Home About us Contact
|
Home About us Contact | ||
|
|
||
Autoimmune Thyroid Disease (autoimmune + thyroid_disease)
Selected AbstractsPrevalence of autoimmune diseases in islet transplant candidates with severe hypoglycaemia and glycaemic lability: previously undiagnosed coeliac and autoimmune thyroid disease is identified by screeningDIABETIC MEDICINE, Issue 2 2007M. Walter Abstract Aims, Autoimmune diseases such as Addison's or coeliac disease can contribute to hypoglycaemia or malabsorption and are more common in Type 1 diabetes (T1DM). This brief report describes the prevalence of known and newly detected autoimmune disease in clinical islet transplant candidates with longstanding T1DM and severe hypoglycaemia and/or glycaemic lability who are routinely screened for coexisting autoimmune disease. Methods, One hundred and twenty-four C-peptide negative T1DM subjects [77 (62%) female, mean age 44 ± 9 years, diabetes duration 28 ± 11 years, body mass index 24.9 ± 3.5 kg/m2] with indications for clinical islet transplantation at the University of Alberta were screened for autoimmune disease by history and measurement of anti-transglutaminase antibodies (positive > 10 U/ml), 09.00 h cortisol (followed by adrenocorticotrophic hormone-stimulation if < 495 nmol/l) and thyroid-stimulating hormone to determine the prevalence of coeliac disease, Addison's disease and autoimmune thyroid disease, respectively. Results, Forty per cent of subjects had one or more coexisting autoimmune disease. The prevalence of autoimmune disease was 35%, coeliac disease 8% and Addison's disease 1.6%. In 11 individuals (9%), one or more autoimmune disease were newly detected (seven coeliac disease and five thyroid disease). Seven of 10 cases of coeliac disease were newly detected. A gluten-free diet in individuals with newly diagnosed coeliac disease reduced gastrointestinal symptoms, but indications for clinical islet cell transplantation persisted. Conclusions, Coexisting autoimmune disease is common in candidates for clinical islet cell transplantation. Screening in this group identified a substantial number of previously unrecognized cases. Clinicians should consider the presence of autoimmune disease even in the absence of classical symptoms. [source] Role of X chromosome defects in primary biliary cirrhosisHEPATOLOGY RESEARCH, Issue 2007Pietro Invernizzi Similar to the majority of autoimmune conditions, primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by a striking female predominance; it is characterized by high titer serum autoantibodies to mitochondrial antigens, elevated serum immunoglobulin M, progressive destruction of intrahepatic bile ducts, and ultimately liver cirrhosis and failure. Familiarity and high concordance rates for the disease among monozygotic twins strongly support the role of genetics in the disease. Experimental efforts have been dedicated by our and other research groups to investigate the role of X chromosome abnormalities (i.e. monosomyrates and inactivation patterns) in autoimmunity. Our recent work has demonstrated enhanced X monosomy in women with PBC as well as two other female-predominant autoimmune diseases, systemic sclerosis and autoimmune thyroid disease. We will review herein the most recent evidence on the role of the X chromosome in PBC onset and discuss the potential implications. Future developments of these findings will be discussed. [source] Non-axial bone fracture but not depression as a risk factor for coeliac diseaseINTERNAL MEDICINE JOURNAL, Issue 3 2010V. P. Tan Abstract Screening for coeliac disease is confined to subgroups at greater risk for the disease, including type 1 diabetes mellitus, autoimmune thyroid disease and family members of affected individuals. This study examined the hypothesis that patients taking antidepressants or presenting with fractures could represent new subgroups at higher risk for coeliac disease. A total of 105 and 199 consecutive patients presenting to hospital taking antidepressants and/or with a fracture was screened with IgA tissue transglutaminase and had their IgA serum levels quantified. Patients with positive serology were offered further diagnostic and management follow up. No patients taking antidepressants had positive serology. Seven with fractures had elevated titres of IgA tissue transglutaminase. All