Riedel Thyroiditis.

CONTEXT: Riedel thyroiditis (RT) is a rare inflammatory autoimmune disease that is often a clinically diagnostic dilemma because of its insidious presentation and nonspecific symptoms. OBJECTIVE: The aim of the present systematic review and meta-analysis is to clarify the presentation, management, and outcomes of RT. STUDY SELECTION: A systematic search of PubMed/MEDLINE and Web of Science was conducted to identify relevant reports published up to September 2019. DATA EXTRACTION: First author, country, patient sex, ethnicity, presentation, biochemical status, duration of symptoms, histology, treatment, follow-up duration, and short- and long-term outcomes. DATA SYNTHESIS: Data from 212 RT patients were retrieved. The mean age was 47 years with a predominantly female population (81%). Neck swelling (89%), dyspnea (50%), and neck pain (41%) were the most common presenting symptoms. Inflammatory markers were elevated in 70% to 97% and thyroid antibody positivity was present in less than 50%. Up to 82% underwent surgical intervention, with the most common being total thyroidectomy in 34% of individuals. Glucocorticoids were used in 70% of individuals with median duration 3 months. Prognosis was reasonable with 90% having resolution or improvement of symptoms. CONCLUSIONS: This analysis is the largest and most comprehensive to date of RT and provides clinicians with vital information on the common presentation features that may alert to the diagnosis and highlight management options.

Expression of TIGIT and FCRL3 is Altered in T Cells from Patients with Distinct Patterns of Chronic Autoimmune Thyroiditis.

BACKGROUND: Co-inhibitory receptors (IR), such as TIGIT and FCRL3, provide a checkpoint against highly destructive immune responses. Co-expression of TIGIT and FCRL3, in particular, has been linked to the HELIOS+ subset of regulatory CD4+FOXP3+T-cells. Of these, CD4+FOXP3-exon(E)2+ cells have higher expression of IR and exhibit strongest suppressive properties. Nevertheless, how the expression of TIGIT, FCRL3, HELIOS, and FOXP3E2 is regulated in chronic autoimmune thyroiditis (AT), is not known. METHODS: Thirty patients with AT [encompassing spontaneously euthyroid (euAT), hypothyroid-untreated and L-thyroxine-treated cases)] and 10 healthy controls (HC) were recruited. FCRL3, TIGIT, HELIOS and FOXP3E2 mRNA expression levels in peripheral blood (PB) T cells were measured via quantitative real-time PCR and compared to clinicopathological factors. RESULTS: The TIGIT and FCRL3 expression levels from T cells of AT cases were inversely related to the thyroid volume, and were significantly increased in hypothyroid patients (on+off L-thyroxine), but not euAT cases. The FCRL3 expression in PB T cells positively correlated with thyroid-peroxidase autoantibody levels; by contrast, T cells from aged AT patients and combined samples (AT+HC) accumulated more TIGIT mRNA. The patients with higher TIGIT mRNA levels had a greater prevalence of hypothyroidism, showing higher peak thyrotropin levels at diagnosis or at follow-up. CONCLUSIONS: Multiple IR, namely FCRL3 and TIGIT, but not the transcription factors HELIOS and FOXP3E2, showed increased mRNA levels in PB T cells from end-stage, long-standing and/or more aggressive AT, in proportion to disease severity. A relation with major clinical subphenotypes was observed, thereby identifying IR as potentially important players in AT.

[Inflammatory diseases of the thyroid gland]. / Entzündungen der Schilddrüse.

This review article deals with the classification, clinical features and morphology of thyroiditis. These inflammatory diseases account for approximately 20 % of all thyroid diseases. The vast majority of cases of thyroiditis are of immunogenic origin while non-immunogenic thyroiditis (caused by pathogens or iatrogenic) is a rarity.

The human leukocyte antigen class II gene has different contributions to autoimmune type 1 diabetes with or without autoimmune thyroid disease in the Japanese population.

