Endocrine Abstracts

Introduction: In polyuria-polydipsia syndrome (PPS) the differentiation between arginine vasopressin deficiency (AVP-D) and primary polydipsia (PP) remains challenging and a stimulation test is required. Apelin is an endogenous hormone that antagonises AVP and seems to play an important role in regulating salt and water homeostasis. The dynamic of apelin plasma levels in patients with PPS undergoing copeptin stimulation tests is unknown.

Methods: Post-hoc secondary analysis of the multicentric randomised cross-over diagnostic CARGOx study (NCT03572166) performed from 09/2018 to 12/2022. Apelin levels from patients with PPS included at the University Hospital Basel were measured upon stimulation with hypertonic saline and arginine infusions. The primary objective was to compare the changes in plasma apelin levels during copeptin-stimulation tests among patients with PPS. Secondary objectives included comparing changes in the apelin/copeptin ratio and comparing the diagnostic ability of apelin, copeptin and their ratio.

Results: Of the 38 patients enrolled at the University Hospital of Basel, 23 (60%) patients had PP and 15 (40%) patients had AVP-D. At baseline median [IQR] apelin levels were 1079 [912, 1225] and 910 [756, 1039] and apelin/copeptin was 336 [218, 336] and 426 [369, 509] in PP and AVP-D respectively. During the hypertonic saline stimulation test, apelin decreased by -241 [-326, -124] and -47.2 [-198, 5.86] (P= 0.022) and apelin/copeptin ratio decreased by -300 [-425, -235] and -69 [-150, -15] in PP and AVP-D respectively (P= 0.001). The AUC [95%-CI] to differentiate PP from AVP-D was 97.1% [90.5, 100] for copeptin, 49.3% [30.4, 68.1] for apelin and 95.6 [87.2, 100] for apelin/copeptin ratio. During the arginine stimulation test, apelin decreased in PP by -39.2 [-96.4, 39.8] and increased in AVP-D by 25.8 [2.8, 113.0] (P= 0.1), and apelin/copeptin ratio decreased by -188 [-326, -68] and -59 [-171, 8] in PP and AVP-D respectively (P= 0.034). The AUC [95%-CI] was 97.1% [79.6, 98.0] for copeptin, 60.5% [39.8, 80.0] for apelin and 83.0% [67.0, 95.3] for apelin/copeptin ratio.

Conclusion: Our findings suggest that apelin and apelin/copeptin ratio decrease during hypertonic infusion to a greater extent in patients with PP as compared to patients with AVP-D. Copeptin remains the best marker to differentiate AVP-D from PP upon hypertonic saline and arginine stimulation. Whether apelin would provide greater diagnostic accuracy using other provocation tests should be further investigated.