Surgical Outcomes of Silent ACTH+ Corticotroph Pituitary Neuroendocrine Tumors: A Multi-Institutional Experience and Review of the Literature

BACKGROUND AND OBJECTIVES: Silent corticotroph pituitary neuroendocrine tumors (PitNETs) constitute approximately 20% of nonfunctional PitNETs and exhibit positive immunostaining for adrenocorticotropic hormone (ACTH). These tumors have been characterized as exhibiting high recurrence rates and poor response to repeat intervention as compared with other subsets of nonfunctional PitNETs. As such, we aimed to evaluate a multi-institutional experience of silent corticotroph (ACTH+) PitNETs to characterize the presentation, radiographic characteristics, and their clinical outcomes. METHODS: An Institutional Review Board-approved retrospective study of patients undergoing resection of PitNET at the University of Washington and University of Southern California between 2011 and 2023 was performed. Patients with negative immunostaining for ACTH and patients with biochemically confirmed Cushing's disease were excluded. Clinical and radiographic presentation and surgical outcomes are reported. RESULTS: A total of 277 patients between the two institutions underwent surgical resection of PitNET with positive immunostaining for ACTH. A total of 91 patients with Cushing's disease were excluded from analysis. The final cohort of patients with silent corticotroph PitNETs was 186. The cohort consisted of 114 women (61.3%) and the average age of all patients was 52.3 ± 14.5 years. There was a substantial rate of extrasellar growth into the suprasellar region (63.7%), cavernous sinus (56.4%), and clival/sphenoid (12.3%) compartments. Gross total resection was achieved in 79.7% of cases. The recurrence/progression-free survival at mean follow-up time of 21.5 months was 85.9%. CONCLUSION: Silent corticotroph PitNETs have high rates of extrasellar growth, often limiting the ability to achieve gross total resection. Recurrence/progression is common, occurring in 13% to 17% of cases within two years, necessitating the need for close postoperative follow-up.