Crooke's cell adenoma of the pituitary: An aggressive variant of corticotroph adenoma

Cushing's disease is caused by functional corticotroph adenomas of the pituitary, mostly noninvasive microadenomas. Classic Crooke's cells are nonneoplastic corticotrophs with cytoplasmic accumulation of cytokeratin filaments in response to glucocorticoid excess. Corticotroph adenomas exhibiting Crooke's change are rare and incompletely understood. We intend to define more clearly the clinicopathological features of Crooke's cell adenomas (CCA). Thirty-six CCAs were retrieved from the files of Mayo Clinic and from our (B.W.S., K.K.) consultation files. The number of informative cases varied for different criteria. Clinical follow-up was obtained in 31 cases. The 27 females and 9 males were 18 to 81 years of age (mean 46 years). At presentation, Cushing's disease was evident in 22/34 (65%); 81% were macroadenomas and 72% were invasive. All were initially treated by transsphenoidal resection. Twenty-five patients were followed for more than 1 year (mean 6.7 years). Of these, 15 (60%) developed recurrent tumor, and 6 (24%) had multiple recurrences. Lastly, 3 of these 25 patients (12%) died of tumor: 1 after multiple local recurrences and 2 from pituitary carcinoma. Compared with typical corticotroph adenomas, CCAs are aggressive. Most are functional adenomas occurring in middle-aged women and are invasive macroadenomas prone to recurrence. Morbidity and mortality rates are substantial. CCAs represent a distinct entity that should be separated from corticotroph adenomas without Crooke's hyaline change.