Peculiarities of steroid spectrum dynamics in patients with rheumatoid arthritis taking long-term systemic glucocorticoids
Abstract. Long-term (more than 3 months) use of glucocorticoids (GCs) in patients with rheumatoid arthritis (RA) is the most common cause of adrenal insufficiency (AI). High-performance liquid chromatography (HPLC) allows for the determination of a spectrum of steroid hormones at low concentrations, minimizing cross-reactions, which opens up new possibilities for an objective estimation of adrenal function.Mazurov V.I., Morozova K.P., Strelnikova E.G., Melnikov E.S.
The aim: to determine the dynamics of the adrenal steroid hormone spectrum in patients with RA taking long-term systemic GCs and to identify the most informative GCs for AI diagnosis.
Material and methods. The study included 34 patients with RA (mean age 58.1 ± 9.6 years; 76.5% females) receiving combination therapy with olokizumab, methotrexate, and prednisolone. The duration of continuous prednisolone treatment was 41 [21.5; 51.0] months at a dose of 8.75 [5; 10] mg daily. Steroid profile was assessed by HPLC at two checkpoints: after achieving low RA activity and after 6 months while reducing GC dose.
Results. Cortisol deficiency was detected in 14.7% of patients, and cortisone levels were decreased in 47.1%, which could serve as laboratory evidence of AI presence. A repeat study after 6 months while reducing/discontinuing GC dose revealed a statistically significant increase in cortisone (p = 0.002) and corticosterone (p = 0.025) levels in 73.5% of patients. Complete withdrawal of systemic GCs was achieved in 73.5% of patients, while disease activity remained low.
Discussion and conclusion. HPLC method for assessing the steroid profile enables the timely diagnosis of rheumatoid arthritis and an objective estimation of adrenal function recovery with a reduction of glucocorticoid dose. Achieving stable remission or low RA activity with effective therapy allows for the successful reduction and withdrawal of glucocorticoids use, with restoration of adrenal function under clinical and laboratory monitoring.
Keywords
rheumatoid arthritis
glucocorticoids
high-performance liquid chromatography
steroid profile
References
1. Мазуров В.И., Гайдукова И.З., Беляева И.Б. Клиническая ревматология. 3-е издание, переработанное и дополненное. Руководство для врачей. Под ред. В.И. Мазурова. М.: Е-ното. 2021; 696 с. (Mazurov VI, Gaidukova IZ, Belyaeva IB. Clinical rheumatology. 3rd edition, revised and enlarged. A guide for doctors. Moscow: E-noto. 2021; 696 pp. (In Russ.)).
ISBN: 978-5-906023-26-1.
2. Filippa MG, Tektonidou MG, Mantzou A, Kaltsas GA, Chrousos GP, Sfikakis PP, Yavropoulou MP. Adrenocortical dysfunction in rheumatoid arthritis: Α narrative review and future directions. Eur J Clin Invest. 2022;52(1):e13635.
PMID: 34097322. https://doi.org/10.1111/eci.13635
3. Liu XX, Zhu XM, Miao Q, Ye HY, Zhang ZY, Li YM. Hyperglycemia induced by glucocorticoids in non-diabetic patients: A meta-analysis. Ann Nutr Metab. 2014;65(4):324–32.
PMID: 25402408. https://doi.org/10.1159/000365892
4. Pujades-Rodriguez M, Morgan AW, Cubbon RM, Wu J. Dose-dependent oral glucocorticoid cardiovascular risks in people with immune-mediated inflammatory diseases: A population-based cohort study. PLoS Med. 2020;17(12):e1003432.
PMID: 33270649. PMCID: PMC7714202. https://doi.org/10.1371/journal.pmed.1003432
5. Ворохобина Н.В., Фогт С.Н., Мазуров В.И., Беляева И.Б., Галахова Р.К., Баландина К.А., Кузнецова А.В. Глюкокортикоид-индуцированная недостаточность коры надпочечников. Медицинский вестник Юга России. 2024;15(3):48–54. (Vorokhobina NV, Fogt SN, Mazurov VI, Beliaeva IB, Galakhova RK, Balandina KA, Kuznetsova AV. Glucocorticoid-induced adrenal insufficiency. Meditsinskiy vestnik Yuga Rossii = Medical Herald of the South of Russia. 2024;15(3):48–54.
EDN: THXKWF. https://doi.org/10.21886/2219-8075-2024-15-3-48-54
6. Lewis A, Thant AA, Aslam A, Aung PPM, Azmi S. Diagnosis and management of adrenal insufficiency. Clin Med (Lond). 2023;23(2):115–18.
PMID: 36958832. PMCID: PMC11046533. https://doi.org/10.7861/clinmed.2023-0067
7. Casals G, Hanzu FA. Cortisol measurements in Cushing’s syndrome: Immunoassay or mass spectrometry? Ann Lab Med. 2020;40(4):285–96.
