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Usenko OY, Khomenko IP, Kovalenko AE, Saliutin RV. Stress and surgical diseases of thyroid gland in environment of the armed conflict (review of literature and own observations). KLINICHESKAIA KHIRURGIIA 2022. [DOI: 10.26779/2522-1396.2022.3-4.73] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Stress and surgical diseases of thyroid gland in environment of the armed conflict (review of literature and own observations)
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Zhu X, Zhang Y, Zhao X, Zhang X, Ru Z, Wu Y, Yang X, Hou B, Qiao H. The relationship between atherosclerotic disease and relapse during ATD treatment. Front Cardiovasc Med 2022; 9:1039829. [DOI: 10.3389/fcvm.2022.1039829] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 09/29/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundClinical relapse is a potential risk for traditional antithyroid drug (ATD) treatment in hyperthyroid patients. Evidence suggests that atherosclerotic disease is closely associated with hyperthyroidism, while the relationship between atherosclerosis and relapse remains unclear.MethodsTwo hundred and twenty-five patients with GD who underwent ATD as their first treatment were studied; 88 and 137 patients were categorized as drug reduction relapse and drug reduction remission, respectively. Logistic regression was used to analyze risk factors of drug reduction relapse in patients with GD.ResultsDuring a median of 48 months followed up 88 patients who relapsed. According to multivariate analyses, atherosclerosis related diseases, FT4, goiter, and anxiety rating scores are independent risk factors for drug reduction. According to K-M survival analysis, patients with atherosclerosis related diseases, FT4 > 18.82 pmol/L, anxiety rating scores > 23, and gradation of goiter ≥ Grade II had a higher risk of relapse than those with lower levels. ROC analysis shown atherosclerosis related diseases significantly improved the predictive accuracy of relapse.ConclusionsAtherosclerotic disease is closely related to the relapse of hyperthyroidism, ATD treatment in hyperthyroid patients with atherosclerosis should be given more attention.
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Wang H, Liu Y, Zhao Y. The association of hepatitis C virus infection and thyroid disease: A systematic review and meta-analysis. Int J Biol Markers 2021; 36:3-9. [PMID: 34825832 DOI: 10.1177/17246008211056959] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Previous studies have reported that hepatitis C virus (HCV) infection may increase the risk of thyroid disease (TD) even thyroid cancer (TC), but quantitative assessments of risk were rare and the results were not consistent. The purpose of this study was to evaluate the impact of HCV infection on TD and TC, and provide clues to explore the relationship between HCV infection and TD and TC. The literature retrieval was performed up to August 20th, 2021 in the database of PubMed, Cochrane library, Web of Science, China National Knowledge Infrastructure and Wang Fang. The risk of HCV for TD or TC was expressed with odds ratio (OR) and 95% confidence intervals (CI). Subgroup analysis was used to explore the source of heterogeneity. Six articles (three studies published as article and three studies published as abstract) were included in this meta-analysis, with a total of 5398 controls and 1925 cases of hepatitis C. The results of meta-analysis found that HCV infection were significantly associated with an increased risk of TD (sum OR = 1.80, 95% CI = 1.54-2.10, P < 0.001, I2 = 74.3%) and TC (sum OR = 16.36, 95% CI = 4.65-57.62, P < 0.001, I2 = 0%). HCV infection may increase the risk of TD and TC. More work is needed in the future to establish a causal role, however an awareness of the possibility of increased risk of TD and TC may lead to earlier diagnosis and better outcomes in patients with hepatitis C.
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Affiliation(s)
- Hongpeng Wang
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, China
| | - Yixiu Liu
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, Chongqing University Cancer Hospital, Chongqing, China
| | - Yanguang Zhao
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, Chongqing University Cancer Hospital, Chongqing, China
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Li J, Bai L, Wei F, Wei M, Xiao Y, Yan W, Wei J. Effect of Addition of Thyroxine in the Treatment of Graves' Disease: A Systematic Review. Front Endocrinol (Lausanne) 2021; 11:560157. [PMID: 33569041 PMCID: PMC7868565 DOI: 10.3389/fendo.2020.560157] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 11/26/2020] [Indexed: 01/02/2023] Open
Abstract
Graves' disease is the most common cause of hyperthyroidism. Antithyroid drugs, radioiodine ablation, and surgery are the main treatments. Research has demonstrated that adding thyroxine to antithyroid therapy can improve the remission rate, and many similar studies have been conducted subsequently. The purpose of this systematic review was to investigate whether adding thyroxine to various treatments for Graves' disease has a clinical benefit in remission/relapse rate, stable thyroid function, occurrence of Graves' ophthalmopathy, etc. A total of 27 studies were included, and the risk of research bias was moderate to high. We discuss the role of thyroxine both in pharmacological and non-pharmacological therapeutic regimens. Overall, the available evidence does not support the indiscriminate addition of thyroxine to various treatments for Graves' disease, especially in combination with oral antithyroid drugs. Further clinical studies are required to explore the indications of thyroxine addition in the treatment of Graves' disease.
