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Cited by 73Growth Hormone and Insulin-like Growth FactorsPituitary Gland Disorders and TreatmentsRheumatoid Arthritis Research and Therapies

Role of the Growth Hormone/Insulin-like Growth Factor-1 Paracrine Axis in Rheumatic Diseases

Denko, Charles W., Malemud, Charles J.·2005·Seminars in Arthritis and Rheumatism
DOI 10.1016/j.semarthrit.2005.03.001
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Abstract

Objectives Hypothalamic-pituitary axis abnormalities have been associated with systemic disturbances in several rheumatic diseases. Longitudinal analysis of erythrocyte, serum, urinary and synovial fluid growth hormone (GH), insulin-like growth factor-1 (IGF-1), and somatostatin levels could provide important surrogate measures of disease activity in rheumatic diseases.Methods The authors reviewed the population and longitudinal studies literature on GH, IGF-1, and somatostatin levels in rheumatic disorders using the PubMed and Medlines databases from the National Library of Medicine. In addition to the literature search, primary data were analyzed for basal somatostatin levels in patients with hand, knee, and spine osteoarthritis (OA) as well as primary and secondary hip OA.Results A review of the literature supports the view that hypothalamic-pituitary axis dysfunction accompanies clinical symptoms in many rheumatic diseases. In studies from our laboratory, serum GH levels were elevated in patients with OA, rheumatoid arthritis (RA), fibromyalgia, and diffuse idiopathic skeletal hyperostosis but not in patients with gout, pseudogout, or systemic lupus erythematosus. In OA and RA, synovial fluid GH levels exceeded serum GH levels. However, the literature remains controversial regarding the significance of changes in IGF-1 levels in rheumatic disorders. Many studies support an inverse relationship between age and IGF-1. Elevated serum GH levels in various rheumatic diseases were not coupled to changes in serum IGF-1 in diffuse idiopathic skeletal hyperostosis, RA, and fibromyalgia. In particular, serum IGF-1 levels in OA were shown to be lower or no different compared with age-matched normal subjects. Further, in OA, impaired articular chondrocyte response to IGF-1 was attributed, in part, to low synovial fluid IGF-1 that further compromised IGF-1 chondrocyte responses as a result of increased levels of synovial fluid IGF-1 binding proteins. Of note, serum somatostatin levels and "specific" somatostatin receptor levels were often lower in RA and systemic lupus erythematosus, but basal serum somatostatin levels were generally not altered in OA.Conclusions The results of these analyses support the view that some rheumatic diseases such as OA and diffuse idiopathic skeletal hyperostosis, heretofore considered to be purely focal and degenerative, could be reclassified as systemic metabolic disturbances. We propose that serum GH, IGF-1, and somatostatin levels be monitored on a longitudinal basis during the course of medical therapy of rheumatic diseases to determine the extent to which changes in clinical symptoms (exemplified by reduced pain and inflammation and improved range of joint motion) are accompanied by changes in the basal concentration of these hypothalamic/pituitary-related hormones.

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Authors
Denko, C. W., & Malemud, C. J.
Affiliations
Case Western Reserve University (US)
Corresponding author
Malemud, Charles J.
Venue
Seminars in Arthritis and Rheumatism
Publisher
Elsevier BV
Published
2005-08
Volume
35
Issue
1
Pages
24-34
ISSN
0049-0172 (ISSN-L)
DOI
10.1016/j.semarthrit.2005.03.001
OpenAlex
W2027832169
Cited by
73
References
117
Citations by year
2026: 2 · 2024: 1 · 2023: 4 · 2022: 6 · 2021: 5 · 2020: 2 · 2019: 1 · 2018: 5 · 2017: 2 · 2016: 2 · 2015: 8 · 2014: 5 · 2013: 3 · 2012: 6
FWCI
2.46
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Seminars in Arthritis and Rheumatism (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Arthritis and Musculoskeletal and Skin Diseases (P60AR020618)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
  • Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
Keywords
growth hormone, insulin-like growth factor I, somatostatin, hypothalamic-pituitary axis, rheumatic diseases, osteoarthritis, rheumatoid arthritis, fibromyalgia, diffuse idiopathic skeletal hyperostosis, synovial fluid, IGF-1 binding proteins, disease activity markers
MeSH terms
Adult, Female, Humans, Hypothalamo-Hypophyseal System, Insulin-Like Growth Factor I, Male, Middle Aged, Osteoarthritis, Rheumatic Diseases, Somatostatin, MEDLINE

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