Endocrine Abstracts

Background: Copeptin (pre-proAVP) secreted in equimolar amounts with vasopressin (AVP) closely reflects AVP release. Previously it was shown that copeptin is stimulated in standard pituitary function tests acting through hypothalamic centres. Furthermore, copeptin has been shown to subtly mirror stress potentially mediated via CRH. To further test a potential direct interaction of CRH with copeptin release which could augment AVP effects on pituitary function, we investigated copeptin response in a standard CRH test, both in healthy controls and patients with pituitary disease.

Patients and methods: 18 healthy controls and 29 subjects with history of pituitary disease were subjected to a standard CRH test and in addition to ACTH and cortisol we measured copeptin by standard assays (ThermoFisher).

Results: Patients with previous pituitary disease were subdivided in a group passing the test (P1) and failing (P2). The latter group included five patients with diabetes insipidus. 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 pmol/l, to 12.65±24.87 pmol/l, P=0.04, at 30 min). In contrast, both groups of pituitary patients lacked a significant CRH response. The mean increase in P2 was from 1.93±1.44 pmol/l to 3.37±3.49 pmol/l, at 30 min, P=ns, and even in P1 where ACTH concentrations increased four-fold (mean 21.48 vs. 91.53 pg/ml, P<0.01) copeptin did not respond (e.g. 4.35±5.81 pmol/l vs. 5.36±6.79 pmol/l, at 30 min, P=ns).

Conclusions: CRH is able to stimulate copeptin release in healthy controls suggesting a direct interaction of CRH and AVP/vasopressin. Interestingly, this relation is altered already in the group of pituitary patients who pass the standard CRH test indicating i) that the CRH-ACTH-cortisol response is largely independent from the AVP system, but ii) the CRH-AVP interaction reflected by copeptin may be much more sensitive to reveal subtle alterations in the regulation of pituitary function.