For the purpose of obtaining an integral picture of anterior pituitary function in canine pituitary-dependent hyperadrenocorticism (PDH), 47 dogs with PDH and eight control dogs received combined administration of four hypophysiotropic hormones (CRH, GHRH, GnRH and TRH) and measurements were made of ACTH, cortisol, GH, LH, PRL and TSH. Basal plasma levels in 47 dogs with PDH were higher for ACTH, cortisol and PRL, lower for GH, and not different for LH (n = 25 noncastrated dogs) and TSH compared with controls (n = 8). In dogs with PDH the responses to combined hypophysiotropic stimulation, measured as increment and area under the curve (AUC), were not different for ACTH, lower for GH and TSH (increments and AUC) and higher for cortisol (increments), LH (AUC, n = 25 noncastrated dogs) and PRL (increments and AUC) than in controls. We conclude that pituitary function is altered in several respects in dogs with PDH. 1) In spite of persisting hypercortisolemia and the neoplastic transformation of the corticotropic cells, these cells usually remain responsive to combined hypophysiotropic stimulation. 2) Basal plasma GH concentrations and GH responsiveness in the combined stimulation test are decreased, probably as a result of the glucocorticoid-induced increase in somatostatin tone. 3) Plasma PRL concentrations and the PRL response to stimulation are increased, probably as a result of cosecretion with ACTH by the transformed corticotropic cells. 4) Despite the well known effect of glucocorticoids of decreasing circulating concentrations of gonadal steroids and thyroxine, the basal plasma concentrations of LH and TSH remain unchanged and there is a tendency to hyperresponsiveness to stimulation for LH and hyporesponsiveness for TSH. The most likely explanation for these changes is a dual effect of glucocorticoids: a direct effect on the gonads and thyroids and/or the transport and metabolism of their secretory products, and an influence on the sensitivity of the feedback control at the hypothalamic-pituitary level.

Pituitary function was assessed before and after transsphenoidal hypophysectomy in 39 dogs with pituitary-dependent hyperadrenocorticism (PDH). Anterior pituitary function was investigated using combined administration of four hypophysiotropic releasing hormones (corticotropin-releasing hormone (CRH), GHRH, GnRH, and TRH) with measurements of ACTH, cortisol, GH, LH, prolactin (PRL), and TSH Pars intermedia function was assessed by measurements of basal plasma alpha-MSH concentrations and adrenocortical function by baseline urinary corticoid/creatinine ratios. At eight weeks after hypophysectomy basal plasma ACTH, cortisol, GH, LH, PRL, and TSH concentrations were significantly lower than before surgery. In seven dogs with elevated alpha-MSH concentrations, the values returned to the normal level after surgery. In the combined anterior pituitary function test there were no plasma GH, LH, PRL, and TSH responses to stimulation, whereas plasma ACTH and cortisol responses were small but significant. Remission of hyperadrenocorticism was obtained in 35 dogs and recurrences occurred in 3 of these within 16 months postoperatively. At 8 weeks after hypophysectomy, these 3 dogs were not discernible, with respect to residual pituitary and adrenocortical function, from the 32 dogs with persisting remission. Urinary corticoid/creatinine ratios in the latter group of dogs did not increase during 22 months after hypophysectomy. In contrast to the presurgical findings, at 8 weeks after hypophysectomy there were significant positive correlations between baseline urinary corticoid/creatinine ratios and basal levels and responses for ACTH, indicating return to normal function of the pituitary-adrenocortical axis. It is concluded that among the adenohypophyseal cells present in the sella turcica after hypophysectomy, the corticotropes have a distinct behavior. Much more so than the other cell types, the unaffected corticotropes tend to remain functional, or a repressed reserve fraction of corticotropes may become functional. This may be due to the removal of the hypothalamic influence of a postulated corticotropin-release inhibiting factor or a diminished inhibitory influence of a postulated paracrine factor. The corticotropes may maintain normocorticism, but may also lead to mild recurrence after relatively long periods of remission.