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

• Conditions: Adrenal Incidentalomas; Alcoholism; Obesity; Cushing's Syndrome

• Registration Number: NCT01504555
• Lead Sponsor: 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-10
• Study First Submitted: 2011-11-15
• Study First Submitted QC: 2012-01-03
• Study First Posted: 2012-01-05
• Status Verified: 2016-09
• Last Update Submitted: 2016-09-23
• Last Update Posted: 2016-09-26
• Primary Completion: 2017-09
• Study Completion: 2017-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 300

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.	1 year	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.

Secondary Outcome Measures

Name	Time	Method
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	Sensitivity = (Number of patients having CS with positive test / total number of patients with CS).; Specificity = (Number of patients not having CS with negative test / total number of patients not having CS).
Identical to primary endpoint, but saliva-DXM measurements replace serum-DXM.	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 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	A saliva cortisol cut-off level will be defined a priori from ROC analysis on all patients with and without Cushing's syndrome.
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
Identical to primary endpoint, but saliva-DXM measurements replace serum-DXM, and saliva-cortisol replace serum-cortisol.	1 year
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.	1 year	A cut-off level for creatinine-adjusted morning urine cortisol will be defined a priori from ROC analysis on all patients with and without Cushing's Syndrome.
Compute a 95% confidence interval for morning s-DXM following overnight DXM-test in healthy subjects using parametric and non-parametric statistics.	1 year
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.	1 year	Parametric descriptive statistics
Evaluate the dexamethasone metabolism in patients with alcohol abuse	1 year	We are evaluating if patients with alcohol abuse metabolise dexamethasone in the same way as normal patients, by looking at the s-dexamethasone and s-cortisol level the day after 1 mg overnight dexamethason suppression test.
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	A saliva cortisone cut-off level will be defined a priori from ROC analysis on all patients with and without Cushing's syndrome.
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.	1 year	A saliva cortisone cut-off level will be defined a priori from ROC analysis on all patients with and without Cushing's syndrome.
Identical to primary endpoint, but saliva-DXM measurements replace serum-DXM and saliva-cortisone replace serum-cortisol.	1 year
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.	1 year	A cut-off level for creatinine-adjusted morning urine cortisol will be defined a priori from ROC analysis on all patients with and without Cushing's syndrome.
Evaluate the dexamethasone metabolism in patients with obesity	1 year	We are evaluating if overweight patients metabolise Dexamethasone in the same way as normal weighted patients, by looking at the s-dexamethasone and s-cortisol level the day after 1 mg overnight Dexamethason suppression test.

Trial Locations

Locations (4)

Haukeland Universitetssykehus- Rusmedisinsk avdeling; 🇳🇴 Bergen, Norway

Haukeland University Hospital- Hormonlaboratory; 🇳🇴 Bergen, Norway

Haukeland Universitetssykehus- Endokrinologisk avdeling; 🇳🇴 Bergen, Norway

Institutt for farmakologi; 🇳🇴 Bergen, Norway