Comparison of Localization Methods in Cushing Disease-Could [¹¹C]C-Methionine PET/CT Replace MRI or BIPSS?

Introduction: Cushing syndrome (CS) is a medical condition resulting from prolonged hypercortisolemia. The most common reason for endogenous CS is ACTH overproduction by pituitary adenoma, and then it is called Cushing disease (CD). The gold standard of CD diagnostic remains bilateral inferior petrosal sinus sampling (BIPSS); nevertheless, non-invasive diagnostic methods are being sought to provide a higher safety profile. The aim of this study was to evaluate whether [¹¹C]C-MET PET/CT can serve as a non-invasive alternative to BIPSS and MRI in CD diagnosis. Methods: This prospective study included 21 patients with CD who underwent BIPSS, MRI of the pituitary, and [¹¹C]C-MET PET/CT. Results: Sensitivity of BIPSS, MRI and [¹¹C]C-MET PET/CT was 100%, 59% and 24%, respectively, while specificity was 100%, 75%, and 13%. Next, we retrospectively compared PET/CT results for patients with corticotrope pituitary adenomas (n = 18) with those for individuals with no pituitary pathology (n = 18), and the results showed significantly higher SUV_max in the study group (3.74 ± 0.90 vs. 1.87 ± 1.17; p < 0.001). In ROC curve analysis, the area under the curve (AUC) was 0.889 (p <0.001; 95% CI 0.784-0.994). For SUV_max 2.60, the calculated sensitivity and specificity were 89% and 78% respectively, and for SUV_max 3.56, sensitivity and specificity were 67% and 89%, respectively. Conclusions: [¹¹C]C-MET PET/CT seems not to be a reliable diagnostic option in the diagnosis of pituitary corticotropic adenomas. BIPSS proved still to be the best diagnostic option for CD. Nevertheless, a higher than normal pituitary accumulation of the radiotracer may suggest the presence of increased amino acid metabolism, thus, the presence of adenoma.