Age-Related Differences in Pre-Operative Characteristics, Invasion, and Immunostaining Among a Large Cohort of Patients Undergoing Endoscopic, Endonasal Resection of Pituitary Adenoma

Background: Patients undergoing endoscopic, endonasal resection of pituitary adenoma (PA) have been shown in prior studies to have differences in pre-operative characteristics by age at surgery, with younger patients having generally smaller tumors with a higher rate of functioning tumors. It is unclear how immunohistochemical and lineage-specific transcription factor biology may differ between younger and older patients undergoing resection of PA, and whether these differences may explain disparities in tumor size, functioning status, and surgical outcomes. Methods: We retrospectively reviewed a large series of patients who underwent endoscopic, endonasal, transsphenoidal resection of PA from 1992 to 2025. We set an arbitrary age cutoff of 45 years to compare characteristics, invasion, immunostaining, and surgical outcomes by age at surgery. Characteristics were compared by t -tests or Chi squared tests where appropriate, with p < 0.05 considered statistically significant. Results: We included 1,758 patients undergoing endoscopic resection of PA, 632 (35.9%) of whom were under 45 at the time of surgery. Younger patients were more likely to be female (64% versus 48%, p < 0.001), had smaller tumors (21.2mm versus 24.8mm, p < 0.001), and were more likely to present with amenorrhea (44% versus 8% among women, p < 0.001). Underlying tumor biology differed significantly, with a lower proportion of non-functioning PAs in young patients (40%) compared with older patients (71%, p < 0.001). Younger patients were more likely than older patients to harbor tumors which stained for prolactin (29% versus 14%, p < 0.001), growth hormone (21% versus 14%, p < 0.001), and ACTH (17% versus 12%, p < 0.001), but were less likely to harbor tumors staining for FSH (13% versus 28%, p < 0.001) or LH (13% versus 27%, p < 0.001). Younger patients more commonly had tumors with positive immunostaining for PIT-1 (5.7% versus 2.8%, p = 0.003) and less commonly for SF-1 (4.7% versus 14%, p < 0.001). The average K i -67 index was higher among younger patients than older (2.8% versus 2.1%, p < 0.001), but rates of cavernous sinus invasion were lower (29% versus 39%, p < 0.001). Length of stay was marginally shorter among younger patients (3.4 versus 3.7 days, p = 0.007), but rates of CSF leak (4.4% versus 2.3%, p = 0.01) and transient diabetes insipidus (4.4% versus 2.3%, p = 0.001) were higher, without a significant difference in the rate of permanent DI (1.4% versus 1.3%, p = 0.90). Younger patients were more likely to experience tumor recurrence (9.8% versus 5.9%, p = 0.04). Conclusion: Young patients undergoing resection of PA are a biologically distinct population with higher rates of smaller, less invasive, and more likely functioning adenomas. These differences are likely related, in part, to differences in presenting symptoms, with amenorrhea dominating the presentation especially for young female patients. Higher rates of CSF leak and transient DI among younger patients may be related to more aggressive resection techniques in this population, though long-term recurrence remained higher among young patients, highlighting the need for vigilant surveillance after surgical resection of PA. Publication History Article published online: 27 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany