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Bartalena L, Smith TJ. Treatment of Hyperthyroidism in Graves' Disease Complicated by Thyroid Eye Disease. J Clin Endocrinol Metab 2025; 110:922-930. [PMID: 39787151 DOI: 10.1210/clinem/dgaf009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Revised: 12/13/2024] [Accepted: 01/08/2025] [Indexed: 01/12/2025]
Abstract
Thyroid eye disease (TED) is the most consequential extrathyroidal manifestation or complication of Graves' disease (GD). Treatment of hyperthyroidism in GD complicated by TED is challenging. Antithyroid drugs (ATDs) and thyroidectomy do not change the natural course of TED, while radioactive iodine (RAI) is associated with a small but well-documented risk of TED de novo occurrence or its progression/worsening. In the presence of mild TED, any treatment for hyperthyroidism can be used, but should RAI treatment be selected, steroid prophylaxis (short course of low-dose prednisone) is strongly recommended if TED is of recent onset and/or risk factors for progression exist. In moderate to severe and active TED, ATDs are the preferred treatment, but thyroidectomy is a valid option. RAI ablation is generally avoided; it might be used when the clinical situation calls for it, but with extreme caution, if an aggressive treatment for TED with high-dose glucocorticoids (with or without orbital radiotherapy) is administered concomitantly. In moderate to severe and inactive TED, all 3 treatments for hyperthyroidism are acceptable, and steroid prophylaxis in RAI-treated patients should be given when risk factors for TED progression are identified. Management of sight-threatening TED represents the absolute priority, and hyperthyroidism should be controlled with ATDs until TED has been controlled. Search Strategies Current guidelines, original articles, clinical trials, systematic reviews, and meta-analyses up to June 2024 were searched using the following terms: "Graves' disease," "management of Graves' disease," "antithyroid drugs," "radioactive iodine," "thyroidectomy," "thyroid eye disease," "Graves' orbitopathy or ophthalmopathy."
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Affiliation(s)
- Luigi Bartalena
- The School of Medicine, University of Insubria, Varese 21100, Italy
| | - Terry J Smith
- Department of Ophthalmology and Visual Sciences and Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48105, USA
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2
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Akkus G, Ulaş B, Binokay H, Odabas F, Soysal RS, Özcan A, Sert M. Graves ophthalmopathy a neglected comorbidity of graves' disease; a detailed investigation and management of sixty-eight patients in a tertiary healthcare center. BMC Endocr Disord 2025; 25:46. [PMID: 39972308 PMCID: PMC11837582 DOI: 10.1186/s12902-025-01875-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Accepted: 02/11/2025] [Indexed: 02/21/2025] Open
Abstract
PURPOSE To compare the measurements of macular thickness, intraocular pressure and RNFL and hormone parameters before and after antithyroid therapy in patients with Graves' Ophthalmopathy (GO). METHODS A prospective observational study conducted at a tertiary care center. Patients with GO were included and scored (Clinical Activity Score, CAS) according to EUGOGO guideline. The participants underwent extensive ophthalmological examinations including intraocular pressure measurements with Goldmann applanation tonometry and RNFL with macular thickness evaluations via optical coherence tomography (OCT). Baseline and follow-up (24 weeks) hormone parameters including free T3, free T4, Thyroid stimulating hormone (TSH), Thyroid receptor autoantibodies (TRAbs) and intraocular measurements (RNFL, macular thickness, intraocular pressure) were performed and compared in the current study. RESULTS Comparisons of baseline and follow-up biochemical parameters TSH, fT3, fT4, TRAbs, anti-TPO (p < 0.001). Although baseline score of CAS was mildly increased in all patients (0.5 ± 0.8 vs. 0.1 ± 0.4, p < 0.001) but it was significantly decreased after the antithyroid therapy. Mean intraocular pressure (14.9 ± 2.8 vs. 14.2 ± 1.9), RNFL (100.2 ± 9.05 vs. 99.9 ± 8.7) and macular thickness (274.7 ± 42.9 vs. 271.2 ± 43.3) were similar between baseline and after antithyroid therapy. And baseline RNFL measurements showed significant negative correlation with serum baseline TRAbs, antiTPO, fT3, fT4 (p < 0.05). CONCLUSION Baseline serum fT3, fT4 and TRAbs in patients with Graves' Disease levels may be the prognostic factors in the evaluation of affecting intraocular structure, especially Retinal Nerve Fiber Layer, in patients with GO.
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Affiliation(s)
- Gamze Akkus
- Faculty of Medicine, Division of Endocrinology, Cukurova University, Adana, 01330, Turkey.
| | - Burak Ulaş
- Faculty of Medicine, Division of Ophthalmology, Cukurova University, Adana, Turkey
| | - Hülya Binokay
- Faculty of Medicine, Division of Biostatistics, Cukurova University, Adana, Turkey
| | - Fulya Odabas
- Faculty of Medicine, Division of Endocrinology, Cukurova University, Adana, 01330, Turkey
| | - Reyhan Sevil Soysal
- Faculty of Medicine, Division of Endocrinology, Cukurova University, Adana, 01330, Turkey
| | - Altan Özcan
- Faculty of Medicine, Division of Ophthalmology, Cukurova University, Adana, Turkey
| | - Murat Sert
- Faculty of Medicine, Division of Endocrinology, Cukurova University, Adana, 01330, Turkey
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3
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Ke C, Yu Y, Li J, Yu Y, Sun Y, Wang Y, Wang B, Lu Y, Tang M, Wang N, Chen Y. Genetic and Plasma Proteomic Approaches to Identify Therapeutic Targets for Graves' Disease and Graves' Ophthalmopathy. Immunotargets Ther 2025; 14:87-98. [PMID: 39935908 PMCID: PMC11812558 DOI: 10.2147/itt.s494692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Accepted: 01/22/2025] [Indexed: 02/13/2025] Open
Abstract
Background The blood proteome is a major source of biomarkers and therapeutic targets. We aimed to identify the causal proteins and potential targets for Graves' disease (GD) and Graves' ophthalmopathy (GO) via systematic genetic analyses. Methods Genome-wide association studies (GWASs) on the UK Biobank- Pharma Proteomics Project (UKB-PPP) collected 2923 Olink proteins from 54,219 participants. We conducted a proteome-wide Mendelian randomization (MR) study with cis-pQTLs to identify candidate proteins for GD and GO risk. Colocalization analysis and the Heidi test were used to examine whether the identified proteins and diseases shared the same variant. More proteins with potential causal associations were identified in Summary-data-based MR (SMR) analyses using trans-pQTLs. Then, downstream analyses were performed to detect protein interactions, gene function, cell type-specific expression and druggable information. Results This study genetically predicted levels of 62 plasma proteins were associated with GD risk. Four proteins (CD40, TINAGL1, GMPR and CXCL10) were prioritized with the evidence of sharing the same variants with GD. Specifically, some proteins had potential associations with GD with trans-pQTLs mapping in CD40. The four prioritized protein-coding genes were mainly enriched in the regulation of apoptotic and death processes. In addition, GMPR was associated with both GO and GD in a consistent direction. BTN1A1 and FCRL1 were prioritized as the causal proteins for GO onset and were not associated with GD. Conclusion By synthesizing proteomic and genetic data, we identified several protein biomarkers for GD, with one linked to both GD and GO and two other protein biomarkers specific to GO onset, which provides valuable insights into the etiology and potential therapeutic targets for the two diseases.
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Affiliation(s)
- Chenxin Ke
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China
| | - Yuefeng Yu
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China
| | - Jiang Li
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China
| | - Yuetian Yu
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China
| | - Ying Sun
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China
| | - Yuying Wang
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China
| | - Bin Wang
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China
| | - Yingli Lu
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China
| | - Mengjun Tang
- Orthopedic Department, Taizhou Hospital of Zhejiang Province, Zhejiang University, Taizhou, People’s Republic of China
| | - Ningjian Wang
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China
| | - Yi Chen
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China
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George A, Mariya A, Eappen M, Karthikeyan M, Sreenath R. Serum autotaxin level: a promising diagnostic biomarker in differentiating Graves' disease and thyroiditis. J Pharm Pharmacol 2025; 77:56-63. [PMID: 39027928 DOI: 10.1093/jpp/rgae073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Accepted: 07/06/2024] [Indexed: 07/20/2024]
Abstract
BACKGROUND Recent studies have suggested that serum autotaxin (ATX) may be a promising diagnostic biomarker in differentiating between Graves' disease (GD) and thyroiditis, as well as serving as a monitoring biomarker for GD. This study will evaluate the use of serum ATX as a diagnostic biomarker in these conditions. METHODS In this prospective interventional study, blood samples were collected from the patients who met both inclusion and exclusion criteria, and serum ATX levels were measured by using the MyBioSource human Autotaxin ELISA kit. RESULTS A total of 32 patients were enrolled, of which 18.8% were newly diagnosed with GD, 21.9% were thyroiditis, and 59.3% were on treatment for GD. Serum autotaxin antigen was significantly higher in GD patients than in thyroiditis (603.3217 ± 444.24 v/s 214.74 ± 55.91, P = <.005). Serum ATX measurement successfully discriminated GD patients from thyroiditis (AUC = 0.952, 95%CI: 0.00-1.00) with an optimal cutoff value of ≥257.20 ng/L (sensitivity = 100 and specificity = 81.71). Monitoring the efficacy of serum ATX was analyzed and showed a significant difference. CONCLUSION The serum ATX was higher in subjects with GD as compared to thyroiditis, and ATX levels were found to be decreased during the treatment period. In conclusion, serum ATX can be used as a diagnostic and monitoring biomarker in GD.
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Affiliation(s)
- Angel George
- Department of Pharmacy Practice, Nirmala College of Pharmacy, Muvattupuzha, Ernakulam, Kerala 686661, India
| | - Anns Mariya
- Department of Pharmacy Practice, Nirmala College of Pharmacy, Muvattupuzha, Ernakulam, Kerala 686661, India
| | - Manu Eappen
- Department of Pharmacy Practice, Nirmala College of Pharmacy, Muvattupuzha, Ernakulam, Kerala 686661, India
| | - Marimuthu Karthikeyan
- Department of Pharmacology, Grace College of Pharmacy, Palakkad, Kerala 678004, India
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Cammisa I, Zona M, Guerriero C, Cipolla C, Rigante D. Skin Sceneries of Thyroid Disorders and Impact of Thyroid on Different Skin Diseases: A Scoping Review Focused on Pediatric Patients. CHILDREN (BASEL, SWITZERLAND) 2024; 11:1488. [PMID: 39767917 PMCID: PMC11674394 DOI: 10.3390/children11121488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/26/2024] [Revised: 11/26/2024] [Accepted: 12/04/2024] [Indexed: 01/11/2025]
Abstract
Thyroid function plays a seminal role in the growth and development of children, and alterations in signaling pathways which interfere with the biosynthesis, transport, and metabolism of thyroid hormones might impact on the skin of such patients: this review explores the relationship between different thyroid disorders and dermatological manifestations with a particular focus on the pediatric population. Common cutaneous conditions associated with thyroid dysfunction may include chronic urticaria, vitiligo, and alopecia, which can be early harbingers of an underlying endocrine disruption. This review also highlights the growing cognizance of a "thyroid-skin axis", with thyroid hormones influencing many physiologic processes within the skin such as keratinocyte proliferation, hair growth, and epidermal differentiation. A precocious recognition of abnormal dermatological signs can be crucial in pediatric patients for a timely diagnosis before any development of complications and for personalized treatments of an underlying thyroid disorder, which can even be symptomless at an initial phase. Despite the lack of standardized guidelines for managing dermatologic manifestations occurring in thyroid diseases, a regular screening to identify endocrine dysfunction is recommended in those children who present chronic urticaria, vitiligo, or alopecia, though further research is needed to decipher mechanisms involved in the thyroid-skin partnership and develop more targeted management approaches.
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Affiliation(s)
- Ignazio Cammisa
- Department of Life Sciences and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (I.C.); (M.Z.)
| | - Margherita Zona
- Department of Life Sciences and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (I.C.); (M.Z.)
| | - Cristina Guerriero
- Department of Dermatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Clelia Cipolla
- Department of Life Sciences and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (I.C.); (M.Z.)
| | - Donato Rigante
- Department of Life Sciences and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (I.C.); (M.Z.)
- Università Cattolica Sacro Cuore, 00168 Rome, Italy
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Pollack-Schreiber N, Fishbein JS, Nwosu BU, Salemi P. Increased incidence of Graves' disease during the COVID-19 pandemic in children and adolescents in the United States. Front Endocrinol (Lausanne) 2024; 15:1426672. [PMID: 39703862 PMCID: PMC11655189 DOI: 10.3389/fendo.2024.1426672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Accepted: 11/14/2024] [Indexed: 12/21/2024] Open
Abstract
Introduction Reports in adults indicate that Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) infection and vaccination trigger the expression of autoimmune disease such as Graves' disease, but the incidence of new onset Graves' disease and its temporal relationship to the peaks of COVID-19 cases in children are unclear. Methods This is a retrospective study of children and adolescents with new-onset Graves' disease diagnosed between September 2017 and August 2022, N=156, mean age of 12.5 ± 4 year (y), with a range of 2.9-17.9y. There were 119 female (76.3%) and 37 male (23.7%) subjects. Subjects were categorized into 2 groups: pre-COVID-19 era Graves' disease (n=63, age 12.5 ± 3.3y), and COVID-19 era Graves' disease (n=93, age 12.4 ± 4.4y). We calculated incidence rate based on new cases of Graves' disease and total number of new patient referrals to our endocrine clinic. We first compared the demographic, clinical and biochemical data between the above 2 groups; and also, between subjects with either a history of COVID-19 infection (n=23) or vaccination (n=17) to a control group (n=63). Results The incidence of Graves' disease was significantly higher during the pandemic: pre-COVID-19 versus the COVID-19 era, n=55, 0.56% vs n=93, 0.9%, p=0.005, after accounting for the total number of annual new patient referrals during the study period. The rise in the cases of Graves' disease followed the spikes in the number of cases of COVID-19 in NY. There was also a statistically significant difference in the race distribution between the pre-COVID-19 and the COVID-19 era (p=0.026). Discussion The incidence of Graves' disease increased significantly in children living in New York during the COVID-19 pandemic. The temporal relationship between the peaks of COVID-19 cases and the increased cases of new onset Graves' disease suggest possible autoimmune triggering by SARS-CoV-2.
