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
Intervention: Pentetreotide; 18F-DOPA; CT scan; MRI; 18-FDG
Intervention description: 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
Intervention MeSH terms: Edetic Acid; Pentetic Acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Diagnostic
Intervention model: Single Group Assignment
Intervention model description: Comparison of results in patients receiving similar imaging scans
Masking: None (Open Label)
Enrollment: 95.0
Sex: All
Minimum age: 18 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: PET; fluorine -18(18F)-DOPA; Pentetreotide; ACTH; Octreotide; Cushing's Syndrome; Ectopic Cushing Syndrome

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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        All eligible patients are invited to participate in this protocol. Patients are adults with
        possible ectopic Cushing syndrome. Since both men and women are affected with ectopic
        Cushing syndrome, both sexes are studied. All ethnic and racial groups are at risk and will
        be included. Patients must be willing to return to the National Institutes of Health (NIH)
        Clinical Center for follow-up studies.

        EXCLUSION CRITERIA:

        Pregnant or lactating women. A pregnancy test is performed in women of childbearing
        potential (up to age 55) unless they have a history of hysterectomy.

        Children (age less than18) are excluded. Because ectopic ACTH secretion is rare in this age
        group, the likelihood of benefit is less and does not balance the risk of radiation.

        Patients taking medications that alter CYP3A4 activity will not be eligible for the
        mifepristone study, since this P450 system metabolizes mifepristone. Such participants
        would receive a clinical high dose (18 mCi) octreoscan (H-OCT) instead, if the standard 6
        mCi octreoscan (L-OCT) was negative. Patients with hypokalemia (K < 3.5 milliequivalent
        (mEq)/L) despite medical therapy with replacement or mineralocorticoid antagonists will
        also be excluded from the mifepristone studies.

        The presence of:

          -  severe active infection.

          -  clinically significantly impaired cardiovascular (e.g., history of abnormally low
             ejection fraction, the presence of moderate pulmonary fluid overload or leg edema, and
             blood pressure over 190/100), abnormal coagulation (partial thromboplastin time or
             prothrombin time elevated by 30 percent above the normal values), hematopoietic
             (hematocrit less than 30 percent, hemoglobin below 10 g/dl, white count below 3000
             K/microliter (UL), and platelets below 100,000 K/mm(3)), hepatic (liver enzymes
             elevated by 3-fold above normal values) or renal function (plasma creatinine level
             over 2.0).

          -  impaired mental capacity or markedly abnormal psychiatric evaluation that precludes
             informed consent.

          -  body weight over 136 kg, which is the limit for the tables used in the scanning areas.

          -  combined blood withdrawal, during the six weeks preceding the study, of greater than
             450 ml.

          -  known allergy to 111-indium pentetreotide or other somatostatin analogues.

          -  strong evidence for Cushing disease. This includes those with positive inferior
             petrosal sinus sampling or a lesion on pituitary MRI.