AIM: Type 1 diabetes (T1D) is associated with autoimmune thyroid disease (AITD). The human leukocyte antigen (HLA) has been extensively studied in these diseases. We aimed to clarify the contribution of AITD on the susceptibility and resistance of the HLA subtype to autoimmune T1D in the Japanese population. METHODS: The frequency of the HLA DR-DQ haplotype was compared between 56 autoimmune T1D patients with AITD and 71 autoimmune T1D patients without AITD, and control subjects. RESULTS: The frequencies of DRB1 0405-DQB1 0401, DRB1 0802-DQB1 0302, and DRB1 0901-DQB1 0303 haplotypes were significantly higher in T1D patients with AITD than in control subjects. The frequencies of DRB1 0101-DQB1 0501, DRB1 0901-DQB1 0303, and DRB1 1302-DQB1 0604 haplotypes were significantly higher in T1D patients without AITD than in control subjects. The frequencies of DRB1 1101-DQB1 0301 and DRB1 1501-DQB1 0602 haplotypes were significantly lower in T1D patients with or without AITD than in control subjects. CONCLUSIONS: Our results suggest that the susceptibility of the HLA subtype to autoimmune T1D differs between T1D with AITD and T1D without AITD, whereas there is no difference between the two groups with regard to HLA subtypes that confer protection against autoimmune T1D.

[What diagnosis can be made by the pathologist in a case of sclerosing thyroiditis?]. / Quel diagnostic l'anatomopathologiste peut-il porter en présence d'une thyroïdite sclérosante ?

The pathology of thyroiditis seems well-established with a recognized classification based on clinical and pathological features. However, problems of differential diagnosis remain between both Riedel's and Quervain's thyroiditis and sclerosing Hashimoto's thyroiditis: these entities sometimes lack the characteristic histological pattern, and the clinico-biological data are not always available to the pathologist. We re-examined 18 cases of thyroiditis with sclerosis, retrieved from our files, diagnosed as Riedel's thyroiditis in five cases, Quervain's thyroiditis in five other cases and sclerosing Hashimoto thyroiditis in eight cases. Only two diagnosed cases of Riedel's thyroiditis were pathognomic. Three cases of Quervain's thyroiditis and four cases of sclerosing Hashimoto's thyroiditis presented a slight or moderate extension of the fibrosis in perithyroidal soft-tissues, raising the differential diagnosis of an incipient Riedel's thyroiditis. A definite diagnosis of the type of thyroiditis with sclerosis remains difficult, because all three pathologies present common points. In cases with a characteristic pattern, the diagnosis is straightforward. However, it appears in our study that half of the diagnoses remain ambiguous, because of the existence of histological features common to different entities. In these cases, we think the diagnosis of sclerosing thyroiditis NOS would be more appropriate, the histology not being sufficiently characteristic to make a more specific diagnosis.

[Epidemiologic study of autoimmune thyroid disease in south Tunisia]. / Etude épidémiologique des maladies autoimmunes thyroïdiennes dans le sud tunisien.

In order to study incidence and prevalence of autoimmune thyroid diseases (AITDs), we studied a retrospective cohort of 1,079 patients explored in the department of Endocrinology of Sfax (south of Tunisia). The overall incidence of AITDs was 9.9%. Mean age was 39.6+15 years; sex ratio 5 F/1M. Graves' disease was the most frequent (45%). Atrophic thyroiditis was present in 32.2% of patients and Hashimoto's thyroiditis in 22.8%. The incidence of AITDs increased from 1990 to 2000 and by 2003 it had fallen to 67 cases per year. TPO antibody was present in two-thirds of patients with Hashimoto thyroiditis, and half of those with atrophic thyroiditis. TG antibodies were less frequent (one-third of patients). Association with other autoimmune diseases was noted in 6.3% of patients: type I diabetes mellitus, adrenal insufficiency and vitiligo. Statistic analysis did not disclose any association between autoantibody levels and thyroid dysfunction. There was an association between TG antibody and TSH levels among patients with Graves' disease and between TG antibody level and age in atrophic thyroiditis patients (p<0.05); a correlation was also noted between these antibodies and other autoimmune diseases (p=0.05). It is difficult to assess the frequency of ATD in the clinical setting. Characteristic features of AITDs in patients seen in south Tunisia were found to be similar to those described in the literature. Other more large-scale representative studies would be useful to establish the epidemiology of AITDs in Tunisia.

