Biochemical Characterization of Pituitary-Dependent Hyperadrenocorticism in the Dog

Abstract

The biochemical characterization of 22 cases of pituitary-dependent hyperadrenocorticism in the dog, is reported. The principal characteristics of the disease include excessive and non-rhythmic production of cortisol, decreased sensitivity of the hypothalamic-pituitary system to the suppressive effects of dexamethasone, decreased responsiveness of the pituitary-adrenocortical system to the stimulus of insulin-induced hypoglycaemia and increased responsiveness of the system to stimulation with lysine-vasopressin. From these observations it is concluded that pituitary-dependent hyperadrenocorticism in the dog is a valid model for study of the pathogenesis of the disease in man. For the diagnosis of hyperadrenocorticism itself, the measurement of the concentration of corticosteroids in a single sample of plasma obtained 8 h after intravenous injection of 0.01 mg dexamethasone/kg was sufficient. The level of 11-hydroxycorticosteroids was less than 140 nmol/1 plasma in normal dogs, whereas higher values were found in dogs with hyperadrenocorticism. For purposes of differential diagnosis, measurement of the level of corticosteroids in the plasma both before and 4 h after intravenous injection of 0.05 mg dexamethasone/kg is adequage: suppression is obtained only in cases of pituitary-dependent hyperadrenocorticism.

GSK1614343, a Novel Ghrelin Receptor Antagonist, Produces an Unexpected Increase of Food Intake and Body Weight in Rodents and Dogs

“…The use of dogs was preferred because the neuroendocrine regulation and the mechanism of control of FI in this species are similar to that in humans [37,38,39]. Interestingly, dogs treated with the compound displayed a significant increase in both weight gain and food consumption when compared with the vehicle-treated group, but only following the subchronic treatment.…”

Accuracy of an Adrenocorticotropic Hormone (ACTH) Immunoluminometric Assay for Differentiating ACTH‐Dependent from ACTH‐Independent Hyperadrenocorticism in Dogs

“…6,7,11,[23][24][25] Spontaneous HAC was confirmed in all dogs, based on a marked increase in serum cortisol concentration (!500 nmol/L) 1 hour after ACTH stimulation, an inadequate decrease in serum cortisol concentration (!40 nmol/L) 8 hours after dexamethasone injection, or both. ADHAC was demonstrated by a LDDST or HDDST exhibiting feedback inhibition 4 or 8 hours after dexamethasone injection.…”

“…During the last 30 years, a number of imaging techniques and endocrine tests, including plasma ACTH measurement, have been developed for this purpose. [5][6][7][8][9][10][11][12][13][14] Over this period, techniques used for ACTH measure have changed from radioimmunoassay (RIA) [15][16][17] to immunoradiometric (IRMA) 18 and immunoluminometric assays (ILMA), 19 with concomitant improvements in the analytical sensitivity and specificity. Despite its widespread use, few surveys have evaluated the diagnostic accuracy of ACTH determination for investigations of the cause of Cushing's syndrome.…”

Hypothalamic Catecholamine Levels in Dogs with Spontaneous Hyperadrenocorticism

“…In this dis ease the hypothalamo-pituitary system is less sensitive to the negative feedback effect of corticosteroids, a characte ristic which is of diagnostic importance in man as well as in dogs [17]. Hypotheses on the pathogenesis of PDH [4,5,10,13,14,21,24,25] are controversial as to whether the exces sive secretion of ACTH by the pituitary gland is due to a de rangement at the hypothalamic or at the pituitary level.…”