Impact on immunophenotype of switching from conventional glucocorticoids to modified-release hydrocortisone in congenital adrenal hyperplasia

Selina Ziegler; Hanna Nowotny; Hannah Choi; Lea Tschaidse; Matthias Auer; Ann-Christin Welp; Adrian Gottschlich; Sebastian Kobold; Simon Rothenfusser; Nicole Reisch

doi:10.1530/endoabs.99.P27

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Endocrine Abstracts (2024) 99 P27 | DOI: 10.1530/endoabs.99.P27

ECE2024 Poster Presentations Adrenal and Cardiovascular Endocrinology (95 abstracts)

Impact on immunophenotype of switching from conventional glucocorticoids to modified-release hydrocortisone in congenital adrenal hyperplasia

Selina Ziegler ¹ , Hanna Nowotny ¹ , Hannah Choi ¹ , Lea Tschaidse ¹ , Matthias Auer ¹ , Ann-Christin Welp ¹ , Adrian Gottschlich ^2,3 , Sebastian Kobold ^2,4,5 , Simon Rothenfusser ² & Nicole Reisch ¹

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¹LMU University Hospital, LMU Munich, Department of Medicine IV; ²LMU University Hospital, LMU Munich, Division of Clinical Pharmacology; ³LMU University Hospital, LMU Munich, Department of Medicine III; ⁴German Cancer Consortium (DKTK), Partner Site Munich; ⁵Helmholtz Munich, Research Center for Environmental Health (HMGU), Neuherberg, Einheit für Klinische Pharmakologie (EKLiP)

Background: Previous research has revealed variances in the composition of immune cells among patients with congenital adrenal hyperplasia (CAH) on conventional glucocorticoid (GC) replacement therapy compared to healthy controls. Modified-release hydrocortisone (MR-HC) optimizes cortisol pharmacokinetics, aligning with a more physiological circadian cortisol rhythm. This study therefore aims to assess the impact on the immune cell profile when transitioning patients with CAH from conventional GCs to MR-HC.

Methods: A cohort comprising 25 patients with classic CAH, including 14 females and 11 males, with a median age of 37 years (IQR 14.25) and a median BMI of 25.29 kg/m² (IQR 3.72), was switched from conventional hydrocortisone (n=13) or prednisolone (n=12) treatment to an equivalent hydrocortisone dose (HDE) of MR-HC (median HDE 30 mg (IQR 10)). This cohort was compared to a group of 25 sex, age, and BMI matched healthy controls. Peripheral mononuclear blood cells were extracted before, 3 months and 6–10 months after the transition to MR-HC. Immune cell subsets were analysed through multicolour flow cytometry after a four-hour stimulation with PMI/ionomycin.

Results: Patients on conventional GCs exhibited a higher percentage of CD4+CD25+ lymphocytes (P=0.0063) compared to healthy controls and MR-HC-treated patients. The transition from conventional GCs to MR-HC resulted in a decrease in the percentage of CD4+CD25+ lymphocytes (P=0,0327). While patients under conventional GC treatment showed a smaller proportion of CD4+CD25+Foxp3+T cells (Tregs) compared to controls (P=0,0026), the MR-HC cohort displayed comparable proportions to controls. Reductions in hydrocortisone doses by 5 mg, referable to efficient therapeutic control between 3 and ≥6 months post-transition to MR-HC, correlated with an increase in T helper cells (P=0.0034) and a decrease in CD94+ NK cells (P=0.0312).

Conclusion: Conventional GC substitution precipitates alterations in the immune phenotype of patients with CAH. In contrast, MR-HC, which more accurately imitates the physiological circadian release of cortisol, causes less changes in the immune cell profile. Additional functional analysis could help to draw further conclusions regarding the functionality of the immune system and its clinical impact.