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Affiliation(s)
- Jun Li
- Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Litao Bai
- The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Fan Wei
- Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Maoying Wei
- Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yao Xiao
- Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Weitian Yan
- Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Junping Wei
- Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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Graves' disease and mental disorders. JOURNAL OF CLINICAL AND TRANSLATIONAL ENDOCRINOLOGY 2019; 19:100207. [PMID: 31763175 PMCID: PMC6864135 DOI: 10.1016/j.jcte.2019.100207] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Revised: 10/04/2019] [Accepted: 10/04/2019] [Indexed: 11/23/2022]
Abstract
Mental disorders merge highly with thyroid diseases. Because of its regulatory effects on serotonin and noradrenalin, T3 has been linked closely to depression and anxiety. It has known that in many cases, the mental symptoms persist even after normalization of thyroid function by treatment. Psychosocial factors including stress have been associated with mental symptoms even after thyroid function normalization in Graves’ disease and a combination of mental disorders have been related to the exacerbation of hyperthyroidism. These findings suggest that psychosomatic approaches based on the bio-psycho-social medical model are important for the treatment of mental disorders associated with Graves’ disease.
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Azizi F, Mehran L, Hosseinpanah F, Delshad H, Amouzegar A. Primordial and Primary Preventions of Thyroid Disease. Int J Endocrinol Metab 2017; 15:e57871. [PMID: 29344036 PMCID: PMC5750785 DOI: 10.5812/ijem.57871] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2017] [Revised: 07/09/2017] [Accepted: 08/14/2017] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Primordial and primary preventions of thyroid diseases are concerned with avoiding the appearance of risk factors, delaying the progression to overt disease, and minimizing the impact of illness. SUMMARY Using related key words, 446 articles related to primordial and primary, preventions of thyroid diseases published between 2001-2015 were evaluated, categorized and analyzed. Prevention and elimination of iodine deficiency are major steps that have been successfully achieved and maintained in many countries of the world in last 2 decades. Recent investigations related to the effect of cigarette smoking, alcohol consumption, and autoimmunity in the prevention of thyroid disorders have been reviewed. CONCLUSIONS The cornerstone for successful prevention of thyroid disease entails timely implementation of its primordial and primary preventions, which must be highly prioritized in related health strategies by health authorities.
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Affiliation(s)
- Fereidoun Azizi
- Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
| | - Ladan Mehran
- Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
| | - Farhad Hosseinpanah
- Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
| | - Hossein Delshad
- Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
| | - Atieh Amouzegar
- Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
- Corresponding author: Atieh Amouzegar, Assistant Professor of Internal Medicine and Endocrinology, Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran, P.O. Box: 19395-4763. Tel: +98-2122432503, Fax: +98-2122402463, E-mail:
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Köhling HL, Plummer SF, Marchesi JR, Davidge KS, Ludgate M. The microbiota and autoimmunity: Their role in thyroid autoimmune diseases. Clin Immunol 2017; 183:63-74. [PMID: 28689782 DOI: 10.1016/j.clim.2017.07.001] [Citation(s) in RCA: 81] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2016] [Revised: 07/02/2017] [Accepted: 07/05/2017] [Indexed: 12/11/2022]
Abstract
Since the 1970s, the role of infectious diseases in the pathogenesis of Graves' disease (GD) has been an object of intensive research. The last decade has witnessed many studies on Yersinia enterocolitica, Helicobacter pylori and other bacterial organisms and their potential impact on GD. Retrospective, prospective and molecular binding studies have been performed with contrary outcomes. Until now it is not clear whether bacterial infections can trigger autoimmune thyroid disease. Common risk factors for GD (gender, smoking, stress, and pregnancy) reveal profound changes in the bacterial communities of the gut compared to that of healthy controls but a pathogenetic link between GD and dysbiosis has not yet been fully elucidated. Conventional bacterial culture, in vitro models, next generation and high-throughput DNA sequencing are applicable methods to assess the impact of bacteria in disease onset and development. Further studies on the involvement of bacteria in GD are needed and may contribute to the understanding of pathogenetic processes. This review will examine available evidence on the subject.
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Affiliation(s)
- Hedda L Köhling
- University Hopital Essen, Institute of Medical Microbiology, Essen, Germany; Cultech Ltd., Baglan, Port Talbot, United Kingdom.
