Русский
Effect of exogenous glucocorticosteroids on adrenal steroidogenesis in patients with rheumatoid arthritis
DOI: https://dx.doi.org/10.18565/therapy.2025.1.29-36
Morozova K.P., Mazurov V.I., Velikanova L.I., Melnikov E.S.
1) I.I. Mechnikov North-Western State Medical University of the Ministry of Healthcare of Russia, Saint Petersburg; 2) V.A. Nasonova Clinical Rheumatology Hospital No. 25, Saint Petersburg
The aim: to determine steroid hormone levels in patients with RA on GC therapy for more than 3 months.
Materials and methods. 46 patients with RA were included in the study. The study of adrenal hormones was carried out using high-performance liquid chromatography.
Results. Patients with RA included in the study received GC therapy at a median dose of 5[2.5; 20] mg equivalent to prednisolone. Most of them (73.9%) were on low doses of prednisolone (≤ 7.5 mg per day), 26.1% were taking medium doses of prednisolone (> 7.5 and ≤ 30 mg per day). The median duration of GC use was 30 months (6; 264). A comparative analysis of the main steroid metabolites was performed between patients with RA and the control group, and statistically significant differences were found in the levels of cortisol, cortisone, 11-dehydroxycorticosterone, 11-deoxycorticosterone, 18-hydroxycorticosterone, and 21-deoxycortisol.
Discussion and conclusion. The prevalence of GC-induced adrenal insufficiency in patients with chronic rheumatic diseases may be as high as 50% after long-term treatment with even low-dose GC. Abrupt withdrawal of GCs during long-term treatment may be dangerous not only for the high risk of RA exacerbations but also for the development of GC withdrawal symptoms. Prolonged GC administration in patients with autoimmune and immunoinflammatory diseases is a widespread problem, and RA is no exception. Russian and international practice shows that in about half of cases patients receiving therapy with GC for more than 3 months develop adrenal insufficiency, which prevents dose reduction and GC withdrawal. Despite the available data, it is necessary to continue to develop clinical algorithms to optimize GC therapy and timely withdrawal based on observations of certain cohorts of patients with rheumatic diseases.
Literature
1. Клиническая ревматология. Руководство для врачей. 3-е издание, переработанное и дополненное. Под ред. В.И. Мазурова. М.: Е-ното. 2021; 696 с. (Clinical rheumatology. Guide for doctors. 3rd edition, revised and enlarged. Ed. by Mazurov V.I. Moscow: E-noto. 2021; 696 pp. (In Russ.)). ISBN: 978-5-906023-26-1. 2. Клинические рекомендации. Ревматоидный артрит. Ассоциация ревматологов России. Рубрикатор клинических рекомендаций Минздрава России. 2024. ID: 250_3. Доступ: https://cr.minzdrav.gov.ru/preview-cr/250_3 (дата обращения – 12.02.2025). (Clinical guidelines. Rheumatoid arthritis. Association of Rheumatologists of Russia. Rubricator of clinical guidelines of the Ministry of Healthcare of Russia. 2024. ID: 250_3. URL: https://cr.minzdrav.gov.ru/preview-cr/250_3 (date of access – 12.02.2025) (In Russ.)). 3. Smolen J.S., Landewe R.B.M., Bergstra S.A. et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023; 82(1): 3–18. https://doi.org/10.1136/ard-2022-223356. PMID: 36357155. 4. Fraenkel L., Bathon J.M., England B.R. et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2021; 73(7): 1108–23. https://doi.org/10.1002/art.41752. PMID: 34101376. 5. Prete A., Bancos I. Glucocorticoid induced adrenal insufficiency. BMJ. 2021; 374: n1380. https://doi.org/10.1136/bmj.n1380. PMID: 34253540 6. Ворохобина Н.