Corticotrophin-releasing Hormone (CRH) Stimulation for 18F-FDG-PET Detection of Pituitary Adenoma in Cushing s Disease

Description

Study Description:

This study is designed as a single institution trial. The study utilizes safe and clinically-validated tools for preoperative workup of subjects with small pituitary tumors. DDAVP stimulation and 18F-labeled fluorodeoxyglucose (FDG) uptake for PET-imaging will be used to detect MRInegative pituitary adenomas in subjects with Cushing s disease. Subjects who have MRI-negative pituitary microadenomas will undergo FDG PETimaging with DDAVP stimulation. Intravenous FDG will be given approximately four hours following DDAVP administration. Within 24 weeks after completion of the FDG high-resolution PET scan, subjects will undergo surgical resection of the pituitary adenoma. Surgical and histological confirmation of adenoma location will be noted. All images will be read independently by neuroradiologists blinded to clinical and histopathological outcomes. The diagnostic and localization accuracy of PET-imaging will be assessed by comparing the PET findings with histopathology.

Objectives:

Cushing s disease (CD) affects 3,000 people in the United States every year and results in significant morbidity and early mortality. The disease is caused by millimeter sized pituitary microadenomas (corticotropinomas) that secrete adrenocorticotropic hormone (ACTH). Surgical resection of corticotropinomas remains the most effective treatment strategy. Preoperative magnetic resonance imaging (MRI) can detect microadenomas in approximately 50-80% of subjects. Subjects with microadenomas invisible on MR imaging are exposed to more invasive explorations of the sella with fewer instances of hormone remission and higher complications. Corticotropinomas can be detected by FDG positron emission tomography (PET) in 50% of subjects. Prior work by us suggests that secretagogue stimulation with corticotropin-releasing hormone (CRH) leads to increased FDG uptake and improved PET detection of pituitary microadenomas.

Since, CRH is no longer available, we will use DDAVP which has a similar biological activity to CRH. If validated, DDAVP-stimulated FDG-PET imaging could provide a complementary imaging modality to improve visualization of ACTH-secreting microadenomas and surgical planning.

Primary Objective:

The primary objective of this study is to determine the detection rate of MRI-negative pituitary adenomas in subjects with Cushing’s disease by DDAVP-stimulated FDG PET imaging. We will analyze whether or not DDAVP-stimulated PET imaging demonstrates

tumor in MRI-negative cases by assessing the accuracy and sensitivity of high-resolution FDG PET-imaging detection of ACTH-adenomas that could not be reliably detected on MR-imaging.

Secondary Objectives:

To assess the accuracy of FDG high-resolution PETimaging localization of ACTH-adenomas in CD compared to surgical and

histologic localization. This will be achieved by comparing actual tumor location confirmed by histological findings during surgical resection to the location predicted by PET- and MR-imaging within subjects.

Endpoints:

Primary Endpoint: The primary outcome measure will be defined as whether or not DDAVP-stimulated PET imaging demonstrates tumor in MRI-negative cases. This will be demonstrated by assessing the accuracy and sensitivity of FDG high-resolution PET-imaging detection of ACTH-adenomas that could not be reliably detected on MR-imaging.

Secondary Endpoints: Location of tumor on preoperative PET-imaging and location of tumor during surgery. Histopathological confirmation of ACTH-adenoma will be the gold-standard to measure the primary and secondary endpoints.