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Affiliation(s)
- Naama Pollack-Schreiber
- Division of Pediatric Endocrinology, Cohen Children’s Medical Center, NorthwellHealth, New Hyde Park, NY, United States
| | - Joanna S. Fishbein
- Biostatistics Unit, Office of Academic Affairs, Northwell Health, New Hyde Park, NY, United States
| | - Benjamin Udoka Nwosu
- Division of Pediatric Endocrinology, Cohen Children’s Medical Center, NorthwellHealth, New Hyde Park, NY, United States
| | - Parissa Salemi
- Division of Pediatric Endocrinology, Cohen Children’s Medical Center, NorthwellHealth, New Hyde Park, NY, United States
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7
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Giordani I, Sykiotis GP. A short review of current knowledge regarding long-term treatment of Graves' disease with antithyroid drugs. Hormones (Athens) 2024:10.1007/s42000-024-00618-y. [PMID: 39636385 DOI: 10.1007/s42000-024-00618-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 11/26/2024] [Indexed: 12/07/2024]
Abstract
Graves' disease is the most common form of hyperthyroidism, especially in younger people. Current European guidelines recommend antithyroid drugs as initial treatment for a period limited to 12-18 months. Definitive treatment such as surgery or radioactive iodine is proposed in the case of contraindication to antithyroid drugs or in the case of recurrence after medical treatment. However, more recent studies show that long-term antithyroid treatment is associated with reduced risk of recurrence without an increase in adverse effects. Such data support the option of long-term treatment of Graves' disease with antithyroid drugs and suggest the necessity for a change to long-standing practices in the field. Herein, after reviewing some general knowledge on Graves' disease treatment, we discuss the evidence regarding long-term treatment of Graves' disease with antithyroid drugs for endocrinologists, internists, and other specialists involved in the management of these patients. We consider the main studies in the field, outline their respective strengths and limitations, and, finally, present our opinion on when, in the light of this new evidence, endocrinologists should consider long-term treatment with antithyroid drugs.
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Affiliation(s)
- Ilaria Giordani
- Service of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
| | - Gerasimos P Sykiotis
- Service of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
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8
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Lanzolla G, Marinò M, Menconi F. Graves disease: latest understanding of pathogenesis and treatment options. Nat Rev Endocrinol 2024; 20:647-660. [PMID: 39039206 DOI: 10.1038/s41574-024-01016-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/20/2024] [Indexed: 07/24/2024]
Abstract
Graves disease is the most common cause of hyperthyroidism in iodine-sufficient areas. The main responsible mechanism is related to autoantibodies that bind and activate the thyrotropin receptor (TSHR). Although Graves hyperthyroidism is relatively common, no causal treatment options are available. Established treatment modalities are antithyroid drugs, which reduce thyroid hormone synthesis, radioactive iodine and surgery. However, emerging drugs that target the main autoantigen (monoclonal antibodies, small molecules, peptides) or block the immune pathway have been recently tested in clinical trials. Graves disease can involve the thyroid exclusively or it can be associated with extrathyroidal manifestations, among which Graves orbitopathy is the most common. The presence of Graves orbitopathy can change the management of the disease. An established treatment for moderate-to-severe Graves orbitopathy is intravenous glucocorticoids. However, recent advances in understanding the pathogenesis of Graves orbitopathy have allowed the development of new target-based therapies by blocking pro-inflammatory cytokine receptors, lymphocytic infiltration or the insulin-like growth factor 1 receptor (IGF1R), with several clinical trials providing promising results. This article reviews the new discoveries in the pathogenesis of Graves hyperthyroidism and Graves orbitopathy that offer several important tools in disease management.
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Affiliation(s)
- Giulia Lanzolla
- Department of Clinical and Experimental Medicine, Endocrinology Unit II, University of Pisa and University Hospital of Pisa, Pisa, Italy
- Department of Orthopaedic Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
| | - Michele Marinò
- Department of Clinical and Experimental Medicine, Endocrinology Unit II, University of Pisa and University Hospital of Pisa, Pisa, Italy
| | - Francesca Menconi
- U.O. Endocrinologia II, Azienda Ospedaliero Universitaria Pisana, University Hospital of Pisa, Pisa, Italy.
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Pang Y, Nguyen WQ, Guerrero LI, Chrisman LP, Hooper MJ, McCarthy MC, Hales MK, Lipman RE, Paller AS, Guitart J, Zhou XA. Deciphering the Etiologies of Adult Erythroderma: An Updated Guide to Presentations, Diagnostic Tools, Pathophysiologies, and Treatments. Am J Clin Dermatol 2024; 25:927-950. [PMID: 39348008 DOI: 10.1007/s40257-024-00886-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/21/2024] [Indexed: 10/01/2024]
Abstract
Erythroderma, an inflammatory skin condition characterized by widespread erythema with variable degrees of exfoliation, pustulation, or vesiculobullous formation, is associated with high morbidity and mortality. Determining the underlying cause of erythroderma frequently presents a diagnostic challenge, which may contribute to the condition's relatively poor prognosis. This review covers the clinical presentation, pathophysiology, diagnosis, and treatment of erythroderma. It discusses similarities and differences among the many underlying etiologies of the condition and differences between erythrodermic and non-erythrodermic presentations of the same dermatosis. Finally, this article explores current research that may provide future tools in the diagnosis and management of erythroderma.
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Affiliation(s)
- Yanzhen Pang
- Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 N Saint Clair, Arkes 1600, Chicago, IL, 60611, USA
| | - William Q Nguyen
- Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 N Saint Clair, Arkes 1600, Chicago, IL, 60611, USA
- University of South Florida Morsani College of Medicine, Tampa, FL, USA
| | - Liliana I Guerrero
- Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 N Saint Clair, Arkes 1600, Chicago, IL, 60611, USA
| | - Lauren P Chrisman
- Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 N Saint Clair, Arkes 1600, Chicago, IL, 60611, USA
| | - Madeline J Hooper
- Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 N Saint Clair, Arkes 1600, Chicago, IL, 60611, USA
| | - Morgan C McCarthy
- Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 N Saint Clair, Arkes 1600, Chicago, IL, 60611, USA
| | - Molly K Hales
- Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 N Saint Clair, Arkes 1600, Chicago, IL, 60611, USA
| | - Rachel E Lipman
- Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 N Saint Clair, Arkes 1600, Chicago, IL, 60611, USA
| | - Amy S Paller
- Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 N Saint Clair, Arkes 1600, Chicago, IL, 60611, USA
| | - Joan Guitart
- Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 N Saint Clair, Arkes 1600, Chicago, IL, 60611, USA
| | - Xiaolong A Zhou
- Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 N Saint Clair, Arkes 1600, Chicago, IL, 60611, USA.
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Acosta GJ, Singh Ospina N, Brito JP. Epidemiologic changes in thyroid disease. Curr Opin Endocrinol Diabetes Obes 2024; 31:184-190. [PMID: 39087407 DOI: 10.1097/med.0000000000000877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/02/2024]
Abstract
PURPOSE OF REVIEW To analyze the evolving epidemiologic trends in thyroid disease, focusing on risk factors, underlying drivers of these changes, and their implications on clinical practice and research priorities. RECENT FINDINGS Thyroid disease remains one of the most prevalent groups of disorders globally, and the shift in its frequency and distribution is multifactorial. The prevalence of hypothyroidism increases with age, although normal thyrotropin ranges appear to be age-dependent, raising concern for potentially inappropriate levothyroxine use. Hyperthyroidism and Graves' disease continue to be predominant in reproductive-age women but exhibit a milder phenotype at diagnosis. Thyroid nodules are increasingly found in asymptomatic patients, likely from more widespread use of neck and chest imaging. Thyroid cancer incidence has risen exponentially over the years, mostly driven by overdiagnosis of low-risk tumors; however, a small rise in incidence of higher risk tumors has been noted. Obesity appears to be a risk factor for thyroid cancer occurrence and more aggressive forms of the disease. SUMMARY Understanding epidemiologic trends in thyroid disease is crucial for guiding clinical practice and research efforts, aiming to optimize patient outcomes while preventing unnecessary and potentially harmful interventions.
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Affiliation(s)
- Gonzalo J Acosta
- Division of Endocrinology, Department of Medicine, University of Florida, Gainesville, Florida
| | - Naykky Singh Ospina
- Division of Endocrinology, Department of Medicine, University of Florida, Gainesville, Florida
| | - Juan P Brito
- Knowledge and Evaluation Research Unit, Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Medicine
- Department of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, Minnesota, USA
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Chatterjee R, Chandra A, Pramanik N, Sil A. Pretibial Myxedema as the Presenting Manifestation of Graves Disease. Am J Med 2024; 137:e188-e189. [PMID: 38969326 DOI: 10.1016/j.amjmed.2024.06.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 06/20/2024] [Accepted: 06/20/2024] [Indexed: 07/07/2024]
Affiliation(s)
- Rupak Chatterjee
- Department of Tropical Medicine, Calcutta School of Tropical Medicine, Kolkata, India
| | - Atanu Chandra
- Department of Internal Medicine, Bankura Sammilani Medical College, Bankura, India.
| | - Netai Pramanik
- Department of Tropical Medicine, Calcutta School of Tropical Medicine, Kolkata, India
| | - Abheek Sil
- Department of Dermatology, Venereology and Leprosy, RG Kar Medical College, Kolkata, India
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Zhang H, Fang L, Cheng Y, Peng Y, Wang H, Jiang M, Zhu L, Li Y, Fang S, Zhou H, Sun J, Song X. Peripheral CD3 +CD4 + T cells as indicators of disease activity in thyroid eye disease: age-dependent significance. Graefes Arch Clin Exp Ophthalmol 2024; 262:2985-2997. [PMID: 38689122 DOI: 10.1007/s00417-024-06496-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 04/19/2024] [Accepted: 04/25/2024] [Indexed: 05/02/2024] Open
Abstract
PURPOSE To provide an in-depth analysis of the association of peripheral lymphocytes and the disease activity of thyroid eye disease (TED). METHODS This retrospective study enrolled 65 active TED patients and 46 inactive TED patients. Comparative analyses of peripheral lymphocyte subsets were conducted between active and inactive patients. Subgroup analyses were performed based on sex, age, disease duration, and severity. Correlation analyses explored the associations between lymphocyte subsets and TED activity indicators. Prediction models for TED activity were established using objective indicators. RESULTS Significantly elevated levels of CD3+CD4+ T cells were observed in active TED patients compared to inactive patients (P = 0.010). Subgroup analyses further revealed that this disparity was most prominent in females (P = 0.036), patients aged 50 years and younger (P = 0.003), those with long-term disease duration (P = 0.022), and individuals with moderate-to-severe disease (P = 0.021), with age exerting the most substantial impact. Subsequent correlation analysis confirmed the positive association between CD3+CD4+ T cells and the magnetic resonance imaging indicator of TED activity among patients aged 50 years and younger (P = 0.038). The combined prediction models for TED activity, established using objective indicators including CD3+CD4+ T cells, yielded areas under curve of 0.786 for all patients and 0.816 for patients aged 50 years and younger. CONCLUSIONS Peripheral CD3+CD4+ T cells are associated with disease activity of TED, especially in patients aged 50 years and younger. Our study has deepened the understanding of the peripheral T cell profiles in TED patients.
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Affiliation(s)
- Haiyang Zhang
- Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Lianfei Fang
- Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Yumeng Cheng
- Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Yuhang Peng
- Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Hui Wang
- Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Mengda Jiang
- Department of Radiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ling Zhu
- Department of Radiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yinwei Li
- Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Sijie Fang
- Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Huifang Zhou
- Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China.
| | - Jing Sun
- Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China.
| | - Xuefei Song
- Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China.
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13
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Ma C, Li H, Lu S, Li X. Thyroid-associated ophthalmopathy: the role of oxidative stress. Front Endocrinol (Lausanne) 2024; 15:1400869. [PMID: 39055057 PMCID: PMC11269105 DOI: 10.3389/fendo.2024.1400869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 06/28/2024] [Indexed: 07/27/2024] Open
Abstract
Thyroid-associated ophthalmopathy (TAO) is an autoimmune condition affecting the eyes, characterized by proptosis, extraocular muscle involvement, and in severe cases, vision impairment including diplopia, optic neuropathy, and potential blindness. The exact etiology of TAO remains elusive; however, increased oxidative stress and decreased antioxidant capacity are pivotal in its pathogenesis. Elevated oxidative stress not only directly damages orbital tissues but also influences thyroid function and autoimmune responses, exacerbating tissue destruction. This review explores the role of oxidative stress in TAO, elucidates its mechanisms, and evaluates the efficacy and limitations of antioxidant therapies in managing TAO. The findings aim to enhance understanding of oxidative stress mechanisms in TAO and propose potential antioxidant strategies for future therapeutic development.
