Plasma renin measurements are unrelated to mineralocorticoid replacement dose in patients with primary adrenal insufficiency
Open accessAbstract
CONTEXT: No consensus exists for optimization of mineralocorticoid therapy in patients with primary adrenal insufficiency. OBJECTIVE: To explore the relationship between mineralocorticoid (MC) replacement dose, plasma renin concentration (PRC), and clinically important variables to determine which are most helpful in guiding MC dose titration in primary adrenal insufficiency. DESIGN: Observational, retrospective, longitudinal analysis. PATIENTS: A total of 280 patients (with 984 clinical visits and plasma renin measurements) with primary adrenal insufficiency were recruited from local databases and the international congenital adrenal hyperplasia (CAH) registry (www.i-cah.org). Thirty-seven patients were excluded from the final analysis due to incomplete assessment. Data from 204 patients with salt-wasting CAH (149 adults and 55 children) and 39 adult patients with Addison disease (AD) were analysed. MAIN OUTCOME MEASURES: PRC, electrolytes, blood pressure (BP), and anthropometric parameters were used to predict their utility in optimizing MC replacement dose. RESULTS: PRC was low, normal, or high in 19%, 36%, and 44% of patients, respectively, with wide variability in MC dose and PRC. Univariate analysis demonstrated a direct positive relationship between MC dose and PRC in adults and children. There was no relationship between MC dose and BP in adults, while BP increased with increasing MC dose in children. Using multiple regression modeling, sodium was the only measurement that predicted PRC in adults. Longitudinally, the change in MC dose was able to predict potassium, but not BP or PRC. CONCLUSIONS: The relationship between MC dose and PRC is complex and this may reflect variability in sampling with respect to posture, timing of last MC dose, adherence, and concomitant medications. Our data suggest that MC titration should not primarily be based only on PRC normalization, but also on clinical parameters such as BP and electrolyte concentration.
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If taken at 2300, Chronocort's delayed release mimics the overnight rise and following morning peak of cortisol.
“If taken at 2300 (11 PM), the delayed release mimics the overnight rise and following morning peak of cortisol (383,384).”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [384]
The References list a study of delayed-release Chronocort, but this paper does not report what happens when it is taken at 2300. The Discussion concerns mineralocorticoid replacement and does not address whether Chronocort mimics the overnight cortisol rise or morning peak; searches for the dosing time and cortisol profile found no such passage. (LLM, conf=0.75)
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References 30 · Cited by 53
Research works printed but not linked: 1
- Charmandari E, Nicolaides NC, Chrousos GP. Adrenal insuffi- ciency. Lancet. 2014;383(9935):2152-2167.
- Authors
- Pofi, R., Prete, A., Thornton-Jones, V., Bryce, J., Ali, S. R., Faisal Ahmed, S., Balsamo, A., Baronio, F., Cannuccia, A., Guven, A., Guran, T., Darendeliler, F., Higham, C., Bonfig, W., de Vries, L., Bachega, T. A. S. S., Miranda, M. C., Mendonca, B. B., Iotova, V., Korbonits, M., Krone, N. P., Krone, R., Lenzi, A., Arlt, W., Ross, R. J., Isidori, A. M., & Tomlinson, J. W.
- Affiliations
- Churchill Hospital (GB)
- University of Birmingham (GB)
- University of Glasgow (GB)
- Developmental Endocrinology Research Group, University of Glasgow, UK
- IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT)
- University of Rome Tor Vergata (IT)
- Saglik Bilimleri University, Zeynep Kamil Women and Children Hospital, Paediatric Endocrinology Clinic, Istanbul, Turkey
- Marmara University, Department of Paediatric Endocrinology and Diabetes, Pendik, Istanbul, Turkey
- Istanbul Faculty of Medicine, Department of Paediatrics, Paediatric Endocrinology Unit, Istanbul University, Çapa, Istanbul, Turkey
- Manchester Academic Health Science Centre (GB)
- Klinikum Wels-Grieskirchen (AT)
- The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children’s Medical Center of Israel, Petah Tikva, Israel
- Unidade De Endocrinologia Do Desenvolvimento, Laboratório De Hormônios E Genética Molecular/Lim42, Hospital Das Clinicas Hcfmusp, Faculdade De Medicina, Universidade De Sao Paulo, Sao Paulo, Brazil
- Universidade de São Paulo (BR)
- Medical University of Varna (BG)
- Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, UK
- University of Sheffield (GB)
- Birmingham Women's Hospital (GB)
- Sapienza University of Rome (IT)
- University Hospitals Birmingham NHS Foundation Trust (GB)
- Corresponding author
- Tomlinson, Jeremy W
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2019-10-16
- Volume
- 105
- Issue
- 1
- Pages
- 314-326
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2980565423
- Cited by
- 53
- References
- 30
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 9 · 2023: 12 · 2022: 6 · 2021: 8 · 2020: 6
- FWCI
- 4.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
- Dspace Repository (Marmara Üniversitesi) (submittedVersion, other-oa)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, other-oa)
- Dspace Repository (Marmara Üniversitesi) (submittedVersion)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Funders
- National Institute for Health Research
- Medical Research Council (MR/P011462/1, G1100236)
- NIHR Oxford Biomedical Research Centre
- NIHR Birmingham Biomedical Research Centre (BRC-1215-20009)
- European Society of Endocrinology
- Seventh European Union Framework Program (201444)
- European Society for Paediatric Endocrinology
- Diurnal Ltd
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Electrolyte and hormonal disorders
- Keywords
- Addison's disease, mineralocorticoid replacement, plasma renin concentration, dose titration, salt-wasting congenital adrenal hyperplasia, blood pressure, sodium, potassium, electrolytes
- MeSH terms
- Adolescent, Adrenal Insufficiency, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Dose-Response Relationship, Drug, Female, Humans, Infant, Infant, Newborn, Longitudinal Studies, Male, Middle Aged, Mineralocorticoids, Renin, Retrospective Studies, Hormone Replacement Therapy, Young Adult
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