{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T14:34:01Z","timestamp":1787582041504,"version":"build-2736575974"},"reference-count":8,"publisher":"The Endocrine Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,8,1]]},"abstract":"\n Context:<\/jats:title>\n Although Crooke's changes in the pituitary corticotrophs were initially described in 1935, the prevalence in which the changes occur in patients with Cushing's syndrome (CS) has not been established.<\/jats:p>\n <\/jats:sec>\n \n Objective:<\/jats:title>\n This study aimed to determine the prevalence and assess clinical features associated with the presence or absence of Crooke's changes in a large set of patients with CS.<\/jats:p>\n <\/jats:sec>\n \n Design:<\/jats:title>\n Information from a prospective computer database and retrospective chart review was analyzed.<\/jats:p>\n <\/jats:sec>\n \n Setting:<\/jats:title>\n The setting was an academic medical center.<\/jats:p>\n <\/jats:sec>\n \n Patients:<\/jats:title>\n Consecutive patients (N = 213) who received surgery with a preoperative diagnosis of Cushing's disease are included.<\/jats:p>\n <\/jats:sec>\n \n Intervention:<\/jats:title>\n The patients received pituitary surgery and specimens obtained underwent pathological analysis.<\/jats:p>\n <\/jats:sec>\n \n Main Outcome Measure:<\/jats:title>\n The presence or absence of Crooke's changes was determined by histopathological analysis of the normal pituitary tissue included with the specimen obtained at surgery. Cortisol production was measured by 24-hour urine cortisol production.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n Crooke's changes occurred in 144 of 177 patients (81%) with a histologically demonstrated ACTH-staining tumor and in 74% of 213 patients diagnosed with CS who had pituitary surgery. The presence of Crooke's changes correlated with the finding of an ACTH-staining tumor removed at surgery and with the degree of hypercortisolism. Among patients with histologically established ACTH-staining tumors the prevalence of Crooke's changes was particularly high in patients with a 24-h urinary free cortisol (UFC) of at least 4-fold the upper limit of normal, in which 91% of patients had Crooke's changes, compared with 74% of patients whose maximum UFC was less than 4-fold the upper limit of normal (P = .008).<\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n Crooke's changes occur in 75\u201380% of patients with CS, and depend on the degree of hypercortisolism and individual variability. Almost all patients with UFC at least 4-fold the upper limit of normal have them, whereas with less severe hypercortisolism the expression of Crooke's changes varies from person to person.<\/jats:p>\n <\/jats:sec>","DOI":"10.1210\/jc.2015-2493","type":"journal-article","created":{"date-parts":[[2015,7,6]],"date-time":"2015-07-06T17:00:56Z","timestamp":1436202056000},"page":"3165-3171","source":"Crossref","is-referenced-by-count":36,"title":["Crooke's Changes In Cushing's Syndrome Depends on Degree of Hypercortisolism and Individual Susceptibility"],"prefix":"10.1210","volume":"100","author":[{"given":"Edward H.","family":"Oldfield","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery (E.H.O., R.G.L., C.L.P., J.A.J),"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Lee","family":"Vance","sequence":"additional","affiliation":[{"name":"Department of Medicine (M.L.V.),"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert G.","family":"Louis","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery (E.H.O., R.G.L., C.L.P., J.A.J),"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie L.","family":"Pledger","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery (E.H.O., R.G.L., C.L.P., J.A.J),"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"John A.","family":"Jane","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery (E.H.O., R.G.L., C.L.P., J.A.J),"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Beatriz S.","family":"Lopes","sequence":"additional","affiliation":[{"name":"Department of Pathology (M.-B.S.L.), University of Virginia Health System, Charlottesville, VA 22903"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071615264847100_B1","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1002\/path.1700410215","article-title":"Change in the basophil cells of the pituitary gland common to conditions which exhibit the syndrome attributed to basophil adenoma","volume":"41","author":"Crooke","year":"1935","journal-title":"J Pathol Bacteriol"},{"key":"2020071615264847100_B2","first-page":"214","article-title":"Cytoplasmic filaments of Crooke's hyaline change belong to the cytokeratin class. An immunocytochemical and ultrastructural study","volume":"116","author":"Neumann","year":"1984","journal-title":"Am J Pathol"},{"key":"2020071615264847100_B3","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/0960-0760(93)90139-N","article-title":"The pathology of Cushing's disease","volume":"45","author":"Kovacs","year":"1993","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2020071615264847100_B4","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1530\/eje.1.02326","article-title":"Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry","volume":"156","author":"Saeger","year":"2007","journal-title":"Eur J Endocrinol"},{"key":"2020071615264847100_B5","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1055\/s-0029-1212095","article-title":"Correlates of long-term hypocortisolism after transsphenoidal microsurgery for Cushing's disease","volume":"107","author":"Flitsch","year":"1999","journal-title":"Exp Clin Endocrinol Diabetes"},{"key":"2020071615264847100_B6","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/S0344-0338(88)80018-9","article-title":"Pituitary pathology in Cushing's disease","volume":"183","author":"Saeger","year":"1988","journal-title":"Pathol Res Pract"},{"key":"2020071615264847100_B7","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/S0344-0338(11)80137-8","article-title":"Further immunohistochemical study of Crooke's hyalin","volume":"187","author":"Uei","year":"1991","journal-title":"Pathol Res Pract"},{"key":"2020071615264847100_B8","first-page":"65","article-title":"Fine structure of Crooke's hyaline change in the human pituitary gland","volume":"94","author":"DeCicco","year":"1972","journal-title":"Arch Pathol"}],"container-title":["The Journal of Clinical Endocrinology & Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/100\/8\/3165\/17636486\/jcem3165.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/100\/8\/3165\/17636486\/jcem3165.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T02:41:13Z","timestamp":1594953673000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/100\/8\/3165\/2830423"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8,1]]},"references-count":8,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2015,8,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2015-2493","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,8,1]]}}}