Equivocal or negative pituitary magnetic resonance imaging (MRI) findings pose a significant challenge in the management of persistent or recurrent Cushing disease (CD), compromising the chances of success of further transsphenoidal surgery (TSS).

To determine the diagnostic utility of 11C-methionine (11C-MET) positron emission tomography/computerized tomography (PET/CT) in localizing residual or relapsing corticotroph adenoma.

We retrospectively analyzed the results of all 11C-MET PET/CT performed at 2 tertiary medical centers between May 2002 and November 2023 in 22 patients with persistent/recurrent CD after initial TSS and equivocal/negative pituitary MRI. In 15 cases, 11C-MET PET/CT images were also co-registered with high-resolution 3D T1 or FLAIR MRI pituitary imaging.

Of 22 patients (18 female; mean age 36 years at diagnosis; mean initial tumor maximum diameter 6.5 mm), 13 had a suspect anomaly on conventional MRI and 9 had a negative MRI. Maximal metabolic activity in the suspect area (SUVmaxT) was found in 14 patients (63.5%; 5/9 patients with negative pituitary MRI and 9/13 with equivocal findings). Based on positive imaging, 12 patients underwent repeat TSS, successful in 7, while 2 patients underwent Gamma Knife radiosurgery (GKRS), both resulting in remission (total remission rate of 64%). Among the 5 patients not cured by TSS, the presence of corticotroph adenoma in the resected tissue was found in 3 cases. Positive 11C-MET PET/CT had a detection rate accuracy of 86% (12/14). Of the 8 PET-negative patients, 2 underwent exploratory TSS, with no remission, and 2 underwent GKRS, with 1 long-term remission.

11C-MET PET/CT imaging can provide valuable diagnostic information to detect a corticotroph microadenoma in more than half of patients with persistent/recurrent CD and equivocal or negative MRI findings, allowing targeted TSS or radiosurgery with a global success rate of 64% in the selected subgroup with positive imaging.