ArticleThe Journal of clinical endocrinology and metabolism2016
TSH/IGF-1 Receptor Cross Talk in Graves' Ophthalmopathy Pathogenesis.
Article in The Journal of clinical endocrinology and metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
91 citing papers in PubMed, 2 syntheses or guidelines pooled it, 156 citations in OpenAlex.
- Efficacy and safety of Tocilizumab for thyroid eye disease: a systemic review and Meta-analysis.Journal of endocrinological investigation · 2025Pooled it
- Efficacy and Safety of intravenous monoclonal antibodies in patients with moderate-to-severe active Graves'ophthalmopathy: a systematic review and meta-analysis.Frontiers in endocrinology · 2023Pooled it
- Antagonistic Autoantibodies to Insulin-Like Growth Factor-1 Receptor Associate with Poor Physical Strength.International journal of molecular sciences · 2020Trial
- Teprotumumab for Thyroid-Associated Ophthalmopathy.The New England journal of medicine · 2017Trial
- Review
- Mouse Model of Graves' Orbitopathy in Current Research and Future Perspectives.Medicina (Kaunas, Lithuania) · 2026Review
- Markers of fibrosis in orbital tissues from patients graves' orbitopathy: a retrospective cohort study.Journal of endocrinological investigation · 2026Article
- Review
- Pediatric Graves' orbitopathy: TRAb and FT-3 are also prognostic factors in children-A tertiary center study.Thyroid research · 2026Article
- Macrophage plasticity in thyroid eye disease: dual effects of inflammation and fibrosis.Frontiers in immunology · 2026Review
- MicroRNAs in thyroid eye disease: expression signatures and clinical implications.Frontiers in immunology · 2026Review
- Article
- Real world effectiveness of Mycophenolate-sodium therapy in patients at risk with Graves' orbitopathy.Thyroid research · 2025Article
- Thyroid hormone signaling in ocular development and diseases.Biological research · 2025Review
- Article
- IGF1R/ARRB1 Mediated Regulation of ERK and cAMP Pathways in Response to Aβ Unfolds Novel Therapeutic Avenue in Alzheimer's Disease.Molecular neurobiology · 2025Article
- Review
- Long-term outcome of Graves' orbitopathy following treatment with sirolimus.Journal of endocrinological investigation · 2025Article
- Linsitinib Decreases Thyrotropin-Induced Thyroid Hormone Synthesis by Inhibiting Crosstalk Between Thyroid-Stimulating Hormone and Insulin-Like Growth Factor 1 Receptors in Human ThyrocytesThyroid : official journal of the American Thyroid Association · 2025Article
- Effects of linsitinib on M22 and IGF:1-treated 3D spheroids of human orbital fibroblasts.Scientific reports · 2025Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
contextThe TSH receptor (TSHR) is considered the main target of stimulatory autoantibodies in the pathogenesis of Graves' ophthalmopathy (GO); however, it has been suggested that stimulatory IGF-1 receptor (IGF-1R) autoantibodies also play a role.
objectiveWe previously demonstrated that a monoclonal stimulatory TSHR antibody, M22, activates TSHR/IGF-1R cross talk in orbital fibroblasts/preadipocytes obtained from patients with GO (GO fibroblasts [GOFs]). We show that cross talk between TSHR and IGF-1R, not direct IGF-1R activation, is involved in the mediation of GO pathogenesis stimulated by Graves' autoantibodies. DESIGN/SETTING/
participantsImmunoglobulins were purified from the sera of 57 GO patients (GO-Igs) and tested for their ability to activate TSHR and/or IGF-1R directly and TSHR/IGF-1R cross talk in primary cultures of GOFs. Cells were treated with M22 or GO-Igs with or without IGF-1R inhibitory antibodies or linsitinib, an IGF-1R kinase inhibitor.
main outcome measuresHyaluronan (hyaluronic acid [HA]) secretion was measured as a major biological response for GOF stimulation. IGF-1R autophosphorylation was used as a measure of direct IGF-1R activation. TSHR activation was determined through cAMP production.
resultsA total of 42 out of 57 GO-Ig samples stimulated HA secretion. None of the GO-Ig samples exhibited evidence for IGF-1R autophosphorylation. Both anti-IGF-1R antibodies completely inhibited IGF-1 stimulation of HA secretion. By contrast, only 1 IGF-1R antibody partially blocked HA secretion stimulated by M22 or GO-Igs in a manner similar to linsitinib, whereas the other IGF-1R antibody had no effect on M22 or GO-Ig stimulation. These findings show that the IGF-1R is involved in GO-Igs stimulation of HA secretion without direct activation of IGF-1R.
conclusionsIGF-1R activation by GO-Igs occurs via TSHR/IGF-1R cross talk rather than direct binding to IGF-1R, and this cross talk is important in the pathogenesis of GO.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.