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Affiliation(s)
- Chao Ma
- Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Haoyu Li
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Hunan Clinical Research Centre of Ophthalmic Disease, Changsha, Hunan, China
| | - Shuwen Lu
- Department of Ophthalmology, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China
| | - Xian Li
- Manchester Royal Eye Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom
- Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom
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14
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Fotso Simo SC, Lin KS, Bukharovich I. Thyrotoxic Cardiomyopathy: A Rare Case of Thyroid Storm Presenting as De Novo Heart Failure. Cureus 2024; 16:e57924. [PMID: 38725773 PMCID: PMC11079851 DOI: 10.7759/cureus.57924] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/09/2024] [Indexed: 05/12/2024] Open
Abstract
Thyroid storm and heart failure represent formidable challenges in clinical practice. Their coexistence, however, poses an even greater threat to the patient's well-being. To facilitate early recognition and appropriate management, an understanding of the complex interplay between these two conditions is crucial. Through comprehensive assessment, vigilant monitoring, and prompt intervention, outcomes can be improved and the morbidity and mortality mitigated. We present a rare case of a 40-year-old male who presented with severe de novo heart failure and a concurrent thyroid storm. Despite an initial left ventricular systolic ejection fraction of 20% and evidence of global dilatation and hypokinesis on echocardiography, appropriate management resulted in improved clinical status and ultimately recovery of cardiac function.
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Affiliation(s)
| | - Kai Shiang Lin
- Internal Medicine, State University of New York Downstate Medical Center, Brooklyn, USA
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15
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Walsh HL, Shoji MK, Gallo RA, Mervis JS, Maeng MM, Elgart GW, Kirsner RS, Wester ST. Upregulation of Insulin-like Growth Factor-1 Receptor Expression in Pretibial Myxedema: Evidence for a Treatment Target. Am J Dermatopathol 2024; 46:153-154. [PMID: 38055967 DOI: 10.1097/dad.0000000000002597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/08/2023]
Affiliation(s)
- Hannah L Walsh
- University of Miami Miller School of Medicine, Miami, FL
| | - Marissa K Shoji
- Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL
| | - Ryan A Gallo
- University of Miami Miller School of Medicine, Miami, FL
| | - Joshua S Mervis
- Dr Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL; and
| | - Michelle M Maeng
- Department of Ophthalmology and Visual Science, Yale School of Medicine, New Haven, CT
| | - George W Elgart
- Dr Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL; and
| | - Robert S Kirsner
- Dr Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL; and
| | - Sara T Wester
- Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL
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16
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Stoynova MA, Shinkov AD, Dimitrova ID, Yankova IA, Kovatcheva RD. Evaluation of disease-specific quality of life and its influencing factors in Bulgarian patients with Graves' orbitopathy. Int Ophthalmol 2024; 44:68. [PMID: 38347322 DOI: 10.1007/s10792-024-02952-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Accepted: 12/04/2023] [Indexed: 02/15/2024]
Abstract
PURPOSE Graves' orbitopathy (GO) profoundly affects patients' quality of life (QoL). Our aim was to assess QoL in patients with different forms of GO and to search for predictors of QoL. METHODS This was a cross-sectional study involving 221 consecutive unselected GO patients (77.4% females, mean age 52 ± 11.6) referred to our clinic in the period 2017-2021. Detailed medical history was obtained from all patients, followed by hormonal and immunological testing and comprehensive ocular status. QoL was assessed by a disease-specific questionnaire (GO-QoL), consisting of two scales-one related to visual functioning (QoL-VF) and the other-to physical appearance (QoL-AP). The results were calculated by formula and expressed as percentages. RESULTS Mild GO patients had significantly higher scores on both scales of GO-QoL compared to moderate-to-severe and sight-threatening GO patients (82.0 vs. 54.6% and 27.3% for QoL-VF; 70.1 vs. 54.4% and 36.9% for QoL-AP). Patients with active GO had significantly poorer QoL-VF (56.6 vs. 76.6%) and QoL-AP (53.1 vs. 67.5%) in comparison to patients with inactive GO. The stepwise linear regression analysis showed that the variables with major predictive value for QoL-VF were: CAS, diplopia score, visual acuity and severity of the symptoms (R2 = 0.44), whereas gender, CAS, diplopia score and proptosis best predicted QoL-AP (R2 = 0.39). CONCLUSIONS The impact of GO on patients' QoL depends on the severity and activity of the disease. The clinical predictors of the impairment of QoL should be taken into account when considering the optimal adjunctive treatment approaches aiming to improve patients' QoL.
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Affiliation(s)
- Mariya Asenova Stoynova
- Medical University of Sofia, Department of Endocrinology, University Hospital of Endocrinology, Sofia, Bulgaria
| | - Alexander Dimitrov Shinkov
- Medical University of Sofia, Department of Endocrinology, University Hospital of Endocrinology, Sofia, Bulgaria
| | - Inna Dimitrova Dimitrova
- Medical University of Sofia, Department of Endocrinology, University Hospital of Endocrinology, Sofia, Bulgaria
| | - Inna Angelova Yankova
- Medical University of Sofia, Department of Endocrinology, University Hospital of Endocrinology, Sofia, Bulgaria
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Nguyen VB, Nguyen VVH, Van Le C, Linh PNT, Thi XN, Vo TT. Pretibial myxedema in Grave's disease: A case report and treatment review of the literature. Clin Case Rep 2024; 12:e8478. [PMID: 38389965 PMCID: PMC10883341 DOI: 10.1002/ccr3.8478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Revised: 12/20/2023] [Accepted: 01/08/2024] [Indexed: 02/24/2024] Open
Abstract
Key Clinical Message Pretibial myxedema is a rare skin lesion in Grave's disease, which required topical glucocorticoid administration in long-term treatment. The patient's lesion has shrunk and become flatter than before treatment. Abstract We present a case of biopsy-verified pretibial myxedema in a 70-year-old male patient with diagnosed hyperthyroidism and no prior history of Graves' disease. Topical corticosteroid and antithyroid drug administration led to successful resolution of the skin lesions. This case emphasizes the importance of considering pretibial myxedema even in atypical presentations of Graves' disease and underscores the value of prompt treatment.
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Affiliation(s)
- Van Bang Nguyen
- Center of Endocrinology and DiabetesFamily HospitalDa NangVietnam
| | | | - Chi Van Le
- Internal Medicine Department, Hue University of Medicine and PharmacyHue UniversityHue CityVietnam
| | | | - Xuan Nguyen Thi
- Center of Endocrinology and DiabetesFamily HospitalDa NangVietnam
| | - Thanh Trang Vo
- Center of Endocrinology and DiabetesFamily HospitalDa NangVietnam
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18
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Schuh A, Ayvaz G, Baldeschi L, Baretić M, Bechtold D, Boschi A, Brix TH, Burlacu MC, Ciric J, Covelli D, Currò N, Donati S, Eckstein AK, Fichter N, Führer D, Horn M, Jabłońska-Pawlak A, Juri Mandić J, Kahaly GJ, Konuk O, Langbein A, Lanzolla G, Marcocci C, Marinò M, Miśkiewicz P, Beleslin BN, Pérez-Lázaro A, Pérez-López M, Ponto KA, Quinn A, Rudofsky G, Salvi M, Schittkowski MP, Tanda ML, Toruner F, Vaidya B, Hintschich CR. Presentation of Graves' orbitopathy within European Group On Graves' Orbitopathy (EUGOGO) centres from 2012 to 2019 (PREGO III). Br J Ophthalmol 2024; 108:294-300. [PMID: 36627174 PMCID: PMC10850632 DOI: 10.1136/bjo-2022-322442] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Accepted: 12/22/2022] [Indexed: 01/12/2023]
Abstract
BACKGROUND Graves' orbitopathy (GO) is subject to epidemiological and care-related changes. Aim of the survey was to identify trends in presentation of GO to the European Group On Graves' Orbitopathy (EUGOGO) tertiary referral centres and initial management over time. METHODS Prospective observational multicentre study. All new referrals with diagnosis of GO within September-December 2019 were included. Clinical and demographic characteristics, referral timelines and initial therapeutic decisions were recorded. Data were compared with a similar EUGOGO survey performed in 2012. RESULTS Besides age (mean age: 50.5±13 years vs 47.7±14 years; p 0.007), demographic characteristics of 432 patients studied in 2019 were similar to those in 2012. In 2019, there was a decrease of severe cases (9.8% vs 14.9; p<0.001), but no significant change in proportion of active cases (41.3% vs 36.6%; p 0.217). After first diagnosis of GO, median referral time to an EUGOGO tertiary centre was shorter (2 (0-350) vs 6 (0-552) months; p<0.001) in 2019. At the time of first visit, more patients were already on antithyroid medications (80.2% vs 45.0%; p<0.001) or selenium (22.3% vs 3.0%; p<0.001). In 2019, the initial management plans for GO were similar to 2012, except for lid surgery (2.4% vs 13.9%; p<0.001) and prescription of selenium (28.5% vs 21.0%; p 0.027). CONCLUSION GO patients are referred to tertiary EUGOGO centres in a less severe stage of the disease than before. We speculate that this might be linked to a broader awareness of the disease and faster and adequate delivered treatment.
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Affiliation(s)
- Anna Schuh
- Department of Ophthalmology, Ludwig Maximilians University Munich, Munich, Germany
| | - Goksun Ayvaz
- Department of Endocrinology and Metabolism, Koru Hospital, Ankara, Turkey
| | - Lelio Baldeschi
- Service d'Ophtalmologie, Université Catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Maja Baretić
- Department of Endocrinology and Diabetes, University Hospital Center Zagreb, Croatia, School of medicine University of Zagreb, Zagreb, Croatia
| | - Dorte Bechtold
- Department of Ophthalmology, Odense University Hospital, Odense C, Denmark
| | - Antonella Boschi
- Service d'Ophtalmologie, Université Catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | | | - Maria-Cristina Burlacu
- Department of Endocrinology, Université Catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Jasmina Ciric
- Clinic of Endocrinology, Diabetes and Diseases of Metabolism, University Clinical Center of Serbia, Belgrade, Serbia
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Danila Covelli
- Department of Endocrinology, Graves' Orbitopathy Center, La Fondazione IRCCS Ca' Granda Ospedale Maggiore di Milano Policlinico, Milano, Italy
| | - Nicola Currò
- Department of Ophthalmology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Simone Donati
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Anja K Eckstein
- Department of Ophthalmology, University of Duisburg-Essen, Essen, Germany
| | - Nicole Fichter
- Department of Ophthalmology, ADMEDICO orbital centre/University Basel, Olten, Switzerland
| | - Dagmar Führer
- Department of Endocrinology, Diabetes and Metabolism, University of Duisburg-Essen, Essen, Germany
| | - Maren Horn
- Department of Ophthalmology, University Medicine Goettingen, Goettingen, Germany
| | | | - Jelena Juri Mandić
- Department of Ophthalmology, Medical School, Kišpatićeva 12, University Clinical Hospital Center Zagreb, Zagreb, Croatia
| | - George J Kahaly
- Department of Medicine I, Johannes Gutenberg University Medical Center, Mainz, Germany
| | - Onur Konuk
- Department of Ophthalmology, Gazi University Medical School, Ankara, Turkey
| | - Amelie Langbein
- Department of Medicine I, Johannes Gutenberg University Medical Center, Mainz, Germany
| | - Giulia Lanzolla
- Department of Clinical and Experimental Medicine, Endocrinology Units, University of Pisa and University Hospital of Pisa, Pisa, Italy
| | - Claudio Marcocci
- Department of Clinical and Experimental Medicine, Endocrinology Units, University of Pisa and University Hospital of Pisa, Pisa, Italy
| | - Michele Marinò
- Department of Clinical and Experimental Medicine, Endocrinology Units, University of Pisa and University Hospital of Pisa, Pisa, Italy
| | - Piotr Miśkiewicz
- Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland
| | - Biljana Nedeljkovic Beleslin
- Clinic of Endocrinology, Diabetes and Diseases of Metabolism, University Clinical Center of Serbia, Belgrade, Serbia
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Antonia Pérez-Lázaro
- Department of Endocrinology, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - Marta Pérez-López
- Department of Ophthalmology, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - Katharina A Ponto
- Department of Ophthalmology, Johannes Gutenberg University Medical Center, Mainz, Germany
| | - Anthony Quinn
- Department of Ophthalmology, Royal Devon University Hospital, Exeter, UK
| | | | - Mario Salvi
- Department of Endocrinology, Graves' Orbitopathy Center, La Fondazione IRCCS Ca' Granda Ospedale Maggiore di Milano Policlinico, Milano, Italy
| | | | - Maria Laura Tanda
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Fusun Toruner
- Department of Endocrinology and Metabolism, Gazi University Medical School, Ankara, Turkey
| | - Bijay Vaidya
- Department of Endocrinology, Royal Devon University Hospital, University of Exeter Medical School, Exeter, UK
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Wang D, Marous C, Celiker P, Deng W, Kristoferson E, Elsayed A, Shinder R, Hodgson N. The association of race with thyroid eye disease presentation and outcomes. FRONTIERS IN OPHTHALMOLOGY 2024; 3:1309850. [PMID: 38983053 PMCID: PMC11182153 DOI: 10.3389/fopht.2023.1309850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Accepted: 12/27/2023] [Indexed: 07/11/2024]
Abstract
Introduction Classification of thyroid eye disease (TED) is largely based on guidelines developed in Europe and North America. Few studies have investigated the presentation and treatment of TED in Black populations. The objective is to examine the manifestations of TED in secondary and tertiary care center-based populations with a significant proportion of Black patients. Materials and methods Retrospective chart review identifying patients with a reported race/ethnicity and a presenting clinical diagnosis of TED at Kings County Hospital and SUNY Downstate Medical Center and affiliated clinics from January 1, 2010 through July 31, 2021. Main outcome measures include age of disease onset, sex, smoking status, insurance status, postal code of residence, clinical exam features, number of follow-up visits, length of follow-up, and treatments received. Results Of the 80 patients analyzed, 49 were Black (61.2%) and 31 were White (38.8%). Between Black and White patients, there were differences in the mean age of presentation (48.1 [range 21-76] vs 56.8 [range 28-87] years, P=0.03), insurance status (51.0% vs 77.4% private insurance, P=0.02), and mean follow up length among those with multiple visits (21.6 [range 2-88] vs 9.7 [range 1-48] months, P=0.02). The distribution of EUGOGO scores were not significantly different between Black and White patients. On initial presentation, fewer Black patients had chemosis (OR 0.21, 95% CI, 0.08 to 0.57, P=0.002), and caruncular swelling (OR 0.19, 95% CI, 0.06 to 0.59, P=0.002) compared to White patients. During the overall disease course, fewer Black patients had subjective diplopia (OR 0.20, 95% CI, 0.07 to 0.56, P=0.002), chemosis (OR 0.24, 95% CI, 0.09 to 0.63, P=0.004), and caruncular swelling (OR 0.18, 95% CI, 0.07 to 0.51, P=0.001) compared to White patients. Black patients received oral steroids (42.9% vs 67.7%, P=0.03), intravenous steroids (18.4% vs 16.1%, P=0.8), orbital decompression surgery (16.7% vs 6.5%, P=0.19), and teprotumumab (22.9% vs 22.6%, P=0.99) at similar rates. Discussion Black patients presented with fewer external exam findings suggestive of active TED compared to White patients, but the rate of compressive optic neuropathy and decompression surgery were similar in the two groups. These differences may be due to disease phenotypes, which warrant further study.
