Clinical efficacy and molecular mechanism of Chinese medicine in the treatment of autoimmune thyroiditis.

ETHNOPHARMACOLOGICAL RELEVANCE: Autoimmune Thyroiditis (AIT) is a common refractory autoimmune disease of the endocrine system that may eventually lead to complete loss of thyroid function, with subsequent severe effects on the metabolism. Because of the deficiency in current clinical management of AIT, the need for alternative therapies is highlighted. With its multi-component and multi-target characteristics, Chinese medicine has good potential as an alternative therapy for AIT. AIM OF THE STUDY: The aim of this study was to systematically summarize the clinical efficacy and safety evaluation of TCM and its active ingredients in the treatment and regulation of AIT. Additionally, we provide an in-depth discussion of the relevant mechanisms and molecular targets to understand the protective effects of traditional Chinese medicine on AIT and explore new ideas for clinical treatment. MATERIALS AND METHODS: The literature related to "Hashimoto", "autoimmune thyroiditis", "traditional Chinese medicine," and "Chinese herbal medicine" was systematically summarized and reviewed from Web of Science Core Collection, PubMed, CNKI, and other databases. Domestic and international literature were analyzed, compared, and reviewed. RESULTS: An increasing number of studies have demonstrated that herbal medicines can intervene in immunomodulation, with pharmacological effects such as antibody lowering, anti-inflammatory, anti-apoptotic thyroid follicular cells, regulation of intestinal flora, and regulation of estrogen and progesterone levels. The signaling pathways and molecular targets of the immunomodulatory effects of Chinese herbal medicine for AIT may include Fas/FasL, Caspase, BCL-2, and TLRs/MyD88/NF-κB et al. CONCLUSIONS: The use of Chinese herbs in the treatment and management of AIT is clinically experienced, satisfactory, and safe. Future studies may evaluate the influence of herbal medicines on the occurrence and development of AIT by modulating the interaction between immune factors and conventional signaling pathways.

Connection between Celiac Disease and Systemic Lupus Erythematosus in Children-A Development Model of Autoimmune Diseases Starting from What We Inherit to What We Eat.

Celiac disease (CD) and systemic lupus erythematosus (SLE) are two diseases intensively studied in all age groups, with an increasing incidence at the global level, possibly due to the increased awareness of the diseases and their accurate diagnosis and as a consequence of the new research and innovation technologies that have appeared in medicine. The first is a controllable condition found in approximately 1% of the entire population in the form of a reaction to environmental stimuli affecting individuals with genetic susceptibility, causing gluten intolerance, gastrointestinal and extradigestive symptoms, starting from subclinical stages and culminating in severe malabsorption. On the other hand, lupus is an autoimmune disease with chameleon-like symptoms and found mainly in the female sex, which leaves its clinical mark on most organs, from the skin, eyes, and kidneys to the cardiovascular, pulmonary, neurological, osteoarticular, and hematological systems. Current studies focus on the correlation between celiac disease and other autoimmune pathologies such as autoimmune thyroiditis (Hashimoto and Graves-Basedow), type I diabetes, and systemic lupus erythematosus. The current review aims to present a summary of the data from the specialized literature regarding the intercurrents between celiac disease and lupus by analyzing the most recent studies published on PubMed.

Hypothyrodism in two children.

Autoimmune thyroiditis (AIT) is the most common form of acquired hypothyroidism in paediatric patients in iodine-replete populations. AIT is characterised by a gradual autoimmune destruction of the thyroid gland. The diagnosis is verified by the presence of thyroid autoantibodies. Symptoms are rarely overt and the biochemical picture at presentation varies. This case report describes two paediatric patients that display heterogeneous clinical pictures to illustrate the variety of symptoms of AIT at presentation.

The pathogenic role of IFN-α in thyroiditis mouse models.