| | | | - Julian R Marchesi
- School of Biosciences, Cardiff University, Cardiff, United Kingdom; Centre for Digestive and Gut Health, Imperial College London, London, W2 1NY, United Kingdom
| | | | - Marian Ludgate
- Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom
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Covelli D, Ludgate M. The thyroid, the eyes and the gut: a possible connection. J Endocrinol Invest 2017; 40:567-576. [PMID: 28063079 DOI: 10.1007/s40618-016-0594-6] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2016] [Accepted: 12/05/2016] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Graves' disease (GD) is an autoimmune disorder responsible for 60-90% of thyrotoxicosis, with an incidence of 1 to 2 cases per 1000 population per year in England. Graves' orbitopathy (GO) is the most frequent extrathyroidal manifestation, not provoked directly by abnormal thyroid hormone levels, but by the consequence of the underlying autoimmune process. The aetiology of autoimmune disorders is due to an interplay between susceptibility genes and environmental factors, such as infections and stress. What triggers the autoimmune reaction to a specific site of the body is not yet clearly understood. The lack of knowledge in GD and GO pathogenesis implicates therapies that only limit damage but do not prevent disease onset. MATERIAL AND METHODS We performed on PubMed and the Cochrane Library a literature search for the articles published until July 2016 by using the search terms 'graves disease' and 'microbiome', 'orbitopathy' and 'autoimmune pathogenesis'. Reference lists of relevant studies were hand-searched for additional studies. CONCLUSION In this scenario, a Marie Sklodowska-Curie funded project INDIGO ( http://www.indigo-iapp.eu/ ) is investigating the role of the gut bacteria in GD and GO pathogenesis. The gut is the first and the widest area of bacteria access, with the highest concentration of T cells in the human body and trained to react to microorganisms. Interestingly, all the environmental factors involved in GD and GO pathogenesis can alter the balance within the microorganisms located in the gut, and influence the immune system, in particular the proportions of regulatory Treg and inflammatory TH17 cells. It is hoped that investigating GD and GO pathogenesis from this novel aspect will identify new targets for prevention and treatment.
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Affiliation(s)
- D Covelli
- Graves' Orbitopathy Centre, Endocrinology, Department of Clinical Sciences and Community Health, Fondazione Ca'Granda IRCCS, University of Milan, via Sforza 35, 20122, Milan, Italy.
| | - M Ludgate
- Division of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK
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Pastore F, Martocchia A, Stefanelli M, Prunas P, Giordano S, Toussan L, Devito A, Falaschi P. Hepatitis C virus infection and thyroid autoimmune disorders: A model of interactions between the host and the environment. World J Hepatol 2016; 8:83-91. [PMID: 26807204 PMCID: PMC4716530 DOI: 10.4254/wjh.v8.i2.83] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 10/28/2015] [Accepted: 12/04/2015] [Indexed: 02/06/2023] Open
Abstract
The hepatitis C virus (HCV) infection is an important public health problem and it is associated with hepatic and extrahepatic manifestations. Autoimmune thyroid diseases are common in HCV infected patients and the standard interferon-based treatment is associated with an increase of the immune-mediated thyroid damage. Recent evidence in the literature analyzed critical points of the mechanisms of thyroid damage, focusing on the balance between the two sides of the interaction: The environment (virus infection with potential cross-reaction) and the host (susceptibility genes with consistent immune response). The spectrum of antiviral treatment for chronic HCV infection is rapidly expanding for the development of dual o triple therapy. The availability of interferon-free combined treatment with direct antiviral agents for HCV is very promising, in order to ameliorate the patient compliance and to reduce the development of thyroid autoimmunity.
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Marinò M, Latrofa F, Menconi F, Chiovato L, Vitti P. Role of genetic and non-genetic factors in the etiology of Graves' disease. J Endocrinol Invest 2015; 38:283-94. [PMID: 25421156 DOI: 10.1007/s40618-014-0214-2] [Citation(s) in RCA: 67] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2014] [Accepted: 11/12/2014] [Indexed: 12/21/2022]
Abstract
In spite of the advancements in understanding the pathogenic mechanisms of Graves' disease (GD), its ultimate cause remains elusive. The majority of investigators agree that GD is likely a multifactorial disease, due to a complex interplay of genetic and non-genetic factors that lead to the loss of immune tolerance to thyroid antigens and to the initiation of a sustained autoimmune reaction. Twin and family studies support a role of genetic factors, among which the HLA complex, CD40, CTLA-4, PTPN22, FCRL3, thyroglobulin, and the TSH receptor may be involved. Among non-genetic factors, iodine, infections, psychological stress, gender, smoking, thyroid damage, vitamin D, selenium, immune modulating agents, and periods of immune reconstitution may contribute the development of the diseases. Here we review in detail the respective role of genetic and non-genetic factors in the etiology of GD, taking advantage of the great bulk of data generated especially over the past 30 years.
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Affiliation(s)
- M Marinò
- Department of Clinical and Experimental Medicine, University Of Pisa, Pisa, Italy.
