Objective
Preoperative imaging identification and localization of adrenocorticotropin hormone (ACTH)-secreting pituitary adenomas is critical for the accurate diagnosis and the successful surgical treatment of Cushing s disease (CD). Unfortunately, over 40 percent of CD patients do not have a visible pituitary adenoma on magnetic resonance (MR)-imaging (the most sensitive imaging modality for ACTH-positive adenoma detection and localization). Lack of MR-imaging for diagnosis and to guide surgical resection results in significantly higher rates of surgical failure compared to cases associated with adenomas visible on MR-imaging. Because ACTH-adenomas are metabolically active compared to the surrounding pituitary gland, (18)F-fludeoxyglucose ((18)F-FDG) positron emission tomography (PET)-imaging in CD patients could be used to detect adenomas not detectable on MR-imaging. Moreover, corticotropin-releasing hormone (CRH) can be given to selectively increase the metabolic activity of ACTH-secreting pituitary adenomas to increase the likelihood of their detection and localization by (18)F-FDG PET-imaging. To determine the effect of CRH stimulation on (18)F-FDG uptake using PET-imaging in CD, we will perform (18)F-FDG high-resolution PET-imaging (with and without CRH stimulation) in CD patients.
Study Population
Thirty male and female CD patients 8 years and older will participate in this study.
Study Design
This is a single center trial to determine the effect of CRH stimulation on (18)F-FDG uptake in high-resolution PET-imaging of ACTH-adenomas in CD patients. CD patients will undergo (18)F-FDG high-resolution PET-imaging without CRH stimulation and (18)F-FDG high-resolution PET-imaging with intravenous CRH stimulation. The order of the PET scans will be randomized and the second PET scan will occur greater than 24 hours but less than 14 days after initial PET-imaging. For (18)F-FDG PET-imaging with CRH stimulation, intravenous (18)F-FDG will be given just before CRH administration. The PET images will be read by radiologists who are blinded to the administration of CRH. Within 12 weeks after completion of the last (18)F-FDG high-resolution PET-imaging scan, patients will undergo surgical resection of the pituitary adenoma. Surgical and histological confirmation of adenoma location will be used to assess the diagnostic and localization accuracy of PET-imaging and to compare to preoperative MR-imaging results in CD patients. Inferior petrosal sinus sampling (IPSS) results will be compared with imaging results and with surgical and histological findings.
Outcome Measures
The primary objective of this study is to determine the effect of CRH stimulation on (18)F-FDG uptake in high-resolution PET-imaging for CD. To assess and compare (18)F-FDG uptake without and with CRH stimulation, we will compare (18)F-FDG standardized uptake values (SUVs) in the region of interest (pituitary gland and pituitary adenoma). Secondary objectives include determining if CRH stimulation enhances detection of ACTH-adenomas as demonstrated on (18)F-FDG high-resolution PET-imaging and assessing the accuracy and sensitivity of (18)F-FDG high-resolution PET-imaging detection of ACTH-adenomas compared to MR-imaging. Measures to assess for these secondary objectives include comparing (18)F-FDG high-resolution PET-imaging (with and without CRH stimulation) detection to (1) MR-imaging detection of adenomas, (2) IPSS results, and (3) actual tumor location confirmed by histological findings to location predicted by PET- and MR-imaging within patients.