of these patients had presented with non-axial fractures, representing a prevalence of 5.2% (95% confidence interval: 1.4,8.9%). Uptake of further investigation and management was poor. Patients presenting with non-axial fractures may be a subgroup in whom coeliac screening may be indicated. There needs to be greater awareness of atypical presentations of coeliac disease. [source] Vitiligo in an urban academic setting,INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 1 2010Taraneh Paravar MD Background, Vitiligo is a depigmenting disease of unknown etiology. A more complete understanding of vitiligo and associated conditions will provide better insight into the etiology and potential treatment options for this condition. We sought to gather information regarding associated conditions and other epidemiologic data on vitiligo. Methods, A retrospective chart review was performed of 135 patients with vitiligo seen between July 1, 2002 and June 30, 2005 at an academic medical center. Epidemiologic characteristics were recorded. Results, The patient population consisted of 80 women and 55 men with mean age of presentation of 36.8 years and average disease duration of 5.7 years. Vitiligo vulgaris was the predominant type of vitiligo and hypothyroidism was the most common co-morbidity. Anti-thyroid peroxidase and anti-thyroglobulin antibodies were found in 37% and 18% of patients, respectively. The highest proportion of thyroid abnormalities was found in age of onset category 21,30. Anti-nuclear antibodies were found in 33% of patients. Conclusion, The prevalence of anti-nuclear and anti-thyroid peroxidase antibodies was higher in our vitiligo study than that reported elsewhere. In addition, autoimmune thyroid disease may be more common in adult-onset vitiligo. [source] Investigation of the functional variant c.-169T > C of the Fc receptor-like 3 (FCRL3) gene in alopecia areataINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 6 2006N. Schäfer A functional variant in the Fc receptor-like 3 (FCRL3) gene has been implicated in susceptibility to autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus and autoimmune thyroid disease. Investigating a large case-control sample of patients with alopecia areata (AA), we found no evidence for the involvement of FCRL3 in susceptibility to AA. [source] Development of liver dysfunction after delivery is possibly due to postpartum autoimmune hepatitis.JOURNAL OF INTERNAL MEDICINE, Issue 4 2002A report of three cases Autoimmune diseases, especially autoimmune thyroid disease, frequently develop after delivery due to the immune rebound mechanism. Most cases involve transient dysfunction of affected organs. Weexamined three patients who developed liver dysfunction after delivery. They were all diagnosed with definite or probable autoimmune hepatitis using the scoring system of the International Autoimmune Hepatitis Group. Moreover, all of them had anti-CYP2D6 antibodies detected by a sensitive radioligand assay. Our findings strongly suggest that liver dysfunction is induced by postpartum autoimmune hepatitis, and clinicians should be aware of this disease. [source] EAACI/GA2LEN task force consensus report: the autologous serum skin test in urticariaALLERGY, Issue 9 2009G. N. Konstantinou Injection of autologous serum collected during disease activity from some patients with chronic spontaneous urticaria (CU) into clinically normal skin elicits an immediate weal and flare response. This observation provides a convincing demonstration of a circulating factor or factors that may be relevant to the understanding of the pathogenesis and management of the disease. This test has become known as the autologous serum skin test (ASST) and is now widely practised despite incomplete agreement about its value and meaning, the methodology and the definition of a positive response. It should be regarded as a test for autoreactivity rather than a specific test for autoimmune urticaria. It has only moderate specificity as a marker for functional autoantibodies against IgE or the high affinity IgE receptor (Fc,RI), detected by the basophil histamine release assay, but high negative predictive value for CU patients without them. It is usually negative in other patterns of CU, including those that are physically induced. Positive ASSTs