[Modern diagnostic approach to autoimmune thyroiditis]. / Der Ultraschall zeigt, was hinter der Funktionsstörung steckt.

High-resolution ultrasonography of the thyroid gland is the major primarytechnical diagnostic procedure in suspected autoimmune thyroiditis (AIT). A diffusely echo-poor thyroid is proof of the presence of AIT. Duplex sonography provides further information about the activity of the disease, and is of differential diagnostic importance for distinguishing postpartum thyroiditis from AIT, or for the investigation of an infiltrating carcinoma. Today, antibody determination serves merely to confirm the diagnosis, with TPO antibodies being the most specific for AIT. The TG antibodies may also be nonspecifically elevated in subacute thyroiditis (de Quervain) or irradiation or radioiodine treatment. For an evaluation of thyroid gland function in AIT, determination of basal TSH is needed.

[Autoimmune thyroiditis]. / Tiroidites autoimunes.

The term autoimmune thyroiditis encompasses a group of high prevalence thyroid disorders, which have been classified in different ways throughout the years. In this article some aspects related to its classification, epidemiology, susceptibility factors, pathogenesis, histology, diagnosis and treatment are reviewed. Some comments on the similar pathogenesis of Graves' disease are also made.

The association of CTLA4 polymorphism with type 1 diabetes is concentrated in patients complicated with autoimmune thyroid disease: a multicenter collaborative study in Japan.

CONTEXT: Transracial studies are a powerful tool for genetic association studies of multifactorial diseases, such as type 1 diabetes. The low incidence of type 1 diabetes in Asian countries, however, makes it difficult to perform large-scale studies in Asia. OBJECTIVE: To overcome this, we have assembled a multicenter study group in Japan and studied the association of CTLA4 polymorphisms with type 1 diabetes relative to autoimmune thyroid disease (AITD) phenotypes. SUBJECTS: Subjects included a total of 1837 samples, including 1114 cases (769 with type 1 diabetes and 345 with AITD) and 723 control subjects. METHODS: The +6230G>A and +49G>A polymorphisms of CTLA4 as well as HLA-DRB1 and -DQB1 were genotyped. RESULTS: The +6230G>A polymorphism was significantly associated with type 1 diabetes complicated with AITD (odds ratio, 1.54; P = 0.027) and with AITD alone (odds ratio, 1.31; P = 0.045) but not with type 1 diabetes without AITD. The association with type 1 diabetes positive for autoantibodies to both pancreatic islets and thyroid was particularly strong (odds ratio, 1.87; P = 0.001). Type 1 diabetic patients with the disease-associated GG genotype were characterized by a significantly higher frequency of AITD (P = 0.013), of positivity for both AITD and antiislet autoantibody (P = 0.00086), and of high-risk HLA genotypes (P = 0.034). CONCLUSIONS: Given the high frequency of AITD in patients with type 1 diabetes, these data suggest the possibility that the association of CTLA4 with type 1 diabetes in previous studies may have been secondary to AITD, suggesting the importance of subclassification of type 1 diabetes relative to AITD in genetic studies.

HLA-DRB1*04 and HLA-DQB1*03 association with the atrophic but not with the goitrous form of chronic autoimmune thyroiditis in a Brazilian population.

