Postoperative changes in circulating brain injury biomarkers in relation to long-term fatigue and cognitive outcomes after surgery for nonfunctioning pituitary adenomas

PURPOSE: Circulating brain injury biomarker levels increase after transsphenoidal surgery for pituitary tumors. However, their relationship with long-term fatigue and cognitive outcomes remains unclear. We investigated whether postoperative changes in glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and tau are associated with fatigue and cognitive outcomes in patients with nonfunctioning pituitary adenomas (NFPAs). METHODS: This prospective cohort study included 68 patients with NFPAs undergoing endoscopic transsphenoidal surgery. Plasma GFAP, NfL, and tau were measured pre- and postoperatively using ultrasensitive assays. Fatigue was assessed using the Multidimensional Fatigue Inventory and cognitive performance with the Repeatable Battery for the Assessment of Neuropsychological Status preoperatively and at 12-months postsurgery. Clinically meaningful changes were defined as ≥ 0.5 standard deviations from baseline. RESULTS: All biomarkers increased significantly after surgery, with tau peaking immediately, GFAP on day 1, and NfL on day 5 (all p < 0.01). Patients with preoperative hypothalamic compression showed greater postoperative increases in GFAP and NfL. At 12-months, fatigue improved at the group level, and cognitive performance remained stable. However, individual outcomes were heterogeneous: clinically meaningful worsening was observed for fatigue in 8/58 patients (14%) and for cognitive performance in 6/31 patients (19%). We identified no significant associations between increased postoperative biomarker levels and changes in fatigue or cognitive performance. CONCLUSIONS: Endoscopic transsphenoidal surgery for NFPAs is associated with transient increases in circulating brain injury biomarkers, particularly in patients with hypothalamic compression. Our findings revealed that these elevations were not related to long-term fatigue or cognitive decline, suggesting that they may reflect short-term surgical effects without sustained functional consequences.