ESPEYB16 15 Editorsߣ Choice (1) (18 abstracts)
15.1. A Copeptin-based approach in the diagnosis of diabetes insipidus
Fenske W , Refardt J , Chifu I , Schnyder I , Winzeler B , Drummond J , Ribeiro-Oliveira A Jr. , Drescher T , Bilz S , Vogt DR , Malzahn U , Kroiss M , Christ E , Henzen C , Fischli S , Tonjes A , Mueller B , Schopohl J , Flitsch J , Brabant G , Fassnacht M & Christ-Crain M
Clinic of Endocrinology, Diabetology and Metabolism and the Clinical Trial Unit, Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland
To read the full abstract: N Engl J Med 2018;379:428–439
In this multi-centre cohort of 156 patients with hypotonic polyuria, direct measurement of hypertonic saline-stimulated plasma copeptin had much greater diagnostic accuracy than a standard water-deprivation test, as judged by the final reference diagnosis, which was determined on the basis of medical history, test results (with copeptin levels masked), and treatment response at a 3-month follow-up visit.
Water-deprivation tests are used commonly to distinguish between (central) Diabetes Insipidus (DI), Renal DI and Primary Polydipsia. However, these tests are often challenging to perform. Patients with Primary Polydipsia are often well-hydrated at the start and it may take much more than 12 hours of water deprivation to reach appropriate urine concentrations; conversely this test is potentially dangerous in patients with DI who quickly become severely dehydrated. Hence these tests require carefully monitoring over a long period – often with a very grumpy child! Furthermore, the existence of (central) ‘Partial DI’ complicates matters; it can be difficult to distinguish this from insufficient duration of testing in Primary Polydipsia.
Copeptin is co-secreted with vasopressin as part of its pre-pro-hormone. It has no known biological function, but the authors show that it serves as an accurate surrogate marker for vasopressin levels, for which an accurate assay has long proved challenging. A plasma copeptin cutoff level of 4.9 pmol/l or less indicated complete or partial central DI, and a level >4.9 pmol/l indicated Primary Polydipsia.
The main disadvantage of the protocol reported here is the hypertonic saline infusion test. Although much shorter than the water deprivation test, it requires close monitoring of plasma sodium levels to achieve the target level of at least 150 mmol/l, and common side-effects are nausea, vertigo, and headache. The authors have presented and will soon publish an alternative stimulation test based on the copeptin level 60-minutes after intravenous administration of Arginine. I suspect that our future junior fellows will be amused by our tales of conducting (hopefully superseded) water deprivation tests.
Volume 16
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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