Diagnostic value of 11C-Methionine PET-CT imaging in persistent or recurrent Cushing's disease after surgery.

Introduction: Equivocal or negative pituitary magnetic resonance imaging (MRI) findings raise a significant challenge in the management of persistent or recurrent Cushing's disease (CD), compromising the chances of success of a further transsphenoidal surgery (TSS). The aim of our study was to determine the diagnostic utility of 11C-methionine (MET) positron emission tomography coupled with computerized tomography (PET/CT) in localizing the residual or relapsing corticotroph adenoma.

Methods: We retrospectively analyzed the results of 11C-MET PET/CT performed in two tertiary medical centers between May 2002 and November 2023 in 22 patients with a persisting or recurrent CD after initial TSS and equivocal or negative pituitary MRI findings. In 15 cases, images obtained from MET PET/CT were also co-registered with high-resolution 3D T1 or FLAIR MRI pituitary imaging. All patients had a proven CD at the time of first surgery.

Results: Twenty-two patients were included (18 females and 4 males), with a mean age of 36 years at diagnosis. Initial tumors were mostly microadenomas with a mean maximum tumor diameter of 6.5 mm. Thirteen out of the 22 patients had a suspect anomaly on conventional MRI that could however not be clearly distinguished from postsurgical changes, while the remaining 9 had a negative MRI. A maximal metabolic activity in the suspected area of the tumor residue (SUVmaxT) was found in 14 patients (63.5%; 5/9 patients with negative pituitary MRI and 9/13 with equivocal findings). On the basis of positive imaging, repeat TSS was performed in 12 patients and was successful in 7, while Gamma Knife radiosurgery (GKRS) was performed in 2 patients allowing remission in both (total remission rate of 64%). Among the 5 patients not cured by TSS, the presence of a corticotroph adenoma in the resected tissue was found in 3 cases. Therefore, when positive, 11C-MET PET/CT had a detection rate accuracy of 86% (12/14). Out of the 8 PET-negative patients, exploratory TSS was performed in 2, with no remission, and GKRS was performed in another two patients, with long-term remission in one.

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