Endocrine Abstracts

JOINT640

Background and Objectives: The differential diagnosis between arginine vasopressin (AVP) deficiency and primary polydipsia remains challenging. The method with the highest diagnostic accuracy is osmotically stimulated copeptin using hypertonic saline infusion. However, this method is limited to experienced hospitals, requires close monitoring, and may be cumbersome for patients. Therefore, an alternative simplified osmotic stimulation test would be highly desirable. Intravenous urea has been shown to stimulate AVP secretion. However, no study investigated the effects of oral urea on copeptin levels.

Methods: Twenty-two healthy adults were included in a randomized double-blind placebo-controlled cross-over trial. Participants underwent two visits after an overnight food fasting and two-hour fluid fasting period. They received a single weight-adapted dose of urea (0.5 g/kg body weight; minimum 30g, maximum 45 g) and placebo in random order. Serum copeptin was measured at baseline, 30, 60, 90, 120, and 150 minutes. In a second step, 13 patients with AVP-deficiency and 13 patients with primary polydipsia were included in a single arm, open label pilot study, receiving urea only. The primary endpoint was the maximum increase in copeptin within 150 minutes after ingestion of the study drink.

Results: In healthy adults, median [IQR] copeptin significantly increased from 4.6 [3.0 – 5.7] pmol/l at baseline to a maximum of 10.1 [7.2 – 11.6] pmol/l at 120 minutes after ingestion of urea, while it remained stable at 3.8 [2.9 – 6.6] pmol/l during placebo (P < 0.001). In patients with AVP-deficiency, copeptin remained below detection limit throughout the test, while in patients with primary polydipsia the peak was seen 150 minutes after ingestion of urea at 7.4 pmol/l [4.3, 10.3]. The best copeptin cut-off for differentiating AVP-deficiency from primary polydipsia was 3.5 pmol/l after 120 minutes, with a sensitivity and specificity of 92%, respectively.

Conclusion: Oral urea stimulates copeptin levels in healthy adults and patients with primary polydipsia, but not in patients with AVP-deficiency, establishing the first oral copeptin-based test in differentiating primary polydipsia from AVP-deficiency.