Post-dexamethasone serum copeptin corresponds to HPA axis responsiveness in human obesity.
Increased activities of the arginine-vasopressin (AVP) system and the hypothalamic-pituitary-adrenal (HPA) axis were shown to be associated with human obesity, but relationships between these systems in obesity remain unclear.



To assess HPA axis responsiveness and its relation to serum concentrations of the AVP-surrogate copeptin in subjects with obesity (OB) in comparison to non-obesity controls (NOC).



In a cross-sectional monocentric study, thirty-nine OB (f/m 25/14; age 36.5±10.0years; body mass index, BMI, 41.5±4.7kg/m2) were compared to twenty-two NOC (f/m 12/10; age 35.3±8.5years; BMI 23.1±2.4kg/m2), matched for age and sex. All individuals underwent the combined dexamethasone/CRH test.



Plasma ACTH and cortisol curve indicators derived from the dex/CRH test (post-CRH concentrations 30min after 100μg CRH; maximum concentration, MAX; area-under-the-curve, AUC; ACTH/cortisol ratios). Copeptin was assessed in 1500h samples of the dex/CRH test (after 1.5mg of oral dexamethasone, prior to CRH administration).



Copeptin serum concentrations were higher in OB (median [IQR]: OB 4.62 [2.60-5.88] vs. NOC 3.04 [2.52-4.29] pmol/l, P=0.04). Correspondingly, OB showed higher post-CRH cortisol concentrations (OB: 51.5 [25.9-159.3] vs. NOC: 28.6 [20.0-41.6] nmol/l, P=0.01) and a lower post-CRH ACTH/cortisol ratio (OB: 0.028 [0.016-0.053] vs. NOC: 0.048 [0.034-0.070] pmol/nmol, P<0.01). Serum copeptin was significantly associated with HPA responsiveness in OB (post-CRH ACTH: R=0.42, P<0.01), driven by OB men (post-CRH ACTH: R=0.76, P<0.01, post-CRH cortisol: R=0.64, P=0.02). All associations withstand adjustments for BMI and age.



The association between increased copeptin with ACTH and cortisol release suggests a potential mechanistic interaction of the AVP system with HPA activation in human obesity. The relation of copeptin and HPA responsiveness should be further validated in situations with pronounced HPA activation, such as depression or multiple sclerosis.
Department of Neurology, University of Leipzig, Leipzig, Germany; Integrated Research and Treatment Center Adiposity Diseases, University of Leipzig, Leipzig, Germany.
Christian
C
Schinke
Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany; Integrated Research and Treatment Center Adiposity Diseases, University of Leipzig, Leipzig, Germany.
Swen
S
Hesse
Department of Neurology, University of Leipzig, Leipzig, Germany; Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig, Germany.
Muriel
M
Stoppe
Department of Neurology, University of Leipzig, Leipzig, Germany.
Klara
K
Meyer
Department of Neurology, University of Leipzig, Leipzig, Germany.
Elisa
E
Schmidt
Department of Neurology, University of Leipzig, Leipzig, Germany.
Johannes
J
Orthgiess
Department of Neurology, University of Leipzig, Leipzig, Germany.
Lukas
L
Bechmann
Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany.
Anke
A
Bresch
Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany; Integrated Research and Treatment Center Adiposity Diseases, University of Leipzig, Leipzig, Germany.
Michael
M
Rullmann
Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany.
Julia
J
Luthardt
Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany; Integrated Research and Treatment Center Adiposity Diseases, University of Leipzig, Leipzig, Germany.
Osama
O
Sabri
Integrated Research and Treatment Center Adiposity Diseases, University of Leipzig, Leipzig, Germany; Department of Medicine, University of Leipzig, Leipzig, Germany.
Matthias
M
Blüher
Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany.
Jürgen
J
Kratzsch
Department of Neurology, University of Leipzig, Leipzig, Germany; Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig, Germany. Electronic address: ThenBerF@medizin.uni-leipzig.de.
Florian
F
Then Bergh
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D003430:Cross-Sectional Studies; D003907:Dexamethasone; D005260:Female; D006020:Glycopeptides / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000503:physiopathology*; D010912:Pituitary-Adrenal Function Tests; D010913:Pituitary-Adrenal System / Q000503:physiopathology*
D006020:Glycopeptides; C048197:copeptins; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone
Copeptin; Dexamethasone crh test; HPA axis; Neuroendocrinology; Obesity