New Imaging Techniques in the Evaluation of Patients With Ectopic Cushing Syndrome
Condition: Cushing Syndrome; Endocrine Disease
MeSH terms: Cardiac Complexes, Premature; Cushing Syndrome; Endocrine System Diseases; Syndrome
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Pentetreotide; 18F-DOPA; CT scan; MRI; 18-FDG
Intervention type(s): Drug; Drug; Device; Device; Drug
Intervention description(s): 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.; 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.; CT scan of chest, abdomen, neck and /or pelvis; MRI scan of head/pituitary, chest, abdomen, neck and /or pelvis; FDG PET scan of body
Other intervention name(s): [111In-diethylenetriaminepentaacetic acid-D-Phe]-pentetreotide; 6-fluoro-L-DOPA; 56494; computed tomography scan; magnetic resonance imaging scan; 18-fluorine fluorodeoxyglucose PET scan
Intervention MeSH terms: Edetic Acid; Pentetic Acid
Intervention model: Single Group Assignment
Intervention model description: Comparison of results in patients receiving similar imaging scans
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: PET; fluorine -18(18F)-DOPA; Pentetreotide; ACTH; Octreotide; Cushing's Syndrome; Ectopic Cushing Syndrome