AbstractObjectiveAs a complex and acute brain dysfunction, if postoperative delirium (POD) occurs in the postoperative period, it will lead to a prolonged length of stay in the critical care unit, with increased hospitalization costs and higher mortality. A few case reports inspired us to pay close attention to pituitary tumor‐associated delirium. We hypothesized that the changes in hormone levels after pituitary tumor resection might be associated with POD occurrence.MethodsRetrospective analysis was performed on data from a single‐center cohort study conducted at Southwest Hospital between January 2018 and May 2022. A total of 360 patients with pituitary tumors who underwent endoscope‐assisted transsphenoidal pituitary tumor resection were divided into two groups at a 1:3 ratio, with 36 patients in the POD group and 108 patients in the non‐POD group matched by propensity score, age, sex, and tumor size. Basic characteristics, pituitary adenoma features, endocrine levels and other biochemical indicators, and Confusion Assessment Method for the Intensive Care Unit (CAM‐ICU) for postoperative delirium were documented for further analysis.ResultsLower insulin‐like growth factor‐1 (IGF‐1,p= .024) and corticotropin‐releasing hormone (CRH,p= .005) levels were closely associated with postoperative delirium and with high levels of blood glucose (GLU,p= .023) after surgery. Subsequent analysis indicated that serum potassium (OR: 0.311, 95% CI 0.103–0.935), sodium (OR: 0.991, 95% CI 0.983–1.000), CRH (OR: 0.964, 95% CI 0.936–0.994), and GLU (OR: 1.654, 95% CI 1.137–2.406) levels in the perioperative period were independent risk factors for delirium.ConclusionsOur study indicated that lower serum CRH, potassium, sodium, and GLU levels may be associated with the occurrence of POD after endoscopic‐assisted transsphenoidal surgery. These data provide preliminary evidence for the management of POD in pituitary adenoma patients after surgery. Further studies are needed to identify pharmacological and nonpharmacological multicomponent treatment strategies.