have been reported in some subjects without CU, including those with multiple drug intolerance, patients with respiratory allergy and healthy controls, although the clinical implications of this are uncertain. It is essential that failsafe precautions are taken to ensure that the patient's own serum is used for skin testing and aseptic procedures are followed for sample preparation and handling. CU patients with a positive ASST (ASST+) are more likely to be associated with HLADR4, to have autoimmune thyroid disease, a more prolonged disease course and may be less responsive to H1-antihistamine treatment than those with a negative ASST (ASST,) although more evidence is needed to confirm these observations conclusively. [source] Acute ataxia, Graves' disease, and stiff person syndromeMOVEMENT DISORDERS, Issue 13 2007Su-Ynn Chia MD Abstract Stiff person syndrome (SPS) has been associated with autoimmune diseases, such as Type 1 diabetes mellitus and autoimmune thyroid disease (Hashimoto's thyroiditis), among others. The association of SPS with hyperthyroidism is extremely rare. We describe a patient with uncontrolled Graves' disease and undiagnosed SPS, who presented initially with acute ataxia simulating a cerebrovascular accident. Initiation of immunosuppressive therapy dramatically improved the patient's Graves' disease within 2 weeks but the neurological symptoms were not alleviated after a follow-up period of 3 years. © 2007 Movement Disorder Society [source] Thyroid autoimmunity in children with features of both type 1 and type 2 diabetesPEDIATRIC DIABETES, Issue 4pt1 2008Ingrid M Libman Aim/hypothesis:, To assess the prevalence of autoimmune thyroid disease (ATD) in insulin-treated youth with clinical features of type 2 diabetes mellitus (T2DM). Methods:, We evaluated prevalence of thyroid peroxidase (TPO) and thyroglobulin (TGA) antibodies at onset of insulin-treated diabetes and follow-up in 183 White and Black children. Of these, 136 had a body mass index (BMI) <85th percentile with 122 (89%) positive for ,-cell autoimmunity [type 1 diabetes mellitus (T1DM)/group I], 25 were overweight (BMI ,85thpercentile) with or without acanthosis nigricans with ,-cell autoimmunity [,double' diabetes (DD)/group II], and 22 were overweight with no conventional ,-cell autoantibodies (group III). Results:, The prevalence of TPO and/or TGA was 39 and 29% (p = 0.19) in White and Black children and 39, 32, and 0% (p = 0.007) in groups I, II, and III, respectively. After a median follow-up of 60 months, 3.7, 4.3, and 0% developed hypothyroidism (increased thyroid-stimulating hormone with or without decreased free T4) in groups I, II, and III, respectively (p = 0.6). In subjects with TPO and/or TGA, hypothyroidism developed in 10 and 14% of groups I and II, respectively (p = 0.7). No child without thyroid antibodies developed hypothyroidism. Conclusions:, In patients with clinical features of T2DM who have evidence of ,-cell autoimmunity (DD), the frequency of thyroid antibodies and ATD is similar to that in classical T1DM. This suggests that TIDM comorbidities may be common in clinical T2DM patients who have ,-cell autoimmunity. Despite their obesity, youth with insulin-requiring diabetes should be screened for thyroid and possibly other T1DM-associated autoimmune diseases. [source] Hepatitis B vaccine and risk of autoimmune thyroid disease: a Vaccine Safety Datalink study,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 7 2007Onchee Yu MS Abstract Purpose Hepatitis B vaccine has been postulated as a possible cause of autoimmune disorders, including autoimmune thyroid diseases (ATD). Cases of Graves' disease and Hashimoto's thyroiditis, following hepatitis B vaccine have been reported to the Vaccine Adverse Events Reporting System (VAERS). To test the hypothesis that hepatitis B vaccine increases the risk of ATD, we conducted a case-control study, within the Vaccine Safety Datalink project. Methods We identified potential cases of Graves' disease and Hashimoto's thyroiditis, among persons aged 18,69 years from administrative data recorded by three health maintenance organizations (HMOs) and verified cases by medical record review. Controls were frequency-matched to cases by birth year, sex, and study site. Vaccine information was collected from administrative records, chart