Residual pituitary function after transsphenoidal hypophysectomy in dogs with pituitary-dependent hyperadrenocorticism B P Meij, J A Mol, M M Bevers 1 and A Rijnberk Department of Clinical Sciences of Companion Animals and 1 Department of Herd Health and Reproduction, Faculty of Veterinary Medicine, Utrecht University, The Netherlands (Requests for offprints should be addressed to B P Meij, Department of Clinical Sciences of Companion Animals, Utrecht University, PO Box 80.154, NL-3508 TD Utrecht, The Netherlands) Abstract Pituitary function was assessed before and after trans- sphenoidal hypophysectomy in 39 dogs with pituitary- dependent hyperadrenocorticism (PDH). Anterior pituitary function was investigated using combined administration of four hypophysiotropic releasing hor- mones (corticotropin-releasing hormone (CRH), GHRH, GnRH, and TRH) with measurements of ACTH, cortisol, GH, LH, prolactin (PRL), and TSH. Pars inter- media function was assessed by measurements of basal plasma -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 -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 hypophysec- tomy, 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 corre- lations 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. Journal of Endocrinology (1997) 155, 531–539 Introduction Since the late 1980s there has been consensus with regard to the therapy of Cushing’s disease. Transsphenoidal pituitary microsurgery is considered the primary treatment (Melby 1988, Thorner et al. 1992), despite a rate of recurrence of 20–30% (McCance et al. 1993, Sonino et al. 1996). In order to minimize the consequences of recur- rences, parameters have been identified that might predict the risk of recurrence at an early stage. Adrenocortico- tropic hormone (ACTH) hyperresponsiveness to an early postoperative stimulation with corticotropin-releasing hor- mone (CRH) seems to be a valuable criterion of recur- rence (Vignati et al. 1994), although early postoperative measurements of plasma and/or urinary cortisol may safely replace tests using supra-pituitary stimulants (Pieters et al. 1989, de Lange & Sluiter 1993, Toms et al. 1993, Trainer et al. 1993, McCance et al. 1996). 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 con- founding 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 531 Journal of Endocrinology (1997) 155, 531–539  1997 Journal of Endocrinology Ltd Printed in Great Britain 0022–0795/97/0155–0531 $08.00/0