Endocrine Abstracts

Background and Objectives: The differential diagnosis between arginine vasopressin (AVP) deficiency (AVP-D, formerly known as central diabetes insipidus) and primary polydipsia (PP) remains challenging. To date, the method with the highest diagnostic accuracy is osmotically-stimulated copeptin – a surrogate marker of AVP – using hypertonic saline infusion. However, this method is often limited to experienced hospitals, requires close monitoring, and may be cumbersome for patients. Therefore, an alternative simplified osmotic stimulation test would be highly desirable. It has been previously demonstrated that intravenous urea increases plasma osmolality and stimulates AVP release. However, no study investigated the effects of oral urea on copeptin levels.

Methods: The aim of this randomized double-blind placebo-controlled study was to investigate whether oral urea stimulates copeptin release in 22 healthy adults. Participants presented for two visits in the morning after an overnight food fasting and two-hour fluid fasting period. They received a single weight-adapted dose of oral urea (0.5 g/kg body weight; minimum 30g, maximum 45 g) and placebo in random order. Serum copeptin was measured at baseline and 30, 60, 90, 120, and 150 minutes after oral urea or placebo intake. The primary endpoint was the maximum increase in copeptin levels within 150 minutes after oral urea intake vs placebo.

Results: When stimulating with placebo, the median [IQR] copeptin level at baseline was 3.8 [2.9 – 6.6] pmol/l and remained stable after 120 minutes at 3.2 [2.8 – 5.6] pmol/l. In contrast, when stimulating with urea, the copeptin level at baseline was 4.6 [3.0 – 5.7] pmol/l and increased after 120 minutes to a maximum of 10.1 [7.2 – 11.6] pmol/l (P< 0.001).

Conclusion: Oral urea leads to an approximately two-fold increase in copeptin levels in healthy adults. Whether this applies to patients with PP and has the potential to discriminate them from patients with AVP-D remains uncertain and is currently being investigated.