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Circulating immune profiles in ACTH-dependent Cushing's syndrome.
Jie Liu1,2, Xiang Zhou2,3, Huijuan Zhu2,3
1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
European Journal of Endocrinology
|April 4, 2026
Summary
ACTH-dependent Cushing's syndrome causes immune dysfunction and infection. This study differentiated Cushing's disease (CD) from ectopic ACTH syndrome (EAS) using immune profiling and predicted infection risk, showing immune recovery post-surgery.
Area of Science:
- Endocrinology
- Immunology
- Medical Diagnostics
Background:
- ACTH-dependent Cushing's syndrome (CS) is linked to significant immune impairment and increased susceptibility to severe infections.
- Differentiating between Cushing's disease (CD) and ectopic ACTH syndrome (EAS) is crucial for appropriate management.
- Understanding immune cell dynamics and recovery post-treatment is essential for patient outcomes.
Purpose of the Study:
- To characterize immune cell phenotypes in ACTH-dependent CS.
- To develop predictive models for distinguishing CD from EAS and assessing infection risk.
- To evaluate immune system recovery following successful surgical remission.
Main Methods:
- A retrospective single-center study included 211 patients with ACTH-dependent CS (173 CD, 38 EAS).
- Flow cytometry analyzed lymphocyte subsets; severe infection incidence was recorded.
- Machine learning models were developed for disease differentiation and infection risk prediction.
Main Results:
- Ectopic ACTH syndrome (EAS) patients exhibited more severe immune suppression than Cushing's disease (CD) patients, with lower CD4+ T cells and CD3+ T cells, and a higher percentage of CD19+ B cells.
- A machine learning model integrating immune and non-immune parameters achieved 75.4% accuracy in differentiating CD from EAS.
- A multivariate model predicted severe infection risk with an AUC of 0.851, incorporating 24h UFC, serum potassium, CD19+ B cell percentage, and CD4+ T cell count.
- Following surgical remission, significant T cell reconstitution was observed within 8 weeks, with a threefold increase in CD4+ T cells.
Conclusions:
- Immune cell profiling effectively distinguishes between CD and EAS in ACTH-dependent CS.
- Predictive models incorporating specific clinical and immunological parameters can identify patients at high risk for severe infections.
- Surgical remission of ACTH-dependent CS promotes substantial immune reconstitution, particularly in T cell populations.
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