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Affiliation(s)
- Diane Wang
- Department of Ophthalmology, SUNY Downstate Medical Center, Brooklyn, NY, United States
- Department of Ophthalmology, Kings County Medical Center, Brooklyn, NY, United States
- Department of Ophthalmology, West Virginia University, Morgantown, WV, United States
| | - Charlotte Marous
- Department of Ophthalmology, SUNY Downstate Medical Center, Brooklyn, NY, United States
- Department of Ophthalmology, Kings County Medical Center, Brooklyn, NY, United States
- Oculoplastic and Orbital Surgery, Wills Eye Hospital, Thomas Jefferson University Hospital, Philadelphia, PA, United States
| | - Pelin Celiker
- Department of Ophthalmology, SUNY Downstate Medical Center, Brooklyn, NY, United States
| | - Wenyu Deng
- Department of Ophthalmology, SUNY Downstate Medical Center, Brooklyn, NY, United States
- Department of Ophthalmology, Kings County Medical Center, Brooklyn, NY, United States
| | - Eva Kristoferson
- Department of Ophthalmology, SUNY Downstate Medical Center, Brooklyn, NY, United States
| | - Ali Elsayed
- Department of Ophthalmology, SUNY Downstate Medical Center, Brooklyn, NY, United States
| | - Roman Shinder
- Department of Ophthalmology, SUNY Downstate Medical Center, Brooklyn, NY, United States
- Department of Ophthalmology, Kings County Medical Center, Brooklyn, NY, United States
- Department of Otolaryngology, SUNY Downstate Medical Center, Brooklyn, NY, United States
| | - Nickisa Hodgson
- Department of Ophthalmology, SUNY Downstate Medical Center, Brooklyn, NY, United States
- Department of Ophthalmology, Kings County Medical Center, Brooklyn, NY, United States
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20
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Lebreton O, Seddiki R, Abba S, Vignes S. [Pretibial myxedema after Graves' disease: A differential diagnosis of lymphedema]. Rev Med Interne 2023; 44:641-645. [PMID: 37827928 DOI: 10.1016/j.revmed.2023.09.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 09/25/2023] [Indexed: 10/14/2023]
Abstract
INTRODUCTION Pretibial myxedema is a rare manifestation of Graves' disease, and pseudotumoral forms may be confused with lower limb lymphedema. OBSERVATIONS We reported 3 cases of pretibial myxedema in 2 women and 1 man, aged 72, 66, and 49 years, treated for Graves' disease 3, 25 and 32 years previously. Two patients were active smokers. Lymphedema diagnosis of the lower limbs was suspected in the presence of bilateral pseudotumoral lesions of the feet, toes and ankles and the presence of a Stemmer's sign (skin thickening at the base of the 2nd toe, pathognomonic of lymphedema). Lymphoscintigraphy in one case was normal, not confirming lymphedema. CONCLUSION Pretibial pseudotumoral myxedema is a differential diagnosis of lower limb lymphedema. This diagnosis is confirmed by questioning the patient about preexisting Graves' disease, the underlying etiology, to decide the appropriate treatment and to encourage cessation of smoking, which is a risk factor for pretibial myxedema.
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Affiliation(s)
- O Lebreton
- Unité de lymphologie, site constitutif du centre national de référence des lymphœdèmes primaires, hôpital Cognacq-Jay, 15, rue Eugène-Millon, 75015 Paris, France
| | - R Seddiki
- Unité de lymphologie, site constitutif du centre national de référence des lymphœdèmes primaires, hôpital Cognacq-Jay, 15, rue Eugène-Millon, 75015 Paris, France
| | - S Abba
- Unité de lymphologie, site constitutif du centre national de référence des lymphœdèmes primaires, hôpital Cognacq-Jay, 15, rue Eugène-Millon, 75015 Paris, France
| | - S Vignes
- Unité de lymphologie, site constitutif du centre national de référence des lymphœdèmes primaires, hôpital Cognacq-Jay, 15, rue Eugène-Millon, 75015 Paris, France.
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Wang L, Zhang M, Wang Y, Shi B. Graves' Orbitopathy Models: Valuable Tools for Exploring Pathogenesis and Treatment. Horm Metab Res 2023; 55:745-751. [PMID: 37903495 DOI: 10.1055/a-2161-5417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/01/2023]
Abstract
Graves' orbitopathy (GO) is the most common extrathyroidal complication of Graves' disease (GD) and severely affects quality of life. However, its pathogenesis is still poorly understood, and therapeutic options are limited. Animal models are important tools for preclinical research. The animals in some previous models only exhibited symptoms of hyperthyroidism without ocular lesions. With the improvements achieved in modeling methods, some progressive animal models have been established. Immunization of mice with A subunit of the human thyroid stimulating hormone receptor (TSHR) by either adenovirus or plasmid (with electroporation) is widely used and convincing. These models are successful to identify that the gut microbiota influences the occurrence and severity of GD and GO, and sex-related risk factors may be key contributors to the female bias in the occurrence of GO rather than sex itself. Some data provide insight that macrophages and CD8+ T cells may play an important pathogenic role in the early stage of GO. Our team also replicated the time window from GD onset to GO onset and identified a group of CD4+ cytotoxic T cells. In therapeutic exploration, TSHR derived peptides, fingolimod, and rapamycin offer new potential options. Further clinical trials are needed to investigate these drugs. With the increasing use of these animal models and more in-depth studies of the new findings, scientists will gain a clearer understanding of the pathogenesis of GO and identify more treatments for patients.
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Affiliation(s)
- Ling Wang
- Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Meng Zhang
- Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yue Wang
- Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Bingyin Shi
- Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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22
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Abstract
Importance Overt hyperthyroidism, defined as suppressed thyrotropin (previously thyroid-stimulating hormone) and high concentration of triiodothyronine (T3) and/or free thyroxine (FT4), affects approximately 0.2% to 1.4% of people worldwide. Subclinical hyperthyroidism, defined as low concentrations of thyrotropin and normal concentrations of T3 and FT4, affects approximately 0.7% to 1.4% of people worldwide. Untreated hyperthyroidism can cause cardiac arrhythmias, heart failure, osteoporosis, and adverse pregnancy outcomes. It may lead to unintentional weight loss and is associated with increased mortality. Observations The most common cause of hyperthyroidism is Graves disease, with a global prevalence of 2% in women and 0.5% in men. Other causes of hyperthyroidism and thyrotoxicosis include toxic nodules and the thyrotoxic phase of thyroiditis. Common symptoms of thyrotoxicosis include anxiety, insomnia, palpitations, unintentional weight loss, diarrhea, and heat intolerance. Patients with Graves disease may have a diffusely enlarged thyroid gland, stare, or exophthalmos on examination. Patients with toxic nodules (ie, in which thyroid nodules develop autonomous function) may have symptoms from local compression of structures in the neck by the thyroid gland, such as dysphagia, orthopnea, or voice changes. Etiology can typically be established based on clinical presentation, thyroid function tests, and thyrotropin-receptor antibody status. Thyroid scintigraphy is recommended if thyroid nodules are present or the etiology is unclear. Thyrotoxicosis from thyroiditis may be observed if symptomatic or treated with supportive care. Treatment options for overt hyperthyroidism from autonomous thyroid nodules or Graves disease include antithyroid drugs, radioactive iodine ablation, and surgery. Treatment for subclinical hyperthyroidism is recommended for patients at highest risk of osteoporosis and cardiovascular disease, such as those older than 65 years or with persistent serum thyrotropin level less than 0.1 mIU/L. Conclusions and Relevance Hyperthyroidism affects 2.5% of adults worldwide and is associated with osteoporosis, heart disease, and increased mortality. First-line treatments are antithyroid drugs, thyroid surgery, and radioactive iodine treatment. Treatment choices should be individualized and patient centered.
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Affiliation(s)
- Sun Y. Lee
- Section of Endocrinology, Diabetes, Nutrition, and Weight Management, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts
| | - Elizabeth N. Pearce
- Section of Endocrinology, Diabetes, Nutrition, and Weight Management, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts
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23
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Перепелова МА, Зайцева ЕЛ, Бессмертная ЕГ, Груша ЯО, Свириденко НЮ, Галстян ГР. [An integrated approach to the treatment of pretibial myxedema based on pulse therapy with prednisolone and electrical neuromyostimulation (FREMS-therapy) in a patient with Graves' disease and thyroid eye disease]. PROBLEMY ENDOKRINOLOGII 2023; 69:32-37. [PMID: 37694865 PMCID: PMC10520899 DOI: 10.14341/probl12888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 12/26/2022] [Accepted: 12/26/2022] [Indexed: 09/12/2023]
Abstract
Graves' disease (GD) is one of the urgent problems of modern endocrinology, characterized by a high frequency, polysystemic damage to the body, a steadily progressive course, diagnostic difficulties, a high degree of disability and often resistance to therapy. The manifestations of the disease include: thyrotoxicosis syndrome with impaired lipid and carbohydrate metabolism, and activation of multiple organ pathology in the form of thyroid eye disease (TED), pretibial myxedema, cardiovascular insufficiency, acropathy, lesions of the nervous, osteoarticular system, and other lesions. The development of multiple organ pathology can have a different sequence, different time intervals and different degrees of severity. Any developments in the direction of clarifying the etiopathogenetic, clinical diagnostic and treatment-rehabilitation measures are of undoubted significance. We present a clinical case of GD, TED and pretibial myxedema, in which an integrated approach was tested in the tactics of treating pretibial myxedema (a combination of pulse therapy with prednisolone and FREMS-therapy), as a result of which positive results were obtained within a short time.
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Affiliation(s)
| | - Е. Л. Зайцева
- Национальный медицинский исследовательский центр эндокринологии
| | | | - Я. О. Груша
- Научно-исследовательский институт глазных болезней им. М.М. Краснова
| | | | - Г. Р. Галстян
- Национальный медицинский исследовательский центр эндокринологии
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24
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Cohen B, Cadesky A, Jaggi S. Dermatologic manifestations of thyroid disease: a literature review. Front Endocrinol (Lausanne) 2023; 14:1167890. [PMID: 37251685 PMCID: PMC10214500 DOI: 10.3389/fendo.2023.1167890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 04/07/2023] [Indexed: 05/31/2023] Open
Abstract
Introduction Thyroid hormone is considered one of the key regulatory hormones for skin homeostasis. Multiple organs are affected by the release of peripheral thyroid hormones (T4 and T3) further regulating various functions at a cellular level. Specifically, skin is considered an important target organ in which the thyroid hormone has a significant impact. Multiple skin diseases are associated with thyroid hormone dysregulation. However, other striking dermatologic manifestations are seen in nails and hair as well. Hypothyroidism, hyperthyroidism, and thyroid cancer can have an array of cutaneous manifestations, and we present the recent updates in this field. Methods A PubMed search was performed for updates in any new skin disease findings and treatments between 2010 and 2022. Research published in the past decade and previously known foundational skin findings associated with thyroid disease were presented in this review. Conclusion Cutaneous manifestations of thyroid disease is one of the first notable signs of thyroid hormone dysregulation. This article reviews the recent updates on the thyroid and skin interplay, and it further discusses overt visible findings and various available treatment modalities.
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Oklar M, Yazicioglu T, Ozen MC, Agackesen A, Gun RD, Tezcan KA. Evaluation of corneal endothelium and correlation with disease severity in patients with Graves' ophthalmopathy: A specular microscopy-based study. Photodiagnosis Photodyn Ther 2023:103592. [PMID: 37146893 DOI: 10.1016/j.pdpdt.2023.103592] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Revised: 04/02/2023] [Accepted: 05/02/2023] [Indexed: 05/07/2023]
Abstract
PURPOSE To investigate the possible corneal endothelial damage in Graves' ophthalmopathy (GO) and its relationship with GO activity. METHODS This cross-sectional study included 101 eyes of 55 patients with GO. Each eye was assigned a specific clinical activity score (CAS). Accordingly, they were classified as active (CAS ≥ 3) or inactive (CAS< 3). The corneal endothelium was measured using a non-contact specular microscope (Tomey EM-4000; Tomey Corp.). Endothelial cell density (ECD), average cell area (ACA), standard deviation of cell area (SD), coefficient of variation in cell area (CV), hexagonal cell ratio (HEX), and central corneal thickness (CCT) were recorded. RESULTS Among the eyes included in the study, 71 had inactive GO and 30 had active GO. ACA and HEX levels were lower (p<0,001) and CV values were higher (p<0.001) in patients with GO than in healthy subjects. Corneal endothelial cell morphology was altered in active GO compared to inactive GO. The SD (p=0,009) and CV (p<0,001) were significantly higher in active GO than in inactive GO. When the parameters examined were correlated with CAS, a statistically significant positive correlation was observed between proptosis (p=0,036, r=0,385) and CV (p=0,001, r=0,595). CONCLUSION Our study confirmed that morphological changes occur in the corneal endothelium of patients with GO. CV and SD values, in conjunction with CAS, can be used as non-invasive and quantitative indices to examine the activity status of GO. The demonstration of endothelial changes even in GO eyes with low CAS may be considered an incentive to include non-contact specular microscopy in the routine clinical evaluation of all patients with GO.
