Inadequately low serum levels of steroid hormones in relation to interleukin‐6 and tumor necrosis factor in untreated patients with early rheumatoid arthritis and reactive arthritis
Abstract
Objective: To compare levels of steroid hormones in relation to cytokines and to study levels of cortisol or dehydroepiandrosterone (DHEA) in relation to other adrenal hormones in untreated patients with early rheumatoid arthritis (RA) and reactive arthritis (ReA) compared with healthy controls. Methods: In a retrospective study with 34 RA patients, 46 ReA patients, and 112 healthy subjects, we measured serum levels of interleukin‐6 (IL‐6), tumor necrosis factor (TNF), adrenocorticotropic hormone (ACTH), cortisol, 17‐hydroxyprogesterone (17‐OH‐progesterone), androstenedione (ASD), DHEA, and DHEA sulfate (DHEAS). Results: RA patients had higher serum levels of IL‐6, TNF, cortisol, and DHEA compared with ReA patients and healthy subjects, but no difference was noticed with respect to ACTH and DHEAS. However, in RA and ReA patients compared with healthy subjects, levels of ACTH, cortisol, ASD, DHEAS, and 17‐OH‐progesterone were markedly lower in relation to levels of IL‐6 and TNF. Furthermore, the number of swollen joints correlated inversely with the ratio of serum cortisol to serum IL‐6 in RA (R Rank = −0.582, P = 0.001) and, to a lesser extent, in ReA (R Rank = −0.417, P = 0.011). In RA patients, the mean grip strength of both hands was positively correlated with the ratio of serum cortisol to serum IL‐6 (R Rank = 0.472, P = 0.010). Furthermore, in these untreated patients with RA and ReA, there was a relative decrease in the secretion of 17‐OH‐progesterone, ASD, and DHEAS in relation to DHEA and cortisol. This indicates a relative predominance of the nonsulfated DHEA and cortisol in relation to all other measured adrenal steroid hormones in the early stages of these inflammatory diseases. Conclusion: This study indicates that levels of ACTH and cortisol are relatively low in relation to levels of IL‐6 and TNF in untreated patients with early RA and ReA compared with healthy subjects. The study further demonstrates that there is a relative increase of DHEA and cortisol in relation to other adrenal hormones, such as DHEAS. This study emphasizes that adrenal steroid secretion is inadequately low in relation to inflammation. Although changes in hormone levels are similar in RA and ReA, alteration of steroidogenesis is more pronounced in RA patients than in ReA patients.
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Adrenocortical dysfunction, also termed relative or functional adrenal insufficiency, has been described in patients with rheumatoid arthritis without any prior risk of, or evidence of, overt adrenal insufficiency.
“Adrenocortical dysfunction, termed also as ‘relative’ or ‘functional’ adrenal insufficiency, has been described in patients with rheumatoid arthritis (RA) without any prior risk of, or evidence of, overt adrenal insufficiency.1–8”
From Diurnal production of cortisol and prediction of treatment response in rheumatoid arthritis: a 6-month, real-life prospective cohort study (2024) · cites this paper as [7]
In chronic inflammatory diseases such as SLE or RA the HPA axis alters markedly, with inadequate ACTH secretion relative to circulating cytokines and inappropriately low spontaneous and stimulated cortisol secretion in relation to inflammation.
“In chronic inflammatory diseases such as systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) the HPA axis alters markedly : (a) secretion of adrenocorticotropic hormone (ACTH) relative to circulating cytokines is inadequate 7 ; (b) patients have inappropriately low sponta- neous and stimulated cortisol secretion in relation to inflammation”
In aging and in chronic inflammatory diseases, both the SNS and the HPA axis are chronically activated.
“Indeed, in aging and in chronic inflammatory diseases, both the SNS and the HPA axis are chronically activated [41, 46–48].”
From Evolutionary medicine and chronic inflammatory state—known and new concepts in pathophysiology (2012) · cites this paper as [48]
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Self-citationFifty Years of Experience with Cortisone Therapy in the Study and Treatment of Rheumatoid Arthritis
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Nocturnal Hormones and Clinical Rhythms in Rheumatoid Arthritis
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Autoimmune diseases and their relation with immunological, neurological and endocrinological axes
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Treatment of reactive arthritis with biological agents: a review
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Immunotherapeutic Implication of IL-6 Blockade
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Large Scale Metabolic Profiling identifies Novel Steroids linked to Rheumatoid Arthritis
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Self-citationBrief ReviewEffects of Stress on Inflammatory Autoimmune Disease: Destructive or Protective?
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Self-citation
- Authors
- Straub, R. H., Paimela, L., Peltomaa, R., Schölmerich, J., & Leirisalo‐Repo, M.
- Affiliations
- University Hospital Regensburg (DE)
- Tekonivelsairaala Orton (FI)
- Helsinki University Hospital (FI)
- Venue
- Arthritis & Rheumatism
- Publisher
- Wiley
- Published
- 2002-03
- Volume
- 46
- Issue
- 3
- Pages
- 654-662
- ISSN
- 0004-3591 (ISSN-L)
- 1529-0131
- OpenAlex
- W2006724319
- Cited by
- 183
- References
- 52
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 6 · 2020: 6 · 2019: 3 · 2018: 8 · 2017: 11 · 2016: 7 · 2015: 11 · 2014: 11 · 2013: 9 · 2012: 7
- FWCI
- 8.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arthritis & Rheumatism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (Str 511/5-1,2)
- Helsinki University Central Hospital Research Funds
- University Hospital Regensburg
- Orton Hospital Invalid Foundation
- Topics
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- rheumatoid arthritis, reactive arthritis, interleukin-6, TNF-α, cortisol, dehydroepiandrosterone, DHEA sulfate, ACTH, adrenal steroids, 17-hydroxyprogesterone, androstenedione, joint swelling, grip strength, untreated patients, early arthritis, adrenal insufficiency
- MeSH terms
- Prohibitins, Adrenal Cortex Hormones, Adult, Aged, Aged, 80 and over, Arthritis, Rheumatoid, Female, Hormones, Humans, Male, Middle Aged, Reference Values, Retrospective Studies, Tumor Necrosis Factor-alpha, Interleukin-6, Cytokines, Arthritis, Reactive
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