review, and telephone interviews with study subjects. We enrolled 355 Graves' disease cases, 418 Hashimoto's thyroiditis cases, and 1102 controls. We assessed the association between ever-receipt of hepatitis B vaccine, as well as receipt of hepatitis B vaccine less than 1 year, 1,5 years and at least 5 years prior to the index date, and the risk of ATD. Results Ever-receipt of hepatitis B vaccine was not associated with risk of Graves' disease (odds ratio (OR), 0.90; 95% confidence interval (CI), 0.62,1.32) or Hashimoto's thyroiditis (OR, 1.23; 95%CI, 0.87,1.73). There was also no association between the time interval since receipt of hepatitis B vaccination and either outcome. Conclusions We did not observe an increased risk of Graves' disease or Hashimoto's thyroiditis, following receipt of hepatitis B vaccine. Copyright © 2007 John Wiley & Sons, Ltd. [source] Does autoimmune thyroid disease affect parathyroid autotransplantation and survival?ANZ JOURNAL OF SURGERY, Issue 5 2009Houman Ebrahimi Abstract Background:, While the increased risk to parathyroid gland preservation has long been recognized during surgery for thyroid cancer, the effect of different benign pathological conditions on parathyroid preservation has not previously been reported. The aim of this study was to examine parathyroid viability in relation to autoimmune thyroid disease. Methods:, This is a retrospective cohort study including all patients having an initial total thyroidectomy (TT) performed by this unit during the period 2004,2005. Results:, A total of 628 patients underwent TT in the study period. For the Graves' disease cases, 45 (62.5%) required the autotransplantation of one or less parathyroid gland, whereas 27 (37.5%) required two or more glands to be autotransplanted. This was significantly higher than for the benign thyroid disease group in which the respective figures were 242 (77.6%) and 70 (22.4%) (P= 0.01). Of the lymphocytic thyroiditis cases, 61 (65.5%) required the autotransplantation of one or less gland, whereas 32 (34.4%) required the autotransplantation of two or more glands. This was also significantly higher (P= 0.03). Temporary hypocalcaemia was significantly higher when two or more glands were autotransplanted (23 out of 177, 13.2%) than one or less gland autotransplanted (18 out of 451, 4.0%, P < 0.01). However, the overall incidence of permanent hypoparathyroidism was 1.0%, and there was no significant difference between the groups. Conclusion:, TT performed for Graves' disease and lymphocytic thyroiditis results in the autotransplantation of more parathyroid glands, leading to a higher incidence of temporary hypocalcaemia post-operatively. Despite this, the incidence of permanent hypoparathyroidism remains low at 1%. [source] Rheumatoid arthritis association with the FCRL3 ,169C polymorphism is restricted to PTPN22 1858T,homozygous individuals in a Canadian populationARTHRITIS & RHEUMATISM, Issue 12 2006William G. Newman Objective Variants in genes encoding the Fc receptor,like 3 (FcRL-3) and the class II major histocompatibility complex (MHC) transactivator proteins have been associated with an increased risk of rheumatoid arthritis (RA) in Japanese and Nordic populations, respectively. The aim of this study was to investigate these associations in a Canadian Caucasian cohort of RA cases and healthy controls. Methods A total of 1,187 RA patients and 462 healthy controls were genotyped for FCRL3 and MHC2TA gene variants associated with RA. Epistasis between the FCRL3 ,169C and the PTPN22 1858T variants was also examined. Results An association was detected between RA and both the FCRL3 ,169C allele (OR 1.19, P = 0.023) and the homozygous genotype (OR 1.41, P = 0.027), but association of the MHC2TA promoter region variant (,168G) with RA was not replicated. Stratification of the RA cohort by PTPN22 genotypes revealed the FCRL3 risk variant and RA association was stronger in the patient subgroup lacking PTPN22 1858T variants (P = 0.004) and was not detectable in the subgroup with PTPN22 1858T variants (P = 0.52). The PTPN22 association with RA was greater in the absence than in the presence of the FCRL3 ,169C allele (P = 0.0008 versus P = 0.001). The PTPN22 1858T variant also increased the risk of autoimmune thyroid disease (AITD) in the RA patients, whereas the FCRL3 