Cushing’s disease and negative MRI: a single-center series, systematic literature review, and meta-analysis
Year: 2026
Type: review
Study designs: Systematic Review, Meta-Analysis
Abstract: Cushing’s Disease (CD) poses diagnostic and therapeutic challenges, particularly when pituitary MRI is negative for a neuroendocrine tumor (PitNET). This study systematically analyzes literature data on the surgical outcomes of patients with MRI-negative CD and presents a novel single-center series. A systematic review and meta-analysis of PubMed, Scopus, and Cochrane databases (2000–2024) were performed. A retrospective analysis of patients with MRI-negative CD who underwent endoscopic pituitary exploration between 2014 and 2021 at the University of Brescia was conducted. A meta-analysis of 35 studies revealed significant heterogeneity across studies (I 2 = 71.09%). The mean surgical disease remission rate of 70% (CI: 65–75%) in MRI-negative CD was significantly lower than in MRI-positive patients (82%; CI: 0.79–0.86). Eight studies reported ACTH hyperplasia in a total of 92 of 470 patients (19.6%). In the institutional series, 21 patients underwent 22 endoscopic pituitary explorations (mean follow-up: 72 months). Histology documented ACTH hyperplasia in 10/22 (45%), ACTH-PitNET in 9, and normal pituitary in 3. Inferior petrosal sinus sampling lateralization was predictive of pathology in 33% of patients. Early and late surgical remission (10/22 and 15/22 patients, respectively) were significantly associated with histology. Surgical complications included one CSF leak requiring reintervention, one case of transient diabetes insipidus, and two patients requiring substitutive therapy for the thyroid axis. About 30% of MRI-negative CD patients do not achieve surgical disease remission. ACTH hyperplasia might partially explain this high rate of failure. Endoscopic pituitary exploration remains a highly effective way to collect important histological data that should be recorded in a multicenter, prospective study.
Source: Neurosurgical Review
Authors: Francesca Ghidoni, Alba Madoglio, Sabrina Chiloiro, Lodovico Terzi di Bergamo, Marika Vezzoli, Simona Serioli, Giada Cosentino, Giorgio Saraceno, Isabella Lupi, Claudio Urbani, Massimo Licini, Renato Candrina, Antonella Giampietro, Ilenia Pirola, Carlo Cappelli, Davide Mattavelli, Vittorio Rampinelli, Marco Ferrari, Fausto Bogazzi, Mirco Cosottini, Roberto Gasparotti, Luca Manetti, Antonio Bianchi, Piero Nicolai, Cesare Piazza, Marco Maria Fontanella, Pietro Luigi Poliani, Francesco Doglietto
Institutions: University of Ferrara, Università Cattolica del Sacro Cuore, Agostino Gemelli University Polyclinic, Istituti di Ricovero e Cura a Carattere Scientifico, Institute of Oncology Research, University of Brescia, Ospedale Papa Giovanni XXIII, University of Pisa, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Fondazione Poliambulanza Istituto Ospedaliero, University of Padua
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,590
OpenAlex ID: W7131296713