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White blood cell count: a valuable tool for suspecting Cushing’s syndrome

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Abstract

Purpose

Simple screening tests to determine whether Cushing's syndrome (CS) should be ruled out are lacking. Tools that enable early diagnosis could reduce morbidity and associated sequelae. The potential of glucocorticoid-induced changes in the white blood cell (WBC) count for raising suspicion of CS is assessed.

Methods

This was a retrospective case‒control study. The WBC counts of 73 cases with CS and 146 matched controls were compared. The number of leukocytes (Leu), the number and percentage of neutrophils (N, Np), the number and percentage of lymphocytes (L, Lp), neutrophil-to-lymphocyte differences in the number and percentage (N-L, Np-Lp), neutrophil-to-lymphocyte ratio in the number and percentage (NLR, NLRp), and leukocyte-to-lymphocyte differences (Leu-L) were evaluated. The area under the ROC curve (AUC) was calculated for each of these parameters. Reference values were estimated that could help disclose occult CS.

Results

All ten parameters showed significant differences between cases and controls. The AUC was greater than 0.7 for all ten parameters, and was the best for the NLRp and Lp (AUC: 0.89). An Lp of 23.9% showed a diagnostic accuracy of 84.9% for the diagnosis of CS. The concordance of an Lp below 24% and more than 8000 leucocytes had a PPV of 78.2% for CS, while the pairing of an Lp over 24% and a Leu below 8000 cells had an NPV of 97.3% for CS.

Conclusion

WBC count assessment can be an effective tool to raise suspicion of CS, prompting diagnostic testing. This simple and universally available test may allow earlier diagnosis of CS before highly evolved phenotypes develop.

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Availability of data and materials

Datasets including matching and main data are uploaded in: Paja, Miguel (2022), “WBC_CUSHING”, Mendeley Data, V1. https://doi.org/10.17632/n85psdwf44.1.

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Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Author information

Authors and Affiliations

  1. Basurto University Hospital, Bilbao, Spain

    M. Paja, I. Merlo, J. Rodríguez-Soto, E. Cruz-Iglesias & A. Oleaga

  2. Basque Country University, Leioa, Spain

    M. Paja & A. Oleaga

  3. Cruces University Hospital, Barakaldo, Spain

    M. D. Moure

  4. Donostia University Hospital, Donostia, Spain

    C. Elías & N. Egaña

  5. Endocrinology Department, Basurto University Hospital. Avda de Montevideo, 18. 48013, Bilbao, Spain

    M. Paja

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  1. M. Paja
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Contributions

All authors contributed to the study’s conception and design. Material preparation and data collection were performed by Miguel Paja, Ignacio Merlo, Josune Rodríguez-Soto, Elena Cruz-Iglesias, M. Dolores Moure, Cristina Elías and Nerea Egaña. Statistical analyses were performed by Miguel Paja and Ignacio Merlo. The first draft of the manuscript was written by Miguel Paja and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. All authors confirm that they had full access to all the data in the study and accept responsibility to submit for publication.

Corresponding author

Correspondence to M. Paja.

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Conflict of interest

The authors have no relevant financial or non-financial interests to disclose. All the authors state that they do not have any conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Ethical approval

The study was approved by the Regional Ethics Committee of the Basque Country (CEIm–E; PI2021088) and the local committees of each institution.

Informed consent

The institutional review board of each participating institution granted a waiver of consent given the deidentified nature of the patient data collected for the analysis.

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Paja, M., Merlo, I., Rodríguez-Soto, J. et al. White blood cell count: a valuable tool for suspecting Cushing’s syndrome. J Endocrinol Invest 46, 141–149 (2023). https://doi.org/10.1007/s40618-022-01892-6

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  • DOI: https://doi.org/10.1007/s40618-022-01892-6

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