Effects of Hormone Stimulation on Brain Scans for Cushing s Disease
Effects of Hormone Stimulation on Brain Scans for Cushing s Disease
Background:

 -  Cushing s disease can be caused by a tumor of the pituitary gland, a small gland about
 the size of a pea located at the base of the brain. These tumors produce high levels of
 hormones, which cause obesity, diabetes, and growth problems. The cure for this type of
 Cushing s disease is to have surgery that removes the tumor but leaves the pituitary
 gland alone. Currently, magnetic resonance imaging scans are the best way to find these
 tumors. However, many of these tumors do not show up on the scan.

 -  Positron emission tomography (PET) scans use radioactive chemicals to light up parts of
 the body that are more active, such as tumors. Researchers want to try to make the small
 Cushing s disease tumors more active to help them show up on the scans. A special
 hormone will be given before the scan to make the tumors more active.

 Objectives:

 - To test the use of hormone stimulation to improve brain scans for Cushing s disease tumors.

 Eligibility:

 - Individuals at least 8 years of age who will be having surgery to remove Cushing s disease
 tumors.

 Design:

 -  Participants will be screened with a medical history, physical exam, blood and urine
 tests, and imaging studies.

 -  They will have three brain scans before surgery. The first scan is a magnetic resonance
 imaging scan to show a full picture of the brain. The second and third scans are PET
 scans.

 -  The first PET scan will be given without the special hormone. The second PET scan will
 be done more than 24 hours but less than 14 days after the first PET scan. The second
 PET scan will be given with the special hormone.

 -  Participants will have tumor removal surgery through another study protocol.
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.
-  INCLUSION CRITERIA:

 To be eligible for entry into the study, patients must meet all the following criteria:

 1. Be 8 years of age or older and able to undergo PET-imaging without needing general
 anesthesia.

 2. Able to provide informed consent (or guardian is able to provide consent in case of
 minor).

 3. Clinical diagnosis of CD based on medical records.

 4. Medically able to undergo resection of pituitary adenoma and planning to undergo
 surgical resection of adenoma within 12 weeks of PET-imaging.

 5. Normal liver enzymes: tests should be completed within 14 days before injection of the
 radiopharmaceutical; SGOT, SGPT less than or equal to 5 times ULN; bilirubin less than
 or equal to 2 times ULN.

 EXCLUSION CRITERIA:

 Candidates will be excluded if they meet any of the following criteria:

 1. Pregnant or nursing women.

 2. Contraindication to MR-scanning, including pacemakers or other implanted electrical
 devices, brain stimulators, some types of dental implants, aneurysm clips (metal clips
 on the wall of a large artery), metallic prostheses (including metal pins and rods,
 heart valves, and cochlear implants), permanent eyeliner, implanted delivery pump, or
 shrapnel fragments

 3. Severe chronic renal insufficiency (glomerular filtration rate < 30 mL/min/1.73 m(2)),
 hepatorenal syndrome or post-liver transplantation.

 4. Elevated blood glucose level above 200 mg/dL on the day of the scan prior to (18)F-FDG
 administration.

 5. Known intolerance to CRH.