Work

Mannitol-stimulated Copeptin for diagnosing Arginine Vasopressin Deficiency: a randomized controlled proof of concept and a single-arm pilot study

Year: 2026

Type: article

Abstract: Differentiating arginine vasopressin (AVP) deficiency from primary polydipsia is challenging. The most accurate test, hypertonic saline–stimulated copeptin, requires intensive monitoring. Intravenous mannitol stimulates AVP release and may provide a simpler alternative. In a randomized double-blind crossover trial, 22 healthy adults received mannitol and placebo in random order, of whom 21 were included in the primary analysis. In a pilot study, 10 patients with AVP deficiency and 10 with primary polydipsia received mannitol. The primary outcome was copeptin after mannitol infusion. Mannitol resulted in a 2.29-fold higher copeptin at 90 minutes (+6.4 pmol/L (95% CI: +5.2, +7.7; p <0.001)) than after placebo at mean baseline copeptin levels in healthy adults. In patients, copeptin after 30 minutes was 11.7 pmol/L (95% CI: 6.5, 17.0) higher in primary polydipsia than in AVP deficiency. Mannitol infusion shows promise as a new diagnostic approach. Larger confirmatory studies are required to validate both the optimal diagnostic cut-off and patient safety. Trial Registration number: NCT06542198 .

Source: Nature Communications

DOI: 10.1038/s41467-026-78875-1