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Beyond Biomarkers: Blending Copeptin and Clinical Cues to Distinguish Central Diabetes Insipidus from Primary Polydipsia in Children

Diana Ciortea,Carmen Loredana Petrea Cliveți,Gabriela Isabela Verga Răuță,S. Berbece,Gabriela Gurău,Silvia Fotea,M. Matei

Published 2025 in Biomedicines

ABSTRACT

Background: Polyuria–polydipsia syndrome (PPS) in children poses a major diagnostic challenge, as central diabetes insipidus (CDI) and primary polydipsia (PP) require distinct treatments. Although copeptin is a robust diagnostic biomarker, using only fixed thresholds may not adequately support decision making in borderline cases. To address this gap, we evaluated a multimodal diagnostic approach that integrates copeptin dynamics with clinical profiling. Methods: In a prospective diagnostic study (2019–2025), 24 children with PPS (CDI = 11, PP = 13) underwent hypertonic saline testing with serial sodium, osmolality, and copeptin sampling. Predictors included stimulated copeptin, peak sodium, peak osmolality, test duration, and tolerability. A Ridge regression model was applied and internally validated with stratified cross-validation. Results: Stimulated copeptin was the strongest discriminator, while sodium/osmolality dynamics and tolerability provided complementary value. The multimodal model achieved cross-validated AUC of 0.937 with 83.3% accuracy, and the procedure was safe and feasible in children. These findings support moving beyond biomarker cut-offs toward integrative diagnostic approaches that better reflect real-world clinical practice. Conclusions: Combining copeptin with clinical profiling in a penalized regression framework yields a robust and interpretable tool for distinguishing CDI from PP. More broadly, such integrative models may enhance diagnostic precision in rare pediatric disorders and provide a foundation for future multicenter validation and clinical decision-support applications.

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