Debono, M., Mallappa, A., Gounden, V. et al. (7 more authors) (2015) Hormonal circadian rhythms in patients with congenital adrenal hyperplasia: identifying optimal monitoring times and novel disease biomarkers. European Journal of Endocrinology, 173 (6). pp. 727-737. ISSN 0804-4643
Abstract
Objectives: The treatment goal in congenital adrenal hyperplasia (CAH) is to replace glucocorticoids while avoiding androgen excess and iatrogenic Cushing's syndrome. However, there is no consensus on how to monitor disease control. Our main objectives were to evaluate hormonal circadian rhythms and use these profiles to identify optimal monitoring times and novel disease biomarkers in CAH adults on intermediate- and long-acting glucocorticoids. Design: This was an observational, cross-sectional study at the National Institutes of Health Clinical Center in 16 patients with classic CAH. Methods: Twenty-four-hour serum sampling for ACTH, 17-hydroxyprogesterone (17OHP), androstenedione (A4), androsterone, DHEA, testosterone, progesterone and 24-h urinary pdiol and 5β-pdiol was carried out. Bayesian spectral analysis and cosinor analysis were performed to detect circadian rhythmicity. The number of hours to minimal (TminAC) and maximal (TmaxAC) adrenocortical hormone levels after dose administration was calculated. Results: A significant rhythm was confirmed for ACTH (r2, 0.95; P<0.001), 17OHP (r2, 0.70; P=0.003), androstenedione (r2, 0.47; P=0.043), androsterone (r2, 0.80; P<0.001), testosterone (r2, 0.47; P=0.042) and progesterone (r2, 0.64; P=0.006). The mean (S.D.) TminAC and TmaxAC for 17OHP and A4 were: morning prednisone (4.3 (2.3) and 9.7 (3.5) h), evening prednisone (4.5 (2.0) and 10.3 (2.4) h), and daily dexamethasone (9.2 (3.5) and 16.4 (7.2) h). AUC0–24 h progesterone, androsterone and 24-h urine pdiol were significantly related to 17OHP. Conclusion: In CAH patients, adrenal androgens exhibit circadian rhythms influenced by glucocorticoid replacement. Measurement of adrenocortical hormones and interpretation of results should take into account the type of glucocorticoid and time of dose administration. Progesterone and backdoor metabolites may provide alternative disease biomarkers.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2015 European Society of Endocrinology. This is an author produced version of a paper subsequently published in European Journal of Endocrinology. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | circadian rhythms; CAH; 17-hydroxyprogesterone; androstenedione; corticotropin; progesterone; androsterone |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Engineering (Sheffield) > Department of Automatic Control and Systems Engineering (Sheffield) The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 18 Jan 2017 16:41 |
Last Modified: | 28 Mar 2018 22:45 |
Published Version: | https://doi.org/10.1530/EJE-15-0064 |
Status: | Published |
Publisher: | BioScientifica |
Refereed: | Yes |
Identification Number: | 10.1530/EJE-15-0064 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:110796 |