Beyond the MRI-positive/MRI-negative dichotomy: A stepwise surgical strategy for Cushing's disease

Cushing's disease (CD) has traditionally been approached through a binary paradigm based on MRI findings, distinguishing MRI-positive from MRI-negative cases. However, this dichotomy incompletely reflects the heterogeneity of corticotroph tumors and complexity of intraoperative decision-making.

We propose a stepwise surgical strategy that moves beyond this binary stratification by conceptualizing CD as a spectrum integrating imaging, biochemical, and intraoperative findings.

This retrospective purposefully selected illustrative case series was drawn from a prospective database of 983 patients treated for CD between 2006 and 2025. All underwent mononostril endoscopic transsphenoidal surgery by an expert pituitary surgical team. Seven cases were chosen to illustrate the CD spectrum presentations, including MRI-positive lesions with invasive features, MRI-equivocal findings, and MRI-negative disease. A stepwise algorithm integrating preoperative imaging, functional analysis, and intraoperative findings guided surgical exploration and resection.

Seven patients were included. In MRI-visible lesions, targeted adenomectomy was performed, with extension to basal dura or cavernous sinus wall when indicated. In MRI-negative or equivocal cases, exploration was guided by repeat imaging, heterogeneous MRI signal, venous sampling, and/or FET-PET. When tumor tissue was identified, selective or enlarged adenomectomy was performed according to infiltration patterns. Early endocrine remission was achieved in 6 patients, while one patient achieved postoperative eucortisolism. Transient diabetes insipidus was the only postoperative complication.

CD may be reconsidered beyond a binary MRI-based paradigm, as a spectrum of scenarios. A stepwise surgical strategy better reflects disease heterogeneity and provides a practical framework for surgical decision-making, particularly in MRI-negative or MRI-equivocal cases.