risk variant was protective against AITD. Conclusion Our findings support an association of RA with an FCRL3 functional polymorphism and reveal that this association is stronger in the absence of PTPN22 risk genotypes. These findings support a genetic heterogeneity across RA populations, suggesting that both the FCRL3 and PTPN22 genes play roles in RA susceptibility, but in different individuals. [source] The +869T/C polymorphism in the transforming growth factor-,1 gene is associated with the severity and intractability of autoimmune thyroid diseaseCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2008H. Yamada Summary The severity of Hashimoto's disease (HD) and the intractability of Graves' disease (GD) vary among patients. To clarify whether the +869T/C polymorphism in the transforming growth factor-,1 (TGF-,1) gene, which is associated with TGF-,1 expression, is involved in the intractability of GD and severity of HD, we genotyped the TGF-,1 +869T/C polymorphism by polymerase chain reaction,restriction fragment length polymorphism method in genomic DNA samples from 33 patients with HD who developed hypothyroidism before they were 50 years old (severe HD) and 30 untreated, euthyroid patients with HD who were older than 50 years (mild HD). We also examined 48 euthyroid patients with GD who had been under treatment and were still positive for anti-thyrotropin receptor antibodies (intractable GD), 20 euthyroid patients with GD in remission and 45 healthy controls. The frequency of the T allele and the TT genotype were higher in patients with severe HD than in those with in mild HD. In contrast, the frequency of the CC genotype was higher in patients with intractable GD than in patients with GD in remission. In conclusion, the +869T/C polymorphism in the TGF-,1 gene is associated with the severity and intractability of autoimmune thyroid disease. [source] Both Th1- and Th2-derived cytokines in serum are elevated in Graves' ophthalmopathyCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2000I. M. M. J. Wakelkamp Increased serum cytokine levels have been reported in patients with autoimmune thyroid disease, but less is known about their levels in patients with Graves' ophthalmopathy (GO). It is not known whether GO is a cell-mediated or humoral autoimmune disease. We investigated whether serum cytokines are elevated in GO patients and whether the cytokines were Th1- or Th2-derived. In addition, elevated cytokines might reflect the activity of GO, and thus we investigated whether cytokine levels could predict the clinical response to orbital radiotherapy. We studied 62 consecutive patients with moderately severe untreated GO and 62 healthy controls, matched for sex, age and smoking habits. Serum concentrations of IL-1RA, sIL-2R, IL-6, sIL-6R, tumour necrosis factor-alpha (TNF- ,) RI and II and sCD30 were measured using highly sensitive ELISAs, in the patients before and 3 and 6 months after radiotherapy. All patients were euthyroid, with anti-thyroid drugs, before and during the entire study period. All baseline cytokine and cytokine receptor levels were significantly elevated in GO patients compared with healthy controls, except for IL-1RA. The levels did not correlate with parameters of the thyroid disease, nor with the duration, activity or severity of GO. However, backward logistic regression analysis showed that IL-6, sCD30 and TNF,RI were able to predict a beneficial response to orbital radiotherapy. We therefore conclude that both Th1- and Th2-derived cytokines are elevated in GO patients compared with its controls. IL-6, sCD30 and TNF,RI had some value for predicting therapeutic outcome to orbital irradiation, and may thus reflect active eye disease. [source] Regulatory T cells in Graves' diseaseCLINICAL ENDOCRINOLOGY, Issue 4 2009Deshun Pan Summary Context, Graves' disease (GD) involves auto-immunity against thyroid cell antigens, but the reasons for induction of auto-immunity are uncertain. We wished to determine whether there was a deficiency of regulatory T cells in patients with active GD. Design, Venous blood samples were obtained from patients with GD before and after treatment, and controls, and peripheral blood mononuclear cells were prepared. Patients and measurements, Regulatory T cells were enumerated by Fluorescent Activated Cell sorting (FACS) in