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

## TL;DR

This study compares [11C]C-Methionine PET/CT with MRI and BIPSS for diagnosing Cushing disease, finding that BIPSS remains the most reliable method.

## Contribution

The study evaluates [11C]C-Methionine PET/CT as a non-invasive alternative to BIPSS and MRI for diagnosing Cushing disease.

## Key findings

- [11C]C-MET PET/CT showed low sensitivity (24%) and specificity (13%) for detecting corticotrope pituitary adenomas.
- Patients with corticotrope adenomas had significantly higher SUVmax values compared to controls.
- BIPSS remains the most reliable diagnostic method for Cushing disease.

## Abstract

This prospective study assessed whether [11C]C-MET PET/CT could serve as a non-invasive alternative to BIPSS and MRI in diagnosing Cushing disease. [11C]C-MET PET/CT showed limited sensitivity (24%) and specificity (13%) for detecting corticotrope pituitary adenomas comparing to other methods. However, additional analysis revealed significantly higher SUVmax values in patients with corticotrope adenomas compared to control group. BIPSS remains the most reliable diagnostic method for CD; however, [11C]C-MET uptake patterns may reflect increased amino acid metabolism, suggesting possible adenoma presence.

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 SUVmax 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 SUVmax 2.60, the calculated sensitivity and specificity were 89% and 78% respectively, and for SUVmax 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.