AIM: Patients with chronic hepatitis C are frequently treated with interferon (IFN)-α. Autoimmune thyroid disease occurs in 20% ~ 40% of IFN-α-treated patients. In this study, the effects of IFN-α administration on triggering and regulating autoimmune thyroiditis in various animal models were evaluated. MAIN METHODS: Exogenous IFN-α was given to naive CBA mice, and both thyroglobulin (TG) immunization-induced (CBA) and spontaneous autoimmune thyroiditis (NOD·H-2 h4) models. Thyroid function, and anti-thyroglobulin antibody (ATA) and B-cell-activating factor (BAFF) levels were measured. Alterations in transcriptome profiles were analyzed. KEY FINDINGS: In the TG-induced thyroiditis model, IFN-α administration reduced plasma free thyroxine levels but did not alter ATA titers, BAFF levels, or the severity of histological changes. Interestingly, even without changes in thyroid functions, four of eight mice in the IFN-α alone group exhibited thyroiditis compared to the control group. Immunologically, mice in the IFN-α group exhibited profound CD3+ cell infiltration in the thyroid and higher plasma BAFF levels compared to the control group. Meanwhile, pathological and serological alterations after IFN-α administration were not observed in the NOD·H-2 h4 model. An RNA sequencing analysis revealed that immunoregulatory signatures were not excited by IFN-α treatment in naive CBA mice. Meanwhile, innate and adaptive immunity, inflammatory cytokine, chemokine, and cell-killing signaling pathways were all stimulated by IFN-α administration after TG immunization of CBA mice. SIGNIFICANCE: We confirmed the remarkable effects of IFN-α in both initiating thyroid immunity and modulating thyroid function and immunoregulatory signatures in established autoimmune thyroiditis. We suggest that IFN-α should be administered with caution in clinical settings.

Association Between Gut Microbiota and Autoimmune Thyroid Disease: A Systematic Review and Meta-Analysis.

Background: Autoimmune thyroid disease (AITD) is characterized by thyroid dysfunction and deficits in the autoimmune system. Growing attention has been paid toward the field of gut microbiota over the last few decades. Several recent studies have found that gut microbiota composition in patients with AITD has altered, but no studies have conducted systematic reviews on the association between gut microbiota and ATID. Methods: We searched PubMed, Web of Science, Embase, and Cochrane databases without language restrictions and conducted a systematic review and meta-analysis of eight studies, including 196 patients with AITD. Results: The meta-analysis showed that the alpha diversity and abundance of certain gut microbiota were changed in patients with AITD compared to the controls. Chao1,the index of the microflora richness, was increased in the Hashimoto's thyroiditis group compared to controls (SMD, 0.68, 95%CI: 0.16 to 1.20), while it was decreased in the Graves' disease group (SMD, -0.87, 95%CI: -1.46 to -0.28). In addition, we found that some beneficial bacteria like Bifidobacterium and Lactobacillus were decreased in the AITD group, and harmful microbiota like Bacteroides fragilis was significantly increased compared with the controls. Furthermore, the percentage of relevant abundance of other commensal bacteria such as Bacteroidetes, Bacteroides, and Lachnospiraceae was increased compared with the controls. Conclusions: This meta-analysis indicates an association between AITD and alteration of microbiota composition at the family, genus, and species levels. Systematic Review Registration: PROSPERO, identifier CRD42021251557.

Insights from a Prospective Follow-up of Thyroid Function and Autoimmunity among COVID-19 Survivors.

