Background/Objective Endonasal transsphenoidal surgery (TSS) remains the preferred treatment for most
               recurrent or residual nonfunctional pituitary adenomas (NFPAs). The objective of this
               study was to compare surgical outcomes from primary and repeat TSS in patients with
               NFPAs at a dedicated tertiary pituitary center.
            
               Methods This is a retrospective review of 1,678 transsphenoidal cases performed at USC between
               1995 and 2015. Inclusion criteria consisted of patients with NFPAs treated with endoscopic
               or microscopic endonasal TSS with a minimum follow-up of 3 months. Patients were categorized
               as primary or repeat TSS. Patient and tumor characteristics were compared preoperatively,
               and postoperative outcomes were analyzed.
            
               Results Two hundred sixty-eight patients met inclusion criteria with appropriate follow-up.
               Of these, 211 patients underwent primary TSS and 57 patients underwent repeat TSS.
               Median follow-up time was 25 months (range: 3−235 months). Both groups had similar
               baseline demographic characteristics and endocrine function. Patients undergoing repeat
               TSS had a higher rate of receiving prior radiation therapy (10.5 vs. 0%, p < 0.001) or radiosurgery (10.5 vs. 0%, p < 0.001). A higher incidence of headaches (37.9 vs. 14.0%, p = 0.001) and visual field deficits (47.2 vs. 27.4%, p = 0.018) were observed in the primary TSS group. Tumor diameter and invasion/extension
               patterns were similar in both groups; however, the rate of gross-total resection (GTR)
               was significantly higher in primary TSS patients (59.0 vs. 27.8%, p = 0.001). In both groups, the presence of cavernous sinus invasion made it less likely
               to achieve GTR (OR = 0.28, CI 95%: 0.17−0.48, p < 0.001) and the use of an endoscopic endonasal approach was more likely to result
               in GTR (OR = 1.73, CI 95%: 1.26−2.38, p = 0.001). There were no mortalities in either group, and complication rates (cerebrospinal
               fluid leak, vision loss, hematoma, stroke, etc.) were comparable between groups. A
               significantly higher rate of early hospital readmission due to hyponatremia was observed
               in the primary TSS group (6.6 vs. 0.0%, p = 0.046). Repeat TSS group demonstrated a lower rate in vision improvement (primary
               TSS: 45.1% vs. repeat TSS: 20.0%, p = 0.005) and higher rate of new panhypopituitarism (primary TSS: 0.5% vs. repeat
               TSS: 7.1%, p = 0.011). A higher percentage of adjuvant radiosurgery was performed in the repeat
               TSS group (primary TSS: 24.1% vs. repeat TSS: 38.9%, p = 0.009).
            
               Conclusion At experienced tertiary pituitary centers, repeat endonasal TSS for NFPAs is associated
               with a similar incidence of surgical complications as in patients undergoing primary
               TSS. However, repeat TSS demonstrated a lower rate of GTR, and carried a higher rate
               for worsening endocrine dysfunction.