Autoimmune chronic lymphocytic thyroiditis appears in two forms, goitrous and atrophic. The evidence available is not enough to prove that the goitrous precedes the atrophic form, but immunogenetic analysis suggests that they may be distinct entities. The distribution of HLA class II alleles DRB1* and DQB1* was verified in patients from the region of Campinas, São Paulo, Brazil with both forms of thyroiditis. Ninety-one patients with primary hypothyroidism through autoimmune thyroiditis were classified as goitrous - 54 patients, 42.27 +/- 11.72 years old, having had hypothyroidism for 8.57 +/- 6.63 years - or atrophic - 37 patients, 42.72 +/- 12.01 years old, hypothyroidism for 6.73 +/- 4.07 years. The distribution of class II alleles was determined, DRB1* and DQB1* were genotyped after purifying DNA blood samples using the DNAzol technique, and the low-resolution PCR-SSP system was utilized for determination of generic alleles. Chi-square and Fisher's exact test were utilized to compare the distribution frequency of HLA alleles and the significant p-values were subjected to Bonferroni correction. We have demonstrated that the DRB1*04 allele is associated with autoimmune thyroiditis, and that there are genotypic differences regarding the presentation forms with a strong association between DRB1*04 and DQB1*03 and the atrophic form only.

Tiroiditis posparto / Postpartum thyroiditis

El 50-60 por ciento de los hipertiroidismos transitorios posparto se deben a una tiroiditis posparto (TPP). Es una tiroiditis subaguda silente y autoinmunitaria, que cursa con una fase inicial de hipertiroidismo y otra, posterior, de hipotiroidismo transitorio o permanente. El hipertiroidismo pocas veces requiere tratamiento y el hipotiroidismo se trata con tiroxina libre de forma transitoria o definitiva. La densidad de incidencia de TPP en un grupo de mujeres no seleccionadas fue del 7,8 por ciento y el mejor momento para diagnosticar la mayor parte de las TPP fue el sexto mes posparto. En el 58 por ciento de las TPP existió hipertiroidismo analítico que se siguió de hipotiroidismo. Los síntomas clínicos fueron muy poco orientativos. De 45 pacientes con TPP, tras un seguimiento medio de 64 ñ 37,7 meses, 14 (31,1 por ciento) han desarrollado hipotiroidismo definitivo (el 40 por ciento de las pacientes que presentaron hipotiroidismo durante la TPP y el 2,3 por ciento de todas las mujeres). Destaca la frecuencia de TPP hallada en la población general, su curso clínico silente, el porcentaje elevado de casos que presentan hipotiroidismo transitorio y la probabilidad alta de evolución a hipotiroidismo definitivo; todo ello, unido a las repercusiones negativas que el hipotiroidismo (clínico y subclínico) durante el embarazo tiene tanto para la madre como para el feto y el recién nacido, obliga a replantearse las recomendaciones sobre el cribado universal para la TPP. Así, parece razonable recomendarlo en todas las mujeres a los 6 meses posparto mediante la determinación de tirotropina basal (AU)

Breast cancer in association with thyroid disorders.

BACKGROUND: The relationship between breast cancer and thyroid diseases is controversial. Discrepant results have been reported in the literature. The incidences of autoimmune and nonautoimmune thyroid diseases were investigated in patients with breast cancer and age-matched control individuals without breast or thyroid disease. METHODS: Clinical and ultrasound evaluation of thyroid gland, determination of serum thyroid hormone and antibody levels, and fine-needle aspiration of thyroid gland were performed in 150 breast cancer patients and 100 control individuals. RESULTS: The mean values for anti-thyroid peroxidase antibodies were significantly higher in breast cancer patients than in control individuals (P = 0.030). The incidences of autoimmune and nonautoimmune thyroid diseases were higher in breast cancer patients than in control individuals (38% versus 17%, P = 0.001; 26% versus 9%, P = 0.001, respectively). CONCLUSION: Our results indicate an increased prevalence of autoimmune and nonautoimmune thyroid diseases in breast cancer patients.

