Arginine-Stimulated Copeptin-Based Diagnosis of Central Diabetes Insipidus in Children and Adolescents

Abstract

Introduction: Diagnosis of central diabetes insipidus (CDI) remains challenging. Water deprivation testing and hypertonic saline infusion, as established diagnostic tests, are mentally and physically demanding for patients. Arginine-stimulated copeptin has been shown as a putative parameter for the differential diagnosis of CDI in adults. Methods: In this single-centre retrospective study, we identified paediatric patients with suspected pituitary disorders who underwent standard arginine testing. Patients with CDI, matched controls, and primary polydipsia (PP) were identified. Diagnoses were confirmed retrospectively using comprehensive clinical and diagnostic characteristics. Serum copeptin concentrations were measured using a commercially available automated immunofluorescence assay (B.R.A.H.M.S Copeptin-proAVP KRYPTOR®) in samples stored for a median of 4.6 years (1.3–10.84) and collected before and 60 min after arginine infusion. Cut-off analyses were performed using ROC curves. Results: Serum samples from 32 patients with CDI, 32 matched controls, and 5 patients with PP (n = 69; 51 males, 18 females) were available for analysis. Median copeptin concentrations increased from 4.47 pmol/L (interquartile range [IQR]: 3.47–8.36) to 6.96 pmol/L (IQR: 4.51–12.89; p < 0.001) in controls, from 1.46 pmol/L (IQR: 1.21–2.12) to 1.44 (IQR: 1.10–1.87; p = 0.645, ns) in CDI, and from 4.40 pmol/L (3.95–6.33) to 9.58 pmol/L (8.19–11.42; p < 0.001) in PP. The published cut-off value of 3.8 pmol/L revealed a sensitivity of 100% and a specificity of 86.5% in confirming CDI. Conclusion: Our results suggest that arginine-stimulated serum copeptin concentrations are a sensitive and specific diagnostic tool for CDI in paediatric patients, which may replace and simplify the conventional diagnostic pathway of water deprivation testing and hypertonic saline infusion.