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      Determinants of clinical outcome in patients with moderate/severe Graves' orbitopathy undergoing treatment with parenteral glucocorticoids: a retrospective study

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          Abstract

          Background

          Graves' orbitopathy (GO) occurs in approximately 25-40% of patients with Graves' disease (GD). High levels of anti-thyrotropin receptor antibodies (TRAbs), smoking habit, sex, older age, longer duration and amount of hyperthyroidism or hypothyroidism are well-recognized risk factors for the occurrence, severity and clinical course of GO. Oxidative stress (OX) has recently been shown to play a role in the pathogenesis of GO, and several clinical conditions related to OX have been investigated regarding the presentation and severity of GO.

          Aim

          We aimed to evaluate the impact of clinical conditions related to oxidative stress on the outcome of intravenous glucocorticoid (ivGCs) therapy in a cohort of patients with active moderate to severe GO (AMS-GOs) treated at a single institution.

          Methods

          We retrospectively studied a series of patients with AMS-GOs who were treated with ivGCs from January 2013 to May 2022. GO clinical evaluation was performed at baseline and at 6 (W6), 12 (W12) and 24 (W24) weeks after starting ivGCs by the seven-point clinical activity score (CAS) alone and by overall clinical criteria (CI) according to the European Group of Graves' Ophthalmopathy (EUGOGO). Total cholesterol and calculated LDL cholesterol (LDLc), triglyceride, body mass index (BMI), diabetes status, history of hypertension (HoH), smoking status, age and sex were used as covariates for the clinical outcome of GO to ivGCs.

          Results and conclusions

          LDLc and HoH negatively and independently modulated the response of AMS-GOs to ivGCs. Notably, slightly elevated LDLc levels (> 130 mg/dl) reduced the response of orbital soft tissue to ivGCs, whereas more elevated LDLc levels (from 175 mg/dl to 190 mg/dl) and HoH were associated with poorer clinical response of eye motility and proptosis.

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          Most cited references42

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          Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)

          Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001)
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            Targeting the IL-6/JAK/STAT3 signalling axis in cancer

            Daniel E. Johnson, Jennifer R. Grandis, Rachel A O'Keefe (2018)
            The IL-6/JAK/STAT3 pathway is aberrantly hyperactivated in many types of cancer, and such hyperactivation is generally associated with a poor clinical prognosis. In the tumour microenvironment, IL-6/JAK/STAT3 signalling acts to drive the proliferation, survival, invasiveness, and metastasis of tumour cells, while strongly suppressing the antitumour immune response. Thus, treatments that target the IL-6/JAK/STAT3 pathway in patients with cancer are poised to provide therapeutic benefit by directly inhibiting tumour cell growth and by stimulating antitumour immunity. Agents targeting IL-6, the IL-6 receptor, or JAKs have already received FDA approval for the treatment of inflammatory conditions or myeloproliferative neoplasms and for the management of certain adverse effects of chimeric antigen receptor T cells, and are being further evaluated in patients with haematopoietic malignancies and in those with solid tumours. Novel inhibitors of the IL-6/JAK/STAT3 pathway, including STAT3-selective inhibitors, are currently in development. Herein, we review the role of IL-6/JAK/STAT3 signalling in the tumour microenvironment and the status of preclinical and clinical investigations of agents targeting this pathway. We also discuss the potential of combining IL-6/JAK/STAT3 inhibitors with currently approved therapeutic agents directed against immune-checkpoint inhibitors.
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              A note on a general definition of the coefficient of determination

              N. J. D. NAGELKERKE (1991)
              Article 0 comments Cited 396 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Rosario Le Moli: URI : https://loop.frontiersin.org/people/266011Role: Role: Role: Role: Role: Role: Role: Role: Role: Role: Role: Role: Role: Role:
                Adriano Naselli: URI : https://loop.frontiersin.org/people/1120923Role: Role: Role: Role: Role: Role: Role: Role: Role: Role: Role: Role: Role: Role:
                Gabriele Costanzo: Role: Role:
                Tommaso Piticchio: Role: Role:
                Dario Tumino: URI : https://loop.frontiersin.org/people/419778Role: Role:
                Gabriella Pellegriti: URI : https://loop.frontiersin.org/people/45233Role: Role:
                Francesco Frasca: URI : https://loop.frontiersin.org/people/28760Role: Role: Role: Role: Role:
                Antonino Belfiore: URI : https://loop.frontiersin.org/people/20871Role: Role: Role: Role: Role:
                Journal
                Journal ID (nlm-ta): Front Endocrinol (Lausanne)
                Journal ID (iso-abbrev): Front Endocrinol (Lausanne)
                Journal ID (publisher-id): Front. Endocrinol.
                Title: Frontiers in Endocrinology
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 1664-2392
                Publication date (Electronic): 04 July 2024
                Publication date Collection: 2024
                Volume: 15
                Electronic Location Identifier: 1401155
                Affiliations
                [1] 1 Endocrinology Unit, Department of Clinical and Experimental Medicine, Garibaldi Nesima Hospital, University of Catania , Catania, Italy
                [2] 2 Department of Medicine and Surgery, University of Enna "Kore" , Enna, Italy
                Author notes

                Edited by: Fausto Bogazzi, University of Pisa, Italy

                Reviewed by: Giulia Lanzolla, University of Pennsylvania, United States

                Giorgio Napolitano, University of Studies G. d'Annunzio Chieti and Pescara, Italy

                *Correspondence: Rosario Le Moli, rlemoli@ 123456unict.it

                †These authors have contributed equally to this work

                ‡ORCID: Rosario Le Moli, orcid.org/0000-0002-1398-9271

                Article
                DOI: 10.3389/fendo.2024.1401155
                PMC ID: 11254611
                PubMed ID: 39027472
                SO-VID: 8a057718-e350-429d-9b1f-ff31cef9a00d
                Copyright © Copyright © 2024 Le Moli, Naselli, Costanzo, Piticchio, Tumino, Pellegriti, Frasca and Belfiore
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                Date received : 14 March 2024
                Date accepted : 17 June 2024
                Page count
                Figures: 2, Tables: 8, Equations: 0, References: 42, Pages: 9, Words: 5092
                Funding
                The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.
                Categories
                Subject: Endocrinology
                Subject: Original Research
                Custom metadata
                section-in-acceptance Thyroid Endocrinology

                ScienceOpen disciplines: Endocrinology & Diabetes
                Keywords: parenteral glucocorticoids,oxidative stress,graves' orbitopathy phenotype,ldl - cholesterol,hypertension
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes
                Keywords: parenteral glucocorticoids, oxidative stress, graves' orbitopathy phenotype, ldl - cholesterol, hypertension

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