Search

The change in the plasma concentration of cortisol after the administration of thyrotrophin releasing hormone (TRH) and LH releasing hormone (LH-RH) was studied in normal dogs and in dogs with pituitary-dependent hyperadrenocorticism (PDH). The normal dogs showed a small but significant increase in the plasma concentration of cortisol 15 min after intravenous injection of TRH and LH-RH. In ten of the dogs with PDH the response to TRH was not significantly different from that in the normal dogs, but in 13 the response was significantly greater. In 15 of the dogs with PDH the response to LH-RH administration was within or below the range of responses in the normal dogs and in only one dog was the response to LH-RH greater than that in the normal dogs. These findings are discussed in relation to the pathogenesis of PDH.

The response has been studied in nine dogs with hyperadrenocorticism due to adrenocortical tumours to the administration of dexamethasone, insulin, lysine-vasopressin and tetracosactide by measuring the changes in plasma cortisol concentration. Administration of dexamethasone did not produce a decrease in the plasma concentration of cortisol in any of these dogs. Administration of insulin caused slight increases in the plasma concentration of cortisol in four out of eight dogs. Lysine-vasopressin increased the plasma concentration of cortisol in eight out of nine dogs, three responded supranormally. Eight out of the nine dogs responded to tetracosactide administration, three responded supranormally. It is concluded that in the dog, in contrast to man, the lysine-vasopressin test cannot be used to differentiate between pituitary-dependent hyperadrenocorticism and hyperadrenocorticism due to an adrenocortical tumour. Apparently pituitary ACTH is not completely depleted in dogs with hyperfunctioning adrenocortical tumours.

Hypothalamic corticotrophin releasing factor (CRF) activity was determined in five dogs with spontaneous hyperadrenocorticism and in three control animals (one untreated, one treated with high doses of ACTH for 2 months and one treated with high doses of cortisone for 2 months). Hypothalamic CRF activity was low or undetectable in four dogs with spontaneous pituitary-dependent hyperadrenocorticism and was reduced in one dog with Cushing's syndrome due to an adrenocortical tumour. The results are compatible with a pituitary origin for pituitary-dependent hyperadrenocorticism in the dog but are not conclusive; direct information about the rates of hypothalamic CRF secretion is required.

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/l 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 4h after intravenous injection of 0·05 mg dexamethasone/kg is adequate: suppression is obtained only in cases of pituitary-dependent hyperadrenocorticism.

Administration of cyproheptadine for 2 months to five dogs with pituitary-dependent hyperadrenocorticism (PDH) at a dose rate of 0·3 mg/kg per 24 h (group 1) and to four dogs with PDH at a dose rate of 1 mg/kg per 24 h (group 2) did not result in any clinical improvement. The hyperadrenocorticoid state, as indicated by the circulating cortisol levels, the urinary corticosteroid excretion and the response of the hypothalamo-pituitary-adrenal axis to lysine-vasopressin, thyrotrophin releasing hormone and dexamethasone did not change consistently, although there was a tendency to normalization of some parameters in the dogs of group 2. However, these changes were not found to be consistent for each individual dog but were limited to one parameter per dog. It is concluded that cyproheptadine is not suitable for the treatment of PDH in the dog.J. Endocr.(1984) 101, 311–314

Dogs with spontaneous pituitary-dependent hyperadrenocorticism were divided into two groups, one with normal plasma concentrations of α-MSH (normal α-MSH dogs, n= 26) and the other with high plasma concentrations of α-MSH (high α-MSH dogs, n= 14), on the presumption that high α-MSH concentrations indicated a parent cell of pars intermedia origin.The urinary corticoid/creatinine ratios of the high α-MSH dogs were significantly higher than those of the normal α-MSH dogs. The percentage decrease of the corticoid/creatinine ratios following dexamethasone administration was significantly higher in the normal α-MSH dogs than in the high α-MSH dogs. Dexamethasone resistance occurred in both the normal α-MSH dogs (4 out of 26) and the high α-MSH dogs (7 out of 14), indicating a relative rather than an absolute difference.The short-term effect of orally administered bromocriptine, at a dose (10 μg/kg body weight) known to be effective in lowering prolactin concentrations in dogs, was investigated by measuring concentrations of cortisol, ACTH and α-MSH in plasma at 4, 6 and 8 h after administration. Significant decreases were observed for cortisol in both groups and for α-MSH only in the high α-MSH dogs.The effect of 5 days of bromocriptine administration (10 μg at 12-h intervals) was assessed by measurements of urinary corticoid/creatinine ratios. Considering both groups as a whole, only the corticoid/creatinine ratios of the high α-MSH dogs decreased significantly on the first day of treatment. In each group there was one dog in which bromocriptine administration lowered the corticoid/creatinine ratios for several days, but the values stayed above the reference range and the animals did not recover.It is concluded that high α-MSH concentrations are not unambiguously associated with the theoretically expected characteristics of pars intermedia disease. The results indicate that the pituitary lesions causing hyperadrenocorticism may not maintain the regulation characteristics of the lobe of origin.J. Endocr. (1988) 118,271–277

The present study describes a radioimmunoassay for plasma adrenocorticotrophin (ACTH) in man with a sensitivity of at least 15 pg/ml. In-vitro studies using various fragments of ACTH showed immunobiological dissociation. However, this phenomenon does not appear to be of major importance in vivo, since stimulation and suppression tests showed overall parallel changes of immunoreactive plasma ACTH and plasma cortisol. The results obtained from patients with various forms of Cushing's syndrome are presented. It is concluded that basal plasma ACTH determinations are useful in the differential diagnosis of Cushing's syndrome and may help in predicting the development of a pituitary tumour after adrenalectomy.The supranormal plasma cortisol response to i.m. injection of lysinevasopressin in subjects with pituitary-dependent Cushing's syndrome is attributed both to an increased ACTH release by the pituitary and to an excessive response of the hyperplastic adrenal cortex. The i.v. infusion of dexamethasone at a rate of 1 mg/h for 5 h in subjects with pituitarydependent Cushing's syndrome was followed by significant and parallel decreases of both immunoreactive plasma ACTH and plasma cortisol. No rise of plasma ACTH levels was found with insulin-induced hypoglycaemia in subjects with untreated pituitary-dependent Cushing's syndrome.