Does Serum-DXM Increase Diagnostic Accuracy of the Overnight DXM Suppression Test in the Work-up of Cushing's Syndrome?

NCT01504555 | Unknown

• 1 other identifier: 2011/1810
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 4

Brief Summary

Background: The evaluation for hypercortisolism includes an overnight 1mg dexamethasone (DXM) suppression test. An important shortcoming is the diagnostic specificity of only 80%, which is likely due to inter-individual differences in gut absorption or metabolism of DXM. Study hypothesis: The investigators hypothesize that serum-DXM measurements will increase the diagnostic accuracy of the overnight DXM-test in the work-up of hypercortisolism. Aims: The primary aim of this prospective study is to evaluate if serum-DXM measured simultaneously with serum-cortisol in morning samples could increase the diagnostic accuracy this diagnostic test. There are several secondary aims. One is to estimate the prevalence and causes of unusual DXM absorption or metabolism. The investigators will also evaluate the feasibility and diagnostic accuracy of salivary DXM. Moreover, the diagnostic accuracy of midnight salivary cortisol and cortisone, and urinary cortisol, will be evaluated and compared. Design: Levels of DXM in morning serum following an overnight DXM-test will be analyzed in patients under evaluation for hypercortisolism (including incidentalomas). A cut-off level to identify inadequate DXM concentrations in serum to suppress endogenous cortisol production will be established based on the negative tests. This cut-off level will then be applied in a retrospective analysis of the diagnostic accuracy of DXM-tests. This prospective study has a blinded design as the DXM measurements are disclosed after the end of the trial.

Conditions

Cushing's Syndrome; Adrenal Incidentalomas; Alcoholism; Obesity

Keywords

hypercortisolism, dexamethasone, alcoholism,obesity.

Outcome Measures

Primary Outcomes (1)

• The difference (in percent) in false positive DXM-tests comparing the outcome of all tests with all tests excluding those with s-DXM below the the cut-off specified below.

  The s-DXM cut-off will be defined a priori from ROC analysis on patients that inadequately suppress s-cortisol categorized as having Cushing's syndrome or being healthy. DXM, dexamethasone; DXM-test, short 1mg dexamethasone suppression test.

  1 year

Secondary Outcomes (15)

• Calculate the positive likelihood ratio [(1-sensitivity)/specificity] for the short DXM-test in the assessment of Cushing's syndrome (CS), after excluding those with s-DXM below the DXM cut-off specified in the primary endpoint.

  1 year

• Calculate the negative likelihood ratio [(1-sensitivity)/specificity] for the short DXM-test in the assessment of Cushing's syndrome, after excluding those with s-DXM below the DXM cut-off specified in the primary endpoint.

  1 year

• Calculate the positive likelihood ratio [(1-sensitivity)/specificity] for midnight salivary cortisol in the assessment of Cushing's syndrome. All study cases are included in this analysis.

  1 year

• Calculate the negative likelihood ratio [(1-sensitivity)/specificity] for midnight salivary cortisol in the assessment of Cushing's syndrome. All study cases are included in this analysis.

  1 year

• Calculate the positive likelihood ratio [(1-sensitivity)/specificity] for midnight salivary cortisone in the assessment of Cushing's syndrome. All study cases are included in this analysis.

  1 year

Study Arms (1)

Patients under investigation for hypercortisolism

Patients undergoing routine evaluation for hypercortisolism at Haukeland University Hospital, Bergen, Norway, will be asked to participate.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients at Haukeland University Hosptial, Bergen, Norway, under routine evaluation for hypercortisolism.Patients under evaluation for obeity at the overweight clinic, and Patients treated for alcohol abuse at the clinic for alcohol addicts at Haukeland University hospital.

You may qualify if:

• Age over 18 years
• Under investigation for hypercortisolism
• Able and willing to make informed consent

You may not qualify if:

• Use of systemic or local glucocorticoids

Sponsors & Collaborators

• Haukeland University Hospital: lead

Study Sites (4)

Haukeland Universitetssykehus- Rusmedisinsk avdeling

Bergen, 5019, Norway

NOT YET RECRUITING

Haukeland Universitetssykehus- Endokrinologisk avdeling

Bergen, 5021, Norway

RECRUITING

Institutt for farmakologi

Bergen, 5021, Norway

RECRUITING

Haukeland University Hospital- Hormonlaboratory

Bergen, 5096, Norway

RECRUITING

Related Publications (3)

• Baid SK, Rubino D, Sinaii N, Ramsey S, Frank A, Nieman LK. Specificity of screening tests for Cushing's syndrome in an overweight and obese population. J Clin Endocrinol Metab. 2009 Oct;94(10):3857-64. doi: 10.1210/jc.2008-2766. Epub 2009 Jul 14.

  PMID: 19602562 BACKGROUND

• Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, Montori VM. The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008 May;93(5):1526-40. doi: 10.1210/jc.2008-0125. Epub 2008 Mar 11.

  PMID: 18334580 BACKGROUND

• Carroll TB, Findling JW. The diagnosis of Cushing's syndrome. Rev Endocr Metab Disord. 2010 Jun;11(2):147-53. doi: 10.1007/s11154-010-9143-3.

  PMID: 20821267 BACKGROUND

Related Links

• Kortisol i spytt ved sykdom i binyrene
• Spyttprøver til kortisolmåling
• Endogent Cushing syndrom

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood, saliva, urine

MeSH Terms

Conditions

Cushing Syndrome; Adrenal incidentaloma; Alcoholism; Obesity

Condition Hierarchy (Ancestors)

Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Grethe Åstrøm Ueland, MD

  Haukeland University Hospital

  STUDY CHAIR

Central Study Contacts

Grethe Åstrøm Ueland, MD

CONTACT

+4790950021; geas@helse-bergen.no

Paal Methli, MD

CONTACT

+4797677930

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2011
• First Posted: January 5, 2012
• Study Start: October 1, 2011
• Primary Completion: September 1, 2017
• Study Completion: September 1, 2017
• Last Updated: September 26, 2016

Record last verified: 2016-09

Locations

NO (4)