Hashimoto Disease
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Publication
Journal: Autoimmunity Reviews
May/6/2014
Abstract
Hashimoto thyroiditis (HT), now considered the most common autoimmune disease, was described over a century ago as a pronounced lymphoid goiter affecting predominantly women. In addition to this classic form, several other clinico-pathologic entities are now included under the term HT: fibrous variant, IgG4-related variant, juvenile form, Hashitoxicosis, and painless thyroiditis (sporadic or post-partum). All forms are characterized pathologically by the infiltration of hematopoietic mononuclear cells, mainly lymphocytes, in the interstitium among the thyroid follicles, although specific features can be recognized in each variant. Thyroid cells undergo atrophy or transform into a bolder type of follicular cell rich in mitochondria called Hürthle cell. Most HT forms ultimately evolve into hypothyroidism, although at presentation patients can be euthyroid or even hyperthyroid. The diagnosis of HT relies on the demonstration of circulating antibodies to thyroid antigens (mainly thyroperoxidase and thyroglobulin) and reduced echogenicity on thyroid sonogram in a patient with proper clinical features. The treatment remains symptomatic and based on the administration of synthetic thyroid hormones to correct the hypothyroidism as needed. Surgery is performed when the goiter is large enough to cause significant compression of the surrounding cervical structures, or when some areas of the thyroid gland mimic the features of a nodule whose cytology cannot be ascertained as benign. HT remains a complex and ever expanding disease of unknown pathogenesis that awaits prevention or novel forms of treatment.
Publication
Journal: JAMA - Journal of the American Medical Association
April/30/2002
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Journal: The Lancet
April/30/2002
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Journal: Endocrine
April/2/2013
Abstract
The thyroid gland is the most common organ affected by autoimmune disease. Other autoimmune diseases, most notably type 1 diabetes mellitus, are increasing in incidence. It is unknown whether autoimmune thyroid diseases are following the same pattern. This review summarizes studies of autoimmune thyroid disease incidence and prevalence since 1950, not only for these measures of occurrences, but also for commenting on identified risk factors for thyroid autoimmunity. We find that incidence of autoimmune thyroid disease is currently higher than in historic series although the studies are so variable in design, patient population, disease definition, and laboratory methods that it is impossible to tell whether this difference is real. Further research is required to assess the possibility of changing disease patterns of autoimmune thyroid disease as opposed to simple changes in diagnostic thresholds.
Publication
Journal: Archives of neurology
February/27/2006
Abstract
BACKGROUND
Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), often termed Hashimoto encephalopathy, is a poorly understood and often misdiagnosed entity.
OBJECTIVE
To characterize the clinical, laboratory, and radiologic findings in patients with SREAT to potentially improve recognition of this treatable entity.
METHODS
Retrospective analysis of clinical features and diagnostic test data.
METHODS
Two affiliated tertiary care referral institutions.
METHODS
Twenty consecutive (6 male) patients diagnosed as having SREAT from 1995 to 2003.
METHODS
Clinical features and ancillary test findings associated with SREAT.
RESULTS
The median age at disease onset was 56 years (range, 27-84 years). The most frequent clinical features were tremor in 16 (80%), transient aphasia in 16 (80%), myoclonus in 13 (65%), gait ataxia in 13 (65%), seizures in 12 (60%), and sleep abnormalities in 11 (55%). All patients were assigned an alternative misdiagnosis at presentation, most commonly viral encephalitis (n = 5), Creutzfeldt-Jakob disease (n = 3), or a degenerative dementia (n = 4). The most frequent laboratory abnormalities were increased liver enzyme levels in 11, increased serum sensitive thyroid-stimulating hormone levels in 11, and increased erythrocyte sedimentation rate in 5. In only 5 patients (25%) did cerebrospinal fluid abnormalities suggest an inflammatory process. Magnetic resonance imaging abnormalities believed to be related to the encephalopathy were present in 5 patients (26%).
CONCLUSIONS
The clinical, laboratory, and radiologic findings associated with SREAT are more varied than previously reported. Misdiagnosis at presentation is common. This treatable syndrome should be considered even if the serum sensitive thyroid-stimulating hormone level and erythrocyte sedimentation rate are normal, the cerebrospinal fluid profile does not suggest an inflammatory process, and neuroimaging results are normal. Until the pathophysiologic mechanism of this and other autoimmune encephalopathies is better characterized, we believe that descriptive terms that reflect an association rather than causation are most appropriate for this syndrome.
