Corticotropin-releasing hormone and adrenocorticotropic hormone concentrations in cerebrospinal fluid of dogs with pituitary-dependent hyperadrenocorticism

Abstract

There is still some controversy concerning the question of whether Cushing's disease in man is caused by a primary dysfunction of the pituitary or a hypothalamic disorder. In the latter option, excessive hypothalamic stimulation of pituitary corticotropes would cause or contribute to the genesis of POMC-secreting adenomas. In the present study cerebrospinal fluid (CSF) CRH levels and levels of ACTH and cortisol in CSF and plasma were measured in clinically healthy dogs, in dogs with pituitary-dependent hyperadrenocorticism (PDH), and in dogs with hyperadrenocorticism due to an adrenocortical tumor (ATH). In CSF from dogs with PDH, CRH concentrations (226.6 +/- 14.4 ng/liter) were significantly (P < 0.05) lower than those in control dogs (309.5 +/- 20.3 ng/liter). In the dogs with ATH, CSF CRH concentrations (211.0 +/- 40.3 ng/liter) were in the range of those in PDH dogs. In dogs with ATH, CSF ACTH levels (13.0 +/- 3.0 ng/liter) were significantly (P < 0.05) lower than those in control dogs (63.4 +/- 3.5 ng/liter), whereas in dogs with PDH, the levels (116.8 +/- 47.5 ng/liter) were not different from those in the control group. In control dogs, the concentrations of CSF CRH and plasma ACTH were significantly correlated (r = 0.635; P < 0.01). This functional dependency appeared to be disturbed in dogs with PDH, as in these dogs CSF CRH concentrations did not correlate with plasma ACTH concentrations. It is concluded that continuous hyperstimulation of pituitary corticotropes with hypothalamic CRH is probably not the cause of excessive ACTH secretion in dogs with pituitary-dependent hyperadrenocorticism.

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

“…This is in concordance with results from earlier studies. In man and dog, it has been shown that the excessive ACTH secretion in Cushing's disease is not caused by persistent hyperstimulation of corticotropes by CRH (29,38), and canine ACTH-producing tumours have been shown to be relatively insensitive to stimulation by hypothalamic hormones in vitro (39).…”

“…Diagnosis of PDH was based upon measurements of corticoid/creatinine ratios in urine before and after dexamethasone administration (28), measurements of plasma ACTH concentration (29) and computed tomography of the pituitary gland (30). Total hypophysectomy was performed by the trans-sphenoidal approach described by Markowitz et al (31), with slight modi®cations.…”

Residual pituitary function after transsphenoidal hypophysectomy in dogs with pituitary-dependent hyperadrenocorticism

“…In the debate over possible ways to decrease the number of recurrences and over the early detection of surgical failure, corticotropic cell hyperplasia has played a confounding role. It was presumed to be due to excessive production of hypothalamic CRH but in recent years it has been demonstrated that CRH concentrations in cerebrospinal fluid of both humans (Kling et al 1991) and dogs (van Wijk et al 1992) with pituitary-dependent hyperadrenocorticism (PDH) are lower than in healthy individuals. Moreover, there is now increasing evidence that the disease originates at the pituitary level by clonal expansion of a single aberrant cell (Pei & Melmed 1996) and that corticotropic hyperplasia does not exist in Cushing's disease (Trouillas et al 1996).…”