Clinical Outcomes of Endoscopic Transsphenoidal Resection of Pituitary Adenoma in Patients With Tobacco Smoking or Nicotine Dependence

Background: While the endoscopic endonasal approach has revolutionized pituitary surgery, postoperative complications contribute to significant morbidity. Tobacco smoking is a well-established risk factor for poor wound healing and adverse outcomes in other skull base procedures, yet its direct influence following transsphenoidal resection is largely unaddressed. This study seeks to define the association between smoking history and adverse outcomes in this population. Methods: This is a retrospective cohort study utilizing the TriNetX global federated research network (2011–2024) to identify adults undergoing primary endoscopic transsphenoidal resection for benign pituitary tumors. Patients were stratified by tobacco use or nicotine dependence. To control for confounding, cohorts were matched via 1:1 propensity score matching (PSM). A panel of outcomes, defined by the PitCOP Delphi consensus, was analyzed. Time-to-event analysis for reoperation was performed, and survival distributions were compared between cohorts. Results: The study population included 11,376 patients: 3,597 smokers and 7,779 non-smokers. Following PSM, 3,219 well-balanced pairs were established. In the matched cohorts, smoking was associated with significantly higher odds of postoperative cerebrospinal fluid leak (OR 1.30; p=0.006), 30-day hospital readmission (OR 1.33; p<.001), and new postoperative hypopituitarism (OR 1.23; p=.0086). Rates of infection and in-hospital mortality were similar. The time-to-event analysis for reoperation showed a higher cumulative incidence in the smoking cohort at 2-year follow-up; however, this difference in survival distributions was not significant after PSM. Conclusions: This large, population-based study suggests that smoking may be associated with adverse outcomes following endoscopic pituitary surgery. Our findings indicate a significant correlation between tobacco use and a triad of major complications: impaired healing of CSF leak repairs, increased morbidity requiring early hospital readmission, and a risk of new-onset hypopituitarism. This evidence reinforces the importance of smoking as a critical, modifiable risk factor and warrants greater emphasis on cessation during preoperative counseling and patient optimization.