Responsiveness to corticotropin-releasing hormone and vasopressin in canine Cushing's syndrome

Abstract

Corticotropin-releasing hormone (CRH) and vasopressin are the most important hypothalamic factors regulating adrenocorticotropic hormone (ACTH) secretion. In this study we have investigated the responsiveness of the pituitary-adrenocortical axis to intravenous administration of CRH or lysine vasopressin (LVP) in 16 control dogs, 22 dogs with pituitary-dependent hyperadrenocorticism and five dogs with hyperadrenocorticism due to an adrenocortical tumor, using doses of CRH and LVP that caused equivalent ACTH responses in the control dogs. After CRH administration, the increment in plasma ACTH was significantly (p < 0.05) lower in dogs with pituitary-dependent hyperadrenocorticism (221 +/- 53 ng/l) than that in control dogs (279 +/- 41 ng/l). In the dogs with pituitary-dependent hyperadrenocorticism, the relative increases in ACTH after CRH were significantly (p < 0.05) lower than those after LVP. Despite the absence of an increase in ACTH following LVP administration in dogs with hyperadrenocorticism due to an adrenocortical tumor, there was a significant increase in plasma cortisol, the increment (790 +/- 238 nmol/l) being not statistically different from that in the control dogs (412 +/- 37 nmol/l). We conclude that in spite of the changes inherent to pituitary-dependent hyperadrenocorticism, i.e. neoplastic transformation of corticotropic cells and hypercortisolism, there is persistence of responsiveness to hypophysiotropic hormones. The ACTH secretion by corticotropic cells in pituitary-dependent hyperadrenocorticism was relatively less sensitive to stimulation with CRH than with LVP. Adrenocortical tumors develop an aberrant sensitivity to LVP.

Effects of corticotrophin-releasing hormone, vasopressin and insulin-like growth factor-I on proliferation of and adrenocorticotrophic hormone secretion by canine corticotrophic adenoma cells in vitro

“…These results con®rm earlier reports on in vitro and in vivo studies (39,45) that demonstrated a relative insensitivity of canine corticotrophic tumour cells to stimulation by CRH.…”

Alterations in anterior pituitary function of dogs with pituitary-dependent hyperadrenocorticism

“…The ACTH response to combined hypophysiotropic stimulation in dogs with PDH was not different from that in control dogs, but occurred at higher ACTH levels. In studies of the responsiveness to single CRH administration, it was found that, in dogs with PDH, increments in plasma ACTH were similar to (Rijnberk et al 1987) or somewhat lower than (Van Wijk et al 1994) those in control dogs. Although not found in dogs, ACTH hyperresponsiveness to CRH is commonly found in humans with Cushing's disease caused by pituitary microadenomas (Orth et al 1982, Pieters et al 1983, Schrell et al 1987, Fukata et al 1993, although testing in individual patients has revealed hyperresponsiveness, normal responsiveness and even unresponsiveness (Pieters et al 1983).…”

In vivo and in vitro effects of AVP and V1a receptor antagonist on Cushing's syndrome due to ACTH‐independent bilateral macronodular adrenocortical hyperplasia

“…There is increasing awareness that the sensitivity of the adrenal gland to AVP is an important factor regulating cortisol secretion in patients with ACTH‐independent Cushing's syndrome. An iv injection of LVP evoked a greater response in plasma cortisol levels in dogs with hypercortisolism due to an adrenocortical tumour than in normal animals, in spite of the absence of an increase in plasma ACTH levels ( van Wijk et al ., 1994 ). An im injection of LVP also induced a marked increase in plasma cortisol without any elevation of plasma ACTH levels ( Perraudin et al ., 1995 ).…”