Image Negative (MR negative) Cushing Disease: A Call to Standardize the Term and Guide to Convey Imaging Certainty

Magnetic resonance imaging (MRI) is central to tumor localization in Cushing disease (CD), and patients with clearly visualized pituitary adenomas experience superior surgical outcomes compared to those with MRI-negative or equivocal disease. With continued advances in MR acquisition and post-processing, subtle signal abnormalities may be increasingly labeled as definite tumors rather than acknowledged as uncertain findings, potentially increasing the risk of inaccurate localization and unnecessary exploration. In this study, we aimed to illustrate this diagnostic challenge and propose a standardized framework for communicating MR imaging confidence to better guide surgical planning and multidisciplinary decision-making.

We conducted a retrospective cohort study of 14 patients with operatively confirmed tumors identified by dynamic photon-counting CTA who had indeterminate MR findings. All MRI cases were independently reviewed by three board-certified neuroradiologists who were blinded to the true location of the adenomas and asked to identify, from the MRIs, where the pituitary adenomas were most likely located and with what confidence. The goal of this exercise was to understand what variance and certainty exist in difficult cases, MR indeterminate cases.

Interrater agreement for MRI interpretations was overall fair (mean weighted κ = 0.22), with moderate agreement between two readers (κ = 0.48) but only slight agreement involving the third reader (κ = 0.06-0.11), demonstrating poor concordance even among highly experienced neuroradiologists. All neuroradiologists agreed (100%) that a system to convey certainty would be helpful to include in the MR report.

Interpretation of MR imaging for pituitary microadenomas in CD can be inherently difficult, and the resulting interrater variability may contribute to differing impressions of lesion location. These discrepancies can, in turn, affect surgical or radiation planning. Communicating the level of diagnostic confidence may help alert treating clinicians when broader exploration or additional imaging could improve treatment outcomes.