BACKGROUND: The occurrence of Graves' disease and Hashimoto thyroiditis after coronavirus disease 2019 (COVID-19) raised concerns that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger thyroid autoimmunity. We aimed to address the current uncertainties regarding incident thyroid dysfunction and autoimmunity among COVID-19 survivors. METHODS: We included consecutive adult COVID-19 patients without known thyroid disorders, who were admitted to Queen Mary Hospital from July 21 to September 21, 2020 and had serum levels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine (fT3), and anti-thyroid antibodies measured both on admission and at 3 months. RESULTS: In total, 122 patients were included. Among 20 patients with abnormal thyroid function tests (TFTs) on admission (mostly low fT3), 15 recovered. Among 102 patients with initial normal TFTs, two had new-onset abnormalities that could represent different phases of thyroiditis. Among 104 patients whose anti-thyroid antibody titers were reassessed, we observed increases in anti-thyroid peroxidase (TPO) (P<0.001) and anti-thyroglobulin (P<0.001), but not anti-thyroid stimulating hormone receptor titers (P=0.486). Of 82 patients with negative anti-TPO findings at baseline, 16 had a significant interval increase in anti-TPO titer by >12 U, and four became anti-TPO-positive. Worse baseline clinical severity (P=0.018), elevated C-reactive protein during hospitalization (P=0.033), and higher baseline anti-TPO titer (P=0.005) were associated with a significant increase in anti-TPO titer. CONCLUSION: Most patients with thyroid dysfunction on admission recovered during convalescence. Abnormal TFTs suggestive of thyroiditis occurred during convalescence, but infrequently. Importantly, our novel observation of an increase in anti-thyroid antibody titers post-COVID-19 warrants further follow-up for incident thyroid dysfunction among COVID-19 survivors.

Thyroid complications of SARS and coronavirus disease 2019 (COVID-19).

We have reviewed the available literature on thyroid diseases and coronavirus disease 2019 (COVID-19), and data from the previous coronavirus pandemic, the severe acute respiratory syndrome (SARS) epidemic. We learned that both SARS and COVID-19 patients had thyroid abnormalities. In the limited number of SARS cases, where it was examined, decreased serum T3, T4 and TSH levels were detected. In a study of survivors of SARS approximately 7% of the patients had hypothyroidism. In the previous evaluation evidence was found that pituitary function was also affected in SARS. Others suggested a hypothalamic-pituitary-adrenal axis dysfunction. One result published recently indicates that a primary injury to the thyroid gland itself may play a key role in the pathogenesis of thyroid disorders in COVID-19 patients, too. Subacute thyroiditis, autoimmune thyroiditis and an atypical form of thyroiditis are complications of COVID-19. Thyroid hormone dysfunction affects the outcome by increasing mortality in critical illnesses like acute respiratory distress syndrome, which is a leading complication in COVID-19. Angiotensin-converting enzyme 2 is a membrane-bound enzyme, which is also expressed in the thyroid gland and the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) uses it for docking, entering as well as replication. Based on the available results obtained in the SARS-CoV-2 pandemic, beside others, we suggest that it is necessary to monitor thyroid hormones in COVID-19.

Autoimmune switch from hyperthyroidism to hypothyroidism in Graves' disease.

We report a case of a 21-year-old young woman who was initially diagnosed with hyperthyroidism secondary to Graves' disease and spontaneously switched to hypothyroidism in a year. While most autoimmune hypothyroidism is due to Hashimoto's disease, in her case, we suspect that her hypothyroidism is due to a switch of antibody dominance from thyroid stimulating hormone (TSH) receptor-stimulating antibody (TS Ab) to TSH receptor-blocking antibody (TB Ab). Switching from dominant TS Ab activity to dominant TB Ab activity is a rare phenomenon. Optimal management of this condition is not known. Loss of follow-up and medication non-adherence has made medical management in this young woman of reproductive age further challenging.

Massive pericardial effusion and cardiac tamponade revealed undiagnosed Turner syndrome: a case report.

