NCT00001849

New Imaging Techniques in the Evaluation of Patients With Ectopic Cushing Syndrome

New Imaging Modalities in the Evaluation of Patients With Ectopic Cushing's Syndrome

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 95 (actual)
• Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) · NIH
• Sex: All
• Age: 18 Years – 90 Years
• Healthy volunteers: Not accepted

Summary

Cushing Syndrome is an endocrine disorder causing an over production of the hormone cortisol. Cortisol is produced in the adrenal gland as a response to the production of corticotropin (ACTH) in the pituitary gland. Between 10% and 20% of patients with hypercortisolism (Cushing Syndrome) have ectopic production of the hormone ACTH. Meaning, the hormone is not being released from the normal site, the pituitary gland. In many cases the ectopic ACTH is being produced by a tumor of the lung, thymus, or pancreas. However, in approximately 50% of these patients the source of the ACTH cannot be found even with the use of extensive imaging studies such as computed tomography (CT) scans, magnetic resonance imaging (MRI), and nuclear scans (111-indium pentetreotide). The ability of these tests to locate the source of the hormone production is dependent on the changes of anatomy and / or the dose and adequate uptake of the radioactive agent. The inability to detect the source of ectopic ACTH production often results in unnecessary pituitary surgery or irradiation. Unlike the previously described tests, positron emission tomography (PET scan) has the ability to detect pathologic tissue based on physiologic and biochemical processes within the abnormal tissue. This study will test whether fluorine-18-fluorodeoxyglucose (FDG), fluorine-18-dihydroxyphenylalanine (F-DOPA) or use of a higher dose of 111-indium pentetreotide can be used to successfully localize the source of ectopic ACTH production.

Detailed description

Between 10 percent and 20 percent of patients with hypercortisolism (Cushing syndrome) have ectopic production of adrenocorticotropin hormone (ACTH) that causes cortisol excess. In approximately 50 percent of these patients, the source of ACTH cannot be found despite very detailed and extensive examination including imaging studies such as computed tomography scanning, magnetic resonance imaging, and octreotide scan (octreoscan) using the conventional low dose of indium-111 pentetreotide. The sensitivity and specificity of these imaging studies depends on anatomic alterations and/or the dose and adequate uptake of radiopharmaceutical. In contrast, positron emission tomography (PET) has the ability to detect pathologic tissue based on physiologic and biochemical processes within the abnormal tissue. This protocol tests whether fluorine-18 dihydroxyphenylalanine (F-DOPA) or use of a higher dose of indium-111 pentetreotide (Octreoscan) can be used to localize successfully the source of ectopic ACTH production. In addition the study examines whether administration of the glucocorticoid antagonist mifepristone can improved the sensitivity of the standard dose Octreoscan. Eligible patients participating in this arm of the study will have a second standard dose scan. Others will receive a higher dose octreoscan instead.

Conditions

• Cushing Syndrome
• Endocrine Disease

Interventions

Type	Name	Description
DRUG	Pentetreotide	Binds primarily to the somatostatin receptors subtypes (sst) 2 and 5. A high dose (18mCi) was used if the conventional dose (6mCi) was negative and scheduling was available. High doses limited to 3 over the course of the study.
DRUG	18F-DOPA	18F-DOPA is a radiolabeled amino acid used as a radiotracer in positron emission tomography (PET). Limited to 3 doses over the course of the study.
DEVICE	CT scan	CT scan of chest, abdomen, neck and /or pelvis
DEVICE	MRI	MRI scan of head/pituitary, chest, abdomen, neck and /or pelvis
DRUG	18-FDG	FDG PET scan of body

Timeline

• Start date: 1999-05-20
• Primary completion: 2019-04-26
• Completion: 2019-04-26
• First posted: 1999-11-04
• Last updated: 2021-04-14
• Results posted: 2021-01-25

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study