RESISTANCE TO VASOPRESSIN ACTION ON THE KIDNEY IN PATIENTS WITH CUSHINGS-DISEASE

Objective: To assess the plasma levels and action of arginine vasopres sin (AVP) in patients with Gushing's disease. There are many reports t hat patients with Addison's disease have increased AVP levels associat ed with hyponatraemia and hypoosmolality, but none on the dynamics of secretion of this neurohormone during osmolality-based stimulation in patients with chronic hypercortisolism. Design and subjects: The plasm a AVP concentration and the urinary and plasma osmolality after a 7.5- h water deprivation test (WDT) were evaluated in 13 patients with Gush ing's disease and 15 normal (control) individuals. In patients with Gu shing's disease we also assessed the urinary osmolality in response to 10 mu g i.v. desmopressin (DDAVP) administered at the end of the WDT. Results: At the end of the WDT, urinary osmolality was significantly lower in patients with Gushing's disease (511.5+/-148.5 mOsm/l) than i n the normal subjects (981.1+/-107.1 mOsm/l, P<0.001), whereas plasma osmolality did not differ between the two groups. Consequently, the ur ine/plasma osmolality ratio (U-osm/P-osm) was lower in patients with G ushing's disease than in normal individuals (1.8+/-0.5 compared with 3 .4+/-0.4, P<0.001). The AVP concentration also was greater (7.3+/-3.1 pmol/l) in those with Gushing's disease than in the controls (3.3+/-2. 3 pmol/l, P<0.005). After administration of DDAVP to the hypercortisol aemic patients, the urinary osmolality attained (718.0+/-200.0 mOsm/l) was Still lower than that in the normal group al the end of WDT (P<0. 005). Conclusions: Patients with Gushing's disease presented higher AV P levels and smaller U-osm/P-osm ratios than normal subjects. After DD AVP, the patients with Gushing's disease were unable to concentrate th e urine adequately. These data suggest that the kidney shows resistanc e to the action of both endogenous and exogenous AVP in patients with Gushing's disease.