Diagnostic Performance of Screening Tests for Cushing s Syndrome

The Diagnostic Performance of Screening Tests for the Diagnosis of Cushing's Syndrome

This study will test the accuracy of screening tests for Cushing s syndrome in overweight people with signs of the disorder. Cushing s syndrome is a rare disorder caused by excess production of the hormone cortisol. Patients may have various problems, such as weight gain, high blood pressure, diabetes, infections, mood problems, trouble concentrating, and increased blood clotting. These symptoms are seen in many other disorders as well, complicating the diagnosis. The reliability of tests currently used to diagnose Cushing s syndrome is not known. To test their accuracy, subjects in this study who test positive for Cushing s syndrome will be evaluated at NIH for 2 years to either confirm or refute the laboratory results.

Patients between 18 and 75 years of age who are being treated at the George Washington University Weight Management Program (GWUWMP) may participate in this study. Candidates will be screened with a medical history, physical examination, measurement of body fat, blood tests, and oral glucose tolerance test. They will also complete a symptoms checklist and quality of life questionnaire.

Participants will be tested for Cushing s syndrome with a saliva collection, 24-hour urine collection, and dexamethasone suppression test (DST). For the DST they will take 1 mg of dexamethasone at night and report to GWUWMP the next morning for a blood draw. All specimens blood, saliva, and urine will be tested for cortisol levels.

People whose test results are abnormal will be seen at the NIH outpatient clinic for a medical history, physical examination, and blood tests; bedtime saliva collection; two 24-hour urine collections; and a 2-day 2-mg DST, followed by administration of corticotropin-releasing hormone (CRH). CRH is a naturally occurring hormone that causes cortisol levels to rise. Pre-treatment with dexamethasone prevents CRH from causing an increase in cortisol in healthy people, but not in patients with Cushing s syndrome. For the 2-day DST, the subject takes 0.5 mg dexamethasone every 6 hours for eight doses. Two hours after the last dose, CRH is injected through a catheter (thin plastic tube) inserted into an arm vein. Blood is drawn just before giving CRH to measure dexamethasone and cortisol levels and after giving CRH to measure cortisol levels.

People whose test results are normal will not be seen further at NIH. Those with high cortisol levels will have repeat urine and saliva tests every 2 to 8 weeks for up to 24 months, and a 1-mg DST every 3 months during routine clinic visits at GWUWMP. People whose increased cortisol is found to be due to another condition besides Cushing s syndrome will be referred for evaluation and possible treatment. Those diagnosed with Cushing s syndrome will have standard tests to identify the tumor causing the disorder, followed by standard medical and surgical treatment.

Study Overview

• Status: Completed
• Conditions: Cushing's Syndrome

Detailed Description

Cushing's syndrome is a rare disorder characterized by a variety of clinical signs and symptoms that reflect chronic exposure to hypercortisolism such as obesity, hypertension, glucose intolerance, infections, psychiatric disturbance, impaired cognition and hypercoagulability. Thus, it is important to screen for this treatable disorder so as to prevent its associated morbidity and mortality. Because many of the signs of Cushing's syndrome are common in the general population, information about the cost-effectiveness and diagnostic efficiency of various screening tests would be useful.

This study will evaluate the diagnostic performance of various screening tests for Cushing's syndrome in overweight patients recruited from a weight loss center who have additional signs of the disorder. Patients with abnormal tests will be seen as outpatients at the NIH for further evaluation for up to two years to confirm or refute the possibility that they have Cushing's syndrome. Patients with the disorder will be treated.

• Study Type: Observational
• Enrollment (Actual): 471

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • GW University Medical Center GW Hospital Center
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center, 9000 Rockville Pike

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• INCLUSION CRITERIA:

Patients presenting for weight loss treatment at the GWUWMP

Patients must have at least two of the signs and symptoms in Table 1 of the protocol, in addition to weight gain. If abdominal pain, backache and/or headache are present, only one of these symptoms can be used in any given patient, so that another feature must be present.

Willing and able to be seen for up to 24 months

Age 18-75

EXCLUSION CRITERIA:

Weight more than 350 pounds, the maximum weight for radiologist examination tables necessary for the evaluation of Cushing's Syndrome

Renal failure, creatinine greater than 2.6, because of possible effects on dexamethasone metabolism

Pregnancy, because it alters interpretation of adrenal function tests

Current use of oral, inhaled or intranasal glucocorticoids or use within 30 days of study

Other significant medical disorders that may complicate participation or interpretation of the results. For example, a patient with a collagen vascular disorder who has taken intermittent high dose glucocorticoids, and might need to do this again, might not be offered participation.

Use of black licorice or chewing tobacco within two weeks of the study or anticipated use during the study

Use of phenytoin, barbiturate, loperamide or opiates within two weeks of the study or anticipated chronic use during the study.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Possible Cushing's; Patients with possible cushion's syndrome

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity and specificity of screening tests	Sensitivity and specificity of screening tests	months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Castro M, Elias PC, Quidute AR, Halah FP, Moreira AC. Out-patient screening for Cushing's syndrome: the sensitivity of the combination of circadian rhythm and overnight dexamethasone suppression salivary cortisol tests. J Clin Endocrinol Metab. 1999 Mar;84(3):878-82. doi: 10.1210/jcem.84.3.5521.
• Crapo L. Cushing's syndrome: a review of diagnostic tests. Metabolism. 1979 Sep;28(9):955-77. doi: 10.1016/0026-0495(79)90097-0.
• Gold PW, Loriaux DL, Roy A, Kling MA, Calabrese JR, Kellner CH, Nieman LK, Post RM, Pickar D, Gallucci W, et al. Responses to corticotropin-releasing hormone in the hypercortisolism of depression and Cushing's disease. Pathophysiologic and diagnostic implications. N Engl J Med. 1986 May 22;314(21):1329-35. doi: 10.1056/NEJM198605223142101.

Study record dates

Study Major Dates

• Study Start: September 19, 2002
• Study Completion: October 30, 2019

Study Registration Dates

• First Submitted: August 8, 2006
• First Submitted That Met QC Criteria: August 8, 2006
• First Posted (ESTIMATE): August 9, 2006

Study Record Updates

• Last Update Posted (ACTUAL): December 16, 2019
• Last Update Submitted That Met QC Criteria: December 13, 2019
• Last Verified: October 30, 2019

More Information

Terms related to this study

• Keywords: Dexamethasone; Cushing Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Endocrine System Diseases; Disease; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Syndrome; Cushing Syndrome
• Other Study ID Numbers: 020309; 02-CH-0309