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Development and validation of a novel index for the differential diagnosis of corticotropin‐dependent Cushing syndrome

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Abstract

Purpose

To develop an index for the differential diagnosis of corticotropin-dependent Cushing syndrome (CS).

Methods

The development cohort included 112 consecutive patients with clinicopathologically confirmed corticotropin-dependent CS at the Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, from December 2004 to May 2020, and data of 126 patients from studies published from 2016 to August 2020, identified through search in PubMed, Embase and the Cochrane Library, was extracted for external validation. The index was calculated as the product of plasma adrenocorticotropic hormone (ACTH, pmol/L) and urinary free cortisol (UFC, nmol/24 h) divided by 10,000. The discriminative ability was tested using receiver operating characteristics (ROC) curve analysis.

Results

In development cohort, area under curve of ROC analysis of the ACTH-UFC index in identifying Cushing disease (CD) was 0.977. The diagnostic accuracy of ACTH-UFC index ≤ 11 was comparable to that of 48 h 8 mg/d high-dose dexamethasone test (HDDST) in identifying CD, with sensitivity, specificity, positive and negative likelihood ratios of 96.6%, 87.5%, 7.73, and 0.04, respectively. The sensitivity of ACTH-UFC index ≤ 11 in parallel combination with pituitary magnetic resonance imaging (MRI) was 100% for identifying CD. The performance of the ACTH-UFC index in parallel or serial combination with pituitary MRI was similar in the validation cohort.

Conclusions

ACTH-UFC index provides a rapid, convenient and non-invasive adjunctive approach for the differential diagnosis of corticotropin-dependent CS, with no risk of aggravating metabolic disturbances. Investigations for ectopic causes of corticotropin-dependent CS should be performed with ACTH-UFC index > 11 and negative contrasted pituitary MRI.

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Data availability

The datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

Code availability

Analytical code of the current study are not publicly available but are available from the corresponding author on reasonable request.

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Acknowledgements

We thank Dr. Junping Wang for assistance in key issues regarding radiology.

Funding

We acknowledge the supports of the National Key R&D Program of China 2019YFA0802502, the National Natural Science Foundation of China 81830025 and 81620108004, and the Tianjin Municipal Science and Technology Commission 17ZXMFSY00150, and 19JCQNJC11800.

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    Authors and Affiliations

    1. Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, No. 154, Anshan, Road, Heping District, Tianjin, 300052, China

      Li Ding, Baoping Wang, Tingting Chen, Ping Li, Weihong Guo, Yuxin Fan, Fang Fang, Jingqiu Cui, Qing He & Ming Liu

    2. Department of Clinical Laboratory, Tianjin Medical University General Hospital, No. 154, Anshan, Road, Heping District, Tianjin, 300052, China

      Zuoliang Dong

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    Contributions

    ML is the guarantor, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors contributed to the study conception and design, material preparation, and data collection. Data analysis were performed by LD, BW, TC, PL, WG, YF. The first draft of the manuscript was written by Li Ding, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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    Correspondence to Qing He or Ming Liu.

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    The authors have nothing to disclose.

    Ethical approval

    The study was approved by the institutional review board, and the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

    Informed consent

    Informed consent of the present study patients was not obtained because the study was a secondary data analysis which not including personally identified information.

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    Li Ding, Baoping Wang and Tingting Chen contributed equally to this work.

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    Cite this article

    Ding, L., Wang, B., Chen, T. et al. Development and validation of a novel index for the differential diagnosis of corticotropin‐dependent Cushing syndrome. Pituitary 24, 507–516 (2021). https://doi.org/10.1007/s11102-021-01126-7

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