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Morning serum cortisol role in the adrenal insufficiency diagnosis with modern cortisol assays

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Abstract

Purpose

To investigate the accuracy of cutoff values of the morning serum cortisol (MSC) using the cortisol stimulus test (CST) insulin tolerance test (ITT) and 250 mcg short Synacthen test (SST) as the reference standard tests, to better define its clinical role as a tool in the diagnostic investigation of adrenal insufficiency (AI) AI.

Methods

An observational study was conducted with a retrospective analysis of MSC in adult patients who had been submitted to a CST to investigate AI between January 2014 and December 2020. The normal cortisol response (NR) to stimulation was defined based on the cortisol assay.

Results

371 patients underwent CST for suspected AI, 121/371 patients (32.6%) were diagnosed with AI. ROC curve analysis showed an area under the curve (AUC) for MSC of 0.75 (95% CI 0.69 – 0.80). The best MSC cutoff values to confirm AI were < 3.65, < 2.35 and < 1.5 mcg/dL with specificity of 98%, 99%, and 100%, respectively. MSC > 12.35, > 14.2 and > 14.5 mcg/dL had sensitivity of 98%, 99%, and 100%, respectively, being the best cutoff values to exclude AI. Almost 25% of patients undergoing CST for possible AI had MSC values between < 3.65 mcg/dL (6.7% of patients) and > 12.35 mcg/dL (17.5% of patients), making the formal CST testing unnecessary if we consider these cutoff values.

Conclusion

With the most modern cortisol assays, MSC could be used as a diagnostic tool, with high accuracy to confirm or exclude AI, avoiding unnecessary CST; thus, reducing expenses and safety risks during AI investigation.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This study was made possible thanks to grants from the Brazilian National Council for Scientific and Technological Development (CNPq) to LVN.

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Authors and Affiliations

  1. Department of Internal Medicine and Endocrine Unit, Federal University of Rio de Janeiro, School of Medicine, Clementino Fraga Filho University Hospital, 255 Professor Rodolpho Paulo Rocco Street, ground floor, University City, Rio de Janeiro, RJ, ZC 21941-617, Brazil

    A. F. D. Fragoso Perozo, P. B. Araújo & L. Vieira Neto

  2. Diagnósticos da América SA (DASA), Rio de Janeiro, RJ, Brazil

    A. F. D. Fragoso Perozo, R. Fontes, F. P. Lopes, P. B. Araújo, Y. Scrank & D. M. V. Gomes

  3. Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione, Rio de Janeiro, Brazil

    A. F. D. Fragoso Perozo & R. Fontes

  4. Department of Clinical Medicine and Endocrine Unit, Federal Fluminense University, School of Medicine, Antônio Pedro University Hospital, Niterói, RJ, Brazil

    A. B. Moraes

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  1. A. F. D. Fragoso Perozo
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  2. R. Fontes
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by AFDFP and LVN. The first draft of the manuscript was written by AFDFP and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to A. F. D. Fragoso Perozo.

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The authors report no conflict of interest in this work.

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All procedures involving human participants were performed in accordance with the ethical standards of the Institutional Ethics Committee at which the studies were conducted. This paper does not contain any studies with animals performed by any of the authors.

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Fragoso Perozo, A.F.D., Fontes, R., Lopes, F.P. et al. Morning serum cortisol role in the adrenal insufficiency diagnosis with modern cortisol assays. J Endocrinol Invest 46, 2115–2124 (2023). https://doi.org/10.1007/s40618-023-02062-y

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