nineteen patients with untreated GD, 9 patients 6,8 weeks post RAI therapy, and 30 control subjects. Twenty-one patients with active GD prior to control of hyperthyroidism, 23 euthyroid controls without known autoimmune thyroid disease, and 10 patients who were euthyroid 6,12 months after RAI treatment were studied for expression of genes found in regulatory T cells by real-time Polymerase Chain reaction (PCR). Results, Percent distribution of CD4+, CD4+CD25+ and CD4+ CD25+int-hi CD127+lo regulatory T cells was similar in active GD patients and control subjects. The number of CD25+ and CD4+ CD25+int-hi CD127+lo cells was similar in GD patients and control subjects, but was lower in recently treated patients. Messenger RNA was prepared from PBMC, and reverse transcribed. Copy DNA abundance was evaluated by Real Time PCR using appropriate primers, for GAPDH (glyceraldehyde phosphate dehydrogenase) as a control housekeeping gene, and 5 genes related to function of regulatory T cells. Message RNA for Gadd45 alpha, Gadd45beta (growth arrest and damage inducible proteins), GITR (glucocorticoid inducible TNF receptor) and CD25 (IL-2R subunit) was more abundant in patients with active GD than in normal controls, and FoxP3 mRNA level was equal to that in controls. Message RNA levels in patients treated and euthyroid for 6 months were also greater than or equal to values in controls. Conclusion, This study provides evidence that there is no deficit in T regulatory cells during active GD, or during the months post therapy. [source] The incidence of autoimmune thyroid disease: a systematic review of the literatureCLINICAL ENDOCRINOLOGY, Issue 5 2008Anita McGrogan Summary Objective, To undertake a systematic review of literature published between 1980 and 2008 on the incidence of autoimmune thyroid disease. Design, All relevant papers found through searches of Medline, EMBASE and ScienceDirect were critically appraised and an assessment was made of the reliability of the reported incidence data. Results, The reported incidence of autoimmune hypothyroidism varied between 2·2/100 000/year (males) and 498·4/100 000/year (females) and for autoimmune hyperthyroidism, incidence ranged from 0·70/100 000/year (Black males) to 99/100 000/year (Caucasian females). Higher incidence rates were found in women compared to men for all types of autoimmune thyroid disease. The majority of studies included in the review investigated Caucasian populations mainly from Scandinavia, Spain, the UK and the USA. It is possible that nonautoimmune cases were included in the incidence rates reported here, which would give an overestimation in the incidence rates of autoimmune disease presented. Conclusion, To our knowledge this is the most comprehensive systematic review of autoimmune thyroid disease conducted in the past two decades. Studies of incidence of autoimmune thyroid disease have only been conducted in a small number of mainly western countries. Our best estimates of the incidence of hypothyroidism is 350/100 000/year in women and 80/100 000/year in men; the incidence of hyperthyroidism is 80/100 000/year in women and 8/100 000/year in men. [source] Increased death risk and altered cancer incidence pattern in patients with isolated or combined autoimmune primary adrenocortical insufficiencyCLINICAL ENDOCRINOLOGY, Issue 5 2008Sophie Bensing Summary Objectives, Primary adrenocortical insufficiency is mostly caused by an autoimmune destruction of the adrenal cortex. The disease may appear isolated or as a part of an autoimmune polyendocrine syndrome (APS). APS1 is a rare hereditary disorder with a broad spectrum of clinical manifestations. In APS2, primary adrenocortical insufficiency is often combined with autoimmune thyroid disease and/or type 1 diabetes. We analysed mortality and cancer incidence in primary adrenocortical insufficiency patients during 40 years. Data were compared with the general Swedish population. Design and patients, A population based cohort study including all patients with autoimmune primary adrenocortical insufficiency (3299) admitted to Swedish hospitals 1964,2004. Measurements, Mortality risk was calculated as the standardized mortality ratio (SMR) and cancer incidence as the standardized incidence ratio (SIR). Results, A more than 2-fold increased mortality risk was