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
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 300
- 试验地点
- 4
- 主要终点
- 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.
研究概览
简要总结
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age over 18 years
- •Under investigation for hypercortisolism
- •Able and willing to make informed consent
排除标准
- •Use of systemic or local glucocorticoids
结局指标
主要结局
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.
时间窗: 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.
次要结局
- 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)
- 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)
- 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)
- 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)
- Evaluate the dexamethasone metabolism in patients with alcohol abuse(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)
- 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)
- 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)
- Evaluate the dexamethasone metabolism in patients with obesity(1 year)