[Hashimoto encephalopathy. Analysis of four case reports]. / Encéphalopathie de Hashimoto. Analyse de quatre observations.

INTRODUCTION: Encephalopathy associated with Hashimoto's thyroiditis has been recognized for more than 30 years and is probably underestimated. EXEGESIS: We report four patients with Hashimoto's thyroiditis who presented neurological or psychiatric features. There were three women and one man, with a mean age of 68 years. Neurological presentations were various: seizures, psychotic episodes, altered consciousness, hallucinations without usual aetiological diseases (infectious, metabolic, neoplasic, vascular, etc.). Neurological investigations (EEG, brain CT, magnetic resonance imaging) were unspecific. In all cases, a moderately high CSF protein level without pleocytosis was found. Patients presented slight hypothyroidism with high titers of antithyroperoxidase antibodies. Despite hormone therapy replacement, neurological features persisted. Outcome was favorable under steroid therapy. CONCLUSION: Hashimoto's encephalopathy must be considered in the face of neuropsychiatric manifestations without obvious etiology. Pathogenic mechanisms are not clear but probably involve autoimmune cerebral vasculitis because of the efficacy of steroids.

Actualización clínica de la enfermedad tiroidea autoinmune / Clinical update in autoimmune thyroid disease

El estudio y tratamiento de la enfermedad tiroidea autoinmune (ETAI) ha ido cumpliendo distintas etapas de investigación en nuestro grupo. Los estudios iniciales en pacientes con enfermedad de Graves (EG) evidenciaron la implicación de la inmunidad celular al demostrar, mediante un test in vitro de inhibición de la migración linfocitaria (test MIF), la sensibilización al antígeno tiroglobulina 19S y cómo el tratamiento con antitiroideos de síntesis (ATS) ejercía un efecto inmunosupresor claro en el grupo de pacientes tratados comparados con aquellos que presentaban un hipertiroidismo activo sin tratamiento1,2. Posteriormente estudiamos las tasas de reactivación con las tres terapias utilizadas en la EG (ATS, cirugía y radioyodo) demostrando que el mayor porcentaje corresponde a los ATS (42 por ciento) con una incidencia máxima a los 24 meses3. En la última década se ha avanzado en el conocimiento etiopatogénico de la ETAI de forma espectacular paralelo al desarrollo de las técnicas moleculares. La identificación del antígeno tiroperoxidasa y la medida de anticuerpos antitiroperoxidasa (Ac-TPO) han desplazado en la clínica diaria a los clásicos anticuerpos antimicrosomales (Ac-MIC) como test diagnóstico en ETAI4.Dado que la ETAI es más prevalente en la mujer en edad fértil, no es desdeñable el papel que el embarazo y el posparto añaden a la evolución de la misma5,6. Los estudios epidemiológicos sobre ETAI en una cohorte importante de gestantes antes de la semana 16 de gestación han puesto de manifiesto que un 9 por ciento presentan títulos positivos de Ac-TPO. A pesar del descenso en los títulos en el último trimestre de embarazo, la progresión hacia un hipotiroidismo clínico o subclínico está asociado con los valores de TSH y con la presencia de Ac-TPO en el primer trimestre7,8.El estudio de los mecanismos etiopatogénicos de la tiroiditis autoinmune (TA), que desde un punto de vista clínico aparece con deficiente función tiroidea y necesidad de tratamiento sustitutivo, cobra actualmente gran relevancia. En su patogenia ya conocemos el papel que desempeñan los Ac-TPO y/o anticuerpos bloqueadores de TSH a su receptor (TBII); sin embargo, no está bien establecida la implicación que tienen otros inmunomoduladores como las interleucinas (IL), el factor de necrosis tumoral (TNF) o el interferón (IFN), en el daño de la célula tiroidea. Otro problema aún sin resolver y de máxima actualidad, por las importantes implicaciones pronósticas y terapéuticas, es el de discernir qué pacientes pueden beneficiarse de la retirada del tratamiento sustitutivo con hormona tiroidea que se instaura como una sentencia de por vida. No hay estudios a largo plazo y, sobre todo, no son conocidos los factores pronósticos, de tipo inmune o genéticos, que puedan contestar a esta pregunta. La terapéutica con hormona tiroidea no está exenta de riesgos, fundamentalmente en el ámbito cardiovascular y del sistema óseo9, por lo que habría que evitar tratamientos injustificados (AU)