BACKGROUND: Patients with Turner syndrome (TS) are prone to autoimmune disorders. Although most patients with TS are diagnosed at younger ages, delayed diagnosis is not rare. CASE PRESENTATION: A 31-year-old woman was presented with facial edema, chest tightness and dyspnea. She had primary amenorrhea. Physical examination revealed short stature, dry skin and coarse hair. Periorbital edema with puffy eyelids were also noticed with mild goiter. Bilateral cardiac enlargement, distant heart sounds and pulsus paradoxus, in combination with hepatomegaly and jugular venous distention were observed. Her hircus and pubic hair was absent. The development of her breast was at 1st tanner period and gynecological examination revealed infantile vulva. Echocardiography suggested massive pericardial effusion. She was diagnosed with cardiac tamponade based on low systolic pressure, decreased pulse pressure and pulsus paradoxus. Pericardiocentesis was performed. Thyroid function test and thyroid ultrasound indicated Hashimoto's thyroiditis and severe hypothyroidism. Sex hormone test revealed hypergonadotropin hypogonadism. Further karyotyping revealed a karyotype of 45, X [21]/46, X, i(X) (q10) [29] and she was diagnosed with mosaic + variant type of TS. L-T4 supplement, estrogen therapy, and antiosteoporosis treatment was initiated. Euthyroidism and complete resolution of the pericardial effusion was obtained within 2 months. CONCLUSION: Hypothyroidism should be considered in the patients with pericardial effusion. The association between autoimmune thyroid diseases and TS should be kept in mind. Both congenital and acquired cardiovascular diseases should be screened in patients with TS.

Vitamin D effects and endocrine diseases.

A lack of vitamin D has been linked to autoimmune diseases including type 1 diabetes, autoimmune thyroiditis and to obesity. The prevalence of vitamin D deficiency is higher in diabetic or obese children and patients with thyroiditis compared to healthy controls. Moreover, low vitamin D values seem to be associated with major complications and poor glycemic control, in particular in obese children. Supplementation with vitamin D, which has immune-regulatory properties, may support our therapies and improve the outcomes in different diseases. Although some studies suggest a possible role of vitamin D in the etiology of autoimmune diseases and obesity, data on supplementation benefits are inconclusive and further studies are needed. In this paper, we focus on the current evidence regarding vitamin D function in endocrine diseases and possible benefits of its supplementation in pediatric age.

Selenoprotein P as Biomarker of Selenium Status in Clinical Trials with Therapeutic Dosages of Selenite.

Selenoprotein P (SELENOP) is an established biomarker of selenium (Se) status. Serum SELENOP becomes saturated with increasing Se intake, reaching maximal concentrations of 5-7 mg SELENOP/L at intakes of ca. 100-150 µg Se/d. A biomarker for higher Se intake is missing. We hypothesized that SELENOP may also reflect Se status in clinical applications of therapeutic dosages of selenite. To this end, blood samples from two supplementation studies employing intravenous application of selenite at dosages >1 mg/d were analyzed. Total Se was quantified by spectroscopy, and SELENOP by a validated ELISA. The high dosage selenite infusions increased SELENOP in parallel to elevated Se concentrations relatively fast to final values partly exceeding 10 mg SELENOP/L. Age or sex were not related to the SELENOP increase. Western blot analyses of SELENOP verified the results obtained by ELISA, and indicated an unchanged pattern of immunoreactive protein isoforms. We conclude that the saturation of SELENOP concentrations observed in prior studies with moderate Se dosages (<400 µg/d) may reflect an intermediate plateau of expression, rather than an absolute upper limit. Circulating SELENOP seems to be a suitable biomarker for therapeutic applications of selenite exceeding the recommended upper intake levels. Whether SELENOP is also capable of reflecting other supplemental selenocompounds in high dosage therapeutic applications remains to be investigated.

Seguimiento del hijo de madre con patología tiroidea autoinmune. ¿Qué no debemos cribar? / Follow-up of infants born to mothers with autoinmune thyroid disease. What should not be screened?

