Exploring the Role of Skull Base Anatomy in Surgical Approach Selection and Endocrinological Outcomes in Craniopharyngiomas

<b>Background/Objectives</b>: Craniopharyngiomas (CPs) are rare, generally benign tumors predominantly located in the sellar and suprasellar regions, associated with significant morbidity and complex surgical management. Despite high overall survival rates, patients frequently experience complications including visual impairment, pituitary dysfunction, diabetes insipidus (DI), and hypothalamic syndrome. Among these, hypothalamic obesity (HO) represents one of the most clinically challenging sequelae, often occurring early, lacking standardized medical treatment, and leading to substantial comorbidity and reduced quality of life. This study reports a single-center experience focusing on the relationship between skull base anatomy, surgical approach selection, and endocrinological outcomes. <b>Methods</b>: A retrospective analysis was conducted on patients diagnosed with CPs who underwent surgery by a dedicated team at our Department from January 2014 to January 2024. The approaches used were endoscopic (ER) and transcranial (TR). Preoperative imaging (volumetric MRI and CT scans) was analyzed using 3DSlicer (open-source software) for anatomical modeling of the tumor and skull base. Clinical outcomes were evaluated through follow-up assessments by a team of neuroendocrinologists. Data on BMI changes, DI onset, and hypopituitarism were collected. Statistical analyses consisted of descriptive comparisons and exploratory regression models. <b>Results</b>: Of 18 patients reviewed, 14 met the inclusion criteria. Larger sphenoid sinus volumes were associated with selection of an endoscopic endonasal approach (<i>p</i> = 0.0351; AUC = 0.875). In ER cases, the osteotomy area was directly related to tumor volume, independent of other anatomical parameters. Postoperatively, a significant increase in BMI (22.39 vs. 26.65 kg/m²; <i>p</i> = 0.0049) and in the incidence of DI (three vs. nine cases; <i>p</i>-value 0.0272) was observed. No clear differential association between surgical approach and endocrinological outcomes emerged in this cohort. <b>Conclusions</b>: Quantitative assessment of skull base anatomy using 3D modeling may support surgical approach selection in patients with craniopharyngiomas, particularly in identifying anatomical settings favorable to endoscopic endonasal surgery. Endocrinological outcomes appeared more closely related to tumor characteristics and hypothalamic involvement than to the surgical route itself. These findings support the role of individualized, anatomy-informed surgical planning within a multidisciplinary framework.