The role of antibodies in Graves' ophthalmopathy

The aim of this study was to investigate the possible pathogenetic role of autoantibodies to eye muscle membrane fractions in 75 patients with Graves' disease (50 patients with infiltrative ophthalmopathy). Autoantibodies directed to four fractions of human eye muscle--as well as thyroid membranes prepared by ultracentrifugation were detected by ELISA and Western blotting techniques. None of autoantibodies to various fractions of eye muscle membrane proved to be specific for Graves' ophthalmopathy, however, the presence of these antibodies and activity of eye symptoms were in correlation. Polyclonal autoantibodies to common epitopes on both thyroid and eye muscle membrane antigens (approximately 60 kD) were revealed that might be involved into pathogenesis of Graves' ophthalmopathy.     

Influence of cigarette smoking on thyroid function, goiter formation and autoimmune thyroid disorders

Both smoking and thyroid dysfunction are frequent in the general population. Many studies have shown that cigarette smoking interferes with thyroid function and with the evolution of thyroid pathology (e.g. goiter formation and thyroid cancer development). Some studies have also suggested a significant correlation of Graves' hyperthyroidism and Graves' ophthalmopathy with the severity of smoking. In addition, cigarette smoking may reduce the effectiveness of some therapeutic modalities, such as orbital radiotherapy or high-dose systemic glucocorticoid administration for severe thyroid eye disease. Tobacco smoking seems to induce similar changes in thyroid function in the adult and the fetus. This review article discusses the effect of cigarette smoking on thyroid function and morphology as well as on thyroid autoimmunity.     

Graves' orbitopathy

Graves' orbitopathy or thyroid associated orbitopathy is the most frequent extrathyroidal manifestation of Graves' disease with autoimmune mechanism which is still incompletely understood. The epidemiologic data provided evidence that severe, infiltrative orbitopathy is present in 3-5% of patients, and the quality of life is impaired even in individuals with mild form of this disease. The anti-TSH receptor and anti-eye muscle autoantibodies have been proved to be involved into pathomechanism of orbitopathy. The accumulation of glucose-aminoglycan and proinflammatory cytokines in retro-orbital fibroblasts are responsible for enlargement of eye muscle and the retro-orbital tissues resulting in inflammation of periorbital tissues and proptosis. Management of orbitopathy can be either medical and surgical. The medical therapy relies on the use of high dose systemic glucocorticoids or retro-orbital irradiation, either alone or in combination. Recent randomized clinical trials have confirmed that glucocorticoids are more effective in intravenous than oral use. Retro-orbital radiotherapy is an effective and safe therapy for orbitopathy and the side effects are avoidable. Somatostatin analogs are not so effective as it has been waited in previous studies. The high dose intravenous immunoglobulins and pentoxifylline therapy are favorable, however, prospective randomized trials have been not yet made. The manifestation of orbitopathy includes both unavoidable (genetic background) and avoidable (smoking, cytokine therapy, iodine exposure, radioiodine therapy) risk factors. Cigarette smoking must be given up by all patients with Graves' disease. Pentoxifylline therapy is advisable for all patients with Graves'diseases, especially for those who have genetic susceptibility to autoimmune disorders and not able to give up cigarette smoking.     

Ophthalmopathy in early thyrotoxicosis--relationship to thyroid receptor antibodies and effects of treatment

A prospective study of 25 newly diagnosed thyrotoxic patients was undertaken to determine the incidence and severity of ophthalmopathy in the early stages of the disease. A quantitative analysis of the ocular muscle changes was made using B scan ultrasonography, and the effects of treatment for the thyroid disease on the course of the eye changes was assessed. Although the majority (75%) of patients showed only mild clinical signs of ophthalmopathy (Werner Class 3 or less), 92% had ultrasonographic evidence of ocular muscle enlargement. Clinical involvement of the extraocular muscles was seen in 12% of the cases. There was an inverse correlation between the serum level of thyroid stimulating hormone receptor antibody (TR Ab) and the size of the extraocular muscles. Recovery of the euthyroid state with treatment was accompanied by a decrease in orbital infiltration in some cases, both clinically (reduced amplitude of intraocular pressure rise on elevation of the globe) and by ultrasonography, but the improvement was not statistically significant.     

