In early MS, the vasopressin peptide copeptin in serum is not a suitable surrogate for hypothalamo-pituitary-adrenal axis activity
Maike Schlingmann1, Muriel Stoppe1, Klara Mayer1, Christian Schinke1, Sarah Haars1, Elisa Schmidt1, Florian Then Bergh1
1Neurology, University of Leipzig
Objective:
To determine if a single measurement of copeptin, the C-terminal part of the AVP precursor (CT-proAVP), a stable and sensitive surrogate for AVP release, may serve as a more simply acquired substitute for the more cumbersome combined dexamethasone-corticotropin-releasing hormone test (DexCRH-test) to assess hypothalamo-pituitary-adrenal (HPA) axis activity in MS.
Background:
Activation of the HPA axis has been observed in MS by using the DexCRH-test, and may affect pathogenesis and clinical course. Vasopressin (AVP) costimulates ACTH secretion with CRH, but is not inhibited by dexamethasone.
Design/Methods:
Open, monocenter study, 44 HC, 55 patients with early relapsing-remitting MS (RRMS), 10 patients with clinically isolated syndrome (CIS). DexCRH-test (1.5 mg oral dexamethasone at 2300h the evening before; 100 µg i.v. synthetic hCRH at 1502h; serum ACTH and cortisol between 1500h and 1615h). Copeptin serum concentration before CRH application, and in a subset at 0900h before dexamethasone. Calculation of AUC for ACTH and cortisol output according to the trapezoidal rule. Independant samples t test, linear regression.
Results:
In HC (n=19) and MS (n=51), copeptin before and after dexamethasone correlated significantly, more stringently in HC (Pearson correlation, r2=0.627) than in MS (r2=0.301, both p<0.001). No correlation was found between copeptin (before or after dexamethasone) and DexCRH test variables in either HC or MS (AUC of ACTH or cortisol secretion; p 0.13-0.35). Copeptin, AUC-ACTH and AUC-cortisol were not significantly different between HC and RRMS/CIS (p=0.35-0.42).
Conclusions:
In HC and MS, copeptin appears equally affected by dexamethasone. Our sample of early RRMS patients predominantly on DMT did not display significant activation of the HPA axis, and had a fairly homogeneous HPA axis activity. At least in this setting, a single measurement of copeptin did not appear suitable as a surrogate marker of HPA axis activity. A sample including more advanced stages and different courses of MS may be more informative.