Under the assumption that the impaired inhibitory effect of glucocorticoids on cell division is an important determinant in the progression of corticotrophic adenomas, it is postulated that the magnitude of proliferation and the resistance to glucocorticoids are correlated. To test this hypothesis, 67 dogs with pituitary-dependent hyperadrenocorticism were studied to determine whether a correlation could be demonstrated between the effect of dexamethasone administration on the activity of the pituitary–adrenocortical axis and the size of the pituitary gland as estimated by computed tomography.

The volumes of the pituitary glands as calculated from summations of subsequent images of pituitary areas, ranged from 11·8 to 3238·6 mm³. Among the three dimensions, the height of the pituitary was the most sensitive indicator of enlargement. Calculation of the pituitary height/brain area ratio (P/B ratio) allowed correction for the size of the dog. The P/B ratio had the highest discriminatory power in distinguishing enlarged (n=41) from non-enlarged (n=26) pituitaries.

The effects of dexamethasone (0·1 mg/kg) on the plasma concentrations of cortisol and ACTH and on the urinary corticoid/creatinine (C/C) ratios were expressed as percentage changes from the initial values. For ACTH, cortisol and C/C ratios these figures for resistance to dexamethasone were significantly correlated with the dimensions of the pituitary, particularly the height, volume and P/B ratio.

It is concluded that the magnitude of the expansion of pituitary corticotrophic adenomas is dependent upon the loss of restraint by glucocorticoids, i.e. the degree of insensitivity to glucocorticoid feedback.

Journal of Endocrinology (1997) 152, 387–394

Abstract

This study was performed to determine whether, in the dog, there is at any time pulsatile release of α-MSH and whether secretion of ACTH from the pars intermedia (PI) contributes to the circulating concentrations of ACTH.

The 24-h secretory profiles of α-MSH, ACTH, and cortisol were determined in eight dogs. Plasma samples were obtained at 10-min intervals via an indwelling jugular catheter during two 12-h periods. Pulsatile secretion of α-MSH was found in all dogs, with wide variations in peak height. Plasma α-MSH levels were usually low (mean 15 pmol/l), but brief, distinct periods of increased plasma α-MSH concentrations as high as 489 pmol/l were found. Analysis of pulse frequency revealed a mean of 4·75 significant α-MSH peaks/24 h. The highest α-MSH peaks were associated with definite changes in the plasma concentrations of ACTH.

In separate studies, the influence of dexamethasone on the 6-h secretory profiles and on the haloperidol-stimulated secretion of α-MSH, ACTH, and cortisol was investigated. In these two studies, plasma ACTH was measured by a highly sensitive immunoradiometric assay. Dexamethasone pretreatment significantly suppressed the plasma concentrations of ACTH, cortisol, and α-MSH to 10·3%, 3·9%, and 74·6% respectively. Dexamethasone pretreatment also significantly reduced the haloperidol-stimulated secretion of ACTH and cortisol, but had no influence on the haloperidol-stimulated secretion of α-MSH. After the administration of haloperidol to the dexamethasone-pretreated dogs, there were small increases in the plasma concentrations of ACTH and cortisol, the latter being significant.

These data demonstrate that α-MSH is secreted spontaneously in a pulsatile manner in the dog and suggest that the canine PI contributes to circulating ACTH concentrations.

Journal of Endocrinology (1997) 152, 113–121

The 6-h plasma profiles of adrenocorticotropic hormone (ACTH), cortisol, α-melanocyte-stimulating hormone (α-MSH), and GH were studied in 17 dogs with pituitary-dependent hyperadrenocorticism (PDH) before and after hypophysectomy. The aim of the study was to investigate the relation between the hormone profile characteristics and recurrence of PDH after surgery.

The hormones were secreted in a pulsatile fashion. The basal plasma cortisol concentration and area under the curve (AUC) for cortisol were significantly higher in the PDH cases than in eight controls. The characteristics of the plasma profiles of ACTH and α-MSH were not significantly different between the PDH cases and the controls. In the PDH cases, less GH was secreted in pulses than in the controls, but the difference was not significant. The basal plasma cortisol concentration, the AUC for ACTH and cortisol, and the pulse frequency of ACTH and cortisol decreased significantly after hypophysectomy for the group of PDH cases. The basal plasma concentrations of ACTH and α-MSH, the AUC for α-MSH, and the characteristics of the plasma GH profiles of the PDH cases remained unchanged after hypophysectomy. No pulses of α-MSH were observed after hypophysectomy. The co-occurrence between the ACTH and cortisol pulses decreased significantly with hypophysectomy. The postoperative pulse frequency of ACTH was the only characteristic with predictive value for the recurrence of PDH after hypophysectomy.

The results of this study demonstrate that ACTH, cortisol, α-MSH, and GH are secreted in a pulsatile fashion in dogs with PDH. Hypophysectomy effectively reduces the secretion of ACTH and cortisol. The presence of ACTH pulses after hypophysectomy is a risk factor for the recurrence of hyperadrenocorticism.