Clinical trial NCT01504555: Does Serum-DXM Increase Diagnostic Accuracy of the Overnight DXM Suppression Test in the Work-up of Cushing's Syndrome?
Official title: Evaluation of the Diagnostic Utility of Serum Dexamethasone Measurements in the Overnight 1mg Dexamethasone Suppression Test in Patients Investigated for Cushing's Syndrome and Incidentalomas
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Cushing's Syndrome
Adrenal Incidentalomas
Alcoholism
Obesity
Keywords: hypercortisolism, dexamethasone, alcoholism,obesity.
Lead sponsor: Haukeland University Hospital
Sponsor class: OTHER
First posted: 2012-01-05
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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.

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.


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* Use of systemic or local glucocorticoids

Primary outcomes:
measure: 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.
timeFrame: 1 year
Secondary outcomes:
measure: 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.
timeFrame: 1 year
measure: 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.
timeFrame: 1 year
measure: 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.
timeFrame: 1 year
measure: 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.
timeFrame: 1 year
measure: 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.
timeFrame: 1 year
measure: Calculate the negative likelihood ratio [(1-sensitivity)/specificity] for midnight salivary cortisone in the assessment of Cushing's syndrome. All study cases are included in this analysis.
timeFrame: 1 year
measure: Identical to primary endpoint, but saliva-DXM measurements replace serum-DXM.
timeFrame: 1 year
measure: Identical to primary endpoint, but saliva-DXM measurements replace serum-DXM, and saliva-cortisol replace serum-cortisol.
timeFrame: 1 year
measure: Identical to primary endpoint, but saliva-DXM measurements replace serum-DXM and saliva-cortisone replace serum-cortisol.
timeFrame: 1 year
measure: Calculate the positive likelihood ratio [(1-sensitivity)/specificity] for creatinine-adjusted cortisol in morning spot urine in the assessment of Cushing's syndrome. All study cases are included in this analysis.
timeFrame: 1 year
measure: Calculate the negative likelihood ratio [(1-sensitivity)/specificity] for creatinine-adjusted cortisol in morning spot urine in the assessment of Cushing's syndrome. All study cases are included in this analysis.
timeFrame: 1 year
measure: Compute a 95% confidence interval for morning s-DXM following overnight DXM-test in healthy subjects using parametric and non-parametric statistics.
timeFrame: 1 year
measure: Quantitatively and qualitatively describe the characteristics of patients with false positive DXM-test and true negative DXM-test based on a standard questionnaire scoring patient history, symptoms and clinical features.
timeFrame: 1 year
measure: Evaluate the dexamethasone metabolism in patients with obesity
timeFrame: 1 year
measure: Evaluate the dexamethasone metabolism in patients with alcohol abuse
timeFrame: 1 year
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: Haukeland Universitetssykehus- Rusmedisinsk avdeling
city: Bergen
country: Norway
facility: Haukeland Universitetssykehus- Endokrinologisk avdeling
city: Bergen
country: Norway
facility: Institutt for farmakologi
city: Bergen
country: Norway
facility: Haukeland University Hospital- Hormonlaboratory
Study officials:
affiliation: Haukeland University Hospital
name: Grethe Åstrøm Ueland, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.