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Affiliation(s)
- Murat Oklar
- Department of Ophthalmology, Kartal Dr. Lütfi Kırdar City Hospital, Istanbul, Turkey.
| | - Titap Yazicioglu
- Department of Ophthalmology, Kartal Dr. Lütfi Kırdar City Hospital, Istanbul, Turkey.
| | - Mehmet Can Ozen
- Department of Ophthalmology, Batman Kozluk State Hospital, Batman, Turkey
| | - Anıl Agackesen
- Department of Ophthalmology, Batman İluh State Hospital, Batman, Turkey
| | - Raziye Donmez Gun
- Department of Ophthalmology, Kartal Dr. Lütfi Kırdar City Hospital, Istanbul, Turkey
| | - Kadriye Aydin Tezcan
- Department of Endocrinology, Kartal Dr. Lütfi Kırdar City Hospital, Istanbul, Turkey
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26
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Martínez-Hernández R, Marazuela M. MicroRNAs in autoimmune thyroid diseases and their role as biomarkers. Best Pract Res Clin Endocrinol Metab 2023; 37:101741. [PMID: 36801129 DOI: 10.1016/j.beem.2023.101741] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/11/2023]
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the posttranscriptional level. They are emerging as potential biomarkers and as therapeutic targets for several diseases including autoimmune thyroid diseases (AITD). They control a wide range of biological phenomena, including immune activation, apoptosis, differentiation and development, proliferation and metabolism. This function makes miRNAs attractive as disease biomarker candidates or even as therapeutic agents. Because of their stability and reproducibility circulating miRNAs have been an interesting area of research in many diseases, and studies describing their role in the immune response and in autoimmune diseases have progressively developed. The mechanisms underlying AITD remain elusive. AITD pathogenesis is characterized by a multifactorial interplay based on the synergy between susceptibility genes and environmental stimulation, together with epigenetic modulation. Understanding the regulatory role of miRNAs could lead to identify potential susceptibility pathways, diagnostic biomarkers and therapeutic targets for this disease. Herein we update our present knowledge on the role of microRNAs in AITD and discuss on their importance as possible diagnostic and prognostic biomarkers in the most prevalent AITDs: Hashimoto's thyroiditis (HT), Graves' disease (GD) and Graves' Ophthalmopathy (GO). This review provides an overview of the state of the art in the pathological roles of microRNAs as well as in possible novel miRNA-based therapeutic approaches in AITD.
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Affiliation(s)
- Rebeca Martínez-Hernández
- Department of Endocrinology, Hospital Universitario de la Princesa, Instituto de Investigación Princesa, Universidad Autónoma de Madrid, C/ Diego de León 62, 28006 Madrid, Spain; Faculty of Medicine, Universidad San Pablo CEU, CEU Universities, Urbanizacion Monteprincipe, Alcorcon, Madrid, Spain.
| | - Mónica Marazuela
- Department of Endocrinology, Hospital Universitario de la Princesa, Instituto de Investigación Princesa, Universidad Autónoma de Madrid, C/ Diego de León 62, 28006 Madrid, Spain.
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27
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Hai YP, Lee ACH, Chen K, Kahaly GJ. Traditional Chinese medicine in thyroid-associated orbitopathy. J Endocrinol Invest 2023; 46:1103-1113. [PMID: 36781592 DOI: 10.1007/s40618-023-02024-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Accepted: 01/24/2023] [Indexed: 02/15/2023]
Abstract
PURPOSE Orbital fibroblasts (OF) are considered the central target cells in the pathogenesis of thyroid-associated orbitopathy (TAO), which comprises orbital inflammation, orbital tissue edema, adipogenesis, fibrosis, oxidative stress and autophagy. Certain active ingredients of traditional Chinese medicine (TCM) demonstrated inhibition of TAO-OF in pre-clinical studies and they could be translated into novel therapeutic strategies. METHODS The pertinent and current literature of pre-clinical studies on TAO investigating the effects of active ingredients of TCM was reviewed using the NCBI PubMed database. RESULTS Eleven TCM compounds demonstrated inhibition of TAO-OF in-vitro and three of them (polydatin, curcumin, and gypenosides) resulted in improvement in TAO mouse models. Tanshinone IIA reduced inflammation, oxidative stress and adipogenesis. Both resveratrol and its precursor polydatin displayed anti-oxidative and anti-adipogenic properties. Celastrol inhibited inflammation and triptolide prevented TAO-OF activation, while icariin inhibited autophagy and adipogenesis. Astragaloside IV reduced inflammation via suppressing autophagy and inhibited fat accumulation as well as collagen deposition. Curcumin displayed multiple actions, including anti-inflammatory, anti-oxidative, anti-adipogenic, anti-fibrotic and anti-angiogenic effects via multiple signaling pathways. Gypenosides reduced inflammation, oxidative stress, tissue fibrosis, as well as oxidative stress mediated autophagy and apoptosis. Dihydroartemisinin inhibited OF proliferation, inflammation, hyaluronan (HA) production, and fibrosis. Berberine attenuated inflammation, HA production, adipogenesis, and fibrosis. CONCLUSIONS Clinical trials of different phases with adequate power and sound methodology will be warranted to evaluate the appropriate dosage, safety and efficacy of these compounds in the management of TAO.
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Affiliation(s)
- Y P Hai
- Molecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Langenbeckstreet 1, 55131, Mainz, Germany
- Department of Endocrinology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
| | - A C H Lee
- Division of Endocrinology and Metabolism, Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China
| | - K Chen
- Department of Endocrinology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
| | - G J Kahaly
- Molecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Langenbeckstreet 1, 55131, Mainz, Germany.
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A retrospective study of clinical features and prognosis of patients with Graves' disease and ophthalmopathy. Nucl Med Commun 2023; 44:137-141. [PMID: 36630217 DOI: 10.1097/mnm.0000000000001649] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
OBJECTIVE To retrospectively investigate the clinical characteristics of patients with Graves' disease (GD) accompanied by ophthalmopathy (GO) and the prognosis of single 131I therapy. METHODS In total, 665 patientswith Graves' disease were enrolled in this study, including 115 patients with GO and 550 patients without GO. On the one hand, the clinical characteristics of the two groups were recorded. On the other hand, the prognosis after more than 6 months of 131I therapy was divided into three groups: recovered, hypothyroidism and unhealed. RESULTS Compared with GD-alone patients, GD patients with GO were younger, had a higher thyrotrophin receptor antibody (TRAb), heavier thyroid mass and higher dose of single 131I therapy (all P < 0.05). Furthermore, patients were younger in the clinical active score ≥3 group and had higher FT4 level in the mild GO group (all P < 0.05). Among these, age and TRAb were independent risk factors for GO in GD patients (P < 0.05). When age was <52.5 years and TRAb was >24.01 IU/L, GD patients were more likely to develop GO (P < 0.001). After at least 6 months of single 131I therapy, compared with GD-alone patients, the prognosis was poor in GD patients with GO (P < 0.05). CONCLUSION Young GD patients with heavy thyroid mass and high TRAb are more likely to have GO. Younger GO patients are more likely to be active stage and the level of thyroid function was inversely correlated with the severity of GO. When the age and TRAb have exceeded the cutoff value, we should pay more attention to the occurrence of GO and shorten the follow-up interval appropriately. Patients with GD combined with GO have a poor prognosis.
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29
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Ugradar S, Goldberg RA, Douglas RS. Changing the face of thyroid eye disease. Eye (Lond) 2023; 37:197-199. [PMID: 35882983 PMCID: PMC9873613 DOI: 10.1038/s41433-022-02186-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 06/20/2022] [Accepted: 07/14/2022] [Indexed: 01/28/2023] Open
Affiliation(s)
- Shoaib Ugradar
- grid.19006.3e0000 0000 9632 6718The Jules Stein Eye Institute University of California, Los Angeles, CA USA
| | - Robert A. Goldberg
- grid.19006.3e0000 0000 9632 6718The Jules Stein Eye Institute University of California, Los Angeles, CA USA
| | - Raymond S. Douglas
- grid.50956.3f0000 0001 2152 9905Cedars-Sinai Medical Center, Los Angeles, CA USA
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30
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Wang Y, Sun Y, Yang B, Wang Q, Kuang H. The management and metabolic characterization: hyperthyroidism and hypothyroidism. Neuropeptides 2023; 97:102308. [PMID: 36455479 DOI: 10.1016/j.npep.2022.102308] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 10/21/2022] [Accepted: 11/08/2022] [Indexed: 11/13/2022]
Abstract
Hyperthyroidism and hypothyroidism are common diseases resulting from thyroid dysfunction, and are simple to diagnose and treat. The traditional treatment for hypothyroidism is thyroid hormone replacement therapy. The traditional treatments for hyperthyroidism include antithyroid drug, iodine radiotherapy, and surgery. Thyroid disease can be fatal in severe cases if untreated. Current statistical reference ranges used for diagnosis based on relevant biochemical parameters have been debated, and insufficient treatment can result in long-term thyroid hormone deficiency, which is associated with increased risk of cardiovascular disease and persistent symptoms. In contrast, overtreatment can result in heart disease and osteoporosis, particularly in older people and pregnant women. Therefore, under- or over-treatment should be avoided and treatment regimens should be monitored closely. A significant proportion of patients who achieve biochemical treatment goals still complain of significant symptoms. Systematic literature review was performed through the Embase (Elsevier), PubMed and Web of Science databases, and studies summarized evidence regarding treatment and management of hypothyroidism and hyperthyroidism, and reviewed clinical practice guidelines. We also reviewed the latest research on the metabolic mechanisms of hyperthyroidism and hypothyroidism, which contributed to understanding of thyroid diseases in the clinic. A reliable algorithm is needed to management, assessment, and treatment patients with hyperthyroidism and hypothyroidism, which can not only improve management efficiency, but also providing a broad application. In addition, the thyroid disorder showed a lipid metabolism tissue specificity in the Ventromedial Hypothalamus, and effect oxidative stress and energy metabolism of whole body. This review summarizes an algorithm for thyroid disease and the latest pathogenesis that would be useful to generalist and subspecialty physicians and others providing care for patients with this condition.
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Affiliation(s)
- Yangyang Wang
- Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Harbin, China
| | - YanPing Sun
- Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Harbin, China
| | - Bingyou Yang
- Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Harbin, China
| | - Qiuhong Wang
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
| | - Haixue Kuang
- Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Harbin, China.
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Abstract
Background: The most prevalent extrathyroidal manifestation of Graves' disease (GD) is Graves' ophthalmopathy (GO). However, only few methods allow for predictions of GO occurrence or progression in patients with GD. Methods: We retrospectively analyzed 1,074 patients with new-onset GD, and divided them into a derivation and a validation cohort based on the date of their GD diagnosis. We then separately analyzed clinical risk factors affecting the occurrence and progression of GO using multivariable regression analysis and created a predictive model based on the factors we identified as significant. Results: Of the 853 GD patients included in the derivation cohort, 101 (11.8%) developed GO. Those who developed GO were more likely to be smokers (25.7% vs. 8.5%, p < 0.001), were younger at the time of their GD diagnosis (35.0 years vs. 42.0 years, p < 0.001), more commonly had a family history of GD (27.7% vs. 17.2%, p = 0.015), and had higher thyrotropin-binding inhibitor immunoglobulin (TBII) levels at the time of their diagnosis (13.5 IU/L vs. 10.0 IU/L, p = 0.020) than those who did not develop GO. Of the 101 GO patients in the derivation cohort, after excluding 8 who initially had active and moderate-to-severe GO, 11 of the remaining 93 had progressed to more active or severe GO. GO patients with confirmed progression had a higher proportion of those older than 45 years (54.5% vs. 19.8%, p = 0.031), and they had a different initial clinical activity score distribution. The multivariable regression analysis identified age at GD diagnosis, sex, smoking history, family history of GD, total cholesterol level, and TBII level at the time of the diagnosis as significant risk factors of GO occurrence, and a predictive model including these risk factors was built to create a nomogram. Conclusions: The predictors of GO occurrence in patients with new-onset GD were female sex, positive smoking history, young age, family history of GD, high cholesterol level, and high TBII level. The predictive nomogram developed in this study may be useful in patient counseling and facilitating informed treatment decision-making.
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Affiliation(s)
- Hwa Young Ahn
- Department of Internal Medicine, Chung-ang University College of Medicine, Seoul, Korea
| | - Jooyoung Lee
- Department of Applied Statistics, and Chung-ang University College of Medicine, Seoul, Korea
| | - Jeong Kyu Lee
- Department of Ophthalmology, Chung-ang University College of Medicine, Seoul, Korea
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32
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Mehta A, Andrew Awuah W, Yarlagadda R, Kalmanovich J, Huang H, Kundu M, Nansubuga EP, Lopes L, Ghosh B, Hasan MM. Investigating thyroid dysfunction in the context of COVID-19 infection. Ann Med Surg (Lond) 2022; 84:104806. [PMID: 36339111 PMCID: PMC9621589 DOI: 10.1016/j.amsu.2022.104806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Accepted: 10/23/2022] [Indexed: 11/07/2022] Open
Abstract
COVID-19 is a contagious viral infection caused by severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2). One of the key features of COVID-19 infection is inflammation. There is increasing evidence pointing to an association between cytokine storm and autoimmunity. One autoimmune disease of interest in connection to COVID-19 is hyperthyroidism. COVID-19 has been shown to decrease TSH levels and induce thyrotoxicosis, destructive thyroiditis, and de novo Graves' disease. It has also been suggested that the immune response against SARS-CoV-2 antigens following vaccination can cross-react through a mechanism called molecular mimicry which can elicit autoimmune reactivity, potentially leading to potential thyroid disease post vaccine. However, if the COVID-19 vaccine is linked to reduced COVID-19 related serious disease, it could potentially play a protective role against post COVID-19 hyperthyroidism (de novo disease and exacerbations). Further studies investigating the complex interplay between COVID-19 or COVID-19 vaccine and thyroid dysfunction can help provide substantial evidence and potential therapeutic targets that can alter prognosis and improve COVID-19 related outcomes in individuals with or without preexisting thyroid disease.