Introducción: La patología tiroidea es un problema frecuente en las mujeres embarazadas. Su etiología suele ser autoinmune siendo la tiroiditis de Hashimoto y la enfermedad de Graves las entidades principales. A pesar de las posibles alteraciones hormonales y del paso transplacentario de anticuerpos estimulantes, la realización de un cribado neonatal específico no ha demostrado su utilidad en el neonato. Pacientes y métodos: Estudio prospectivo (noviembre de 2013-diciembre de 2016) de los hijos de madre con patología tiroidea autoinmune nacidos en un hospital universitario nivel III. Los recién nacidos se seleccionaron en maternidad. Se excluyeron los casos de asfixia perinatal. Los datos se recogieron de las historias clínicas de madres y recién nacidos. Resultados: Se incluyeron 191 recién nacidos. El 90% de las madres estaban diagnosticadas de hipotiroidismo autoinmune, de cuyos hijos solo un 5,8% tuvo alguna alteración analítica tratándose de leves ascensos de tirotropina, con normalización al mes de vida, no correlacionándose con los niveles de anti-TPO. Se diagnosticó una hipertirotropinemia transitoria que precisó tratamiento durante el primer año de vida. El 36,8% de los hijos de madre con Graves tuvo algún control analítico alterado en los primeros 7 días de vida, no diagnosticándose ningún caso de hipertiroidismo y solo una hipertirotropinemia transitoria. Conclusiones: La experiencia de nuestro centro en el manejo del cribado neonatal tiroideo muestra un elevado número de controles analíticos con un escaso rendimiento diagnóstico. No encontramos relación entre niveles de anticuerpos anti-TPO y disfunción tiroidea. Apoyamos las recomendaciones de mantener el cribado neonatal universal como única exploración en los hijos de madre hipotiroidea

Introduction: Thyroid dysfunction is a common problem in pregnant women. It is usually of an autoimmune origin, with Hashimotós thyroiditis and Graveś disease being the most common conditions. Although hormonal changes and transplacental antibody transfer may occur, specific neonatal screening has not been shown to be useful. Patients and method: A prospective study of newborns of women with autoimmune thyroid disease born at a level III university hospital (November 2013-December 2016). Neonates were selected during their stay at the maternity. Babies with perinatal asphyxia were excluded. Data were collected from the clinical histories of mothers and newborns. Results: A total of 191 neonates were included. Ninety percent of mothers had been diagnosed with autoimmune hypothyroidism. Only 5.8% of newborns had some laboratory disorder, consisting of slightly increased thyroid-stimulating hormone levels, which returned to normal at the age of one month and did not correlate to thyroid peroxidase antibody levels. Transient hyperthyrotropinemia was diagnosed in one newborn and required thyroxin treatment during the first year of life. Among newborns from mothers with Graveś disease, 36.8% had some abnormal laboratory value during the first 7 days of life, but there were no cases of hyperthyroidism and only one of transient hyperthyrotropinemia. Conclusions: Experience at our hospital in screening of newborns from hypothyroid mothers reveals a high number of laboratory controls with a poor diagnostic yield. No relationship was found between thyroid peroxidase antibody levels and thyroid dysfunction. We support the recommendations to continue testing serum thyroid-stimulating hormone and FT4 levels at 48h of life in newborns of mothers with autoimmune hypothyroidism

Endocrine disruptors and thyroid autoimmunity.

Many papers evaluated the effect of the environmental, or occupational endocrine disruptors (ED), on the thyroid gland, that can lead to thyroid autoimmunity. A higher prevalence of autoimmune thyroid diseases (AITD) was observed in people living in polluted areas near to petrochemical plants, and in petrochemical workers, but also in area contaminated with organochlorine pesticides, or with polychlorinated biphenyls, or near aluminum foundries. The exposure to Hg in chloralkali workers, or in swordfish consumers has been also found to increase AITD prevalence. Vanadium has been shown to increase the inflammatory response of thyrocytes. A beneficial effect of omega-3 fatty acids, and of myo-inositol and selenomethionine have been shown to counteract the appearance of AITD in subjects exposed to environmental or occupational ED. More large studies are needed to investigate the potential roles of ED in the induction of AITD, and of agents or habits that are able to prevent them.

Thyro-entero-gastric autoimmunity: Pathophysiology and implications for patient management.