- Endocrinology Unit, University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
| | - F Latrofa
- Department of Clinical and Experimental Medicine, University Of Pisa, Pisa, Italy
- Endocrinology Unit, University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy
| | - F Menconi
- Department of Clinical and Experimental Medicine, University Of Pisa, Pisa, Italy
- Endocrinology Unit, University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy
| | - L Chiovato
- Unit of Endocrinology, Department of Internal Medicine and Medical Therapy, University of Pavia, Fondazione Salvatore Maugeri IRCCS, Pavia, Italy
| | - P Vitti
- Department of Clinical and Experimental Medicine, University Of Pisa, Pisa, Italy
- Endocrinology Unit, University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy
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Tompa A, Jakab M, Biró A, Major J. [Genetic and immune-toxicologic studies on abnormal thyroid functions in hospital employees exposed to cytostatic drugs]. Orv Hetil 2015; 156:60-6. [PMID: 25563683 DOI: 10.1556/oh.2015.30064] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
INTRODUCTION Environmental exposure to harmful chemicals may produce severe consequences. AIM The aim of the authors was to perform geno- and immune-toxicological monitoring in female employees occupationally exposed to cytostatic agents in hospitals and compare the findings to those obtained from controls. METHOD Altogether 642 women working in hospital who were occupationally exposed to cytostatic drugs and 262 control women participated in the study. Frequency of chromosome aberrations, immune phenotype and activation of lymphocytes, and the production of reactive oxygen-species in neutrophil granulocytes were determined. RESULTS Markedly higher number (n=39) of thyroid alterations was observed among exposed subjects as compared to controls (n=3). In persons with abnormal thyroid functions, the frequency of chromosome aberrations (3.69%) was significantly higher (3.69%) than in exposed subjects without thyroid alterations (2.43%) and in controls (1.70% and 1.60% in control subjects with and without thyroid alterations, respectively). Significantly increased ratio of helper T lymphocytes and decreased ratio of cytotoxic T cells and transferrin-receptor (CD71) expressing B cells were observed in exposed subjects having abnormal thyroid functions as compared to controls. In addition, the ratio of B cells, CD71 expressing T cells and production of reactive oxygen-intermediates was significantly decreased in exposed subjects with thyroid alterations in comparison to exposed subjects without thyroid alterations. CONCLUSIONS The results indicate increased geno- and immune-toxic effects among exposed subjects having thyroid alterations. Further data are needed to clearly establish the underlying pathophysiological mechanism of this finding.
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Affiliation(s)
- Anna Tompa
- Országos Kémiai Biztonsági Intézet Citogenetikai és Immunológiai Csoport Budapest Semmelweis Egyetem, Általános Orvostudományi Kar Népegészségtani Intézet Budapest Nagyvárad tér 4. 1089
| | - Mátyás Jakab
- Országos Kémiai Biztonsági Intézet Citogenetikai és Immunológiai Csoport Budapest
| | - Anna Biró
- Országos Kémiai Biztonsági Intézet Citogenetikai és Immunológiai Csoport Budapest
| | - Jenő Major
- Országos Kémiai Biztonsági Intézet Citogenetikai és Immunológiai Csoport Budapest
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Conte-Devolx B, Vialettes B. Can stress induce dysimmune dysthyroidism? ANNALES D'ENDOCRINOLOGIE 2013; 74:483-6. [PMID: 24262983 DOI: 10.1016/j.ando.2013.09.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/07/2013] [Revised: 07/30/2013] [Accepted: 09/10/2013] [Indexed: 01/29/2023]
Abstract
Hyperthyroidism due to Graves' disease is autoimmune in origin. The initiation of dysimmunity responsible for the disease is still poorly understood. Numerous population studies show that genetic factors have a major role, but the environment and any kind of stress also contribute to the onset of the disease. There remains the recurring question for medical experts of the accountability of stress in the onset of Graves' disease. To date, it is impossible to establish a direct link between this disease and a specific stress. The relationship can only be hypothetical, indirect and partial.
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Affiliation(s)
- Bernard Conte-Devolx
- Department of endocrinology, diabetes, metabolic diseases, Timone hospital, rue St-Pierre, 13005 Marseille, France.
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Topcu CB, Celik O, Tasan E. Effect of stressful life events on the initiation of graves' disease. Int J Psychiatry Clin Pract 2012; 16:307-11. [PMID: 22136213 DOI: 10.3109/13651501.2011.631016] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
OBJECTIVE The aim of this study was to investigate the relationship between stressful life events (LESs) and its effect on the initiation of Graves' disease (GD) and toxic nodular goitre (TNG). PATIENTS AND METHOD Forty-five patients with GD, 24 patients with TNG and 36 healthy control (CG) were included to the study. Graves and TNG patients had diagnosed within the last 12 months, with clinical and biochemical confirmation in Endocrinology Metabolism Outpatient Clinic of Cerrahpasa Medical School. The Holmes-Rahe Stress Scale and the Life Experience Survey (LES) was the psychological evaluation instrument used in this study. RESULTS There was no significant difference according to Holmes-Rahe scale (Graves & TNG P = 0.329, Graves & Control P = 0.115, TNG and control P = 0.571). According to LES scale when negative event number, positive event number, neutral events and their effects are considered, between Graves and TNG groups no statistically difference was observed (P = 0.139, P = 0.083, P = 0.167, P = 0.162, P = 0.861). The number and impact of negative SLEs were significantly higher in GD compared to CG (P = 0.015, P < 0.001). CONCLUSION According to LES scale GD patients has significant difference with respect to CG when negative event number and impact are considered.
