Tschaidse, L., Reisch, N. orcid.org/0000-0002-7469-6069, Arlt, W. orcid.org/0000-0001-5106-9719 et al. (15 more authors) (2023) Modified-release hydrocortisone is associated with lower plasma renin activity in patients with salt-wasting congenital adrenal hyperplasia. European Journal of Endocrinology, 188 (1). lvac006. pp. 109-117. ISSN 0804-4643
Abstract
Objective Poorly controlled salt-wasting (SW) congenital adrenal hyperplasia (CAH) patients often require high 9α-fluorocortisol doses as they show high levels of 17-hydroxyprogesterone (17OHP), which is a mineralocorticoid (MC)-receptor antagonist.
Design We investigated the renin–angiotensin–aldosterone system in patients with SW-CAH receiving twice daily modified-release hydrocortisone (MR-HC, Efmody) compared with standard glucocorticoid (GC) therapy.
Methods Data were analyzed from the 6-month, phase 3 study of MR-HC (n = 42) versus standard GC therapy (n = 41). MC replacement therapy remained unchanged throughout the study. Blood pressure, serum potassium, serum sodium, plasma renin activity (PRA), and serum 17OHP and androstenedione concentrations were analyzed at baseline, 4, 12, and 24 weeks.
Results The median serum 17OHP in the morning was significantly lower on MR-HC compared with standard GC at 24 weeks (2.5 nmol L–1 (IQR 8.3) versus 10.5 nmol L–1 (IQR 55.2), P = .001). PRA decreased significantly from baseline to 24 weeks in patients on MR-HC (0.83 ng L–1 s–1 (IQR 1.0) to 0.48 ng L–1 s–1 (IQR 0.61), P = .012) but not in patients on standard GC (0.53 ng L–1 s–1 (IQR 0.66) to 0.52 ng L–1 s–1 (IQR 0.78), P = .613). Serum sodium concentrations increased from baseline to 24 weeks in patients on MR-HC (138.8 ± 1.9 mmol L–1 to 139.3 ± 1.8 mmol L–1, P = .047), but remained unchanged on standard GC (139.8 ± 1.6 mmol L–1 to 139.3 ± 1.9 mmol L–1, P = .135). No significant changes were seen in systolic and diastolic blood pressure and serum potassium levels.
Conclusion 6 months of MR-HC therapy decreased PRA and increased sodium levels indicating a greater agonist action of the 9α-fluorocortisol dose, which may be due to the decreased levels of the MC-receptor antagonist 17OHP.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2023. Published by Oxford University Press on behalf of (ESE) 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. |
Keywords: | 21-hydroxylase deficiency; adrenal insufficiency; aldosterone; dexamethasone; fludrocortisone; hydrocortisone; plasma renin activity; prednisolone; Humans; Hydrocortisone; Adrenal Hyperplasia, Congenital; Renin; Fludrocortisone; Glucocorticoids; 17-alpha-Hydroxyprogesterone; Potassium; Sodium |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health |
Funding Information: | Funder Grant number SHEFFIELD TEACHING HOSPITALS NHS FOUNDATION TRUST UNSPECIFIED |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 24 Jan 2024 17:00 |
Last Modified: | 24 Jan 2024 17:00 |
Published Version: | http://dx.doi.org/10.1093/ejendo/lvac006 |
Status: | Published |
Publisher: | Oxford University Press (OUP) |
Refereed: | Yes |
Identification Number: | 10.1093/ejendo/lvac006 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:208067 |