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An Optimized Pathway for the Differential Diagnosis of ACTH-Dependent Cushing's Syndrome Based on Low-Dose
Kang Chen1,2, Shi Chen1, Lin Lu1
1Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Centre, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Insights
The low-dose dexamethasone suppression test (LDDST) can effectively differentiate Cushing's disease (CD) from ectopic ACTH syndrome (EAS), similar to the high-dose test. A new diagnostic pathway combining LDDST with bilateral petrosal sinus sampling (BIPSS) accurately distinguishes these conditions.
Area of Science:
- Endocrinology
- Diagnostic Medicine
- Clinical Research
Background:
- The diagnosis of Cushing's syndrome (CS) traditionally relies on low-dose dexamethasone suppression test (LDDST), while high-dose dexamethasone suppression test (HDDST) differentiates Cushing's disease (CD) from ectopic ACTH syndrome (EAS).
- The utility of HDDST is debated, with suggestions that LDDST might suffice.
- Current diagnostic pathways often combine dexamethasone suppression tests with imaging and invasive procedures like bilateral petrosal sinus sampling (BIPSS), but optimal strategies remain unclear.
Purpose of the Study:
- To develop and validate an optimized diagnostic pathway for differentiating CD from EAS, primarily based on LDDST.
- To compare the diagnostic performance of LDDST and HDDST in distinguishing CD and EAS.
Main Methods:
- A retrospective study analyzed data from 269 CD and 29 EAS patients who underwent both LDDST and HDDST between 2011 and 2019.
- Diagnostic accuracy was assessed using area under the curve (AUC) for urine free cortisol and serum cortisol with LDDST, and compared with HDDST.
- A novel diagnostic pathway was proposed, reserving BIPSS for specific cases identified by LDDST results and pituitary adenoma size.
Main Results:
- LDDST using urine free cortisol demonstrated a higher AUC (0.881) than serum cortisol (0.685) for differentiating CD and EAS.
- LDDST showed a higher AUC (0.883) than HDDST (0.834) in the overall patient cohort.
- With a cutoff of <26%, LDDST achieved 39.4% sensitivity and 100% specificity.
- The proposed pathway, integrating LDDST and selective BIPSS, achieved an overall sensitivity of 97.7% and specificity of 86.7%.
Conclusions:
- LDDST is a valuable tool for differentiating CD and EAS, performing comparably to HDDST at specific cutoff points.
- The developed diagnostic pathway, incorporating LDDST and judicious use of BIPSS, offers an accurate and potentially more efficient approach for diagnosing CD versus EAS.
Context:
Traditionally, low-dose dexamethasone suppression test (LDDST) was used to confirm the diagnosis of Cushing's syndrome (CS), and high-dose dexamethasone suppression test (HDDST) was used to differentiate Cushing's disease (CD) and ectopic adrenocorticotropin (ACTH) syndrome (EAS), but some studies suggested that HDDST might be replaced by LDDST. For the differential diagnosis of CS, dexamethasone suppression test was usually combined with other tests such as bilateral petrosal sinus sampling (BIPSS) and pituitary magnetic resonance imaging, but the optimal pathway to incorporate these tests is still controversial.
Objectives:
To develop an optimized pathway for the differential diagnosis of CD and EAS based on LDDST.
Design And Setting:
Single-center retrospective study (2011-2019).
Patients:
Two hundred sixty-nine CD and 29 EAS patients with pathological diagnosis who underwent consecutive low- and high-dose DST.
Results:
For the differential diagnosis of CD and EAS, the area under curve (AUC) of LDDST using urine free cortisol (0.881) was higher than that using serum cortisol (0.685) (p < 0.001) in head-to-head comparison among a subgroup of 108 CD and 10 EAS. The AUC of LDDST (0.883) was higher than that of HDDST (0.834) among all the included patients. With the cutoff of <26%, the sensitivity and specificity of LDDST were 39.4% and 100%. We designed a new pathway in which BIPSS was only reserved for those patients with unsuppressed LDDST and adenoma <6mm, yielding an overall sensitivity of 97.7% and specificity of 86.7%.
Conclusion:
LDDST had similar value to HDDST in differentiating CD and EAS using the specific cutoff point. The pathway that combined LDDST and BIPSS could differentiate CD and EAS accurately.
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