Publication
Journal: American Journal of Medicine
February/24/2010
Abstract
BACKGROUND
Common autoimmune disorders tend to coexist in the same subjects and to cluster in families.
METHODS
We performed a cross-sectional multicenter study of 3286 Caucasian subjects (2791 with Graves' disease; 495 with Hashimoto's thyroiditis) attending UK hospital thyroid clinics to quantify the prevalence of coexisting autoimmune disorders. All subjects completed a structured questionnaire seeking a personal and parental history of common autoimmune disorders, as well as a history of hyperthyroidism or hypothyroidism among parents.
RESULTS
The frequency of another autoimmune disorder was 9.67% in Graves' disease and 14.3% in Hashimoto's thyroiditis index cases (P=.005). Rheumatoid arthritis was the most common coexisting autoimmune disorder (found in 3.15% of Graves' disease and 4.24% of Hashimoto's thyroiditis cases). Relative risks of almost all other autoimmune diseases in Graves' disease or Hashimoto's thyroiditis were significantly increased (>10 for pernicious anemia, systemic lupus erythematosus, Addison's disease, celiac disease, and vitiligo). There was relative "clustering" of Graves' disease in the index case with parental hyperthyroidism and of Hashimoto's thyroiditis in the index case with parental hypothyroidism. Relative risks for most other coexisting autoimmune disorders were markedly increased among parents of index cases.
CONCLUSIONS
This is one of the largest studies to date to quantify the risk of diagnosis of coexisting autoimmune diseases in more than 3000 index cases with well-characterized Graves' disease or Hashimoto's thyroiditis. These risks highlight the importance of screening for other autoimmune diagnoses if subjects with autoimmune thyroid disease present with new or nonspecific symptoms.
Publication
Journal: Immunity
July/26/2011
Abstract
A chief Ca(2+) entry pathway in immune cells is store-operated Ca(2+) (SOC) influx, which is triggered by depletion of Ca(2+) from the endoplasmic reticulum (ER). However, its physiological role in B cells remains elusive. Here, we show that ER calcium sensors STIM1- and STIM2-induced SOC influx is critical for B cell regulatory function. B cell-specific deletion of STIM1 and STIM2 in mice caused a profound defect in B cell receptor (BCR)-induced SOC influx and proliferation. However, B cell development and antibody responses were unaffected. Remarkably, B cells lacking both STIM proteins failed to produce the anti-inflammatory cytokine IL-10 because of defective activation of nuclear factor of activated T cells (NFAT) after BCR stimulation. This resulted in exacerbation of experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. Our data establish STIM-dependent SOC influx as a key signal for B cell regulatory function required to limit autoimmunity.
Publication
Journal: A.M.A. archives of surgery
April/30/2003
Publication
Journal: Journal of Clinical Pathology
October/31/1998
Abstract
The preparation of stable formolized sheep cells coated with thyroglobulin and their use for the detection of auto-antibodies in human thyroiditis is described. This provides an easy laboratory test which gives results closely comparable with those using fresh tanned cells. The agglutination titres do not closely parallel the antibody content of the serum but a good correlation may be obtained by inhibiting agglutination with thyroglobulin. The diagnostic usefulness of the test in treating disorders of the thyroid is discussed and related to the results of tests for the other two immune systems involved in thyroiditis. The tanned red cell test may be used to differentiate Hashimoto's disease from thyroid cancer and non-toxic colloid goitre, and to assess the choice of treatment in patients with Graves' disease. It has proved of particular value in genetic studies of auto-immunity.
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Publication
Journal: The Journal of pathology and bacteriology
October/31/1998
Publication
Journal: European Journal of Endocrinology
April/7/2013
Abstract
OBJECTIVE
No consensus exists on the association between papillary thyroid carcinoma (PTC) and Hashimoto's thyroiditis (HT). To resolve this controversy, this study aimed to evaluate the relationship between the two conditions using a meta-analysis.
METHODS
We searched relevant published studies using citation databases including PubMed, Embase, and ISI Web of Science. The effect sizes of clinicopathologic parameters were calculated by odds ratio (OR), weighted mean difference, or hazard ratio (HR). The effect sizes were combined using a random-effects model.
