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

Nature Reviews Endocrinology (2024)Cite this article

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A Publisher Correction to this article was published on 08 May 2024

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Abstract

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.

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 assessed via stimulation with 3,4-methylenedioxymethamphetamine (that is, MDMA); whether oxytocin treatment is a future option for patients with AVP deficiency should be investigated in larger studies.

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Fig. 1: The hypothalamic–posterior pituitary axis.
Fig. 2: Algorithm for diagnostic approach in patients with suspected arginine vasopressin deficiency.
Fig. 3: Prevalence of hyponatraemia in patients with arginine vasopressin deficiency and strategies for the desmopressin escape method.
Fig. 4: Psychoactive behavioural responses and plasma concentrations of oxytocin in response to the MDMA provocation test.

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Authors and Affiliations

  1. Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland

    Cihan Atila, Julie Refardt & Mirjam Christ-Crain

  2. Department of Clinical Research University of Basel, University Hospital Basel, Basel, Switzerland

    Cihan Atila, Julie Refardt & Mirjam Christ-Crain

  3. Department of Internal Medicine, Section of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands

    Julie Refardt

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  1. Cihan Atila
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The authors contributed equally to all aspects of the article.

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C.A., J.R. and M.C.-C. received occasional kits for copeptin measurements from Thermo Fisher AG, the manufacturer of the copeptin assay.

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Atila, C., Refardt, J. & Christ-Crain, M. Arginine vasopressin deficiency: diagnosis, management and the relevance of oxytocin deficiency. Nat Rev Endocrinol (2024). https://doi.org/10.1038/s41574-024-00985-x

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