Crooke Cell Adenoma Confers Poorer Endocrinological Outcomes Compared with Corticotroph Adenoma: Results of a Multicenter, International Analysis

Crooke cell adenomas (CCA) are a rare, aggressive subset of adrenocorticotrophin secreting pituitary corticotroph adenomas (sCTA) found in 5–10% of patients with Cushing’s disease. Multiple studies support worse outcomes in CCA but are limited by small sample size and single-institution databases. We compared outcomes in CCA and sCTA using a multicenter, international retrospective database of high-volume skull base centers. Patients surgically treated for pituitary adenoma from January 2017 through December 2020 were included. 2826 patients from 12 international centers were compared (n=20 CCA and n=480 sCTA). No difference in baseline demographics, tumor characteristics or postoperative complications was seen. Microsurgical approaches (60% CCA vs. 62.3% sCTA) were most common. Gross total resection (GTR) was higher in CCA patients (100% vs. 83%, p=0.05). Among patients that had GTR according to intraoperative findings, fewer CCA patients had postoperative hormone normalization of pituitary function (50% vs. 77.8%, p<0.01) and remission of hypersecretion by 3-6 months (75% vs. 84.3%, p<0.01). This was present despite CCA having better local control rates (100% vs. 96%, p<0.01) and fewer patients with remnant on MRI (0% vs. 7.2%, p<0.01). A systematic literature review of 35 studies reporting on various treatment strategies reiterated the high rate of residual tumor, persistent hypercortisolism, and tumor-related mortality in CCA patients. This modern, multicenter series of patients with CCA reflects their poor prognosis and reduced post-surgical hormonal normalization. Further work is necessary to better understand the pathophysiology of CCA to devise more targeted treatment approaches.