PMID: 32067427. PMCID: PMC7054699. https://doi.org/10.3343/alm.2020.40.4.285
8. Hameedat F, Hawamdeh S, Alnabulsi S, Zayed A. High performance liquid chromatography (HPLC) with fluorescence detection for quantification of steroids in clinical, pharmaceutical, and environmental samples: A review. Molecules. 2022;27(6):1807.
PMID: 35335170. PMCID: PMC8949805. https://doi.org/10.3390/molecules27061807
9. Ingrasciotta Y, Jin Y, Foti SS, Landon JE, Tari M, Mattace-Raso F et al. Real-world patient characteristics and use of disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis: A cross-national study. Clin Rheumatol. 2023;42(4):1047–59.
PMID: 36534353. PMCID: PMC10017582. https://doi.org/10.1007/s10067-022-06478-4
10. Beuschlein F, Else T, Bancos I, Hahner S, Hamidi O, van Hulsteijn L et al. European Society of Endocrinology and Endocrine Society Joint clinical guideline: Diagnosis and therapy of glucocorticoid-induced adrenal insufficiency. J Clin Endocrinol Metab. 2024;109(7):1657–83.
PMID: 38724043. PMCID: PMC11180513. https://doi.org/10.1210/clinem/dgae250
11. Krasowski MD, Drees D, Morris CS, Maakestad J, Blau JL, Ekins S. Cross-reactivity of steroid hormone immunoassays: Clinical significance and two-dimensional molecular similarity prediction. BMC Clin Pathol. 2014;14:33.
PMID: 25071417. PMCID: PMC4112981. https://doi.org/10.1186/1472-6890-14-33
12. Cooper MS, Stewart PM. 11β-hydroxysteroid dehydrogenase type 1 and its role in the hypothalamus-pituitary-adrenal axis, metabolic syndrome, and inflammation. J Clin Endocrinol Metab. 2009;94(12):4645–54.
PMID: 19837912. https://doi.org/10.1210/jc.2009-1412
13. Stimson RH, Andersson J, Andrew R, Redhead DN, Karpe F, Hayes PC, Olsson T, Walker BR. Cortisol release from adipose tissue by 11beta-hydroxysteroid dehydrogenase type 1 in humans. Diabetes. 2009;58(1):46–53.
PMID: 18852329. PMCID: PMC2606892. https://doi.org/10.2337/db08-0969
14. Lawrence NR, Keevil B, Elder C, Fearnside J, Caunt S, Dixon S et al. OR30-01 waking salivary 11-hydroxyandrostenedione and cortisone as a novel non-invasive test for adrenal insufficiency. J Endocr Soc. 2023;7(Suppl_1):bvad114.351.
PMCID: PMC10554779. https://doi.org/10.1210/jendso/bvad114.351
15. Vulto A, Bergthorsdottir R, van Faassen M, Kema IP, Johannsson G, van Beek AP. Residual endogenous corticosteroid production in patients with adrenal insufficiency. Clin Endocrinol (Oxf). 2019;91(3):383–90.
PMID: 31059146. PMCID: PMC6851705. https://doi.org/10.1111/cen.14006
About the Authors
Vadim I. Mazurov, MD, Dr.Sci. (Medicine), professor, academician of RAS, vice president of RSMSIM, chief scientific advisor, director of the Research institute of rheumatology, head of the Department of therapy and rheumatology named after E.E. Eichwald, I.I. Mechnikov North-Western State Medical University of the Ministry of Healthcare of Russia; head of the Center for Autoimmune Diseases, V.A. Nasonova Clinical Rheumatology Hospital No. 25 (Saint Petersburg); chief external expert – rheumatologist at the Healthcare Committee of the Government of Saint Petersburg, Honored Scientist 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
Kira P. Morozova, MD, postgraduate student of the Department of therapy and rheumatology named after E.E. Eichwald, I.I. Mechnikov North-Western State Medical University of the Ministry of Healthcare of Russia; rheumatologist at V.A. Nasonova Clinical Rheumatology Hospital No. 25 (Saint Petersburg). Address: 190068, Saint Petersburg, 30 Bolshaya Podyacheskaya St.
E-mail: kiramoroz194@gmail.com
ORCID: https://orcid.org/0000-0002-4113-3104
Elena G. Strelnikova, PhD (Chemistry), senior researcher at the Department of chromatography research, I.I. Mechnikov North-Western State Medical University of the Ministry of Healthcare of Russia. Address: 191015, Saint Petersburg, 41 Kirochnaya St.
Email: Istrelnikova@inbox.ru
ORCID: https://orcid.org/0000-0002-1208-8092. Scopus Author ID: 58864205400. SPIN: 6631-6962
Evgeny S. Melnikov, MD, PhD (Medicine), assistant at the Department of therapy and rheumatology named after E.E. Eichwald, I.I. Mechnikov North-Western State Medical University of the Ministry of Healthcare of Russia; rheumatologist at V.A. Nasonova Clinical Rheumatology Hospital No. 25 (Saint Petersburg). Address: 190068, Saint Petersburg, 30 Bolshaya Podyacheskaya St.
Email: emelnikov@euat.ru
ORCID: https://orcid.org/0000-0002-8521-6542
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