ESPE Abstracts

Introduction: The diagnosis of arginine vasopressin deficiency (AVD, formerly central diabetes insipidus) remains a challenge. Timely and accurate differentiation between AVD and primary polydipsia (PP) is pivotal for effective management. In recent years, stimulated copeptin has emerged as a promising tool to diagnose AVD.

Methods: In this single centre retrospective study, we identified paediatric patients with suspected pituitary insufficiency who underwent standard insulin tolerance testing (ITT). Patients with AVD and a non-matched control group without polyuria-polydipsia syndrome which underwent ITTs were identified. Diagnosis of AVD was 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 collected before and 30, 45 and 60 minutes after insulin injection. Cut-off analyses were performed using ROC curves.

Results: 25 patients with AVD and 43 non-matched controls were available for analysis. Median copeptin concentrations of 1.51 pmol/l (IQR: 0.91-1.95) increased at a median of 30 minutes to a maximum of 1.95 pmol/l (IQR: 1.31-2.39) in AVD patients (P = 0.113), and from 4.41 pmol/l (IQR: 3.36-6.68) to a maximum of 8.39 pmol/l (IQR: 4.95-19.72) (P <0.001) in controls. Median serum osmolarities at 0 minutes were 288.5 mmol/l (IQR: 282.3-293.5) in AVD patients and 281.0 mmol/l (274.0-286.0) in controls (P <0.001). ROC analysis resulted in a cut-off of 3.0 pmol/l for maximum copeptin (91.7 % sensitivity, 94.1 % specificity) for the diagnosis of AVD. Height, weight, BMI, chronological age at the time of ITT and sample storage time showed no significant effect on basal and stimulated copeptin concentrations in multivariate regression analysis for all patients (basal: P = 0.729, 30min: P = 0.079, 45min: P = 0.073 and 60min: P = 0.236). Basal and stimulated serum copeptin concentrations were similar in females and males (P = 0.690, P = 0.215, P = 0.219 and P = 0.283). Growth hormone, cortisol, ACTH and the minimum blood glucose levels showed no impact on maximum copeptin concentrations (P = 0.694), but a significant influence on basal copeptin (P <0.001).

Conclusion: Our results suggest that insulin-stimulated serum copeptin concentrations are a sensitive and specific diagnostic tool for AVD in paediatric patients, which allows us to test multiple pituitary hormone axes simultaneously in a single test. Further studies are required to establish age-specific reference ranges for basal and insulin-stimulated copeptin concentrations and to quantify the severity of AVP deficiency.