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, Lorenzo Tucci Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria Di Bologna , Bologna , Italy Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna , Bologna , Italy Search for other works by this author on: Oxford Academic Flaminia Fanelli Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna , Bologna , Italy Center for Applied Biomedical Research, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna , Bologna , Italy Search for other works by this author on: Oxford Academic Ilaria Improta Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria Di Bologna , Bologna , Italy Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna , Bologna , Italy Search for other works by this author on: Oxford Academic Valentina Bissi Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna , Bologna , Italy Center for Applied Biomedical Research, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna , Bologna , Italy Search for other works by this author on: Oxford Academic Claudia Lena Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna , Bologna , Italy Search for other works by this author on: Oxford Academic Greta Galante Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna , Bologna , Italy Center for Applied Biomedical Research, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna , Bologna , Italy Search for other works by this author on: Oxford Academic Marco Mezzullo Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna , Bologna , Italy Center for Applied Biomedical Research, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna , Bologna , Italy Search for other works by this author on: Oxford Academic Matteo Magagnoli Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna , Bologna , Italy Center for Applied Biomedical Research, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna , Bologna , Italy Search for other works by this author on: Oxford Academic Anna Bianca Lalumera Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria Di Bologna , Bologna , Italy Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna , Bologna , Italy Search for other works by this author on: Oxford Academic Giacomo Colombin Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria Di Bologna , Bologna , Italy Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna , Bologna , Italy Search for other works by this author on: Oxford Academic
https://orcid.org/0000-0002-1670-0074 , Kimberly Coscia Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria Di Bologna , Bologna , Italy Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna , Bologna , Italy Search for other works by this author on: Oxford Academic Laura Rotolo Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria Di Bologna , Bologna , Italy Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna , Bologna , Italy Search for other works by this author on: Oxford Academic Valentina Vicennati Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria Di Bologna , Bologna , Italy Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna , Bologna , Italy Search for other works by this author on: Oxford Academic Uberto Pagotto Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria Di Bologna , Bologna , Italy Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna , Bologna , Italy Center for Applied Biomedical Research, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna , Bologna , Italy Search for other works by this author on: Oxford Academic Guido Di Dalmazi Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria Di Bologna , Bologna , Italy Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna , Bologna , Italy Corresponding author: Guido Di Dalmazi, Unit of Endocrinology and Diabetes Prevention and Care Unit, Department of Medical and Surgical Sciences, University of Bologna, IRCCS S. Orsola Polyclinic, Via Massarenti 9, 40138 Bologna, Italy. E-mail: guido.didalmazi@unibo.it; Phone n°: +39 051 2143009 Search for other works by this author on: Oxford Academic
European Journal of Endocrinology, lvae037, https://doi.org/10.1093/ejendo/lvae037
Published:
04 April 2024
Article history
Received:
24 October 2023
Revision received:
21 February 2024
Accepted:
11 March 2024
Published:
04 April 2024
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Lorenzo Tucci, Flaminia Fanelli, Ilaria Improta, Valentina Bissi, Claudia Lena, Greta Galante, Marco Mezzullo, Matteo Magagnoli, Anna Bianca Lalumera, Giacomo Colombin, Kimberly Coscia, Laura Rotolo, Valentina Vicennati, Uberto Pagotto, Guido Di Dalmazi, Monitoring adrenal insufficiency through salivary steroids: a pilot study, European Journal of Endocrinology, 2024;, lvae037, https://doi.org/10.1093/ejendo/lvae037
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Abstract
Background
Various glucocorticoid replacement treatments (GRT) are available for adrenal insufficiency (AI). However, their effectiveness in restoring glucocorticoid rhythm and exposure lacks adequate biochemical markers. We described the diurnal salivary cortisol (SalF) and cortisone (SalE) rhythm among different GRTs and analysed the associations between saliva-derived parameters and life quality questionnaires.
Methods
Control subjects (CS, n=28) and AI patients receiving hydrocortisone (HC, n=9), cortisone acetate (CA, n=23), dual-release hydrocortisone once (DRHC-od, n=10) and twice a day (DRHC-td, n=6) collected 9 saliva samples from 07:00 to 23:00. Patients compiled Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale and Addison disease specific quality-of-life questionnaires. SalE and SalF were measured by liquid chromatography-mass spectrometry. Exposure was monitored using SalE for HC and DRHC, and SalF for CA. Area under the curve (AUC) was computed. Different GRTs were compared by Z-scores calculated from saliva-derived parameters. Questionnaires results predictors were evaluated with multiple regression analysis.
Results
Compared to controls, all GRTs resulted in glucocorticoid over-exposure in the morning. HC, CA, and DRHC-td caused over-exposure also in afternoon and evening. Compared to other treatments, CA determined increased Z-score-07:00 (p<0.001), DRHC-td determined increased Z-score-AUC07:00→14:00 (p=0.007) and DRHC-od induced lower Zscore-AUC14:00→23:00 (p=0.015). Z-scores-AUC14:00→16:00 ≥ 0.619 best predicted questionnaire scores.
Conclusions
None of the GRTs mimics normal glucocorticoid rhythmicity and exposure. SalE, SalF and Z-score may be useful markers for monitoring and comparing different GRTs. Excess glucocorticoid in early afternoon best associated with depressive symptoms and worse life and sleep quality.
Accepted manuscripts
Accepted manuscripts are PDF versions of the author’s final manuscript, as accepted for publication by the journal but prior to copyediting or typesetting. They can be cited using the author(s), article title, journal title, year of online publication, and DOI. They will be replaced by the final typeset articles, which may therefore contain changes. The DOI will remain the same throughout.
This content is only available as a PDF.
© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Issue Section:
ORIGINAL RESEARCH
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