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Affiliation(s)
- Ceyhan Bedia Topcu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Cerrahpasa Medical School, University of Istanbul, Istanbul, Turkey
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Effraimidis G, Tijssen JGP, Brosschot JF, Wiersinga WM. Involvement of stress in the pathogenesis of autoimmune thyroid disease: a prospective study. Psychoneuroendocrinology 2012; 37:1191-8. [PMID: 22226433 DOI: 10.1016/j.psyneuen.2011.12.009] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2011] [Revised: 12/10/2011] [Accepted: 12/11/2011] [Indexed: 11/16/2022]
Abstract
BACKGROUND An association between stress and autoimmune thyroid disease (AITD) (especially Graves' hyperthyroidism) has been reported, but all studies so far on this topic have been retrospective. OBJECTIVE To evaluate prospectively the relationship between stress and (i) de novo occurrence of thyroid antibodies and (ii) development of overt autoimmune hyper-/hypothyroidism. STUDY DESIGN Two nested case-control studies in a prospective cohort of 790 euthyroid women who were 1st or 2nd degree relatives of AITD patients. Follow-up was five year, with annual assessments including questionnaires on stressful life events, daily hassles, and mood. In study A, cases were subjects who developed TPO-Ab but remained euthyroid during follow-up (called event). In study B, cases were subjects who developed overt hypothyroidism (TSH>5.7 mU/l and FT4<9.3 pmol/l) or overt hyperthyroidism (TSH<0.4 mU/l and FT4>20.1 pmol/l) during follow-up (called event). For each case, two controls were selected, matched for age and duration of follow-up; controls in study A remained TPO-Ab negative, and in study B remained without overt hyper-/hypothyroidism. OUTCOMES Contrast in questionnaire responses between cases and controls at baseline, at one year prior to the event and at time of event. RESULTS Exposure to stress was not different between subjects who developed or did not develop TPO-Ab (study A). No differences were observed in stress questionnaires between hyper-/hypothyroid cases and controls at any time point, but hypothyroid cases had less negative feelings than controls at the time of diagnosis (study B). CONCLUSION The data suggest that stress is not involved in the pathogenesis of AITD.
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Affiliation(s)
- Grigoris Effraimidis
- Departments of Endocrinology and Metabolism, Academical Medical Centre, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
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The evolving role of selenium in the treatment of graves' disease and ophthalmopathy. J Thyroid Res 2012; 2012:736161. [PMID: 22315699 PMCID: PMC3270443 DOI: 10.1155/2012/736161] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2011] [Accepted: 10/17/2011] [Indexed: 11/18/2022] Open
Abstract
Graves' disease (GD) and ophthalmopathy (GO) are organ-specific autoimmune-inflammatory disorders characterized by a complex pathogenesis. The inflammatory process is dominated by an imbalance of the antioxidant-oxidant mechanism, increased production of radical oxygen species (ROS), and cytokines which sustain the autoimmune process and perpetuate the disease. Recently, selenium, which is a powerful antioxidant, has been successfully applied in patients with mild GO, slowing the progression of disease, decreasing the clinical activity score, and appreciably improving the quality of life. The mechanisms of selenium action are variable. The aim of this review is to summarize the actions of selenium in GD and GO. Selenium as selenocysteine is incorporated in selenoproteins, such as glutathione peroxidase which catalyzes the degradation of hydrogen peroxide and lipid hydroperoxide that are increasingly produced in hyperthyroidism. Moreover, selenium decreases the formation of proinflammatory cytokines, while it contributes, in synergy with antithyroid drugs, to stabilization of the autoimmune process in GD and alleviation of GO. It is now to be clarified whether enforced nutritional supplementation has the same results and whether prolonging selenium administration may have an impact on the prevention of disease.
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Cepon TJ, Snodgrass JJ, Leonard WR, Tarskaia LA, Klimova TM, Fedorova VI, Baltakhinova ME, Krivoshapkin VG. Circumpolar adaptation, social change, and the development of autoimmune thyroid disorders among the Yakut (Sakha) of Siberia. Am J Hum Biol 2011; 23:703-9. [DOI: 10.1002/ajhb.21200] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2011] [Revised: 05/02/2011] [Accepted: 05/16/2011] [Indexed: 11/09/2022] Open
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Tsatsoulis A. The role of stress in the clinical expression of thyroid autoimmunity. Ann N Y Acad Sci 2007; 1088:382-95. [PMID: 17192582 DOI: 10.1196/annals.1366.015] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
During stress, activation of the hypothalamic-pituitary-adrenal axis and the sympathoadrenal system leads to increased secretion of glucocorticoids and catecholamines, respectively, in order to maintain homeostasis. Recent evidence suggests that stress hormones, acting on antigen-presenting immune cells, may influence the differentiation of bipotential T helper (Th) cells away from Th1 and toward a Th2 phenotype. This results in suppression of cellular immunity and potentiation of humoral immunity. Thyroid autoimmunity is clinically expressed as Hashimoto's thyroiditis (HT) and its variants (sporadic or postpartum thyroiditis) or as Grave's disease (GD). The different phenotypic expression of thyroid autoimmunity is largely dependent on the balance of Th1 versus Th2 immune response. A predominantly Th1-mediated immune activity may promote apoptotic pathways on thyroid follicular cells leading to thyroid cell destruction and HT. Conversely, predominance of Th2-mediated immune response may induce antigen-specific B lymphocytes to produce anti-TSH receptor (TSHr) antibodies causing GD. The weight of evidence from epidemiological and case-control studies supports an association between stress and GD. On the other hand, there is little information available on the effect of stress on HT, but there is evidence for an increase in postpartum thyroiditis, following the cellular immune suppressive effect of pregnancy. Whether stress has a causative effect on GD remains elusive. Circumstantial evidence supports the hypothesis that stress may influence the clinical expression of thyroid autoimmunity in susceptible individuals favoring the development of GD by shifting the Th1-Th2 balance away for Th1 and toward Th2. Conversely, recovery from stress or the immune suppressive effect of pregnancy may induce a Th2 to Th1 "return shift" leading to autoimmune (sporadic) or postpartum thyroiditis, respectively.