The association between autoimmune atrophic gastritis and thyroid disorders has been observed since the early 1960s and the expression "thyrogastric syndrome" was coined to indicate the presence of thyroid autoantibodies or autoimmune thyroid disease in patients with pernicious anemia, a late clinical stage of autoimmune atrophic gastritis. More recently, it was confirmed that autoimmune thyroid disorders, in particular Hashimoto's thyroiditis, may be frequently associated with other organ-specific, immune-mediated disorders, such as autoimmune atrophic gastritis or celiac disease. The association of Hashimoto's thyroiditis with autoimmune atrophic gastritis or celiac disease in adult patients is currently considered part of the polyglandular autoimmune syndromes which include several autoimmune disorders associated with an autoaggressive impairment of endocrine glands. From a clinical point of view, the thyro-entero-gastric autoimmunity may lead to potentially serious consequences like anemia, micronutrients deficiencies, and drugs malabsorption, as well as to an increased risk for malignancies. These alterations may frequently present in an underhand manner, with consequent diagnostic and treatment delays. Many aspects of the association between thyroid, gastric and intestinal autoimmune diseases still await clarification. The present review focuses on the embryological, genetic and pathophysiological aspects of thyro-entero-gastric autoimmunity. In particular, the current diagnostic criteria of autoimmune thyroid disease, autoimmune atrophic gastritis, and celiac disease are reviewed, along with the evidences for their association in poly-autoimmunity syndromes. The benefits of proactive screening of autoimmune thyroid disorders in patients with autoimmune gastritis or enteropathy and viceversa are also discussed.

Lower proportion of CD19+IL-10+ and CD19+CD24+CD27+ but not CD1d+CD5+CD19+CD24+CD27+ IL-10+ B cells in children with autoimmune thyroid diseases.

Introduction: As it is generally known, regulatory B cells (Bregs) control inflammation and autoimmunity. The significance of Bregs in the population of children with autoimmune thyroid diseases (AITD) still offers plenty of potential to explore. The aim of this study was to estimate the expression of Bregs (phenotype CD19+CD24+CD27+IL-10+, CD19+IL-10+, CD1d+CD5+CD19+IL-10+ and CD1d+CD5+CD19+CD24+CD27+) in a paediatric cohort with AITD and in health controls.Materials and methods: A total of 100 blood samples were obtained from 53 paediatric patients with Graves' disease (GD) (N = 12 newly diagnosed, mean age 12.5 ± 3.5 and N = 17 during methimazole therapy, mean age 12.7 ± 4.4), Hashimoto's thyroiditis (HT) (N = 10 newly diagnosed, mean age 13.3 ± 2.9 and N = 10 during L-thyroxine therapy, mean age 13.7 ± 3.4) and compared with healthy controls (C) (N = 15, mean age 13.1 ± 3.1). The expressions of the immune cell populations were analysed by four-color flow cytometry using a FASC Canto II cytometer (BD Biosciences).Results: There was a decreasing tendency in the number of lymphocytes B producing IL-10 (B10) cells among all B lymphocytes and more widely, also among all lymphocytes, in each study group, as compared to C. We reported a reduction in IL-10 production in Bregs with the expression of CD19+CD24+CD27+IL-10 and CD1d+CD5+CD19+IL-10+ in both untreated and treated AITD.Conclusions: Our data demonstrate that the reduction in the number of Bregs with CD19+CD24+CD27+IL-10+ and CD19+IL-10+ expression could be responsible for breaking immune tolerance and for AITD development in children.

Hashimotos' thyroiditis: Epidemiology, pathogenesis, clinic and therapy.

Hashimoto's thyroiditis (HT), the most frequent autoimmune thyroid disorders (AITDs), is the leading cause of hypothyroidism in the iodine-sufficient areas of the world. About 20-30% of patients suffers from HT, whose cause is thought to be a combination of genetic susceptibility and environmental factors that causes the loss of immunological tolerance, with a consequent autoimmune attack to the thyroid tissue and appearance of the disease. The pathologic features of lymphocytic infiltration, especially of T cells, and follicular destruction are the histological hallmark of autoimmune thyroiditis (AIT), that lead to gradual atrophy and fibrosis. An important role in the immune-pathogenesis of AITDs is due to chemokines and cytokines. In about 20% of patients, AITDs are associated with other organ specific/systemic autoimmune disorders. Many studies have demonstrated the relationship between papillary thyroid cancer and AITD. The treatment of hypothyroidism, as result of AIT, consists in daily assumption of synthetic levothyroxine.