What is the role of allergic sensitization in Graves' disease?

INTRODUCTION: Recent data supported the presence of T helper 2 dominance in the immune processes of Graves' disease and allergic diseases. A common role of regulatory T cells in the antigen- (or allergen-) specific immune responses was also demonstrated. AIMS: To study whether allergic events may play a role in the initiation or progression of autoimmune Graves' disease. The occurrence of seasonal allergy may explain the fluctuation in the onset of Graves' disease. METHODS: The presence of specific IgE levels against inhalative allergens was investigated in 327 patients with thyroid disease (Graves' disease, Hashimoto's thyroiditis, euthyroid goitre). Western blot method was used for the measurement of allergen-specific IgE levels with densitometric evaluation. RESULTS: Allergic sensitization was found in 88 cases (58%) for Graves' disease, 51 cases (46%) for Hashimoto's thyroiditis and 31 cases (55%) for euthyroid goitre. According to allergens, significant difference was demonstrated by Penicillium notatum, Dermatophagoides farinae, alder - rye (pollens) between Graves' disease (depending ophthalmopathy) and euthyroid goitre. In the four groups based on allergen seasonality, the month of the onset in Graves' disease was associated with the season of early tree and mugwort allergy (P < 0.019 between Graves' disease and Hashimoto's thyroiditis). The number of cases, in whom the onset of Graves' disease in a given month was similar to the month of allergic season, was 17 cases vs 7 cases with Hashimoto's thyroiditis (P < 0.028). CONCLUSIONS: The allergic sensitization was more frequent in Graves' disease, and the allergic seasonality may explain the fluctuation in the onset of Graves' disease.     

Novel approaches to the management of graves' ophthalmopathy

Severe Graves' ophthalmopathy constitutes a complex therapeutic challenge and treatment outcome often is not satisfactory. Established methods of treatment include high-dose glucocorticoids, orbital radiotherapy and orbital decompression. Recently, the use of intravenous glucocorticoids has been shown to provide more favorable results than oral glucocorticoids. Novel treatments under investigation include somatostatin analogues, intravenous immunoglobulins and antioxidants. Low-dose immunosuppressive drugs (namely cyclosporine and, possibly, methotrexate) might be useful as an adjunct to established methods, particularly in view of a glucocorticoid-sparing action. Because cytokines play an important role in the pathogenesis of the disease, cytokine antagonists, which are currently evaluated in rheumatoid arthritis and other autoimmune conditions, might constitute in the future a valuable tool for the management of eye disease. Prevention of Graves' ophthalmopathy would be desirable, but so far it is limited to secondary prevention (arrest of progression of subclinical disease to clinical disease) and tertiary prevention (avoidance of deterioration or complications of clinical disease): among preventive measures smoking withdrawal is probably the most important one. Primary prevention (in the absence of disease) is only speculative, but oral tolerance induction or vaccination with the offending antigen(s) might prove beneficial for prevention of Graves' ophthalmopathy in genetically susceptible individuals.     

Surgical rehabilitation in patients with Graves' ophthalmopathy; favorable results of orbital decompression via coronal approach]

Bilateral decompression of the orbit by a coronal approach was performed for cosmetic rehabilitation in 53 female patients with proptosis in the non-inflammatory stage after Graves' ophthalmopathy. Proptosis reduction averaged 5.9 mm Hertel value one year after surgery. All patients were satisfied with the cosmetic result obtained. Advantages of the technique used are: good access to all orbital walls facilitating adequate proptosis reduction; no visible scars after surgery; only very few complications. In our group there was no loss of visual acuity and the incidence of diplopia after surgery of only 4% is the lowest reported in the literature.     

