DIFFERING RESPONSES OF CORTISOL TO OCRF DURING ENDONASAL AND ORAL TREATMENT WITH DDAVP

Arginine vasopressin (AVP) exerts a potentiating effect on the respons es of cortisol and ACTH to ovine CRF (oCRF). A stimulation test using AVP plus oCRF to assess ACTH reserve has been proposed. In central dia betes insipidus, long-term substitution therapy is commonly undertaken with desmopressin (DDAVP), an analogue of the natural hormone which h as a greater antidiuretic action but whose effects on the ACTH-cortiso l axis are still controversial. The aim of our study was to evaluate t he variations in the responses of ACTH and cortisol to oCRF in various phases of the treatment of central diabetes insipidus: no treatment, endonasal treatment with DDAVP solution and oral treatment with DDAVP in tablet form. Seven patients suffering from central diabetes insipid us underwent testing with oCRF during the various phases of treatment. In the absence of DDAVP treatment, normal responses were registered f or cortisol (basal 164.1 +/- 29.4 ng ml-(1), peak 396.1 +/- 37.9 ng ml -(1) P < 0.05) and ACTH (basal 20.4 +/- 3.9 pg ml(-1), peak 86.3 +/- 2 0.9 pg ml(-1); P < 0.05) in all patients. During oral treatment with D DAVP, no variation in cortisol response to oCRF was seen. By contrast, when DDAVP was administered endonasally, a significant reduction in c ortisol responsiveness to oCRF (secretory area: 2429 +/- 548 ng ml(-1) 120 min) was noted in comparison with that found during the other two tests (no treatment: 3070 +/- 704 ng ml(-1) 120 min; oral DDAVP: 3419 +/- 650 ng ml(-1) 120 min; P < 0.05) performed. There is no clear exp lanation for this phenomenon, but an interesting hypothesis is that DD AVP acts as a weak agonist which exerts only a slight stimulatory effe ct on the corticotropic hypophyseal cells but which is able to compete with the natural hormone for receptor binding.