Adoptive transfer murine model of granulomatous experimental autoimmune thyroiditis.

Experimental autoimmune thyroiditis (EAT) is a chronic inflammatory autoimmune disease that can be induced in genetically susceptible animals by immunization with mouse thyroglobulin (MTg) in an appropriate adjuvant or by the adoptive transfer of MTg-sensitized donor spleen cells, activated in vitro with MTg, into naive recipients. In the adoptive transfer model used in our laboratory, donor cells activated with MTg alone induce a relatively mild chronic lymphocytic form of EAT (L-EAT), in which the thyroid infiltrate consists primarily of mononuclear cells, and the thyroid inflammation persists for several months. When the same donor cells are activated with MTg together with anti-IL-2R and/or IL-12, a more severe and histologically distinct granulomatous form of EAT is induced in recipient mice. In addition to having distinct histopathologic features, granulomatous EAT (G-EAT) differs from L-EAT in that granulomatous thyroid lesions are not chronic. After reaching maximal severity 21 days after cell transfer, G-EAT thyroid lesions either resolve or the thyroids become atrophic and fibrotic by day 35. In this review, the histopathologic features of G-EAT and L-EAT are described, and our studies with the adoptive transfer G-EAT model which have focused on the mechanisms involved in induction of G-EAT in mice, and the evolution of G-EAT lesions to resolution of inflammation or fibrosis, are reviewed.

[Cytological diagnosis of Hashimoto's hyperthyroidism].

OBJECTIVE: To assess the value of thyroid fine needle biopsy (FNB) in Hashimoto's hyperthyroidism. METHODS: FNB for was performed 58 (5 males and 53 females, aged from 13 to 66 years) of 1 031 patients who was performed clinically dignosised as having hyperthyroidism according to clinic symptoms, the results of physical and, laboratory examination, especially the increased the serum circle antibody and lowered sTSH during March 1995 to February 1998. Their smears were classified into 4 types according to the degree of degeneration of adenoidal cell and lymphocyte invasion. RESULTS: Hyperthyroidism was observed in 5 cases, I type in 9, II type in 9, III type in 4, and IV type in 31 (53%). CONCLUSIONS: FNB is helpful in diagnosis of hyperthyroidism.

[Morphology and clinical aspects of immune thyroid diseases]. / Morphologie und Klinik der Immunthyreopathien.

The aetiopathogenesis of autoimmune thyroid disease is still a matter for discussion. Morphologically, these illnesses are associated with a broad spectrum of overlapping changes. Thus, pathology cannot serve as the logical basis for a new classification. Therefore this overview makes use of the conventional nomenclature of clinically established entities and includes recently defined lesions. Besides histological characteristics, details of differential diagnostic value are presented in the context of clinical and laboratory data relevant for pathological classification.

[Morphology and clinical features of autoimmune thyroid diseases]. / Morphologie und Klinik der Immunthyreopathien.

The aetiopathogenesis of autoimmune thyroid diseases is the subject of various partly contradicting hypotheses and theories. Morphologically, these illnesses are associated with a broad spectrum of overlapping changes. Thus, pathology either can not serve as the logical basis for a new classification of autoimmune thyroid diseases. This overview therefore makes use of the conventional nomenclature of clinically established entities and includes recently defined lesions. Besides histological characteristics details of differential diagnostic value are presented in the context of clinical and laboratory data relevant for pathological typing.