RESULTS
Thirty-eight eligible studies including 10 648 PTC cases were selected. Histologically proven HT was identified in 2471 (23.2%) PTCs. HT was more frequently observed in PTCs than in benign thyroid diseases and other carcinomas (OR=2.8 and 2.4; P<0.001). PTCs with coexisting HT were significantly related to female patients (OR=2.7; P<0.001), multifocal involvement (OR=1.5; P=0.010), no extrathyroidal extension (OR=1.3; P=0.002), and no lymph node metastasis (OR=1.3; P=0.041). Moreover, PTCs with HT were significantly associated with long recurrence-free survival (HR=0.6; P=0.001).
CONCLUSIONS
Our meta-analysis showed that PTC is significantly associated with pathologically confirmed HT. PTC patients with HT have favorable clinicopathologic characteristics compared with PTCs without HT. However, patients with HT need to be carefully monitored for the development of PTC.
Publication
Journal: Journal of Autoimmunity
April/10/2008
Abstract
The autoimmune thyroid diseases (AITD) comprise a cadre of complex diseases whose underlying pathoetiology stems from a genetic-environmental interaction, between susceptibility genes (e.g. CTLA-4, HLA-DR, thyroglobulin) and environmental triggers (e.g. dietary iodine), that orchestrates the initiation of an autoimmune response to thyroid antigens, leading to the onset of disease. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Several AITD susceptibility genes have been identified, with HLA genes, in particular, appearing to be of major importance. Early studies showed association of HLA-DR3 with Graves' disease (GD) in Caucasians. More recently, the importance of an amino acid substitution at position 74 of the DR beta 1 chain of HLA-DR3 (DRb1-Arg74), in susceptibility to Graves' disease, has been shown. Furthermore, there is increasing evidence for a genetic interaction between thyroglobulin variants and DRb1-Arg74 in conferring risk for GD. Mechanistically, the presence of an arginine at position 74 elicits a significant structural change in the peptide binding pocket of HLA-DR, potentially affecting the binding of pathogenic thyroidal peptides. Future therapeutic interventions may attempt to exploit this new bolus of knowledge by endeavoring to block or modulate pathogenic peptide presentation by HLA-DR.
Publication
Journal: Thyroid
November/15/2010
Abstract
BACKGROUND
Autoimmune thyroid diseases (AITD), including Graves' disease and Hashimoto's thyroiditis, arise due to complex interactions between environmental and genetic factors. There are sound data coming from epidemiological, family, and twin studies demonstrating a strong genetic influence on the development of AITD. In this review we summarize the new findings on the genetic susceptibility to AITD focusing on emerging mechanisms of susceptibility.
CONCLUSIONS
Candidate gene analysis, whole-genome linkage screening, genome-wide association studies, and whole-genome sequencing are the major technologies that have advanced this field, leading to the identification of at least seven genes whose variants have been associated with AITD. One of the major ones is the HLA-DR gene locus. Recently, it was shown that substitution of the neutral amino acids Ala or Gln with arginine at position beta 74 in the HLA-DR peptide-binding pocket is key to the etiology of both Graves' disease and Hashimoto's thyroiditis. Several other genes have also been shown to confer susceptibility to AITD. These can be classified into two groups: (i) immune regulatory genes (cytotoxic T lymphocyte-associated protein 4, CD40, protein tyrosine phosphatase-22, and CD25) and (ii) thyroid-specific genes (thyroglobulin and thyrotropin receptor genes). The influence of individual genes on the development of AITD when assessed in a population appears to be weaker than would be expected from the data showing strong genetic susceptibility to AITD. Two possible mechanisms explaining this discrepancy are gene-gene interactions and subset effects.
CONCLUSIONS
Significant progress has been made in our understanding of the immunogenetic mechanisms leading to thyroid autoimmunity. For the first time we are beginning to unravel these mechanisms at the molecular level. It is hoped that these new data will be translated into novel therapies and prevention strategies in AITD, such as costimulatory blockade.
Publication
Journal: Journal of Surgical Research
November/23/2008
Abstract
BACKGROUND
Hashimoto's thyroiditis (HT) is the most common cause of hypothyroidism and is characterized by gradual autoimmune mediated thyroid failure with occasional goiter development. HT is seven times more likely to occur in women than in men. Papillary thyroid cancer (PTC), the most prevalent form of cancer in the thyroid, is 2.5 times more likely to develop in women than men. Given the relatively high prevalence of these diseases and the increased occurrence in women, we analyzed data from our institution to determine if there is a correlation between Hashimoto's thyroiditis and PTC in women.
