Effects of Hormone Stimulation on Brain Scans for Cushing s Disease

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.