В., Фогт С.Н., Мазуров В.И. с соавт. Глюкокортикоид-индуцированная недостаточность коры надпочечников. Медицинский вестник Юга России. 2024; 15(3): 48–54. (Vorokhobina N.V., Fogt S.N., Mazurov V.I. et al. Glucocorticoid-induced adrenal insufficiency. Meditsinskij vestnik Yuga Rossii = Medical Herald of the South of Russia. 2024; 15(3): 48–54 (In Russ.)). https://doi.org/10.21886/2219-8075-2024-15-3-48-54. EDN: THXKWF. 7. Объедкова Е.В. Разработка схемы определения стероидных гормонов и нестероидных противовоспалительных препаратов в биологических жидкостях методом ВЭТСХ. Дисс. … канд. мед. наук. СПб. 2014; 180 с. Доступ: https://dissercat.com/content/razrabotka-skhemy-opredeleniya-steroidnykh-gormonov-i-nesteroidnykh-protivovospalitelnykh-pr (дата обращения – 31.01.2025). (Obiedkova E.V. Development of a scheme for the determination of steroid hormones and nonsteroidal anti-inflammatory drugs in biological fluids by the HPTLC method. Dissertation for the title of PhD (Medicine). Saint Petersburg. 2014; 180 pp. URL: https://dissercat.com/content/razrabotka-skhemy-opredeleniya-steroidnykh-gormonov-i-nesteroidnykh-protivovospalitelnykh-pr (date of access – 12.02.2025) (In Russ.)). 8. Великанова Л.И., Шафигуллина З.Р., Ворохобина Н.В. с соавт. Диагностическое значение высокоэффективной жидкостной хроматографии кортикостероидов при заболеваниях гипофизарно-надпочечниковой системы. Проблемы эндокринологии. 2005; 51(6): 9–11. (Velikanova L.I., Shafigullina Z.R., Vorokhobina N.V. et al. Diagnostic value of high performance liquid chromatography of corticosteroids in diseases of the pituitary system. Problemy endokrinologii = Problems of Endocrinology. 2005; 51(6): 9–11 (In Russ.)). https://doi.org/10.14341/probl20055169-11. EDN: WINYCX. 9. Beuschlein F., Else T., Bancos I. et al. European Society of Endocrinology and Endocrine Society Joint Clinical Guideline: Diagnosis and therapy of glucocorticoid-induced adrenal insufficiency. Eur J Endocrinol. 2024; 190(5): G25–G51. https://doi.org/10.1093/ejendo/lvae029. PMID: 38714321. 10. Filippa M.G., Tektonidou M.G., Mantzou A. et al. Adrenocortical dysfunction in rheumatoid arthritis: Α narrative review and future directions. Eur J Clin Invest. 2022; 52(1): e13635. https://doi.org/10.1111/eci.13635. PMID: 34097322. 11. Borresen S.W., Klose M., Baslund B. et al. Adrenal insufficiency is seen in more than one-third of patients during ongoing low-dose prednisolone treatment for rheumatoid arthritis. Eur J Endocrinol. 2017; 177(4): 287–95. https://doi.org/10.1530/EJE-17-0251. PMID: 28877961. 12. Furst D.E., Saag K.G. Glucocorticoid withdrawal. URL: https://www.uptodate.com/contents/glucocorticoid-withdrawal (date of access – 12.02.2025). 13. Paragliola R.M., Papi G., Pontecorvi A., Corsello S.M. et al. Treatment with synthetic glucocorticoids and the hypothalamus-pituitary-adrenal axis. Int J Mol Sci. 2017; 18(10): 2201. https://doi.org/10.3390/ijms18102201. PMID: 29053578. PMCID: PMC5666882. 14. Mebrahtu T.F., Morgan A.W., Keeley A. et al. Dose dependency of iatrogenic glucocorticoid excess and adrenal insufficiency and mortality: A cohort study in England. J Clin Endocrinol Metab. 2019; 104(9): 3757–67. https://doi.org/10.1210/jc.2019-00153. PMID: 31009052. PMCID: PMC6656418. 15. Jamilloux Y., Liozon E., Pugnet G. et al. Recovery of adrenal function after long-term glucocorticoid therapy for giant cell arteritis: A cohort study. PLoS One. 2013; 8(7): e68713. https://doi.org/10.1371/journal.pone.0068713. PMID: 23894335. PMCID: PMC3722149. 