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Affiliation(s)
- Aashna Mehta
- University of Debrecen-Faculty of Medicine, Debrecen, 4032, Hungary
| | | | - Rohan Yarlagadda
- Rowan University School of Osteopathic Medicine, Stratford, NJ, USA
| | | | - Helen Huang
- Royal College of Surgeons in Ireland, University of Medicine and Health Science, Dublin, Ireland
| | - Mrinmoy Kundu
- Institute of Medical Sciences and SUM Hospital, Bhubaneswar, India
| | | | - Leilani Lopes
- Western University of Health Sciences, College of Osteopathic Medicine of the Pacific-Northwest, Lebanon, OR, USA
| | | | - Mohammad Mehedi Hasan
- Department of Biochemistry and Molecular Biology, Faculty of Life Science, Mawlana Bhashani Science and Technology University, Tangail, Bangladesh
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33
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Xie F, Johnson EF, Youssef MJ. Thyroid Dermopathy and Acropachy. Mayo Clin Proc 2022; 97:2314-2315. [PMID: 36464464 DOI: 10.1016/j.mayocp.2022.08.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 07/31/2022] [Accepted: 08/05/2022] [Indexed: 12/03/2022]
Affiliation(s)
- Fangyi Xie
- Department of Dermatology, Mayo Clinic, Rochester, MN
| | - Emma F Johnson
- Department of Dermatology, Mayo Clinic, Rochester, MN; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | - Molly J Youssef
- Department of Dermatology, Mayo Clinic, Rochester, MN; Department of Pediatrics, Mayo Clinic, Rochester, MN.
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34
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Dottore GR, Lanzolla G, Comi S, Menconi F, Mencacci LC, Dallan I, Marcocci C, Marinò M. Insights into the role of DNA methylation and gene expression in Graves' orbitopathy. J Clin Endocrinol Metab 2022; 108:e160-e168. [PMID: 36334311 DOI: 10.1210/clinem/dgac645] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 09/15/2022] [Accepted: 10/31/2022] [Indexed: 11/08/2022]
Abstract
CONTEXT A role of DNA methylation in Graves' orbitopathy (GO) has been proposed. Design. To investigate DNA methylation and gene expression in orbital fibroblasts from control and GO patients, under basal conditions or following challenge with an anti-TSH receptor antibody (M22) or cytokines involved in GO; to investigate the relationship between DNA methylation and cell function (proliferation); to perform a methylome analysis. Setting. Referral Center. Materials. Orbital fibroblasts from six GO and six control patients. Intervention. None. Main Outcome Measure. Methylome analysis of the whole genome. Results. Global DNA methylation increased significantly both in control and GO fibroblasts upon incubation with M22. Expression of two selected genes (CYP19A1 and AIFM2) was variably affected by M22 and interleukin-6. M22 increased cell proliferation in control and GO fibroblasts, which correlated with global DNA methylation. Methylome analysis revealed 19,869 DNA regions differently methylated in GO fibroblasts, encompassing 3,957 genes and involving CpG islands, shores and shelves. One-hundred and nineteen gene families and subfamilies, 89 protein groups, 402 biological processes and seven pathways were involved. Three genes found to be differentially expressed were concordantly hyper- or hypomethylated. Among the differently methylated genes, insulin-like growth factor-1 receptor and several fibroblast growth factors and receptors were included. CONCLUSIONS We propose that, when exposed to an autoimmune environment, orbital fibroblasts undergo hyper- or hypomethylation of certain genes, involving CpG promoters, which results in differential gene expression, which may be responsible for functional alterations, in particular higher proliferation, and ultimately for the GO phenotype in vivo.
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Affiliation(s)
- Giovanna Rotondo Dottore
- Department of Clinical and Experimental Medicine, Endocrinology Unit II, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy
| | - Giulia Lanzolla
- Department of Clinical and Experimental Medicine, Endocrinology Unit II, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy
| | - Simone Comi
- Department of Clinical and Experimental Medicine, Endocrinology Unit II, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy
| | - Francesca Menconi
- Department of Clinical and Experimental Medicine, Endocrinology Unit II, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy
| | - Lodovica Cristofani Mencacci
- Department of Surgical, Medical and Molecular Pathology, ENT Unit I, University of Pisa and University Hospital of Pisa, Italy, Via Paradisa 2, 56124, Pisa, Italy
| | - Iacopo Dallan
- Department of Surgical, Medical and Molecular Pathology, ENT Unit I, University of Pisa and University Hospital of Pisa, Italy, Via Paradisa 2, 56124, Pisa, Italy
| | - Claudio Marcocci
- Department of Clinical and Experimental Medicine, Endocrinology Unit II, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy
| | - Michele Marinò
- Department of Clinical and Experimental Medicine, Endocrinology Unit II, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy
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Abstract
Graves' orbitopathy (GO) is an orbital autoimmune disorder and the main extrathyroidal manifestation of Graves' disease, the most common cause of hyperthyroidism. GO affects about 30% of Graves' patients, although fewer than 10% have severe forms requiring immunosuppressive treatments. Management of GO requires a multidisciplinary approach. Medical therapies for active moderate-to-severe forms of GO (traditionally, high-dose glucocorticoids) often provide unsatisfactory results, and subsequently surgeries are often needed to cure residual manifestations. The aim of this review is to provide an updated overview of current concepts regarding the epidemiology, pathogenesis, assessment, and treatment of GO, and to present emerging targeted therapies and therapeutic perspectives. Original articles, clinical trials, systematic reviews, and meta-analyses from 1980 to 2021 were searched using the following terms: Graves' disease, Graves' orbitopathy, thyroid eye disease, glucocorticoids, orbital radiotherapy, rituximab, cyclosporine, azathioprine, teprotumumab, TSH-receptor antibody, smoking, hyperthyroidism, hypothyroidism, thyroidectomy, radioactive iodine, and antithyroid drugs. Recent studies suggest a secular trend toward a milder phenotype of GO. Standardized assessment at a thyroid eye clinic allows for a better general management plan. Treatment of active moderate-to-severe forms of GO still relies in most cases on high-dose systemic-mainly intravenous-glucocorticoids as monotherapy or in combination with other therapies-such as mycophenolate, cyclosporine, azathioprine, or orbital radiotherapy-but novel biological agents-including teprotumumab, rituximab, and tocilizumab-have achieved encouraging results.
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Affiliation(s)
- Luigi Bartalena
- Department of Medicine and SurgeryUniversity of InsubriaVareseItaly
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Califaretti E, Dall'armellina S, Rovera G, Finessi M, Deandreis D. The role of PET/CT in thyroid autoimmune diseases. THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING : OFFICIAL PUBLICATION OF THE ITALIAN ASSOCIATION OF NUCLEAR MEDICINE (AIMN) [AND] THE INTERNATIONAL ASSOCIATION OF RADIOPHARMACOLOGY (IAR), [AND] SECTION OF THE SOCIETY OF... 2022; 66:218-228. [PMID: 35612371 DOI: 10.23736/s1824-4785.22.03464-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Autoimmune thyroid diseases (AITD) are a heterogeneous group of disorders. They include, in particular, Graves' disease and Hashimoto's thyroiditis with a wide range of different functional status ranging from subclinical biochemical abnormalities to severe hyperthyroidism or severe hypothyroidism respectively. Furthermore, other conditions more frequently infectious or drug related can cause an immune reaction in the thyroid tissue. In AITDs, positron emission tomography/computed tomography (PET/CT) does not play a primary role for disease diagnosis or management, but accidental findings can occur in both symptomatic and asymptomatic patients, and they should be recognized and well interpreted. A comprehensive literature search of the PubMed databases was conducted to identify papers (systematic review, prospective and retrospective study, case report) evaluating the role of PET/CT in thyroid autoimmune diseases. Thyroid diffuse uptake of 18F-fluoro-2-deoxy-2-d-glucose ([18F]FDG) has been shown to be frequently associated with AITDs, but also with immune-induced thyroid disorders related to SARS-CoV-2 or immunotherapy, while malignant lesions more often have a focal aspect. Other radiopharmaceuticals as [68Ga]-DOTA-peptides, [68Ga]-fibroblast activation protein inhibitors (FAPIs) and [68Ga]-prostate specific membrane antigen ([68Ga]-PSMA) showed similar findings. In conclusion, PET/CT scan in AITDs does not play a primary role in the diagnosis, but the occasional finding of a thyroid uptake must always be described in the report and possibly investigated for a better patient's management.
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Affiliation(s)
- Elena Califaretti
- Unit of Nuclear Medicine, Department of Medical Sciences, Città della Salute e della Scienza, University of Turin, Turin, Italy
| | - Sara Dall'armellina
- Unit of Nuclear Medicine, Department of Medical Sciences, Città della Salute e della Scienza, University of Turin, Turin, Italy
| | - Guido Rovera
- Unit of Nuclear Medicine, Department of Medical Sciences, Città della Salute e della Scienza, University of Turin, Turin, Italy
| | - Monica Finessi
- Unit of Nuclear Medicine, Department of Diagnostic Imaging and Interventional Radiology, Città della Salute e della Scienza, Turin, Italy -
| | - Désirée Deandreis
- Unit of Nuclear Medicine, Department of Medical Sciences, Città della Salute e della Scienza, University of Turin, Turin, Italy
- Unit of Nuclear Medicine, Department of Diagnostic Imaging and Interventional Radiology, Città della Salute e della Scienza, Turin, Italy
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Dauguet M, Abba S, Lebrun-Vignes B, Vignes S. Des lésions végétantes des jambes. Rev Med Interne 2022; 43:450-451. [DOI: 10.1016/j.revmed.2022.03.340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Revised: 03/20/2022] [Accepted: 03/22/2022] [Indexed: 10/18/2022]
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Bartalena L, Piantanida E, Gallo D, Ippolito S, Tanda ML. Management of Graves' hyperthyroidism: present and future. Expert Rev Endocrinol Metab 2022; 17:153-166. [PMID: 35287535 DOI: 10.1080/17446651.2022.2052044] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Accepted: 03/08/2022] [Indexed: 10/18/2022]
Abstract
INTRODUCTION Graves' disease (GD) is an autoimmune disorder due to loss of tolerance to the thyrotropin receptor (TSHR) and ultimately caused by stimulatory TSHR antibodies (TSHR-Ab). GD may be associated with extrathyroidal manifestations, mainly Graves' orbitopathy. Treatment of GD relies on antithyroid drugs (ATDs), radioactive iodine (RAI), thyroidectomy. The major ATD limitation is the high recurrence rate after treatment. The major drawback of RAI and thyroidectomy is the inevitable development of permanent hypothyroidism. AREAS COVERED Original articles, clinical trials, systematic reviews, meta-analyses from 1980 to 2021 were searched using the following terms: Graves' disease, management of Graves' disease, antithyroid drugs, radioactive iodine, thyroidectomy, Graves' orbitopathy, thyroid-eye disease. EXPERT OPINION ATDs are the first-line treatment worldwide, are overall safe and usually given for 18-24 months, long-term treatment may decrease relapses. RAI is safe, although associated with a low risk of GO progression, particularly in smokers. Thyroidectomy requires skilled and high-volume surgeons. Patients play a central role in the choice of treatment within a shared decision-making process. Results from targeted therapies acting on different steps of the autoimmune process, including iscalimab, ATX-GD-59, rituximab, blocking TSHR-Ab, small molecules acting as antagonists of the TSHR, are preliminary or preclinical, but promising in medium-to-long perspective.
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Affiliation(s)
- Luigi Bartalena
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Eliana Piantanida
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Daniela Gallo
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Silvia Ippolito
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Maria Laura Tanda
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
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Rajabi MT, Rafizadeh SM, Mohammadi A, Eshraghi B, Mohammadi N, Hosseini SS, Rajabi MB, Keshmirshekan MM, Shahriari M, Poursayed Lazarjani SZ, Parandin MM. Mycophenolate Mofetil (CellCept®) in Combination With Low Dose Prednisolone in Moderate to Severe Graves' Orbitopathy. Front Med (Lausanne) 2022; 9:788228. [PMID: 35223896 PMCID: PMC8873183 DOI: 10.3389/fmed.2022.788228] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 01/17/2022] [Indexed: 11/17/2022] Open
Abstract
Although corticosteroids are currently the first-choice drug for thyroid eye disease (TED), in 20–30% of cases, patients show poor or non-existent responses, and when the drug is withdrawn, 10–20% of patients relapse. Thus, in this study, we aimed to investigate the efficacy of the combined use of mycophenolate mofetil (CellCept®) and low dose oral prednisolone in patients with moderate to severe Graves' orbitopathy (GO). For the first time, we investigated the relationship between TED-related parameters and proptosis reduction. In a prospective, non-randomized, interventional case series, 242 patients with moderate-to-severe GO were, assigned to receive oral prednisolone (5 mg/ d) and mycophenolate mofetil (CellCept®) (one 500 mg tablet twice per day according to the therapeutic response). The patients were monitored regularly during the 3rd, 6th, 12th, and 18th month of treatment. The main outcome measures were the clinical activity score (CAS), intraocular pressure (IOP), diplopia, proptosis and visual acuity. We also assessed the relationship between the main outcomes with proptosis changes and time to improvement (months). Adverse effects were recorded during each visit. The clinical response rate increased from 67.7% on the third month to 89.2% on the sixth month, and 94.2% on the 12th month. This therapeutic response continued until the 18th month of follow-up. The CAS responses [disease inactivation (CAS <3)] improved during our study: 70.6% on the third month, 90.0% on the sixth month, and 92.5% at 12th month. These conditions continued until the 18th month of follow-up. Proptosis improvement was 52% on the third month, 71% on the sixth month, 83% on the 12th month, and 87.1% on the 18th month. Changes in IOP and visual acuity were not significant (P = 0.568 and 0.668, respectively). The patient showed significant improvement in the Gorman score. A Shorter duration of treatment was seen in patients with earlier onset of intervention, younger age, and lack of all extraocular muscle (EOM) enlargement on computed tomography (CT) scan (p < 0.05). In addition, a better response (more reduction) in proptosis was related to: younger age at disease, earlier treatment intervention (less interval from the time the diagnosis of moderate-to-severe GO was made until medication initiation), shorter treatment time (less time to improvement), less IOP, lack of EOM enlargement on CT scan, and lack of diplopia (P < 0.05). Adverse events occurred in six patients. Findings show that mycophenolate mofetil (CellCept®) plus low-dose prednisolone can be introduced as a new optimal dosing regimen in GO due to its better effect on chronic complications such as proptosis and diplopia.
