Crooke's Changes In Cushing's Syndrome Depends on Degree of Hypercortisolism and Individual Susceptibility.

Abstract

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. 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. Information from a prospective computer database and retrospective chart review was analyzed. The setting was an academic medical center. Consecutive patients (N = 213) who received surgery with a preoperative diagnosis of Cushing's disease are included. The patients received pituitary surgery and specimens obtained underwent pathological analysis. 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. 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). Crooke's changes occur in 75-80% 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.