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Immunophenotypic implications of reverse-circadian glucocorticoid treatment in congenital adrenal hyperplasia.
Int. J. Mol. Sci. 26:1479 (2025)
Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) requires lifelong glucocorticoid replacement to manage cortisol deficiency and excessive androgen production. Conventional circadian treatment (CT) tries to mimic natural cortisol rhythms, whereas reverse-circadian treatment (RC) prioritizes the suppression of adrenal androgen excess overnight through evening dosing. Limited data exist on the immunological impact of these regimens. A bi-centric study was conducted, including 41 pediatric and adolescent CAH patients. Peripheral blood samples were collected from patients on conventional treatment (n = 38) or RC (n = 16), with 11 RC patients switching to conventional treatment. Immune cell phenotypes, cytokine profiles, and natural killer (NK) cell cytotoxicity were assessed. Patients receiving RC showed lower percentages of CD4+CD25+ T cells (p = 0.0139). After the switch, patients with RC presented with a higher percentage of non-classical monocytes (p = 0.0255) and a lower percentage of Th17 cells (p = 0.0195). A lower expression of CD107 was observed with RC (p < 0.0001), as well as a higher percentage of NKp30 (p = 0.0189). Comparing patients after the switch from RC to HC, patients with RC presented with a lower NKG2D expression (p = 0.0420). Both conventional treatment and RC exhibited distinct immunological impacts, with CT showing modest advantages in normalizing immune phenotypes. These findings suggest that CT may offer immunological benefits for managing young patients with congenital adrenal hyperplasia.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Circadian ; Congenital Adrenal Hyperplasia ; Glucocorticoids ; Immunophenotype; Modified-release Hydrocortisone; Regulatory T-cells; Children; Identification; Insufficiency; Mortality; Therapy; Health; Adult; Sleep
ISSN (print) / ISBN
1422-0067
e-ISSN
1661-6596
Quellenangaben
Volume: 26,
Issue: 4,
Article Number: 1479
Publisher
MDPI
Publishing Place
Basel
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Unit for Clinical Pharmacology (KKG-EKLiP)
Grants
Yellow4FLAVI project - European Union
DFG
French National Research Agency (ANR)
German Research Foundation (DFG)
Eva Luise und Horst Koehler Stiftung and Else Kroener-Fresenius-Stiftung
Deutsche Forschungsgemeinschaft (DFG)
DFG
French National Research Agency (ANR)
German Research Foundation (DFG)
Eva Luise und Horst Koehler Stiftung and Else Kroener-Fresenius-Stiftung
Deutsche Forschungsgemeinschaft (DFG)