Resistance to vasopressin action on the kidney in patients with Cushing's disease

M Knoepfelmacher, M. Pradal, R. Dio, L. Salgado, M Semer, B. Wajchenberg, B Liberman
1997 European Journal of Endocrinology  
Objective: To assess the plasma levels and action of arginine vasopressin (AVP) in patients with Cushing's disease. There are many reports that patients with Addison's disease have increased AVP levels associated 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 plasma AVP concentration and the urinary and plasma osmolality after a 7.5-h water
more » ... ter a 7.5-h water deprivation test (WDT) were evaluated in 13 patients with Cushing's disease and 15 normal (control) individuals. In patients with Cushing's disease we also assessed the urinary osmolality in response to 10 mg 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 Cushing's disease (511.5Ϯ148.5 mOsm/l) than in the normal subjects (981.1Ϯ107.1 mOsm/l, P<0.001), whereas plasma osmolality did not differ between the two groups. Consequently, the urine/plasma osmolality ratio (U osm /P osm ) was lower in patients with Cushing's disease than in normal individuals (1.8Ϯ0.5 compared with 3.4Ϯ0.4, P<0.001). The AVP concentration also was greater (7.3Ϯ3.1 pmol/l) in those with Cushing's disease than in the controls (3.9Ϯ2.3 pmol/l, P<0.005). After administration of DDAVP to the hypercortisolaemic patients, the urinary osmolality attained (718.0Ϯ200.0 mOsm/l) was still lower than that in the normal group at the end of WDT (P<0.005). Conclusions: Patients with Cushing's disease presented higher AVP levels and smaller U osm /P osm ratios than normal subjects. After DDAVP, the patients with Cushing's disease were unable to concentrate the urine adequately. These data suggest that the kidney shows resistance to the action of both endogenous and exogenous AVP in patients with Cushing's disease. European Journal of Endocrinology 137 162-166 Subjects and methods We studied nine women and four men, aged between 23 and 45 years, with pituitary adrenocorticotrophic hormone (ACTH)-dependent hyperadrenocorticism. Clinical hypercortisolism was identified by the presence
doi:10.1530/eje.0.1370162 pmid:9272104 fatcat:5khasqw3tbegtlv7omifm56ydm