Wiebke K Fenske1,2, Ingeborg Schnyder3, Gilbert Koch4, Carla Walti3, Marc Pfister4, Peter Kopp5, Martin Fassnacht6, Konrad Strauss6, Mirjam Christ-Crain3. 1. Leipzig University Medical Center, Integrated Center for Research and Treatment Adiposity Diseases, Leipzig, Germany. 2. Internal Medicine (Endocrinology and Nephrology), University of Leipzig, Germany, Leipzig, Germany. 3. Department of Endocrinology, Diabetology, and Metabolism, University Hospital of Basel, Basel, Switzerland. 4. Pediatric Pharmacology and Pharmacometrics, University Children's Hospital of Basel, Basel, Switzerland. 5. Division of Endocrinology, Metabolism, and Molecular Medicine and Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. 6. Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany.
Abstract
Context: Copeptin is the C-terminal fragment of the arginine vasopressin (AVP) prohormone whose measurement is more robust than that of AVP. Similar release and clearance characteristics have been suggested promoting copeptin as a surrogate marker. Objective: To characterize the physiology of osmotically regulated copeptin release and its half-life in direct comparison with plasma AVP. Design: Ninety-one healthy volunteers underwent a standardized three-phase test protocol including (1) osmotic stimulation into the hypertonic range by hypertonic-saline infusion followed by osmotic suppression via (2) oral water load and (3) subsequent glucose infusion. Plasma copeptin, AVP, serum sodium, and osmolality levels were measured in regular intervals. Results: In phase 1, an increase in median osmotic pressure [289 (286; 291) to 311 (309; 314) mOsm/kg H2O] caused similar release kinetics of plasma copeptin [4 (3.1; 6) to 29.3 (18.6; 48.2) pmol/L] and AVP [1 (0.7; 1.6) to 10.3 (6.8; 18.8) pg/mL]. Subsequent osmotic suppression to 298 (295; 301) mOsm/kg at the end of phase 3 revealed markedly different decay kinetics between both peptides-an estimated initial half-life of copeptin being approximately 2 times longer than that of AVP (26 vs 12 minutes). Conclusion: Copeptin is released in equimolar amounts with AVP in response to osmotic stimulation, suggesting its high potential as an AVP surrogate for differentiation of osmotic disorders. Furthermore, we here describe the decay kinetics of copeptin in response to osmotic depression enabling to identify a half-life for copeptin in direct comparison with AVP.
Context:Copeptin is the C-terminal fragment of the arginine vasopressin (AVP) prohormone whose measurement is more robust than that of AVP. Similar release and clearance characteristics have been suggested promoting copeptin as a surrogate marker. Objective: To characterize the physiology of osmotically regulated copeptin release and its half-life in direct comparison with plasma AVP. Design: Ninety-one healthy volunteers underwent a standardized three-phase test protocol including (1) osmotic stimulation into the hypertonic range by hypertonic-saline infusion followed by osmotic suppression via (2) oral water load and (3) subsequent glucose infusion. Plasma copeptin, AVP, serum sodium, and osmolality levels were measured in regular intervals. Results: In phase 1, an increase in median osmotic pressure [289 (286; 291) to 311 (309; 314) mOsm/kg H2O] caused similar release kinetics of plasma copeptin [4 (3.1; 6) to 29.3 (18.6; 48.2) pmol/L] and AVP [1 (0.7; 1.6) to 10.3 (6.8; 18.8) pg/mL]. Subsequent osmotic suppression to 298 (295; 301) mOsm/kg at the end of phase 3 revealed markedly different decay kinetics between both peptides-an estimated initial half-life of copeptin being approximately 2 times longer than that of AVP (26 vs 12 minutes). Conclusion:Copeptin is released in equimolar amounts with AVP in response to osmotic stimulation, suggesting its high potential as an AVP surrogate for differentiation of osmotic disorders. Furthermore, we here describe the decay kinetics of copeptin in response to osmotic depression enabling to identify a half-life for copeptin in direct comparison with AVP.
Authors: Chelsi Flippo; Christina Tatsi; Ninet Sinaii; Maria De La Luz Sierra; Elena Belyavskaya; Charalampos Lyssikatos; Meg Keil; Elias Spanakis; Constantine A Stratakis Journal: J Endocr Soc Date: 2022-04-06
Authors: Jeremy A Sandgren; Guorui Deng; Danny W Linggonegoro; Sabrina M Scroggins; Katherine J Perschbacher; Anand R Nair; Taryn E Nishimura; Shao Yang Zhang; Larry N Agbor; Jing Wu; Henry L Keen; Meghan C Naber; Nicole A Pearson; Kathy A Zimmerman; Robert M Weiss; Noelle C Bowdler; Yuriy M Usachev; Donna A Santillan; Matthew J Potthoff; Gary L Pierce; Katherine N Gibson-Corley; Curt D Sigmund; Mark K Santillan; Justin L Grobe Journal: JCI Insight Date: 2018-10-04
Authors: Clara O Sailer; Bettina Winzeler; Sandrine A Urwyler; Ingeborg Schnyder; Julie Refardt; Anne Eckert; Nimmy Varghese; Martin Fassnacht; Irina Chifu; Elizabeth A Lawson; Joseph G Verbalis; Wiebke Fenske; Mirjam Christ-Crain Journal: Eur J Endocrinol Date: 2021-08-03 Impact factor: 6.558