Arginine-stimulated copeptin based diagnosis of central diabetes insipidus in children and adolescents.

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 minutes 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 (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.