Diagnostic Value of 11C-Methionine PET-CT Imaging in Persistent or Recurrent Cushing Disease After Surgery

J Clin Endocrinol Metab. 2025 Sep 16;110(10):2845-2852. doi: 10.1210/clinem/dgaf047.

Abstract

Context: 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).

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

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: 11C-Methionine PET/CT; functional imaging; persistent/recurrent Cushing disease; therapeutic intervention.

MeSH terms

  • ACTH-Secreting Pituitary Adenoma* / diagnostic imaging
  • ACTH-Secreting Pituitary Adenoma* / surgery
  • Adenoma* / diagnostic imaging
  • Adenoma* / surgery
  • Adolescent
  • Adult
  • Carbon Radioisotopes
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Methionine*
  • Middle Aged
  • Neoplasm Recurrence, Local* / diagnostic imaging
  • Neoplasm Recurrence, Local* / surgery
  • Pituitary ACTH Hypersecretion* / diagnosis
  • Pituitary ACTH Hypersecretion* / diagnostic imaging
  • Pituitary ACTH Hypersecretion* / pathology
  • Pituitary ACTH Hypersecretion* / surgery
  • Positron Emission Tomography Computed Tomography* / methods
  • Retrospective Studies
  • Young Adult

Substances

  • Methionine
  • Carbon Radioisotopes
  • carbon-11 methionine