江苏海安地区40岁以上人群支气管哮喘患病率及影响因素

目的 探究海安地区40岁以上人群支气管哮喘患病率及其发病的流行病学特征.方法 采用分层随机抽样法对江苏海安地区40岁以上常住居民进行问卷调查及肺功能测定,分析哮喘患病情况及流行病学特征.结果 研究共收集有效问卷2 237份,发现支气管哮喘患者116例,发病率为5.19％;哮喘患病率与性别、年龄、家族史、主被动吸烟、职业...     

A case of Hypothyroid Graves' disease with extremely high titers of TSAb

Graves' ophthalmopathy in hypothyroid state is called Hypothyroid Graves' Disease, which is a comparatively rare disease. We experienced a case of a 57 year old man with severe exophthalmos and diplopia, which are typical symptoms of Graves' opthalmopathy, and with an extremely high thyroid-stimulating antibody(TSAb) level. He also had a firm diffuse goiter and hypothyroidism with positive anti-thyroglobulin and anti-thyroid microsomal antigen. These findings suggested Hashimoto's thyroiditis. Severity of ophthalmopathy and TSAb level were improved during replacement therapy with T4. Although a thyroid stimulation-blocking antibody was also detected in this patient, we thought that hypothyroidism in this case was based on destructive change in the thyroid with Hashimoto's thyroiditis. Therefore, we should be aware of the fact that there are cases of hypothyroidism with Graves' ophthalmopathy and a high level of TSAb.     

Prevalence and risk factors for smoking among adolescents

OBJECTIVE: Tobacco smoking is one of the main causes of preventable disease and premature disability. The study was aimed at measuring smoking prevalence and related risk factors among adolescents. METHODS: A population-based cross-sectional study was carried out in a representative sample of 1,187 adolescents aged 10 to 19 years living in the urban area of Pelotas, southern Brazil. All adolescents were interviewed separately using a confidential coded questionnaire. Kaplan-Meier test was performed for survival curve analysis. RESULTS: The overall smoking prevalence rate in the sample was 12.1% (95% CI 10.3%-14%). Boys and girls had similar prevalence rates. The following were the risk factors for smoking found in the multivariate logistic regression analysis: older age (OR=28.7; 95% CI 11.5-71.4), older smoking siblings (OR=2.4; 95% CI 1.5-3.8), three or more smoking friends (OR=17.5; 95% CI 8.8-34.8) and low schooling (OR=3.5; 95% CI 1.5-8.0). CONCLUSIONS: The prevalence of smoking among adolescents in the city of Pelotas was high. Campaigns against tobacco use should be aimed at the community and families, targeting adolescents. The government must adopt legal actions in order to prevent adolescents to have access to to smoking.     

Surgical management of Graves' ophthalmopathy.

While most patients with Graves' ophthalmopathy have minor or largely cosmetic problems, severe ocular morbidity can occur and lead to blindness or eye loss. In this article the role of surgery in the management of Graves' ophthalmopathy is reviewed.     

Prevalence of peripheral arterial disease: persistence of excess risk in former smokers

