficiency. This Review discusses advances in diagnosis and management of arginine vasopressin deficiency. In addition, the possibility of oxytocin deficiency in these patients is considered, as well as oxytocin provocation testing and the future therapeutic potential of oxytocin replacement. Key points Central diabetes insipidus has been renamed to arginine vasopressin (AVP) deficiency and nephrogenic diabetes insipidus to AVP resistance. Polyuria–polydipsia syndrome comprises AVP deficiency or resistance and primary polydipsia. Copeptin-based stimulation tests have simplified and improved the diagnostic procedure for AVP deficiency and of these, the hypertonic saline test with measurement of plasma levels of copeptin has the highest diagnostic accuracy. AVP deficiency can be treated with desmopressin, but this treatment confers a risk of hyponatraemia; patients should be instructed to use the desmopressin escape method to decrease the risk of hyponatraemia. Oxytocin deficiency can occur in patients with AVP deficiency and can be