Copeptin levels increase in response to both insulin-induced hypoglycemia and arginine but not to clonidine: data from GH-stimulation tests

Background: The diagnosis of the polyuria-polydipsia syndrome is challenging. Copeptin is a robust biomarker of arginine vasopressin (AVP) secretion. Arginine, which stimulates growth hormone (GH), has been shown also to stimulate copeptin secretion via unknown mechanisms. Aim: The aim was to investigate copeptin levels in response to three different GH stimulation tests in patients suspected of GH deficiency. Methods: In this cross-sectional study, we measured plasma copeptin levels at baseline and at 60, 105, and 150 min in patients undergoing a stimulation test for growth hormone deficiency with either arginine (n = 16), clonidine (n = 8) or the insulin tolerance test (ITT) (n = 10). Results: In patients undergoing the arginine test, the mean age was 9 years, and 10 years for clonidine. The ITT was only performed in adult patients (>18 years) with a mean age of 49 years. Copeptin level increased significantly from baseline to 60 min after arginine (P <0.01) and ITT (P < 0.01). By contrast, copeptin level tended to decrease after clonidine stimulation (P = 0.14). Conclusion: These data support that infusion of arginine increases plasma copeptin levels and reveal a comparable response after an ITT. We hypothesize that the underlying mechanism is abrogation of somatostatin-induced AVP suppression.