Objective: To determine the age-standardised prevalence of peripheral arterial disease (PAD) and associated risk factors, particularly smoking.
Method: Design: Cross-sectional survey of a randomly selected population. Setting: Metropolitan area of Perth, Western Australia. Participants: Men aged between 65–83 years.
Results: The adjusted response fraction was 77.2%. Of 4,470 men assessed, 744 were identified as having PAD by the Edinburgh Claudication Questionnaire and/or the ankle-brachial index of systolic blood pressure, yielding an age-standardised prevalence of PAD of 15.6% (95% confidence intervals (CI): 14.5%, 16.6%). The main risk factors identified in univariate analyses were increasing age, smoking — current (OR=3.9, 95% CI 2.9–5.1) or former (OR=2.0, 95% CI 1.6–2.4), physical inactivity (OR=1.4, 95% CI 1.2–1.7), a history of angina (OR=2.2, 95% CI 1.8–2.7) and diabetes mellitus (OR=2.1, 95% CI 1.7–2.6). The multivariate analysis showed that the highest relative risk associated with PAD was current smoking of 25 or more cigarettes daily (OR=7.3, 95% CI 4.2–12.8). In this population, 32% of PAD was attributable to current smoking and a further 40% was attributable to past smoking by men who did not smoke currently.
Conclusions: This large observational study shows that PAD is relatively common in older, urban Australian men. In contrast with its relationship to coronary disease and stroke, previous smoking appears to have a long legacy of increased risk of PAD.
Implications: This research emphasises the importance of smoking as a preventable cause of PAD.     

Risk of papillary thyroid cancer in women in relation to smoking and alcohol consumption

Both smoking and alcohol consumption may influence thyroid function, although the nature of these relations is not well understood. We examined the influence of tobacco and alcohol use on risk of papillary thyroid cancer in a population-based case-control study. Of 558 women with thyroid cancer diagnosed during 1988-1994 identified as eligible, 468 (83.9%) were interviewed; this analysis was restricted to women with papillary histology (N = 410). Controls (N = 574) were identified by random digit dialing, with a response proportion of 73.6%. We used logistic regression to calculate odds ratios (OR) and associated confidence intervals (CI) estimating the relative risk of papillary thyroid cancer associated with cigarette smoking and alcohol consumption. A history of ever having smoked more than 100 cigarettes was associated with a reduced risk of disease (OR = 0.7, 95% CI = 0.5-0.9). This reduction in risk was most evident in current smokers (OR = 0.5, 95% CI = 0.4-0.7). Women who reported that they had ever consumed 12 or more alcohol-containing drinks within a year were also at reduced risk (OR 0.7, 95% CI = 0.5-1.0). Similar to the association noted with smoking, the reduction in risk was primarily present among current alcohol consumers. The associations we observed, if not due to chance, may be related to actions of cigarette smoking and alcohol consumption that reduce thyroid cell proliferation through effects on thyroid stimulating hormone, estrogen, or other mechanisms.     

郑州社区居民甲状腺结节患病及影响因素

目的 了解河南省郑州市社区居民甲状腺结节患病情况及影响因素。方法 采用分层整群抽样方法,抽取郑州社区3 478名≥18岁居民进行调查。结果 甲状腺结节患病率为21.28%,随年龄的增长而增加,各年龄组患病率差异有统计学意义（P<0.05）;女性甲状腺结节患病率为24.83%,男性为17.33%,女性高于男性（P<0.05）;甲状腺单发结节患病率为12.65%,高于多发结节患病率的8.63%（P<0.05）;女性甲状腺单发结节患病率为14.50%,多发结节患病率为10.34%,均高于男性的10.61%和6.73%,差异均有统计学意义（P<0.05）;多因素logistic回归分析结果表明,高龄（OR=6.349）、女性（OR=2.584）、文化程度低（OR=1.467）、工作压力大（OR=4.629）、生气频率高（OR=1.835）、吸烟（OR=1.445）、经常食用海产品（OR=1.751）、患有甲状腺疾病（OR=2.756）是甲状腺结节发生的危险因素。结论 郑州社区居民甲状腺结节患病率较高,甲状腺结节的发生可能与年龄、性别、文化程度、工作压力、生气频率、食用海产品及甲状腺疾病有关。     

Two cases of hyperthyroidism and ophthalmopathy following hypothyroidism

Two cases of Graves' disease emerging in previously hypothyroid patients are described. After two years of thyroid hormone substitution due to 'idiopathic' hypothyreosis (patient 1) and Hashimoto's thyroiditis (patient 2), the substitution had to be stopped. The persisting clinical and laboratory signs of immune hyperthyreosis, including positivity for TBII and TSAb, were accompanied by the signs of mild ophthalmopathy. The antibody-spectrum changes during the course of the disease are discussed.     