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Abstract
Autoimmune thyroid diseases (AITD) are the far most common autoimmune disorders, their prevalence in Western countries exceeding 5% of the general population. In the large majority of individual cases the clinical impact of AITD is not severe, however, their widespread diffusion renders them a significant health problem. AITD are heterogeneous in their clinical presentation: the two main forms are autoimmune thyroiditis (AT) and Graves' disease (GD). Although they probably share, at least in part, a common genetic background and may occur in the same family as well as in the same individual, they are definitely two distinct diseases both in their clinical presentation and their pathophysiology. In fact, AT causes structural thyroid damage (mainly via cell-mediated immune destruction of thyroid follicular cells) which results, as a rule, in functional impairment (hypothyroidism); however, depending on clinical variants, evolution towards hypothyroidism may be very low, or thyroid function impairment occurs after an initial phase of mild thyrotoxicosis due to relatively rapid gland destruction. GD patients have hyperthyroidism, often severe, due to autoantibody-mediated thyrotropin receptor stimulation, with thyroid cell hyperplasia and hyperfunction. Such a functional heterogeneity is a key feature for the clinical management: as a matter of fact, therapy of AITD is mainly therapy of thyroid dysfunction. Moreover, since hyperthyroidism is quite early perceived by the patient as a cause of discomfort, the timing of the natural history of GD is relatively well defined; on the other hand, AT may be asymptomatic for a long time and defining its natural history in a single patient may be difficult. In some AITD patients (mainly, but not exclusively, with GD), clinical features not directly related to thyroid dysfunction, such as orbitopathy, are present. Graves' orbitopathy is probably related, at least in part, to autoantibodies directed to thyrotropin receptor; it may be, in a minority of patients, severe and sight-threatening, and represents an independent clinical problem.
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Abstract
While many studies have shown a connection between stress and autoimmune disease, most of the evidence for stress contributing to the onset and course of autoimmune disease is circumstantial and the mechanisms by which stress affects autoimmune disease are not fully understood. The best circumstantial evidence for an effect of stress on autoimmune thyroid disease is the well-known relationship between the onset of Graves' hyperthyroidism and major stress but even this is debated. However, most of the recent case-control studies have supported stress as a factor that affects the onset and clinical course of Graves' disease. On the other hand, there have been few reports concerning the possible relationship between stress and Hashimoto's thyroiditis. Because the onset and course of Hashimoto's thyroiditis is generally insidious, the effect of stress on Hashimoto's thyroiditis might be overlooked. Numerous human and animal studies have demonstrated that psychological and physiologic stressors induce various immunologic changes. Stress affects the immune system either directly or indirectly through the nervous and endocrine systems. These immune modulations may contribute to the development of autoimmunity as well as the susceptibility to autoimmune disease in genetically predisposed individuals. Stress can be one of the environmental factors for thyroid autoimmunity.
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Affiliation(s)
- Tetsuya Mizokami
- Department of Clinical and Biomedical Sciences: Barwon Health, The Geelong Hospital, Geelong, Victoria, Australia
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Matos-Santos A, Nobre EL, Costa JG, Nogueira PJ, Macedo A, Galvão-Teles A, de Castro JJ. Relationship between the number and impact of stressful life events and the onset of Graves' disease and toxic nodular goitre. Clin Endocrinol (Oxf) 2001; 55:15-9. [PMID: 11453947 DOI: 10.1046/j.1365-2265.2001.01332.x] [Citation(s) in RCA: 55] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND In the last few decades, several studies have suggested a possible association between Stressful Life Events (SLEs) and the onset of Graves' Disease (GD). However, others have criticised this association and it has not yet been possible to prove it unequivocally. At present, we are not aware of studies correlating SLE and non autoimmune thyrotoxicosis. OBJECTIVE To assess possible associations between SLEs, the onset of GD and the onset of non autoimmune thyrotoxicosis (toxic nodular goitre, TNG). DESIGN A case-control retrospective study. PATIENTS This study included 93 subjects, divided into three groups of 31 each: GD, TNG and control (CG). The GD and TNG patients had thyroid disease diagnosed within the last 12 months, with clinical and biochemical confirmation. In the CG, psychopathological and endocrine disturbances had been ruled out. All three groups consisted of nine males (29%) and 22 females (71%). The mean age was 38.4 +/- 10.9 years in the GD group, 48.3 +/- 11.1 years in the TNG group and 41.1 +/- 11.8 years in the CG group. SLEs were evaluated (number and impact) for the 12 months preceding the onset of symptoms of thyroid disease. MEASUREMENTS SLE occurrences and their impact on each group of cases were measured. To assess SLEs, we used the Life Experiences Survey (LES). Our statistical analysis included descriptive techniques and parametric and/or nonparametric comparative tests. P < 0.01 was considered statistically significant. Odds ratios were also calculated. RESULTS Patients with GD had a significantly greater number of SLEs compared to the TNG group and the CG (P < 0.001). The number and impact of negative SLEs were significantly higher in GD compared to TNG and CG (P < 0.001). The difference between TNG and CG was not significant (P > 0.01). GD had a higher impact of positive SLEs than TNG (P = 0.004), and no significant differences were found between the GD group and CG. Neutral SLEs were similar in the three groups. CONCLUSIONS These results suggest that SLEs are a precipitating factor of the onset of GD. We also demonstrated that SLEs do not seem to have any conclusive relationship with the onset of TNG.