observed in both women (SMR 2·9, 95% CI 2·7,3·0) and men (SMR 2·5, 95% CI 2·3,2·7). Highest risks were observed in patients diagnosed in childhood. SMR was higher in APS1 patients (SMR 4·6, 95% CI 3·5,6·0) compared with patients with APS2 (SMR 2·1, 95% CI 1·9,2·4). Cancer incidence was increased (SIR 1·3, 95% CI 1·2,1·5). When tumours observed during the first year of follow-up were excluded, only the cancer risk among APS1 patients remained increased. Cause-specific cancer incidence analysis revealed significantly higher incidences of oral cancer, nonmelanoma skin cancer, and male genital system cancer among patients. Breast cancer incidence was lower than in the general population. Conclusions, Our study shows a reduced life expectancy and altered cancer incidence pattern in patients with autoimmune primary adrenocortical insufficiency. [source] Cellular immune responses in autoimmune thyroid diseaseCLINICAL ENDOCRINOLOGY, Issue 4 2004A. P. Weetman Summary Recent research in autoimmune thyroid disease (AITD) has largely focused on delineation of the autoantigens and their epitopes, but there is now renewed interest in the immunoregulatory properties of T cells, an understanding of which may explain the emergence of AITD in experimental settings. T cell recognition of autoantigens has shown considerable intra- and interindividual heterogeneity, and a mixed pattern of cytokine production indicates that both the Th1 and Th2 limbs of the helper T cell response are involved in all types of AITD. It is now clear that secretion of chemokines and cytokines within the thyroid accounts for the accumulation and expansion of the intrathyroidal lymphocyte pool, and that the thyroid cells themselves contribute to this secretion. The thyroid cells also produce a number of proinflammatory molecules which will tend to exacerbate the autoimmune process. Thyroid cell destruction in autoimmune hypothyroidism is dependent on T cell-mediated cytotoxicity with the likely additional effect of death receptor-mediated apoptosis. [source] Propylthiouracil and carbimazole associated-antineutrophil cytoplasmic antibodies (ANCA) in patients with Graves' diseaseCLINICAL ENDOCRINOLOGY, Issue 6 2004L. Harper Summary objective, Propylthiouracil treatment of Graves' disease has been postulated to provoke antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. We aimed to investigate whether carbimazole therapy was also associated with increased risk of ANCA. design, The occurrence of ANCA and the relationship to thionamide treatment was investigated in a cross-sectional study in a consecutive series of 407 patients' with Graves' disease, 200 with Hashimoto's thyroiditis and 649 normal euthyroid subjects. measurements, ANCA was measured by indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA) for proteinase 3 and myeloperoxidase-ANCA. results, The prevalence of ANCA, as measured by IIF, was increased in the Graves' disease cohort (19·9%) compared with euthyroid controls (4·6%; P < 0·001). The prevalence of MPO-ANCA (measured by ELISA) was also increased in Graves' disease (P = 0·019). ANCA prevalence was more strongly associated with propylthiouracil treatment than carbimazole (P = 0·0265), although risk of ANCA was also higher in Graves' patients treated with carbimazole than controls (RR 2·2, P < 0·0001). ANCA positivity was not increased in patients with Hashimoto's thyroiditis. conclusion, This study revealed a high prevalence of ANCA in treated patients with Graves' disease but not in those with Hashimoto's thyroiditis. Furthermore, within the Graves' disease population, ANCA development was associated with propylthiouracil usage to a greater extent than carbimazole. These findings suggest that the altered immune environment associated with autoimmune thyroid disease is not sufficient to develop ANCA but treatment with thionamides is important in promoting ANCA development. [source] Risk factors of primary thyroid dysfunction in early infants born to mothers with autoimmune thyroid diseaseACTA PAEDIATRICA, Issue 8 2005Junfen Fu Abstract Aim: To assess whether the state of maternal thyroid function and the pattern of thyroid alterations during gestation would affect the infants' thyroid function and to evaluate the risk factors affecting early infants' thyroid function by means of multiple logistic