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

Phase 2

Completed

Conditions: Cushing Syndrome
Endocrine Disease

Interventions: Drug: Pentetreotide
Drug: 18F-DOPA
Device: CT scan
Device: MRI
Drug: 18-FDG

Registration Number: NCT00001849

Lead Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Brief 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 95

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Patients with Cushing Syndrome	MRI	Patients receive various types of radiologic or nuclear medicine scans to identify tumor
Patients with Cushing Syndrome	Pentetreotide	Patients receive various types of radiologic or nuclear medicine scans to identify tumor
Patients with Cushing Syndrome	18F-DOPA	Patients receive various types of radiologic or nuclear medicine scans to identify tumor
Patients with Cushing Syndrome	CT scan	Patients receive various types of radiologic or nuclear medicine scans to identify tumor
Patients with Cushing Syndrome	18-FDG	Patients receive various types of radiologic or nuclear medicine scans to identify tumor

Primary Outcome Measures

Name	Time	Method
Sensitivity of Imaging Modalities for the Detection of ACTH-secreting Non-pituitary Tumor in Patients	six months or less	The percentage of patients in whom imaging correctly identified an ACTH-secreting non-pituitary tumor within six months of resection or in which imaging identified a recurrence at a site of previous resection.
Sensitivity of Imaging Modalities for the Detection of ACTH-secreting Non-pituitary Tumor in Specific Lesions	six months or less	The percentage of lesions for which imaging correctly identified an ACTH-secreting non-pituitary tumor within six months of resection or for which imaging identified a recurrence at a site of previous resection.

Secondary Outcome Measures