Prevalence of peripheral arterial disease: persistence of excess risk in former smokers

OBJECTIVE: To determine the age-standardised prevalence of peripheral arterial disease (PAD) and associated risk factors, particularly smoking. METHOD: Design: Cross-sectional survey of a randomly selected population. Setting: Metropolitan area of Perth, Western Australia. Participants: Men aged between 65-83 years. RESULTS: The adjusted response traction was 77.2%. Of 4,470 men assessed, 744 were identified as having PAD by the Edinburgh Claudication Questionnaire and/ or the ankle-brachial index of systolic blood pressure, yielding an age-standardised prevalence of PAD of 15.6% (95% confidence intervals (CI): 14.5%: 16.6%). The main risk factors identified in univariate analyses were increasing age, smoking-current (OR = 3.9, 95% CI 2.9-5.1) or former (OR = 2.0, 95% CI 1.6-2.4), physical inactivity (OR = 1.4, 95% CI 1.2-1.7), a history of angina (OR = 2.2, 95% Cl 1.8-2.7) and diabetes mellitus (OR = 2.1, 95% Cl 1.7-2.6). The multivariate analysis showed that the highest relative risk associated with PAD was current smoking of 25 or more cigarettes daily (OR = 7.3, 95% Cl 4.2-12.8). In this population, 32% of PAD was attributable to current smoking and a further 40% was attributable to past smoking by men who did not smoke currently. CONCLUSIONS: This large observational study shows that PAD is relatively common in older, urban Australian men. In contrast with its relationship to coronary disease and stroke, previous smoking appears to have a long legacy of increased risk of PAD. IMPLICATIONS: This research emphasises the importance of smoking as a preventable cause of PAD.     

Associations between respiratory illnesses and secondhand smoke exposure in flight attendants: A cross-sectional analysis of the Flight Attendant Medical Research Institute Survey

ABSTRACT: BACKGROUND: Secondhand tobacco smoke (SHS) is associated with increased risk of respiratory illness, cancer, and cardiovascular disease. Prior to smoking bans on airlines in the late 1980s, flight attendants were exposed to a significant amount of SHS. In the present study, we examine associations between flight attendant SHS exposure and development of respiratory illnesses and cardiovascular disease. METHODS: Between December 2006 and October 2010, three hundred sixty-two flight attendants completed an online questionnaire with information regarding experience as a flight attendant, medical history, smoking history, and SHS exposure. Rates of illnesses in flight attendants were compared with an age and smoking history matched population sample from NHANES 2005-2006. Logistic regression analysis was used to examine the association of reported medical conditions and pre-ban years of exposure. RESULTS: Compared with the sample from NHANES 2005-2006, flight attendants had increased prevalence of chronic bronchitis (11.7% vs. 7.2%, p < 0.05), emphysema/COPD (3.2% vs. 0.9%, p < 0.03), and sinus problems (31.5% vs. 20.9%, p < 0.002), despite a lower prevalence of medical illnesses including high blood pressure, diabetes, high cholesterol, heart failure, cancer, and thyroid disease. Amongst flight attendants who reported never smoking over their lifetimes, there was not a significant association between years of service as a flight attendant in the pre-smoking ban era and illnesses. However, in this same group, there was a significantly increased risk of daily symptoms (vs. no symptoms) of nasal congestion, throat, or eye irritation per 10-year increase of years of service as a flight attendant prior to the smoking ban (OR 2.14, 95% CI 1.41 - 3.24). CONCLUSIONS: Flight attendants experience increased rates of respiratory illnesses compared to a population sample. The frequency of symptoms of nasal congestion, throat or eye irritation is associated with occupational SHS exposure in the pre-smoking ban era.     