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Affiliation(s)
- Mohammad Taher Rajabi
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Mohsen Rafizadeh
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Abbas Mohammadi
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
- *Correspondence: Abbas Mohammadi ; orcid.org/0000-0001-7295-8494
| | - Bahram Eshraghi
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Nader Mohammadi
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Mohammad Bagher Rajabi
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Mansoor Shahriari
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyedeh Zahra Poursayed Lazarjani
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
- Department of Eye, Eye Research Center, Amiralmomenin Hospital, School of Medicin, Guilan University of Medical Science, Rasht, Iran
| | - Mohammad Mehdi Parandin
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
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The Role of Oxidative Stress and Therapeutic Potential of Antioxidants in Graves' Ophthalmopathy. Biomedicines 2021; 9:biomedicines9121871. [PMID: 34944687 PMCID: PMC8698567 DOI: 10.3390/biomedicines9121871] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 12/04/2021] [Accepted: 12/07/2021] [Indexed: 12/22/2022] Open
Abstract
Graves’ ophthalmopathy (GO) is the most common extrathyroidal manifestation of Graves’ disease. It is characterized initially by an inflammatory process, followed by tissue remodeling and fibrosis, leading to proptosis, exposure keratopathy, ocular motility limitation, and compressive optic neuropathy. The pathogenic mechanism is complex and multifactorial. Accumulating evidence suggests the involvement of oxidative stress in the pathogenesis of GO. Cigarette smoking, a major risk factor for GO, has been shown to induce reactive oxygen species (ROS) generation and oxidative damage in GO orbital fibroblasts. In addition, an elevation in ROS and antioxidant enzymes is observed in tears, blood, and urine, as well as orbital fibroadipose tissues and fibroblasts from GO patients. In vitro and in vivo studies have examined the efficacy of various antioxidant supplements for GO. These findings suggest a therapeutic role of antioxidants in GO patients. This review summarizes the current understanding of oxidative stress in the pathogenesis and potential antioxidants for the treatment of GO.
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Lui DTW, Lee KK, Lee CH, Lee ACH, Hung IFN, Tan KCB. Development of Graves' Disease After SARS-CoV-2 mRNA Vaccination: A Case Report and Literature Review. Front Public Health 2021; 9:778964. [PMID: 34888290 PMCID: PMC8650637 DOI: 10.3389/fpubh.2021.778964] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 11/02/2021] [Indexed: 01/14/2023] Open
Abstract
Background: Mounting evidence has revealed the interrelationship between thyroid and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to explain the thyroid dysfunction and autoimmune thyroid disorders observed after coronavirus disease 2019 (COVID-19). There are limited reports of thyroid dysfunction after SARS-CoV-2 vaccination. Methods: We report a case of a 40-year-old Chinese woman who developed Graves' disease after BNT162b2 mRNA vaccine. A search of PubMed and Embase databases from 1 September 2019 to 31 August 2021 was performed using the following keywords: "COVID," "vaccine," "thyroid," "thyroiditis," and "Graves." Results: A 40-year-old Chinese woman who had 8-year history of hypothyroidism requiring thyroxine replacement. Her anti-thyroid peroxidase and anti-thyroglobulin antibodies were negative at diagnosis. She received her first and second doses of BNT162b2 mRNA vaccine on 6 April and 1 May 2021, respectively. She developed thyrotoxicosis and was diagnosed to have Graves' disease 5 weeks after the second dose of vaccine, with positive thyroid stimulating immunoglobulin level, diffuse goiter with hypervascularity on thyroid ultrasonography and diffusely increased thyroid uptake on technetium thyroid scan. Both anti-thyroid peroxidase and anti-thyroglobulin antibodies became positive. She was treated with carbimazole. Literature search revealed four cases of Graves' disease after SARS-CoV-2 vaccination, all after mRNA vaccines; and nine cases of subacute thyroiditis, after different types of SARS-CoV-2 vaccines. Conclusion: Our case represents the fifth in the literature of Graves' disease after SARS-CoV-2 vaccination, with an unusual presentation on a longstanding history of hypothyroidism. Clinicians should remain vigilant about potential thyroid dysfunction after SARS-CoV-2 vaccination in the current pandemic.
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Affiliation(s)
| | | | | | | | | | - Kathryn Choon Beng Tan
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong SAR, China
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Lanzolla G, Sabini E, Leo M, Menconi F, Rocchi R, Sframeli A, Piaggi P, Nardi M, Marcocci C, Marinò M. Statins for Graves' orbitopathy (STAGO): a phase 2, open-label, adaptive, single centre, randomised clinical trial. Lancet Diabetes Endocrinol 2021; 9:733-742. [PMID: 34592164 DOI: 10.1016/s2213-8587(21)00238-2] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 08/06/2021] [Accepted: 08/06/2021] [Indexed: 12/21/2022]
Abstract
BACKGROUND A protective action of statins on development of Graves' orbitopathy suggests that statins might be used for treatment of the disease. We aimed to assess the efficacy of the addition of a statin, atorvastatin, to intravenous glucocorticoids (ivGCs) on Graves' orbitopathy outcomes in patients with hypercholesterolaemia. METHODS We did a randomised, open-label, phase 2, adaptive, clinical trial at a single, tertiary, referral hospital in Pisa, Italy. Patients with moderate-to-severe, active Graves' orbitopathy, with a low-density lipoprotein cholesterol concentration between 2·97 and 4·88 mmol/L were eligible for inclusion. Patients were randomly assigned (1:1) in 11 blocks of eight, using a computer-based system, to the ST group or the NST group. The ST group received ivGCs (methylprednisolone 500 mg once a week for 6 weeks followed by 250 mg once a week for an additional six weeks) for 12 weeks and oral atorvastatin (20 mg once a day) for 24 weeks. The NST group only received the ivGC regimen. Patients were unmasked to group allocation; however, the ophthalmological investigator was masked to randomisation. The primary endpoint was the Graves' orbitopathy outcome (composite evaluation of exophthalmos, clinical activity score, eyelid aperture, and diplopia) at 24 weeks in the modified intention-to-treat (ITT) population (patients who attended the week 12 visit). Patients were considered responders when at least two of the following criteria were fulfilled in the most affected eye, without worsening in any of the same measures in both eyes: (1) reduction in exophthalmos of 2 mm or more, with no increase by 2 mm or more in the other eye; (2) reduction of clinical activity score by two or more points; (3) reduction in eyelid aperture by 2 mm or more, with no increase by 2 mm or more in the other eye; and (4) disappearance or improvement (change from constant to inconstant, intermittent, or absent, or from inconstant to intermittent or absent) of diplopia, and (5) improvement in visual acuity by 0·2 decimals or more. The trial is registered with EUDRACT, 2018-001317-33, and ClinicalTrials.gov, NCT03110848. FINDINGS Between June 1, 2020, and Nov 30, 2020, 119 patients were screened for inclusion, of whom 88 (74%) patients were enrolled and randomly assigned to one of the two treatment groups (44 [50%] to the ST group and 44 [50%] to the NST group). Eight (9%) patients did not attend the 12 week visit; 80 (91%) patients (18 [23%] men and 62 [78%] women) were included in the modified ITT population (41 [51%] in the ST group and 39 [49%] in the NST group]. The proportion of Graves' orbitopathy composite evaluation responders at 24 weeks was higher in the ST group (21 [51%] of 41 patients) than the NST group (11 [28%] of 39 patients; attributable risk 0·23 [95% CI 0·02-0·44]; p=0·042). 26 adverse events occurred in 21 (24%) of 88 patients in the safety population. One (2%) of 44 patients in each group required treatment discontinuation, with no serious adverse events and no difference between groups. INTERPRETATION Addition of oral atorvastatin to an ivGC regimen improved Graves' orbitopathy outcomes in patients with moderate-to-severe, active eye disease who were hypercholesterolaemic. Future phase 3 studies, which could potentially recruit patients regardless of low-density lipoprotein cholesterol concentration, are required to confirm this association. FUNDING Associazione Allievi Endocrinologia Pisana.
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Affiliation(s)
- Giulia Lanzolla
- Department of Clinical and Experimental Medicine, Endocrinology Units, University of Pisa and University Hospital of Pisa, Pisa, Italy
| | - Elena Sabini
- Department of Clinical and Experimental Medicine, Endocrinology Units, University of Pisa and University Hospital of Pisa, Pisa, Italy
| | - Marenza Leo
- Department of Clinical and Experimental Medicine, Endocrinology Units, University of Pisa and University Hospital of Pisa, Pisa, Italy
| | - Francesca Menconi
- Department of Clinical and Experimental Medicine, Endocrinology Units, University of Pisa and University Hospital of Pisa, Pisa, Italy
| | - Roberto Rocchi
- Department of Clinical and Experimental Medicine, Endocrinology Units, University of Pisa and University Hospital of Pisa, Pisa, Italy
| | - Angela Sframeli
- Department of Surgical, Medical and Molecular Pathology, Ophthalmopathy Unit I, University of Pisa and University Hospital of Pisa, Pisa, Italy
| | - Paolo Piaggi
- Department of Information Engineering, University of Pisa and University Hospital of Pisa, Pisa, Italy
| | - Marco Nardi
- Department of Surgical, Medical and Molecular Pathology, Ophthalmopathy Unit I, University of Pisa and University Hospital of Pisa, Pisa, Italy
| | - Claudio Marcocci
- Department of Clinical and Experimental Medicine, Endocrinology Units, University of Pisa and University Hospital of Pisa, Pisa, Italy
| | - Michele Marinò
- Department of Clinical and Experimental Medicine, Endocrinology Units, University of Pisa and University Hospital of Pisa, Pisa, Italy.
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Sacristán-Gómez P, Serrano-Somavilla A, González-Amaro R, Martínez-Hernández R, Marazuela M. Analysis of Expression of Different Histone Deacetylases in Autoimmune Thyroid Disease. J Clin Endocrinol Metab 2021; 106:3213-3227. [PMID: 34272941 PMCID: PMC8530745 DOI: 10.1210/clinem/dgab526] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Indexed: 11/19/2022]
Abstract
CONTEXT Histone deacetylases (HDACs) and histone acetyltransferases (HAT) have an important role in the regulation of gene transcription as well as in the development and function of CD4+Foxp3+ T regulatory (Treg) cells. Our group and others have reported that patients with autoimmune thyroid disease (AITD) show abnormalities in the levels and function of different Treg cell subsets. OBJECTIVE We aimed to analyze the levels of expression of several HDACs and the Tip60 HAT in the thyroid gland and immune cells from patients with AITD. METHODS The expression of HDAC1-11 and the Tip60 HAT, at RNA and protein levels, were determined in thyroid tissue from 20 patients with AITD and 10 healthy controls and these findings were correlated with clinical data. HDAC9 and Tip60 levels were also analyzed in thyroid cell cultures, stimulated or not with proinflammatory cytokines, as well as in different cell subsets from peripheral blood mononuclear cells. RESULTS Altered expression of different HDACs was observed in thyroid tissue from AITD patients, including a significant increase in HDAC9, at RNA and protein levels. Likewise, HDAC9 expression was increased in peripheral blood mononuclear cells particularly in Treg cells in patients with AITD. In contrast, Tip60 expression was reduced in thyroid gland samples from patients with Hashimoto thyroiditis. CONCLUSION Our results indicate that HDAC expression is dysregulated in thyroid gland and immune cells from patients with AITD, suggesting involvement in the pathogenesis of this condition.
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Affiliation(s)
- Pablo Sacristán-Gómez
- Department of Endocrinology, Hospital Universitario de la Princesa, Instituto de Investigación Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER GCV14/ER/12), Madrid, Spain
| | - Ana Serrano-Somavilla
- Department of Endocrinology, Hospital Universitario de la Princesa, Instituto de Investigación Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER GCV14/ER/12), Madrid, Spain
| | - Roberto González-Amaro
- Department of Immunology, School of Medicine, UASLP, 78210 San Luis Potosí, SLP, Mexico
- Center for Applied Research in Health and Biomedicine, UASLP, 78210 San Luis Potosí, SLP, Mexico
| | - Rebeca Martínez-Hernández
- Department of Endocrinology, Hospital Universitario de la Princesa, Instituto de Investigación Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER GCV14/ER/12), Madrid, Spain
- Rebeca Martínez-Hernández, PhD, Hospital de la Princesa, C/ Diego de León 62, 28006 Madrid, Spain.
| | - Mónica Marazuela
- Department of Endocrinology, Hospital Universitario de la Princesa, Instituto de Investigación Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER GCV14/ER/12), Madrid, Spain
- Correspondence: Monica Marazuela, MD, PhD, Hospital de la Princesa, C/ Diego de León 62, 28006 Madrid, Spain.
