CRH stimulation improves 18F-FDG-PET detection of pituitary adenomas in Cushing's disease

Objective In MRI-negative cases Cushing's disease (CD), surgeons perform a more extensive exploration of the pituitary gland, with fewer instances of hormonal remission. F-18-fluoro-deoxy-glucose (F-18-FDG) positron emission tomography (PET) has a limited role in detecting adenomas that cause CD (corticotropinomas). Our previous work demonstrated corticotropin-releasing hormone (CRH) stimulation leads to delayed, selective glucose uptake in corticotropinomas. Here, we prospectively evaluated the utility of CRH stimulation in improving F-18-FDG-PET detection of adenomas in CD. Methods Subjects with a likely diagnosis of CD (n=27, 20 females) each underwent two F-18-FDG-PET studies [without and with ovine-CRH (oCRH) stimulation] on a high-resolution PET platform. Standardized-uptake-values (SUV) in the sella were calculated. Two blinded neuroradiologists independently read F-18-FDG-PET images qualitatively. Adenomas were histopathologically confirmed, analyzed for mutations in the USP8 gene and for glycolytic pathway proteins. Results The mean-SUV of adenomas was significantly increased from baseline (3.6 +/- 1.5) with oCRH administration (3.9 +/- 1.7; one-tailed p=0.003). Neuroradiologists agreed that adenomas were visible on 21 scans, not visible on 26 scans (disagreed about 7, kappa=0.7). oCRH-stimulation led to the detection of additional adenomas (n=6) not visible on baseline-PET study. Of the MRI-negative adenomas (n=5), two were detected on PET imaging (one only after oCRH-stimulation). USP8 mutations or glycolytic pathway proteins were not associated with SUV in corticotropinomas. Conclusions The results of the current study suggest that oCRH-stimulation may lead to increased F-18-FDG uptake, and increased rate of detection of corticotropinomas in CD. These results also suggest that some MRI invisible adenomas may be detectable by oCRH-stimulated FDG-PET imaging. Clinical trial information F-18-FDG-PET imaging with and without CRH stimulation was performed under the clinical trial NIH ID 12-N-0007 (clinicaltrials.gov identifier NCT01459237). The transsphenoidal surgeries and post-operative care was performed under the clinical trial NIH ID 03-N-0164 (clinicaltrials.gov identifier NCT00060541).