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Affiliation(s)
- A Matos-Santos
- Serviço De Endocrinologia, Diabetes e Metabolismo, Hospital Militar Principal, Lg Da Estrela, 1249-075 Lisboa, Portugal
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Abstract
INTRODUCTION Destruction of hair follicles by lymphocytes induces alopecia aerata. Hence, immunological mechanisms are involved in this disease, as for numerous dermatoses. Nonetheless, alopecia aerata appears to be a psychosomatic disease. Is there any contradiction? CURRENT KNOWLEDGE AND KEY POINTS Alopecia aerata often occurs after stress, particularly during mourning. Psychiatric disorders are more frequent in patients with alopecia than in healthy subjects. But these disorders might be secondary to the visible hair disease. Psychopathological mechanisms need to be clarified but alexithymia seems to be the key for understanding how stress could induce hair loss. In the skin (and the scalp) all functions are narrowly controlled by nerve fibers. Among these functions are hair growth and immunity. Immune cells and hair follicle cells possess receptors for neurotransmitters, which are synthesized by neuronal endings. When activated, these receptors are able to modulate cell properties. The same phenomena are described with stress-induced hormones. In alopecia aerata, like in numerous other diseases, psychosomatics and immunology are not opposed because immune cells are controlled by the nervous system through neurotransmitters. FUTURE PROSPECTS AND PROJECTS Research needs to be thorough in both the fields of psychology and neurobiology. Psychotherapies or psychotropes appear to be useful in the treatment of alopecia aerata.
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Affiliation(s)
- L Misery
- Service de dermatologie, hôpital Nord, 42055 Saint-Etienne, France
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Affiliation(s)
- A P Weetman
- University of Sheffield Division of Clinical Sciences, Northern General Hospital, United Kingdom
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Felz MW, Stein PP. The many 'faces' of Graves' disease. Part 1. Eyes, pulse, skin, and neck provide important clues to diagnosis. Postgrad Med 1999; 106:57-64. [PMID: 10533508 DOI: 10.3810/pgm.1999.10.1.710] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
The variety in clinical appearance of patients with Graves' disease suggests that predominant symptoms affecting one body system may be either compelling or misleading to clinicians during the initial assessment. However, each patient in these case presentations had additional bedside evidence of many of the recognized multisystem manifestations of hyperthyroidism, as detected on more extensive evaluation. Laboratory tests confirmed the diagnosis in each instance. While these cases are not meant to represent all reported manifestations of Graves' disease, grouping of symptoms into memorable "faces" is helpful for definitive clinical recognition and precise diagnosis of this complex and challenging syndrome.
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Affiliation(s)
- M W Felz
- Department of Family Medicine, Medical College of Georgia School of Medicine, Augusta 30912, USA.
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Chiovato L, Marinò M, Perugi G, Fiore E, Montanelli L, Lapi P, Cavaliere R, Ciampi M, Patronelli A, Placidi G, Placidi GF, Cassano GB, Pinchera A. Chronic recurrent stress due to panic disorder does not precipitate Graves' disease. J Endocrinol Invest 1998; 21:758-64. [PMID: 9972676 DOI: 10.1007/bf03348042] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
A role of psychic stress in precipitating hyperthyroid Graves' disease has been suggested, but the evidence in support of this pathogenetic mechanism is conflicting. In this study we investigated the possible occurrence of Graves' disease in patients with panic disorder, a psychiatric condition characterized by recurrent endogenous stress. The study group included 87 consecutive patients suffering from panic disorder since 1 to 30 years: 17 males (mean age 31.3, range 26-43 years) and 70 females (mean age 37.6, range 15-73 years). Two hundred and sixty-two normal subjects with no present or past history of psychiatric disorder served as controls. Patients were submitted to a full evaluation of the thyroid that included physical examination, assays for free thyroid hormones, TSH, thyroglobulin (TgAb), thyroperoxidase (TPOAb) and TSH receptor (TRAb) antibodies, and thyroid echography. The prevalence of circulating TgAb and/or TPOAb in patients with panic disorder did not differ from that in the control group. Twelve patients with panic disorder (13.7%) had circulating TgAb and/or TPOAb, but none had TRAb. Three out of 12 patients with thyroid antibodies, indicating a genetic susceptibility to autoimmune thyroid disease, had a family history of clinical thyroid autoimmunity, and 4 of them had a hypoechogenic pattern of the thyroid at ultrasound suggesting autoimmune thyroiditis. None of the patients with panic disorder had a previous history of hyperthyroidism. On examination, clinical hyperthyroidism or endocrine ophthalmopathy were not found in any of them. A small goiter was appreciated by palpation in 16 patients (18.3%). Free thyroid hormones and TSH were within the normal range in all patients but one: a 55-year old lady with normal serum free thyroid hormones and undetectable TSH. During an 18-month follow-up she did not develop hyperthyroidism and her TSH spontaneously returned in the normal range. Considering the individual duration of panic disorder, evidence for previous or present Graves' hyperthyroidism was not found for a total of 478 patient-years of exposure to recurrent endogenous stress in the whole study group, and for a total of 39 patient-years in patients with a genetic susceptibility to autoimmune thyroid disease. In conclusion, we found that recurrent endogenous stress did not precipitate Graves' hyperthyroidism in a series of 87 patients with panic disorder, encompassing a total of 478 patient-years of exposure to stress. Failure to activate the hypothalamic-pituitary-adrenal axis by endogenous stress due to panic disorder as opposed to exogenous stress due to life-events might explain why panic disorder does not precipitate Graves' hyperthyroidism.