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Kurihara M, Kinjo S, Tokuda Y. Rare presentation of Graves' disease with myalgia: A case report. Clin Case Rep 2021; 9:e04629. [PMID: 34646557 PMCID: PMC8499851 DOI: 10.1002/ccr3.4629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Revised: 06/21/2021] [Accepted: 07/06/2021] [Indexed: 11/30/2022] Open
Abstract
A 42-year-old woman presented with myalgia, which ameliorated a week after treatment. She was diagnosed with Graves' disease. The presence of concomitant autoimmune diseases is important considerations for patients with Graves' disease presenting with myalgia. Thyrotoxicosis should be included as a rare differential diagnosis for myalgia.
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Affiliation(s)
- Masaru Kurihara
- Department of Hospital MedicineUrasoe General HospitalOkinawaJapan
| | - Shunichi Kinjo
- Department of Hospital MedicineUrasoe General HospitalOkinawaJapan
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Mir SUI, Laway BA. Elephantiatic Graves' Dermopathy Successfully Treated with Intralesional Steriod. Indian J Endocrinol Metab 2021; 25:471-472. [PMID: 35300437 PMCID: PMC8923328 DOI: 10.4103/ijem.ijem_367_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 10/18/2021] [Indexed: 11/16/2022] Open
Affiliation(s)
- Sajad Ul Islam. Mir
- Department of Endocrinology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
| | - Bashir A. Laway
- Department of Endocrinology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
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Ippolito S, Cusini C, Lasalvia P, Gianfagna F, Veronesi G, Gallo D, Masiello E, Premoli P, Sabatino J, Mercuriali A, Lai A, Piantanida E, Tanda ML, Bartalena L. Change in newly diagnosed Graves' disease phenotype between the twentieth and the twenty-first centuries: meta-analysis and meta-regression. J Endocrinol Invest 2021; 44:1707-1718. [PMID: 33346898 PMCID: PMC8285314 DOI: 10.1007/s40618-020-01479-z] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Accepted: 11/09/2020] [Indexed: 12/11/2022]
Abstract
PURPOSE According to a few recent studies, the clinical phenotype of Graves' disease (GD) at onset is becoming milder in recent years, in terms of prevalence and severity of hyperthyroidism, goiter and overt eye disease. The aim of this study was to assess the change in GD phenotype across the late twentieth and the early twenty-first centuries. MATERIALS AND METHODS We carried out a systematic search of studies published between 1/1/1980 and 12/31/2017 describing naïve GD patients at diagnosis. We collected epidemiological, clinical, biochemical and serological data reported in the selected studies, and (1) conducted a single-arm meta-analysis to compare clinical and biochemical characteristics of naïve GD patients before and after year 2000 and (2) performed a meta-regression to identify the trend of the observed clinical presentations. RESULTS Eighty selected articles were related to the period before the year 2000, 30 to the years 2000-2017. According to demographics, the two defined populations were homogeneous at meta-analysis: overall estimated female prevalence was 81% [95% CI 79-82], mean estimated age of the entire population was 39.8 years [95% CI 38.4-41.1], with no significant differences between pre- and post-2000 groups (p > 0.05). The overall estimated prevalence of smokers was 40% [95% CI 33-46], with no significant difference between the two groups (p > 0.05). Mean estimated free thyroxine (FT4) and free triiodothyronine (FT3) levels at diagnosis were higher in the pre-2000 group: 4.7 ng/dl [95% CI 4.5-4.9] for FT4 and 14.2 pg/ml [95% CI 13.3-15.1] for FT3, as compared to the post-2000 group: 3.9 ng/dl [95% CI 3.6-4.2] for FT4 and 12.1 pg/ml [95% CI 11.0-13.3] for FT3 (all p < 0.01). Goiter estimated prevalence was higher in the pre-2000 group, 87% [95% CI 84-90], than in the post-2000 group, 56% [95% CI 45-67]. Estimated prevalence for Graves' Orbitopathy (GO) was 34% [95% CI 27-41] in the pre-2000 group and 25% [95% CI 19-30] in the post-2000 group (p = 0.03). Accordingly, meta-regression adjusted for covariates showed an average annual reduction of FT4 (- 0.040 ± 0.008 ng/dl, p < 0.0001), FT3 (- 0.316 ± 0.019 pg/ml, p < 0.0001), goiter prevalence (- 0.023 ± 0.008%, p = 0.006), and goiter size (- 0.560 ± 0.031 ml, p < 0.0001). CONCLUSIONS Our meta-analysis and meta-regression confirmed that GD phenotype at diagnosis is nowadays milder than in the past; we hypothesize that conceivable factors involved in this change are iodoprophylaxis, worldwide decrease in smoking habits, larger use of contraceptive pill and micronutrient supplementation, as well as earlier diagnosis and management.
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Affiliation(s)
- S Ippolito
- Department of Medicine and Surgery, University of Insubria, 21100, Varese, Italy
| | - C Cusini
- Department of Medicine and Surgery, University of Insubria, 21100, Varese, Italy
| | - P Lasalvia
- Research Centre in Epidemiology and Preventive Medicine (EPIMED), University of Insubria, 21100, Varese, Italy
| | - F Gianfagna
- Research Centre in Epidemiology and Preventive Medicine (EPIMED), University of Insubria, 21100, Varese, Italy
- Mediterranea Cardiocentro, 80122, Napoli, Italy
| | - G Veronesi
- Research Centre in Epidemiology and Preventive Medicine (EPIMED), University of Insubria, 21100, Varese, Italy
| | - D Gallo
- Department of Medicine and Surgery, University of Insubria, 21100, Varese, Italy
| | - E Masiello
- Department of Medicine and Surgery, University of Insubria, 21100, Varese, Italy
| | - P Premoli
- Department of Medicine and Surgery, University of Insubria, 21100, Varese, Italy
| | - J Sabatino
- Department of Medicine and Surgery, University of Insubria, 21100, Varese, Italy
| | - A Mercuriali
- Department of Medicine and Surgery, University of Insubria, 21100, Varese, Italy
| | - A Lai
- Department of Medicine and Surgery, University of Insubria, 21100, Varese, Italy
| | - E Piantanida
- Department of Medicine and Surgery, University of Insubria, 21100, Varese, Italy
| | - M L Tanda
- Department of Medicine and Surgery, University of Insubria, 21100, Varese, Italy
| | - L Bartalena
- Department of Medicine and Surgery, University of Insubria, 21100, Varese, Italy.
- Department of Medicine and Surgery, University of Insubria, Endocrine Unit, ASST dei Sette Laghi, Viale L. Borri, 57, 21100, Varese, Italy.
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Du T, Jiang W, Luo H, Chen F, Yuan G, Zhang M, Liu Z. Bilateral breast myxedema caused by Graves' disease and responsive to multipoint subcutaneous injection of long-acting glucocorticoid: Case report. Medicine (Baltimore) 2021; 100:e26469. [PMID: 34160454 PMCID: PMC8238392 DOI: 10.1097/md.0000000000026469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Accepted: 06/07/2021] [Indexed: 01/04/2023] Open
Abstract
RATIONALE With the absence of ophthalmopathy, thyroid dermopathy especially lesions at atypical locations is a very rare presentation. We herein report an original case of bilateral breast myxedema caused by Grave's disease. PATIENT CONCERNS A 21-year-old unmarried woman presented with a 4-month history of Grave's disease and a 1-month history of progressive bilateral breast enlargement. She had symmetrical bilateral breast enlargement with redness and nonpitting thickening of the skin, diffusely enlarged thyroid glands, and no exophthalmos. DIAGNOSIS Ultrasonography, magnetic resonance imaging scan, and skin biopsy confirmed the diagnosis of bilateral breast myxedema. INTERVENTIONS The patient was treated with multipoint subcutaneous injections of triamcinolone acetonide in each breast every month. OUTCOMES The bilateral breast returned approximately to its normal size after therapy for 6 months. CONCLUSIONS Our case illustrates that multipoint subcutaneous injection of glucocorticoids is beneficial for bilateral breast myxedema.
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Affiliation(s)
- Tingting Du
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, Branch of National Clinical Research Center for Metabolic Disease, Hubei
| | - Wangyan Jiang
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, Branch of National Clinical Research Center for Metabolic Disease, Hubei
| | - Hongchang Luo
- Department of Ultrasonography, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fuqiong Chen
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, Branch of National Clinical Research Center for Metabolic Disease, Hubei
| | - Gang Yuan
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, Branch of National Clinical Research Center for Metabolic Disease, Hubei
| | - Muxun Zhang
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, Branch of National Clinical Research Center for Metabolic Disease, Hubei
| | - Zhelong Liu
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, Branch of National Clinical Research Center for Metabolic Disease, Hubei
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Chen X, Dong J, Zhang L, Zhao X, Shi R, Pan M, Zheng J. Local immune microenvironment of skin may play an important role in the development of pretibial myxedema. Exp Dermatol 2021; 30:1820-1824. [PMID: 34047397 PMCID: PMC8597019 DOI: 10.1111/exd.14402] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 05/02/2021] [Accepted: 05/20/2021] [Indexed: 01/26/2023]
Abstract
Pretibial myxedema (PTM), characterized by the accumulation of glycosaminoglycans in dermis is an autoimmune skin disorder, which is almost always associated with Graves’ disease (GD). Although fibroblast stimulated by thyroid‐stimulating hormone receptor (TSHR) antibody, cytokines and growth factors have been postulated as target of the autoimmune process in the dermopathy, the pathogenesis of PTM remains unclear. We hypothesize that the local immune microenvironment of the skin including the antigens and antibodies, T cells, B cells, plasma cells and fibroblasts may play an important role in the development of PTM. Results obtained on PTM patients indicate increased thyroid‐stimulating hormone receptor antibodies (TRAb) in the blood positively correlate with the dermal thickness of the lesions. Further analysis shows that there were more CD3+ T cells and CD20+ B cells in the skin lesions. These T and B cells are in close contact, indicating that inducible skin‐associated lymphoid tissue (iSALT) may be formed in the area. In addition, we found that the infiltrating plasma cells can secrete TRAb, proving that B cells in the skin other than the thyroid are an additional source of TSHR antibodies. Meanwhile, the T and B cells in the skin or skin homogenate of patients can promote the proliferation of pretibial fibroblasts. In conclusion, our results provide evidence that the local immune microenvironment of the skin may play an important role in the development of PTM.
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Affiliation(s)
- Xiaoying Chen
- Department of Dermatology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiaoyun Dong
- Department of Burn, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Li Zhang
- Department of Dermatology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoqing Zhao
- Department of Dermatology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ruofei Shi
- Department of Dermatology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Meng Pan
- Department of Dermatology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jie Zheng
- Department of Dermatology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Smoking effect on peripapillary and macular microvascular structure in inactive Graves' ophthalmopathy. Int Ophthalmol 2021; 41:3411-3417. [PMID: 34019189 DOI: 10.1007/s10792-021-01904-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 05/14/2021] [Indexed: 10/21/2022]
Abstract
OBJECTIVE The aim of this study was to evaluate the smoking effect on peripapillary and macular microvascular structure in patients with inactive Graves' ophthalmopathy (GO) and to compare these structures with those of healthy control subjects. METHODS A total of 34 healthy participants (control group), 22 inactive GO patients with smoking (smoker group) and 19 inactive GO patients with non-smoking (non-smoker group) were recruited in this prospective study. After detailed ophthalmological examination, vessel densities (VD) of the superficial capillary plexus (SCP), deep capillary plexus (DCP), retinal peripapillary capillary (RPC) and foveal avascular zone (FAZ) area, and acircularity index (AI) of the FAZ were analysed with optical coherence tomography angiography (OCTA) for each eye. RESULTS Vessel density in the total peripapillary; superior and inferior sectors of RPC were significantly lower in inactive GO patients with smoking (p < 0.05 for all sectors) compared to control group. Besides, the FAZ AI was significantly higher in smoker and non-smoker inactive GO groups compared to healthy subjects (p = 0.0001, p = 0.0001, respectively). No significant difference was found in the FAZ area, and all SCP, DCP macular measurements between groups (p > 0.05 for all). CONCLUSION OCTA findings of lower peripapillary VD in the smoker group show smoking effect on the optic disc head microvasculature in inactive GO patients. These results could reflect early subclinical optic disc vasculature damage in smoker inactive GO subjects.
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Changes in the Ocular Parameters of Patients with Graves' Disease after Antithyroid Drug Treatment. ACTA ACUST UNITED AC 2021; 57:medicina57050414. [PMID: 33922887 PMCID: PMC8146600 DOI: 10.3390/medicina57050414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 04/16/2021] [Accepted: 04/22/2021] [Indexed: 11/24/2022]
Abstract
Background and Objectives: To find the differences in ocular axial length, keratometric measurements, and intraocular lens (IOL) power in patients with Graves’ disease (GD) after treatment with a thionamide antithyroid drug (ATD), methimazole. Materials and Methods: The medical charts of 28 patients (4 males and 24 females; mean age: 47.2 ± 21.2 years) were studied. Each patient was examined twice using an IOL Master Device and keratometry at the first visit (before ATD treatment) and after 1 month of ATD treatment. The IOL power was calculated for each patient using the Hoffer Q, SRK-2, and SRK/T formulas according to axial length. Results: After 1 month, the axial length increased (right and left eyes: p < 0.001 and p = 0.05, respectively). Based on keratometry, changes in the horizontal and vertical optical power [in diopters (D)] were not statistically significant. However, the IOL power changed after 1 month of ATD treatment in 64.3% of the patients. In 14 patients (50%), there was a 0.5–1.0 D IOL power decrease in single eyes; in two patients (7.1%), an IOL power decrease of 0.5–1.0 D in both eyes; and in two patients (7.1%), a 0.5 D IOL power increase in single eyes. The calculated IOL power values were lower after ATD treatment (right and left eyes, p = 0.010 and p = 0.018, respectively). Conclusions: The IOL power changed in 64.3% of GD patients after ATD treatment. Therefore, avoiding cataract surgery at the early stage of ATD treatment would be appropriate for selecting a more accurate IOL power.
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