16. Albrecht K., Callhoff J., Schneider M., Zink A. High variability in glucocorticoid starting doses in patients with rheumatoid arthritis: Observational data from an early arthritis cohort. Rheumatol Int. 2015; 35(8): 1377–84. https://doi.org/10.1007/s00296-015-3229-x. PMID: 25663291. 17. Hua C., Buttgereit F., Combe B. Glucocorticoids in rheumatoid arthritis: Current status and future studies. RMD Open. 2020; 6(1): e000536. https://doi.org/10.1136/rmdopen-2017-000536. PMID: 31958273. PMCID: PMC7046968. 18. Prior J.A., Roddy E., Solis-Trapala I. et al. How do clinicians prescribe bridging glucocorticoids in people starting or escalating disease-modifying anti-rheumatic drugs for rheumatoid arthritis: A service evaluation survey. Rheumatol Adv Pract. 2023; 7(3): rkad102. https://doi.org/10.1093/rap/rkad102. PMID: 38025093. PMCID: PMC10665131. 19. Borresen S.W., Klose M., Baslund B. et al. Adrenal insufficiency is seen in more than one-third of patients during ongoing low-dose prednisolone treatment for rheumatoid arthritis. Eur J Endocrinol. 2017; 177(4): 287–95. https://doi.org/10.1530/EJE-17-0251. PMID: 28877961.
About the Autors
Kira P. Morozova, MD, postgraduate student of the Department of therapy, rheumatology, examination of temporary disability and quality of medical care with a course in hematology and transfusiology named after E.E. Eichwald of I.I. Mechnikov North-West State Medical University of the Ministry of Healthcare of Russia, rheumatologist at V.A. Nasonova Clinical Rheumatology Hospital No. 25. Address: 191015, Saint Petersburg, 30 Bol`shaya Pod`yacheskaya St.
E-mail: kiramorozoba@mail.ru
ORCID: https://orcid.org/0000-0002-4113-3104
Vadim I. Mazurov, MD, Dr. Sci. (Medicine), professor, academician of RAS, vice president of RSMSIM, principal scientific advisor and director of the Research Institute of Rheumatology, head of the Department of therapy, rheumatology, examination of temporary disability and quality of medical care with a course in hematology and transfusiology named after E.E. Eichwald of I.I. Mechnikov North-West State Medical University of the Ministry of Healthcare of Russia, head of Autoimmune center of V.A. Nasonova Clinical Rheumatology Hospital No. 25, chief freelance specialist – rheumatologist of the Healthcare Committee of the Government of Saint Petersburg, Honored Worker of Science of the Russian Federation. Address: 191015, Saint Petersburg, 41 Kirochnaya St.
E-mail: maz.nwgmu@yandex.ru
ORCID: https://orcid.org/0000-0002-0797-2051. Scopus Author ID: 16936315400. eLibrary SPIN: 6823-5482
Lyudmila I. Velikanova, Dr. Sci (Biology), professor, head of the Chromatography Research Laboratory of I.I. Mechnikov North-West State Medical University of the Ministry of Healthcare of Russia. Address: 191015, Saint Petersburg, 41 Kirochnaya St.
E-mail: velikanova46@gmail.com
ORCID: https://orcid.org/0000-0002-9352-4035. eLibrary SPIN: 5586-4851
Evgeny S. Melnikov, MD, assistant at the Department of therapy, rheumatology, examination of temporary disability and quality of medical care with a course in hematology and transfusiology named after E.E. Eichwald of I.I. Mechnikov North-West State Medical University of the Ministry of Healthcare of Russia, rheumatologist at V.A. Nasonova Clinical Rheumatology Hospital No. 25. Address: 191015, Saint Petersburg, 30 Bol`shaya Pod`yacheskaya St.
E-mail: emelnikov@euat.ru
ORCID: https://orcid.org/0000-0002-8521-6542. eLibrary SPIN: 4544-0596
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