Copeptin as a marker of an altered CRH axis in pituitary disease.
BACKGROUND
Copeptin (pre-proAVP) secreted in equimolar amounts with vasopressin closely reflects vasopressin release. Copeptin has been shown to subtly mirror stress potentially mediated via corticotrophin-releasing hormone. To further test a potential direct interaction of corticotrophin-releasing hormone with copeptin release, which could augment vasopressin effects on pituitary function, we investigated copeptin response to corticotrophin-releasing hormone.


PATIENTS AND METHODS
Cortisol, adrenocorticotropin and copeptin were measured in 18 healthy controls and 29 subjects with a history of pituitary disease during standard corticotrophin-releasing hormone test.


RESULTS
Patients with previous pituitary disease were subdivided in a group passing the test (P1, n = 20) and failing (P2, n = 9). The overall copeptin response was higher in controls than in subjects with pituitary disease (area under the curve, p = 0.04 for P1 + P2) with a maximum increase in controls from 3.84 ± 2.86 to 12.65 ± 24.87 pmol/L at 30 min, p < 0.05. In contrast, both groups of pituitary patients lacked a significant copeptin response to corticotrophin-releasing hormone, and even in P1, where adrenocorticotropin concentrations increased fourfold (mean, 21.48 vs. 91.53 pg/mL, p < 0.01), copeptin did not respond (e.g., 4.35 ± 5.81 vs. 5.36 ± 6.79 pmol/L, at 30 min, p = ns).


CONCLUSIONS
Corticotrophin-releasing hormone is able to stimulate copeptin release in healthy controls suggesting a direct interaction of corticotrophin-releasing hormone and vasopressin/vasopressin. Interestingly, this relation is altered already in the group of pituitary patients who pass the standard corticotrophin-releasing hormone test indicating (1) the corticotrophin-releasing hormone-adrenocorticotropin-cortisol response is largely independent from the vasopressin system, but (2) the corticotrophin-releasing hormone-vasopressin interaction reflected by copeptin may be much more sensitive to reveal subtle alterations in the regulation of pituitary function.
['Lewandowski|Krzysztof C|KC|', 'Lewiński|Andrzej|A|', 'Skowrońska-Jóźwiak|Elżbieta|E|', 'Malicka|Katarzyna|K|', 'Horzelski|Wojciech|W|', 'Brabant|Georg|G|http://orcid.org/0000-0001-8532-7632']
D000302:Adrenal Cortex D000324:Adrenocorticotropic Hormone D000328:Adult D015415:Biomarkers D003346:Corticotropin-Releasing Hormone D005260:Female D006020:Glycopeptides D006801:Humans D006854:Hydrocortisone D007030:Hypothalamo-Hypophyseal System D007118:Immunoassay D007700:Kinetics D008297:Male D008875:Middle Aged D010900:Pituitary Diseases D010902:Pituitary Gland D018019:Receptors, Corticotropin-Releasing Hormone D011994:Recombinant Proteins D012720:Severity of Illness Index D015398:Signal Transduction D013268:Stimulation, Chemical
Copeptin Pituitary CRH test Diabetes insipidus