OBJECTIVEThe aim of this study is to characterize the incidence, aggressiveness, and clinical outcomes of silent TPIT+ PitNETs, as well as treatment strategies in the event of recurrence/progression. We also review the current literature surrounding TPIT+ silent corticotrophs.METHODSAn institutional review board-approved retrospective study of prospectively acquired patients undergoing resection of PitNETs at the University of Washington and University of Southern California between 2011 and 2023 was performed. A prospectively maintained Research Electronic Data Capture database at each institution was queried for patients with tumors immunostaining positive for TPIT and included for study regardless of adrenocorticotropic hormone (ACTH) status. Exclusion criteria included patients with biochemically confirmed Cushing disease. Patient demographics, preoperative radiographic findings, and surgical outcomes were documented. Descriptive statistics were reported for the patient cohort and recurrence/progression free survival analysis was measured and visualized using Kaplan-Meier and Swimmer plots.RESULTSA total of 1475 patients underwent surgical resection of PitNET with a total of 107 TPIT-immunoreactive tumors. Of these, 37 (34.6%) patients were diagnosed with Cushing disease preoperatively and were excluded from the analysis, leaving 70 (65.4%) patients with TPIT+ silent corticotroph PitNETs. A total of 56 (80%) tumors were only TPIT+, while 14 (20%) stained positive for multiple transcription factors including steroidogenic factor-1, pituitary-specific positive transcription factor 1, or both. The cohort consisted of 45 (64.3%) ACTH+ tumors and 25 (35.7%) ACTH tumors. There were 19 (27.1%) men and 51 (72.9%) women, with mean age 51.3 years. Radiographically, growth beyond the sella into the suprasellar space 54 (77.1%), cavernous sinus 41 (51.4%), and clival/sphenoid 12 (17.1%) compartments was common. A total of 67 (95.7%) of cases were treated via an endoscopic endonasal approach. Gross total resection (GTR) was achieved in 47 (70.1%) of cases. Of those undergoing GTR, two (4.3%) experienced tumor recurrence. Of those undergoing subtotal resection, four (20%) experienced tumor progression (P = 0.06). The median recurrence/progression free survival of TPIT+ tumors was 51.3 months. When stratified by extent of resection, median recurrence free survival was 38.3 months for GTR versus median progression free survival of 51.3 months for subtotal resection (P = 0.88).CONCLUSIONSWith the addition of TPIT staining, the diagnosis of silent corticotroph PitNETs increased substantially versus those defined by ACTH immunostaining alone. Regardless of hormone status, these tumors continue to exhibit high rates of extrasellar growth and high rates of recurrence/progression.