Does Serum-DXM Increase Diagnostic Accuracy of the Overnight DXM Suppression Test in the Work-up of Cushing's Syndrome?
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Purpose
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.
| Study Type: | Observational |
| Study Design: | Observational Model: Case-Only Time Perspective: Prospective |
| 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 |
- 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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
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.
- 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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
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).
- 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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- 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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- 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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]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 cortisone in the assessment of Cushing's syndrome. All study cases are included in this analysis. [ Time Frame: 1 year ] [ Designated as safety issue: No ]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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Identical to primary endpoint, but saliva-DXM measurements replace serum-DXM, and saliva-cortisol replace serum-cortisol. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Identical to primary endpoint, but saliva-DXM measurements replace serum-DXM and saliva-cortisone replace serum-cortisol. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- 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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]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.
- 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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- 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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]Parametric descriptive statis
- Evaluate the dexamethasone metabolism in patients with obesity [ Time Frame: 1 year ] [ Designated as safety issue: No ]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 supression test.
- Evaluate the dexamethasone metabolism in patients with alcohol abuse [ Time Frame: 1 year ] [ Designated as safety issue: No ]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 supression test.
Biospecimen Retention: Samples Without DNA
Blood, saliva, urine
| Estimated Enrollment: | 300 |
| Study Start Date: | October 2011 |
| Estimated Study Completion Date: | December 2012 |
| Estimated Primary Completion Date: | December 2012 (Final data collection date for primary outcome measure) |
| Groups/Cohorts |
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Patients under investigation for hypercortisolism
Patients undergoing routine evaluation for hypercortisolism at Haukeland University Hospital, Bergen, Norway, will be asked to participate.
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Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Probability Sample |
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.
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
Contacts and Locations| Contact: Grethe Åstrøm Ueland, MD | +4790950021 | geas@helse-bergen.no |
| Contact: Paal Methli, MD | +4797677930 |
| Norway | |
| Haukeland Universitetssykehus- Endokrinologisk avdeling | Recruiting |
| Bergen, Norway, 5021 | |
| Contact: Grethe Åstrøm Ueland, Doctor +4790950021 geas@helse-bergen.no | |
| Contact: Hrafnkell Baldur Thordarsson, Doctor +4755972995 hraf@helse-bergen.no | |
| Principal Investigator: Grethe Ueland, MD | |
| Sub-Investigator: Hrafnkell Baldur Thordarsson, MD | |
| Sub-Investigator: Eystein Husebye, Prof.Dr.Med | |
| Sub-Investigator: Kristian Løvås, Prof.Dr.Med | |
| Haukeland University Hospital- Hormonlaboratory | Recruiting |
| Bergen, Norway, 5096 | |
| Contact: Grethe Åstrøm Ueland, Doctor +4790950021 geas@helse-bergen.no | |
| Contact: Paal Methli, Doctor +4797677930 | |
| Principal Investigator: Grethe Åstrøm Ueland, Doctor | |
| Sub-Investigator: Paal Methli, Doctor | |
| Institutt for farmakologi | Recruiting |
| Bergen, Norway, 5021 | |
| Contact: Simon Steinar Hustad, Dr.Med | |
| Haukeland Universitetssykehus- Rusmedisinsk avdeling | Not yet recruiting |
| Bergen, Norway, 5019 | |
| Contact: Pia Synøve Kloster, Cand.med 55975000 | |
| Sub-Investigator: Pia Synøve Kloster, Cand.med | |
| Study Chair: | Grethe Åstrøm Ueland, MD | Haukeland University Hospital |
More Information
Additional Information:
Publications:
| Responsible Party: | Haukeland University Hospital |
| ClinicalTrials.gov Identifier: | NCT01504555 History of Changes |
| Other Study ID Numbers: | 2011/1810 |
| Study First Received: | November 15, 2011 |
| Last Updated: | December 10, 2012 |
| Health Authority: | Norway: Regional Ethics Commitee |
Keywords provided by Haukeland University Hospital:
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hypercortisolism, dexamethasone, alcoholism,obesity. |
Additional relevant MeSH terms:
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Cushing Syndrome Alcoholism Obesity Adrenocortical Adenoma Adrenal Gland Neoplasms Alcohol-Related Disorders Substance-Related Disorders Mental Disorders Adrenocortical Hyperfunction Adrenal Gland Diseases Endocrine System Diseases Overnutrition Nutrition Disorders Overweight Body Weight |
Signs and Symptoms Adrenal Cortex Neoplasms Endocrine Gland Neoplasms Neoplasms by Site Neoplasms Adrenal Cortex Diseases Dexamethasone acetate Dexamethasone Dexamethasone 21-phosphate BB 1101 Anti-Inflammatory Agents Therapeutic Uses Pharmacologic Actions Antiemetics Autonomic Agents |
ClinicalTrials.gov processed this record on May 19, 2013