METHODS
From May 1994 to January 2007, 1198 patients underwent thyroid surgery at our institution. Of these, 217 patients were diagnosed with HT (196 women, 21 men). The data from these patients were statistically analyzed using SPSS.
RESULTS
PTC occurred in 63 of 217 (29%) HT patients and 230 of 981 (23%) patients without HT (P = 0.051). Of these groups, 41 (65%) and 158 (69%) patients, respectively, had tumor sizes>>/=1.0 cm; 56/196 women (29%) with HT had coexistent PTC compared with 160/730 women (22%) without HT (P = 0.03). Among women with any type of thyroid malignancy, 56/59 cases (95%) with HT had PTC compared with 159/196 cases (81%) in women without HT (P = 0.006). Additionally, female HT patients with goiters had a significantly lower rate of PTC (9% versus 36%, P < 0.001) compared with women without goiters. These differences were not observed in men with HT.
CONCLUSIONS
These data demonstrate that HT is associated with an increased risk of developing PTC. Female patients with HT undergoing thyroidectomy are 30% more likely to have PTC. Thus, more aggressive surveillance for PTC may be indicated in patients with HT, especially in women.
Publication
Journal: Journal of Clinical Endocrinology and Metabolism
March/1/2010
Abstract
BACKGROUND
Th17 lymphocytes play an important role in different chronic inflammatory and autoimmune conditions.
OBJECTIVE
The aim of the study was to explore the status of Th17 cells in patients with autoimmune thyroid diseases (AITD).
METHODS
We assessed the serum levels and in vitro synthesis of IL-17 and IL-22 and of different cytokines (IL-6, IL-15, and IL-23) involved in the differentiation of Th17 cells in the peripheral blood and thyroid glands of 26 patients with AITD, eight with Graves' disease, and 18 with Hashimoto's thyroiditis (HT) as well as 10 healthy controls.
RESULTS
We found enhanced levels of T cells synthesizing IL-17 and IL-22 in the peripheral blood from AITD patients, mainly in those with HT. In addition, a stronger expression of IL-17 and IL-22 and an enhanced number of IL-23R(+) cells was detected in thyroid glands from HT patients compared with Graves' disease or controls. Furthermore, increased concentrations of IL-6 and IL-15 were detected in sera from HT patients, whereas serum levels of IL-23 tended to be higher in these patients. Finally, an enhanced in vitro differentiation of T lymphocytes into Th17 cells induced by IL-23/IL-6 was observed in AITD patients. Accordingly, a strong induction of RORC2 gene was detected in lymphocytes from HT patients when stimulated with IL-23.
CONCLUSIONS
Our results indicate that there is an increased differentiation of Th17 lymphocytes and an enhanced synthesis of Th17 cytokines in AITD, mainly in HT. These phenomena may have an important role in the pathogenesis of thyroid autoimmunity.
Publication
Journal: Journal of Clinical Endocrinology and Metabolism
April/9/2013
Abstract
BACKGROUND
The link between Hashimoto's thyroiditis (HT) and papillary thyroid cancer (PTC) has long been a topic of controversy. There are conflicting reports; some suggest that these two are positively correlated, whereas other studies report no relationship.
METHODS
We performed a systematic literature review of original studies that investigated the correlation between HT and PTC. The two main search engines used to identify articles were OVID Medline and PubMed. The included studies were categorized into a fine-needle aspiration biopsy (FNAB) group and an archival thyroidectomy specimen group.
RESULTS
There is no clear evidence to support the correlation between HT and PTC. Population-based FNAB studies report no linkage, whereas many of the studies of thyroidectomy specimens report a positive relationship. The average prevalence rate of PTC in patients with HT was 1.20% in 8 FNA studies of 18 023 specimens and 27.56% in 8 archival thyroidectomy studies of 9 884 specimens. The relative risk ratio of finding evidence of PTC in HT specimens ranged from .39 to 1.00 in the FNA group (average RR = .69) in contrast to 1.15 to 4.16 from the archival thyroidectomy studies (average RR = 1.59). In addition, there are many studies in the literature that propose a genetic link between HT and PTC involving the PI3K/Akt pathway and RET/PTC gene rearrangements.
