Outcomes of the Transsphenoidal Approach for ACTH-Secreting Pituitary Tumours and the Role of Postoperative ACTH in Predicting the Late Recurrence of Cushing’s Disease: A Retrospective Analysis of 50 Cases

<b>Background/Objectives</b>: The endoscopic transsphenoidal approach constitutes an excellent technique for adrenocorticotropin hormone (ACTH)-producing pituitary tumours. It is associated with subnormal postoperative serum cortisol levels, which may guide decisions regarding immediate re-operation. <b>Methods</b>: The authors retrospectively reviewed patients with Cushing's disease who had undergone endoscopic transsphenoidal surgery between 2013 and 2023. All operations were performed by neurosurgeons and skull-base otolaryngologists. Surgical outcomes were evaluated in combination with prognostic factors such as cortisol and ACTH levels in terms of long-term remission and late recurrence rates of Cushing's disease. <b>Results</b>: Fifty patients aged between 15 and 69 (average 37.8) years were evaluated, having undergone 50 operations. The median follow-up was 76.5 months (range: 23-122 months). Major complications with a transient CSF leak resulting from the surgical approach occurred in three patients. Two patients in the series experienced minor complications, developing a deep vein thrombosis, and thirteen patients developed transient diabetes insipidus. The initial remission rate was 84% (n = 42/50). Initial non-remission occurred in eight (8) patients (16%), with three macro- and five microadenomas. A total of 3 of the 42 patients with initial remission had a late recurrence after 50 months follow-up and required repeat transsphenoidal surgery. Seven patients (16.6%) who did not exhibit early postoperative cortisol reduction subsequently achieved remission. Male gender was the only factor that was significantly associated with lower remission rates in either short- or long-term follow-up (<i>p</i> = 0.003 and 0.038, respectively). An immediate postoperative ACTH nadir of ≤5 pg/mL was significantly related to long-term remission (<i>p</i> = 0.004). In our study, a significant correlation was confirmed between remission of the disease and 24 h urinary cortisol values, both early and late (<i>p</i> = 0.019), and serum cortisol <138 nmol/L. In this retrospective study from a single institution specialising in pituitary tumour management, the endoscopic transsphenoidal approach was shown to be both safe and effective. Additionally, we found that the risk of relapse in patients with Cushing's disease persisting for more than 5 years after surgery is real but low. Moreover, failure to achieve an early postoperative cortisol reduction does not preclude a subsequent remission. <b>Conclusions</b>: Our findings demonstrate that ACTH, postoperative serum cortisol, and urinary free cortisol are valuable predictors of relapse over a five-year period and are closely correlated to each other.