2026 Proffered Presentations
S031: CHASING THE INVISIBLE: A SYSTEMATIC STRATEGY FOR ENDOSCOPIC PITUITARY EXPLORATION IN MRI-NEGATIVE CUSHING'S DISEASE WITH SURGICAL OUTCOMES
Gianluca L Fabozzi1; Thibault Passeri1; Rakhmon Egamberdiev1; Hussam Abou-Al-Shaar1; Ivo Peto1; Pouneh K Fazeli2; Eric W Wang3; Garret Choby3; Georgios A Zenonos1; Carl H Snyderman3; Paul A Gardner1; 1Department of Neurological Surgery, University of Pittsburgh Medical School (UPMC), Pittsburgh, Pennsylvania; 2Neuroendocrinology Unit, Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh Medical School (UPMC), Pittsburgh, Pennsylvania; 3Department of Otolaryngology, University of Pittsburgh Medical School (UPMC), Pittsburgh, Pennsylvania
Introduction: Cushing’s disease (CD) is a rare, potentially life-threatening disorder caused by ACTH-secreting pituitary neuroendocrine tumors (PitNETs). The endoscopic endonasal approach (EEA) represents the first-line treatment and an accurate preoperative identification of microadenomas is essential for selective removal. However, up to 30–50% of ACTH-secreting tumors remain undetectable even with high-resolution MRI, leaving neurosurgeons with the challenging scenario of pituitary exploration without a distinct target.
Objective: This study aims to provide a comprehensive description of a standardized,step by step surgical strategy for pituitary gland exploration in MRI-negative CD, while evaluating surgical outcomes and identifying predictors of long-term remission in patients treated at a tertiary referral center over the past 12 years.
Methods: We retrospectively analysed data from 22 consecutive MRI-negative, surgery-naïve CD patients treated between 2012 and 2024. MRI negativity was defined as the absence of both direct and indirect radiological signs of adenoma and included review by radiologist and surgeon. Patients with recurrent disease or overt lesions were excluded. Patients undergoing early re-exploration -within 7 days- due to lack of postoperative cortisol drop were included. All surgeries were performed via a 2-surgeon, four-hands binostril EEA with the following protocol: wide bilateral sphenoidotomy, extensive sellar exposure, cruciate or inverted V-shaped dural opening, intraoperative indocyanine green (ICG) angiography and prolonged inspection, followed by stepwise vertical gland incisions, frozen section analysis, and selective medial cavernous sinus (CS) wall resection, when indicated.
Results: MRI-negative CD accounted for 22.7% of all CD patients treated during the examined timeframe. Twenty-two patients were included (18 females, 81.8%; mean age 43.6 years). Twenty-seven procedures were performed, with 5 patients (22.7%) requiring early reoperation within one week due to absent postoperative cortisol decline. Long-term remission was achieved in 16/22 patients (72.7%). Of those patients who achieved remission, remission was achieved in 14/16 (87.5%) after the first operation and 2/16 (12.5%) after early re-exploration. No recurrences were observed during a mean follow-up of 28.7 months (range 2.5–90.2). Persistent disease was present in 6 patients (27.3%), all without intraoperative adenoma visualization and with negative or inconclusive histopathology. Notably, 14 of the 16 patients achieving long-term remission had positive final histology (87.5%). Predictors of remission included pseudocapsule presence (p=0.0152), clear intraoperative visualization (p=0.0011), positive intraoperative histology (p=0.0243), and final histopathological confirmation of an ACTH-secreting adenoma (p=0.0007). Gender, age, number of procedures, ICG use, and medial CS wall resection did not significantly influence outcomes. All 14 patients with histopathologically proven ACTH-secreting PitNETs achieved durable remission. Postoperative complications were limited to transient AVP-deficiency (n=1) and SIADH (n=3); no postoperative cerebrospinal fluid leaks occurred. Free mucosal graft reconstruction was routinely used (85.6%).
Conclusions: Systematic endoscopic pituitary exploration represents an effective and safe treatment for MRI-negative CD, achieving durable remission in nearly three-quarters of patients - rates comparable to those reported in CD series with radiological overt PitNETs. Intraoperative lesion detection, pseudocapsule presence, positive intraoperative, permanent histological confirmation were predictive of remission. Within this complex scenario, a systematic and stepwise intraoperative strategy during pituitary exploration provides an effective balance between maximizing remission rates and preserving gland function.