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Affiliation(s)
- L Chiovato
- Department of Endocrinology, University of Pisa, Italy
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Brix TH, Kyvik KO, Hegedüs L. What is the evidence of genetic factors in the etiology of Graves' disease? A brief review. Thyroid 1998; 8:727-34. [PMID: 9737369 DOI: 10.1089/thy.1998.8.727] [Citation(s) in RCA: 64] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Graves' disease (GD) is generally thought of as a multifactorial disorder in which genetic susceptibility interacts with environmental and endogenous factors to cause disease. The importance of genetic factors is suggested by the clustering of GD within families and by a higher concordance rate for disease in monozygotic than dizygotic twins. This has, however, recently been shown to be less pronounced than previously thought. During the last decade, much effort has been put into characterization of the genetic background of GD. Until recently most studies have examined associations between GD and the human leukocyte antigen (HLA) region, but recent advances in molecular techniques have opened the way for whole-genome screening. A number of HLA and non-HLA candidate genes have been proposed, but despite several large investigations within multiplex families no major susceptibility genes have been identified. This brief review discusses relevant articles published from 1940 through 1997 regarding the influence of genetic factors in the etiology of GD. Ongoing studies will focus on whole genome screening in multiplex families as well as population based twin studies. However, the possibility of GD being a heterogeneous disease without a single well-defined genotype and phenotype should be left open.
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Affiliation(s)
- T H Brix
- Department of Endocrinology M, Odense University Hospital, Denmark
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Brix TH, Kyvik KO, Hegedüs L. What is the evidence of genetic factors in the etiology of Graves' disease? A brief review. Thyroid 1998; 8:627-34. [PMID: 9709918 DOI: 10.1089/thy.1998.8.627] [Citation(s) in RCA: 39] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Graves' disease (GD) is generally thought of as a multifactorial disorder in which genetic susceptibility interacts with environmental and endogenous factors to cause disease. The importance of genetic factors is suggested by the clustering of GD within families and by a higher concordance rate for disease in monozygotic than in dizygotic twins. This has, however, recently been shown to be less pronounced than previously thought. During the last decade much effort has been put into characterization of the genetic background of GD. Until recently, most studies have examined associations between GD and the human leukocyte antigen (HLA) region, but recent advances in molecular techniques have opened the way for whole genome screening. A number of HLA and non-HLA candidate genes have been proposed, but despite several large investigations within multiplex families no major susceptibility genes have been identified. This brief review discusses relevant articles published from 1940 through 1997 regarding the influence of genetic factors in the etiology of GD. Ongoing studies focus on whole genome screening in multiplex families as well as population-based twin studies. However, the possibility of GD being a heterogeneous disease without a single well-defined genotype and phenotype should be left open.
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Affiliation(s)
- T H Brix
- Department of Endocrinology M, Odense University Hospital, Odense C, Denmark
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Weetman AP, Ajjan RA, Watson PF. Cytokines and Graves' disease. BAILLIERE'S CLINICAL ENDOCRINOLOGY AND METABOLISM 1997; 11:481-97. [PMID: 9532335 DOI: 10.1016/s0950-351x(97)80708-2] [Citation(s) in RCA: 23] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Cytokines are an extraordinarily diverse group of molecules, with pleiotropic and often overlapping effects. They are crucial to the autoimmune response, and, in particular, regulation of CD4+ and CD8+ T-cell function depends on the balance of cytokines produced during an immune response. It is also now clear that cytokines are produced by a wide array of cells, including the thyroid follicular cells (TFCs). Intrathyroidal lymphocytes produce a heterogeneous pattern of cytokines and we have summarized the likely effects of these. In Graves' disease, TFCs can themselves express immunologically important molecules as the result of cytokine stimulation and these could contribute to the perpetuation of the autoimmune process. In addition, cytokines have a number of generally inhibitory effects on thyroid hormone production which would tend to counter the stimulatory effects of thyroid-stimulating hormone receptor antibodies in Graves' disease.
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Affiliation(s)
- A P Weetman
- Department of Medicine, Northern General Hospital, Sheffield, UK
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