Clinical Parameters to Distinguish Silent Corticotroph Adenomas from Other Nonfunctioning Pituitary Adenomas

Background: It is difficult to distinguish silent corticotroph adenomas (SCAs) from other nonfunctioning pituitary adenomas (NFPAs) preoperatively. This study aimed to determine the preoperative clinical parameters associated with SCAs. Methods: This was a retrospective single-center study of patients who underwent surgery for NFPAs during 2011–2016 in our tertiary hospital and who had preoperative combined pituitary function test (CPFT) and immunohistochemical staining results available. After we excluded patients with increased 24-hour urinary free cortisol to preclude overt Cushing's disease, 341 patients were finally enrolled. The medical records, including the CPFT and immunohistochemistry results, of the patients were reviewed. Results: The age and tumor size were similar between patients with SCAs and other NFPAs. The SCA group had a greater proportion of women (89.2% vs. 57.6%, P < 0.001), cavernous sinus invasion (35.1% vs. 20.7%, P = 0.047), and intratumoral hemorrhage on preoperative sella magnetic resonance imaging (32.4% vs. 9.2%, P < 0.001) compared with the NFPA group. In the preoperative CPFT, the cortisol response was not significantly different between groups. However, the peak adrenocorticotropic hormone (ACTH) (67.80 ± 49.83 vs. 85.67 ± 78.97 pg/mL, P = 0.061) tended to be lower, and the ΔACTH (53.71 ± 50.14 vs. 72.67 ± 75.82 pg/mL, P = 0.046) was significantly lower in SCAs. After we excluded patients with preoperative hypopituitarism caused by mass effects, the peak ACTH (69.39 ± 39.45 vs. 119.75 ± 89.84 pg/mL, P = 0.001) and ΔACTH (58.58 ± 36.51 vs. 107.66 ± 86.05 pg/mL, P = 0.001) were significantly lower in SCAs than in other NFPAs. Conclusions: Female sex, cavernous sinus invasion, intratumoral hemorrhage on sella magnetic resonance imaging, and decreased ACTH response in the CPFT are independent indicators of SCAs.