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

Abstract

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 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.

Inherited secondary nephrogenic diabetes insipidus: concentrating on humans

“…The presence of sNDI with cystinosis has been reported recurrently (12,32,36,39,41). However, in our own clinical experience, it is clearly not universal.…”

Decrease of nitric oxide and increase in diastolic blood pressure are two events that affect renal function in dogs with pituitary dependent hyperadrenocorticism

“…Although administration of glucocorticosteriods increases GFR in the short term (Wen et al, 2000), chronic exposition, as is the case of HAC, provokes the opposite effect (Haentjens et al, 2005;Smets et al, 2010) as there is a long-term counter-productive effect of cortisol on GFR that persists even in HAC individuals in remission. Considering that most (65%) of the dogs studied presented a normal GFR, despite already showing proteinuria and an affected RI, this would indicate that filtration is not affected early on and that the polyuria typical of PDH would not be due to a greater filtration, but mainly because the vasopressin hormone is affected (Baas et al, 1984;Knoepfelmacher et al, 1997). Both GFR and RT did not correlate with cortisol (at least directly) and this could be explained by the hypothesis postulated by Haentjens et al (2005).…”

Copeptin and arginine vasopressin at high altitude: relationship to plasma osmolality and perceived exertion

“…Using data from the reported literature the median copeptin level in healthy individuals ranges from 3.2 to 6.6 pmol/L (Jochberger et al 2006). Basal levels of AVP are 1.15-2.4 pmol/L when osmolality is below 285 mOsmol/kg (Knoepfelmacher et al 1997). Our data is unique in that it demonstrates equal copeptin values in males and females.…”