CONCLUSIONS
Although limited by the lack of definitive pathology, population-based FNA studies did not find a statistically significant correlation between HT and PTC. Thyroidectomy studies, which reported a statistically significant positive correlation, are subject to selection bias. More prospective studies with longer follow-up are needed to further elucidate this relationship.
Publication
Journal: Arthritis and rheumatism
April/26/2009
Abstract
OBJECTIVE
In the era of genome-wide association studies, familial risks are used to estimate disease heritability and the likelihood of candidate-gene identification. This study was undertaken to estimate associations of rheumatoid arthritis (RA) with any of 33 autoimmune diseases and related conditions among parents and offspring, singleton siblings, twins, and spouses.
METHODS
The Multigeneration Register in Sweden was used as a reliable source of information on Swedish families throughout the last century. Data on autoimmune diseases in individual family members were obtained through linkage to the Hospital Discharge Register. The standardized incidence ratio (SIR) was calculated as a measure of the relative risk of RA in family members of patients with RA or any of 33 other autoimmune diseases or related conditions, as compared with the relative risk of RA in those lacking an affected family member.
RESULTS
Among a total of 447,704 patients, 47,361 were diagnosed as having RA. The SIRs for RA were 3.02 in offspring of affected parents, 4.64 in siblings, 9.31 in multiplex families, 6.48 in twins, and 1.17 in spouses. Significant associations with the familial risk of RA in offspring according to parental proband were observed for ankylosing spondylitis (SIR 2.96), localized scleroderma (SIR 2.40), Sjögren's syndrome (SIR 2.25), systemic lupus erythematosus (SIR 2.13), systemic sclerosis (SIR 1.65), Hashimoto thyroiditis/hypothyroidism (SIR 1.54), pernicious anemia (SIR 1.53), sarcoidosis (SIR 1.40), psoriasis (SIR 1.36), Wegener's granulomatosis (SIR 1.34), and asthma or polymyalgia rheumatica (SIR 1.32).
CONCLUSIONS
This is the first study to compare the familial risks of RA in relation to a large number of autoimmune diseases and related conditions using data from a single population. The high discordant familial risks in this population suggest that there is extensive genetic sharing between RA and the associated diseases.
Publication
Journal: Journal of Neurology, Neurosurgery and Psychiatry
July/16/2012
Abstract
The concept of antibody mediated CNS disorders is relatively recent. The classical CNS paraneoplastic neurological syndromes are thought to be T cell mediated, and the onconeural antibodies merely biomarkers for the presence of the tumour. Thus it was thought that antibodies rarely, if ever, cause CNS disease. Over the past 10 years, identification of autoimmune forms of encephalitis with antibodies against neuronal surface antigens, particularly the voltage gated potassium channel complex proteins or the glutamate N-methyl-D-aspartate receptor, have shown that CNS disorders, often without associated tumours, can be antibody mediated and benefit from immunomodulatory therapies. The clinical spectrum of these diseases is not yet fully explored, there may be others yet to be discovered and some types of more common disorders (eg, epilepsy or psychosis) may prove to have an autoimmune basis. Here, the known conditions associated with neuronal surface antibodies are briefly reviewed, some general aspects of these syndromes are considered and guidelines that could help in the recognition of further disorders are suggested.
Publication
Journal: Journal of the American College of Surgeons
June/28/2007
Abstract
BACKGROUND
The link between inflammation and cancer is well-established, but the link between Hashimoto thyroiditis (HT) and thyroid cancer remains controversial. The purpose of our study was to determine the incidence of patients with thyroid cancer and associated HT at our institution, to correlate our patient population demographics with the Surveillance, Epidemiology and End Results (SEER) database, and to assess the expression of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in patients with HT.
METHODS
Demographic and histologic data were collected from patients undergoing thyroid resection at the University of Texas Medical Branch from 1987 to 2002 and compared with the SEER database. Immunohistochemistry for phosphorylated Akt (a marker of PI3K activity), Akt isoforms and PTEN (an inhibitor of PI3K) was performed on paraffin-embedded blocks of resected thyroid tissue.
RESULTS
Our patient population demographics and thyroid cancer incidence by histologic type were similar to patients in the SEER database. Ninety-eight (37.7%) resected specimens had pathologic changes consistent with HT; 43 (43.8%) had an associated well-differentiated thyroid cancer. Increased phosphorylated Akt, Akt1, and Akt2 expression was noted in regions of HT and thyroid cancer compared with regions of normal surrounding thyroid tissue.