regression. Methods: In a cross-sectional study, 78 neonates born to mothers with Graves disease or Hashimoto thyroiditis were examined and followed clinically and biochemically. Neonates born to healthy mothers during the same period were set as controls. Tests of thyroid function, antithyroid peroxidase antibody (TPOAb), antithyroglobulin antibody (TGAb), anti-TSH receptor antibody (TRAb) and antithyroid-stimulating antibody (TSAb) were performed both in early infants and their mothers. All possible maternal and/or infantile risk factors for thyroid dysfunction during early infancy were analysed by means of multiple-factor logistical regression. Results: The overall prevalence of underlying subtle thyroid abnormalities in these 78 infants was 52.6%, which was significantly higher than that witnessed among infants from healthy mothers (5.4,, p<0.01). By using multiple logistic regression analysis, the state of maternal thyroid function in gestation, the type of autoimmune thyroid disease during pregnancy and the level of TRAb in the newborn were significantly correlated with the early infants' thyroid dysfunction. Conclusion: Maternal autoimmune thyroid disease during pregnancy will affect infant thyroid function. Therefore, appropriate management of maternal autoimmune thyroid disease throughout pregnancy is essential in the prevention of undesirable neonatal outcomes. [source] The influence of human leucocyte antigen (HLA) genes on autoimmune thyroid disease (AITD): results of studies in HLA-DR3 positive AITD familiesCLINICAL ENDOCRINOLOGY, Issue 1 2002Yoshiyuki Ban Summary objective Population-based, case,control studies have consistently shown association of Graves' disease (GD) with human leucocyte antigen (HLA)-DR3 in Caucasian populations. HLA association studies in Hashimoto's thyroiditis (HT) have also suggested an association with DR3, as well as with other HLA alleles. In contrast, HLA linkage studies in autoimmune thyroid disease (AITD) have been largely negative. The aim of the present study was to investigate the role of HLA in AITD and to explain the observed associations, but lack of linkage, by examining only AITD families with the associated allele, DR3. patients We studied 99 probands (60 with GD and 39 with HT) from 99 multiplex, multigenerational Caucasian AITD families, and 135 age- and sex-matched Caucasian controls in association studies. In addition, a dataset of 34 Caucasian AITD families (out of the 99 families) with HLA-DR3 positive probands were analysed in linkage studies. design HLA typing was performed using the technique of group-specific polymerase chain reaction-amplification with restriction enzyme digestion. Whole genome screening was performed using the ABI microsatellite panels. For fine mapping of the HLA region, we used the following markers: D6S276, D6S464, D6S439, D6S273, tumour necrosis factor , and D6S1610. LOD scores were calculated using the LIPED and GeneHunter programs. results Case,control association analyses using the probands from our 99 Caucasian families showed an association of GD with DRB1*03 [P = 0·00032, relative risk (RR) = 3·4]. Linkage analysis for the HLA region in the 34 DR3 positive AITD families showed negative LOD scores throughout the region. The two-point LOD score at marker D6S273 (the closest to HLA-DRB1) was ,3·0, and the multipoint LOD score was ,7·6, demonstrating strong evidence against linkage to the HLA region in the subset of DR3 positive families. Whole genome screening in the subset of 34 DR3 positive families revealed one locus showing evidence for linkage to AITD: D3S1580 on chromosome 3q27 with a maximum two-point LOD score of 2·1. conclusions The HLA locus did not cosegregate with disease in DR3 positive families, suggesting that HLA genes are not major genes for AITD expression even within DR3 positive families; Hence, although HLA-DR3 was associated with GD in the probands, it was most likely a modulating gene and not causative; and, as the DR3 positive families showed evidence for linkage with D3S1580, it may imply that the DR3 gene modulated the effect of a susceptibility gene within the D3S1580 locus. [source] Apoptosis and autoimmune thyroid disease: following a TRAIL to thyroid destruction?CLINICAL ENDOCRINOLOGY, Issue 1 2001James D. Bretz [source] | |||||||||||||||||||||||||