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

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ClinicalTrials.gov Identifier: NCT00001849
Recruitment Status : Recruiting
First Posted : November 4, 1999
Last Update Posted : October 19, 2017
Information provided by (Responsible Party):

Study Description
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 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 CT scans, MRIs, 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 [18-F]-fluorodeoxyglucose (FDG) or use of a higher dose of [111In-DTPA-D-Phe]-pentetreotide can be used to successfully localize the source of ectopic ACTH production.<TAB>

Condition or disease Intervention/treatment Phase
Cushing Syndrome Drug: Pentetreotide Drug: 18-F-fluorodeoxyglucose Drug: (18F)-L-3,4-dihydroxyophenylalanine (18F-DOPA) Phase 1 Phase 2

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 using the conventional low dose of indium-111 pentetreotide ([(111)In-DTPA-D-Phe]-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 [18F]-L-3,4-dihydroxyphenylalanine (18F-DOPA) or use of a higher dose of [111In-DTPA-D-Phe]-pentetreotide 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 [111 In-DTPA-D-Phe] pentetreotide. Patients participating in this arm of the study will have a second standard dose scan rather than a higher dose scan. Others will receive a higher dose octreoscan instead.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 202 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: New Imaging Modalities in the Evaluation of Patients With Ectopic Cushing's Syndrome
Study Start Date : February 26, 1999
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2019

Arms and Interventions

Outcome Measures

Primary Outcome Measures :
  1. Sensitivity, specificity and diagnostic accuracy of imaging modalities for the detection of ACTH-secreting non-pituitary tumor

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 NIH for follow-up studies.


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 H-OCT instead, if the L-OCT were negative. Patients with hypokalemia (K < 3.5 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 (PT and PTT elevated by 30 percent above the normal values), hematopoietic (hematocrit less than 30 percent, hemoglobin below 10 g/dl, white count below 3000 K/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 [111In-DTPA-D-Phe]-pentetreotide or other somatostatin analogues.
  • strong evidence for Cushing disease. This includes those with positive IPSS or a lesion on pituitary MRI.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00001849

Contact: Raven N McGlotten, R.N. (301) 827-0190 mcglottenr@mail.nih.gov
Contact: Lynnette K Nieman, M.D. (301) 496-8935 niemanl@mail.nih.gov

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: Lynnette K Nieman, M.D. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
More Information

Additional Information:
Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT00001849     History of Changes
Other Study ID Numbers: 990055
First Posted: November 4, 1999    Key Record Dates
Last Update Posted: October 19, 2017
Last Verified: September 14, 2017

Keywords provided by National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) ):
Cushing's Syndrome
Ectopic Cushing Syndrome

Additional relevant MeSH terms:
Cushing Syndrome
Cardiac Complexes, Premature
Pathologic Processes
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Adrenocortical Hyperfunction
Adrenal Gland Diseases
Endocrine System Diseases
Fluorodeoxyglucose F18
Molecular Mechanisms of Pharmacological Action