CONCLUSIONS
Patients with HT were three times more likely to have thyroid cancer, suggesting a strong link between chronic inflammation and cancer development. PI3K/Akt expression was increased in both HT and well-differentiated thyroid cancer, suggesting a possible molecular mechanism for thyroid carcinogenesis.
Publication
Journal: Human Molecular Genetics
April/11/2013
Abstract
Autoimmune thyroid disease (AITD), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), is one of the most common of the immune-mediated diseases. To further investigate the genetic determinants of AITD, we conducted an association study using a custom-made single-nucleotide polymorphism (SNP) array, the ImmunoChip. The SNP array contains all known and genotype-able SNPs across 186 distinct susceptibility loci associated with one or more immune-mediated diseases. After stringent quality control, we analysed 103 875 common SNPs (minor allele frequency >0.05) in 2285 GD and 462 HT patients and 9364 controls. We found evidence for seven new AITD risk loci (P < 1.12 × 10(-6); a permutation test derived significance threshold), five at locations previously associated and two at locations awaiting confirmation, with other immune-mediated diseases.
Publication
Journal: Journal of Autoimmunity
July/26/2007
Abstract
Autoimmune thyroid diseases (AITD) are common autoimmune diseases, affecting up to 5% of the general population. Thyroid-directed autoimmunity is manifested in two classical autoimmune conditions, Hashimoto's thyroiditis, resulting in hypothyroidism and Graves' disease resulting in hyperthyroidism. Autoimmune thyroid diseases arise due to an interplay between environmental and genetic factors. In the past decade significant progress has been made in our understanding of the genetic contribution to the etiology of AITD. Indeed, several AITD susceptibility genes have been identified. Some of these susceptibility genes are specific to either Graves' disease or Hashimoto's thyroiditis, while others confer susceptibility to both conditions. Both immunoregulatory genes and thyroid specific genes contribute to the pathogenesis of AITD. The time is now ripe to examine the mechanistic basis for the contribution of genetic factors to the etiology of AITD. In this review, we will focus on the contribution of non-MHC II genes.
Publication
Journal: Thyroid
July/15/2009
Abstract
BACKGROUND
T helper type 1 (Th1), Th2, and Th17 cells produce interferon (IFN)-gamma, interleukin (IL)-4, and IL-17A, respectively. We reported that IFN-gamma and IL-4 gene polymorphisms, which are related to higher IFN-gamma and lower IL-4 production, respectively, are more frequent in patients with severe Hashimoto's disease (HD) than in those mild HD. We now aim to investigate the proportion of peripheral Th1, Th2, and Th17 cells in patients with autoimmune thyroid disease (AITD).
METHODS
We studied 17 patients with HD who developed hypothyroidism and were treated with l-thyroxine, referred to as severe HD; 17 untreated patients with HD who were euthyroid, referred to as mild HD; 18 euthyroid patients with Graves' disease (GD) who remained positive for anti-thyrotropin receptor antibody (TRAb) despite being treated with anti-thyroid drugs for more than 5 years, referred to as intractable GD; and 17 patients with GD who were euthyroid and negative for TRAb for more than 2 years after cessation of anti-thyroid drugs, referred to as GD in remission; and 10 control subjects without AITD. By the definitions in this study Th1 cells were CD4(+)IFN-gamma(+)IL-4(-)IL-17A(-) cells, Th2 cells were CD4(+)IFN-gamma(-)IL-4(+)IL-17A(-) cells, and CD4(+)IFN-gamma(-)IL-4(-)IL-17A(+) cells were Th17 cells.
RESULTS
The proportion of peripheral Th1 cells was higher in patients with severe HD than in patients with mild HD (p < 0.05), and the proportion of peripheral Th2 cells was lower in patients with severe HD than in patients with mild HD (p < 0.001). Therefore the Th1/Th2 ratio was higher in severe than in mild HD patients (p < 0.001). The proportion of peripheral Th17 cells in patients with AITD was higher than in control subjects and the proportion of these cells in patients with intractable GD was higher than in patients with GD in remission (p < 0.05).