Smoking among adolescents and young adults in Belo Horizonte, Minas Gerais State, Brazil: the influence of family setting and social group

The study aimed to estimate smoking prevalence in Belo Horizonte, Minas Gerais State, Brazil, and related risk factors among adolescents. We used data from the household survey conducted by the Brazilian National Cancer Institute (2002-2003). The following variables were analyzed: demographic data; physical activity; smoking; and alcohol consumption. The study included information on 630 adolescents (15-24 years of age) living in Belo Horizonte. Multivariate logistic regression analyses were carried out, with hierarchical entry of variables into the model and the generalized estimating equation (GEE) method. Overall smoking prevalence was 11.7%. The following factors were associated with smoking: alcohol consumption (OR = 20.6), older age (OR = 1.2), paternal smoking (OR = 4.0), sibling smoker (OR = 2.5), and best friend smoker (OR = 5.2). Smoking prevalence among adolescents was high, increasing with age and alcohol consumption.     

Intravenous cyclophosphamide pulse therapy is effective for refractory Graves' ophthalmopathy

Graves' ophthalmopathy is the most frequent extrathyroidal manifestation of Graves' disease. Although glucocorticoids and orbital radiotherapy have been used and are effective for the disease, we often experience cases refractory to either therapy. We report here a case that did not respond satisfactorily to either therapy and was later successfully treated by intravenous cyclophosphamide (IV-CY) pulse therapy. A 31 year old woman presented with typical Graves' disease and ophthalmopathy. After establishing a euthyroid state, she received intravenous glucocorticoid pulse therapy and orbital radiotherapy. Although this induced the resolution of the ophthalmopathy, it was temporary and thyroid-stimulating antibody (TSAb) increased to high titers, associated with relapse of ophthalmopathy 2 months after the treatment. Four courses of IV-CY pulse therapy were administered, which resulted in complete improvement of the symptoms and normalization of the TSAb titers. We suggest that IV-CY pulse therapy might be useful for Graves' ophthalmopathy, especially for patients refractory to glucocorticoid pulse therapy.     

湖北省慢性阻塞性肺疾病流行病学调查及影响因素分析

目的 了解湖北省四个监测点慢性阻塞性肺疾病（chronic obstructive pulmonary disease,COPD）的患病情况及相关影响因素。方法 2014-2015年在湖北省开展2 400人的人群调查,按照多阶段分层整群抽样的方法抽取40岁及以上的居民,对人群进行问卷调查、身体测量和肺功能检查。采用复杂抽样设计的χ²检验和非条件Logistic回归模型对该人群COPD患病相关因素进行分析。结果 共调查40岁以上成年人2 389人,COPD患病人数为213人（占8.92%）。经复杂加权后患病率为12.36%（95%CI：6.95%~17.77%）,乡村患病率（13.96%）高于城镇（9.04%）,男性患病率（17.47%）高于女性（6.54%）。χ²检验结果显示,地区、性别、年龄、收缩压、体质指数（body mass index,BMI）和是否吸烟是COPD患病的相关因素（均有P<0.05）。多因素Logistic回归分析结果显示,与40~岁年龄组相比,年龄在50~岁（OR=2.316,95%CI：1.999~2.683）、60~岁（OR=4.641,95%CI：2.479~8.687）和70岁及以上（OR=9.066,95%CI：5.735~14.333）会增加COPD患病风险;吸烟（OR=3.376,95%CI：2.357~4.834）和使用家庭取暖污染燃料（OR=1.734,95%CI：1.264~2.380）也是COPD患病的危险因素;与低体重相比,超重（OR=0.599,95%CI：0.367~0.978）和肥胖（OR=0.404,95%CI：0.218~0.752）的人群患COPD的风险较低。结论 湖北省乡村人群中男性的COPD患病率较高,年龄大、有吸烟史、使用家庭取暖污染燃料的人群患COPD的风险较高,应开展有针对性的干预措施。