LAUSR

Abstract Background: Autonomous glucocorticoid excess in patients with Cushing disease (CD) may lead to negative feedback suppression, resulting in Crooke's hyaline change (CC) of the non-tumorous corticotrophs in the pituitary. Objective: To determine the prognostic implication of evidence of CC on histopathology examination following pituitary surgery for CD. Methods: This was a retrospective review of patients from a single clinic with preoperative diagnosis of CD, who had pituitary surgery and pathology specimens that were reviewed by two pathologists for the presence of CC in non-tumorous adenohypophysis. Results: The cohort included 47 patients (37 female) with at least one available pathology sample for evaluation; 11 patients had two samples. Evaluation of CC was not possible in 15 pathology samples from 13 patients, mainly due to lack of non-tumorous pituitary tissue (8 samples), crush artifact (4 samples), or other reason (3 samples). Among 34 patients with adequate pathology sample for evaluation of CC, in 28 patients (82%) there was evidence of CC and in 6 patients (18%) the samples were negative for CC; 2 of these had corticotroph hyperplasia. During the mean (SD) follow-up of 62 months (40), recurrent or persistent disease was evident in 14 cases, while 18 patients were in remission; 2 cases with CC were lost to follow-up. Remission rates were lower in patients with no histological evidence of CC (2/6 patients, 33%), compared to those with CC (16/26 patients, 62%). Repeat pituitary surgery was completed in 7 patients (27%) with CC, 4 cases (67%) without CC, and one case (31%) with no data regarding CC. Conclusions: In most patients with clinical suspicion of CD there is CC in the non-tumorous corticotrophs. The absence of CC may point to increased risk of persistent or recurrent disease. While in some cases this may be attributed to corticotroph hyperplasia, in others this may reflect altered cellular feedback regulation in the non-tumorous corticotrophs. Further studies are required to determine the molecular pathogenesis of these findings with respect to various clinical conditions manifesting with ACTH excess.