CONCLUSIONS
The peripheral Th1/Th2 cell ratio is related to the severity of HD, and the proportion of Th17 cells is related to the intractability of GD. We hypothesize that these patterns of peripheral Th cell subsets may be expressed within the thyroid.
Publication
Journal: Journal of Clinical Endocrinology and Metabolism
September/16/2007
Abstract
BACKGROUND
Cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) polymorphisms have been widely examined for their associations with autoimmune thyroid diseases [Graves' disease (GD) and Hashimoto thyroiditis (HT)], but their relative population effect remains unclear.
OBJECTIVE
The aim was to generate large-scale evidence on whether the CTLA-4 polymorphisms (A49G and CT60) and haplotypes thereof increase the susceptibility to GD and/or HT.
METHODS
Meta-analyses of group-level data were reviewed from 32 (11,019 subjects) and 12 (4,479) published and unpublished studies for the association of the A49G polymorphism with GD and HT, respectively (PubMed and HuGeNet search until July 2006). There were 15 (n = 7246) and six (n = 3086) studies available for the CT60 polymorphism, respectively. Meta-analyses of individual-level data from 10 (4906 subjects) and five (2386) collaborating teams for GD and HT, respectively, were also reviewed.
METHODS
Association of gene variants and haplotypes with GD and HT was measured.
RESULTS
Group-level data suggested significant associations with GD and HT for both A49G [odds ratios 1.49 (P = 6 x 10(-14)) and 1.29 (P = 0.001) per G allele, respectively] and CT60 [1.45 (P = 2 x 10(-9)) and 1.64 (P = 0.003) per G allele, respectively]. Results were consistent between Asian and Caucasian descent subjects. Individual-level data showed that compared with the AA haplotype, the risk conferred by the GG haplotype was 1.49 (95% confidence interval 1.31,1.70) and 1.36 (95% confidence interval 1.16,1.59) for GD and HT, respectively. Data were consistent with a dose-response effect for the G allele of CT60.
CONCLUSIONS
The CT60 polymorphism of CTLA-4 maps an important genetic determinant for the risk of both GD and HT across diverse populations.
Publication
Journal: CNS Drugs
January/2/2008
Abstract
Hashimoto's encephalopathy is a term used to describe an encephalopathy of presumed autoimmune origin characterised by high titres of antithyroid peroxidase antibodies. In a similar fashion to autoimmune thyroid disease, Hashimoto's encephalopathy is more common in women than in men. It has been reported in paediatric, adult and elderly populations throughout the world. The clinical presentation may involve a relapsing and remitting course and include seizures, stroke-like episodes, cognitive decline, neuropsychiatric symptoms and myoclonus. Thyroid function is usually clinically and biochemically normal.Hashimoto's encephalopathy appears to be a rare disorder, but, as it is responsive to treatment with corticosteroids, it must be considered in cases of 'investigation negative encephalopathies'. Diagnosis is made in the first instance by excluding other toxic, metabolic and infectious causes of encephalopathy with neuroimaging and CSF examination. Neuroimaging findings are often not helpful in clarifying the diagnosis. Common differential diagnoses when these conditions are excluded are Creutzfeldt-Jakob disease, rapidly progressive dementias, and paraneoplastic and nonparaneoplastic limbic encephalitis. In the context of the typical clinical picture, high titres of antithyroid antibodies, in particular antithyroid peroxidase antibodies, are diagnostic. These antibodies, however, can be detected in elevated titres in the healthy general population. Treatment with corticosteroids is almost always successful, although relapse may occur if this treatment is ceased abruptly. Other forms of immunomodulation, such as intravenous immune-globulin and plasma exchange, may also be effective. Despite the link to autoimmune thyroid disease, the aetiology of Hashimoto's encephalopathy is unknown. It is likely that antithyroid antibodies are not pathogenic, but titres can be a marker of treatment response. Pathological findings can suggest an inflammatory process, but features of a severe vasculitis are often absent. The links between the clinical pictures, thyroid disease, auto-antibody pattern and brain pathology await further clarification through research. It may be that Hashimoto's encephalopathy will be subsumed into a group of nonvasculitic autoimmune inflammatory meningoencephalopathies. This group may include disorders such as limbic encephalitis associated with voltage-gated potassium channel antibodies. Some authors have suggested abandoning any link to Hashimoto and renaming the condition 'steroid responsive encephalopathy associated with autoimmune thyroiditis' to better reflect current, if limited, understanding of this condition.
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