Predictive outcome measures of adult short stature in patients with severe acquired autoimmune hypothyroidism. / Variables predictivas de talla baja adulta en pacientes con hipotiroidismo adquirido grave de origen autoinmune.

Hypothyroidism caused by Hashimoto's thyroiditis is the most common reason for thyroid dysfunction in children. Our objective was to analyze its impact on final stature in relation to height and pubertal stage at the time of diagnosis in children younger than 18 years with severe autoimmune hypothyroidism. Out of 79 patients, 78.5 % were girls. Those with goiter (56 %) had a better height at diagnosis than those without goiter (mean standard deviation score for height: 0.2 versus -2.42; p < 0.0001). Five girls (6.3 %) had precocious puberty. When considering the final stature of patients (n: 33), among those with short stature at the time of diagnosis, pubertal children had a significantly shorter final stature than prepubertal children (mean standard deviation score for height: -2.82 versus -1.52; p = 0.0311). The late diagnosis of severe hypothyroidism in pediatrics has a negative impact on final stature, especially in those who were pubertal patients at the time of diagnosis.

El hipotiroidismo por tiroiditis de Hashimoto es la causa más frecuente de disfunción tiroidea en niños. Nuestro objetivo fue analizar el impacto en la talla final según la talla y el estadio puberal al momento del diagnóstico en menores de 18 años con hipotiroidismo grave de origen autoinmune. De los 79 pacientes, el 78,5 % fueron mujeres. Los que presentaron bocio (el 56 %) mostraron mejor talla en el diagnóstico que los que no lo tenían (puntaje de desvío estándar de media de talla: 0,2 vs. -2,42; p < 0,0001). Cinco niñas (el 6,3 %) presentaron pubertad precoz. De los pacientes con talla final (n: 33), dentro de los que presentaron talla baja al momento del diagnóstico, los púberes tuvieron una talla final significativamente menor que los prepúberes (puntaje de desvío estándar media: -2,82 vs. -1,52; p = 0,0311). El diagnóstico tardío de hipotiroidismo grave en pediatría tiene un impacto negativo en la talla final, especialmente, en los pacientes puberales al momento del diagnóstico.

Sphk1/S1P/S1PR1 Signaling is Involved in the Development of Autoimmune Thyroiditis in Patients and NOD.H-2h4 Mice.

Background: There is growing evidence that sphingosine-1-phosphate (S1P), a pleiotropic bioactive sphingolipid metabolite synthesized intracellularly by two closely related sphingosine kinases (SphKs), SphK1 and SphK2, is involved in inflammation. However, the role of SphKs/S1P/S1P receptors (S1PRs) in autoimmune thyroiditis (AIT) has not been studied to date. Methods: This study examined whether SphK1/S1P/S1PR1 signaling is aberrantly altered in thyroid tissues and serum of both AIT patients and a spontaneously autoimmune thyroiditis (SAT) mouse model. Murine CD4+T cells were employed to further investigate the downstream signaling of SphK1/S1P/S1PR1. Furthermore, a total of 102 NOD.H-2h4 mice, randomly divided into different groups, were used to investigate the therapeutic effect of S1PR1 blockade and its potential mechanism. Results: We found that components of the SphK1/S1P/S1PR1 pathway were abnormally expressed in patients with Hashimoto thyroiditis and in a SAT mouse model. In addition, S1P could activate signal transducer and activator of transcription 3 (STAT3) through S1PR1 and its downstream signaling pathways in CD4+T cells of NOD.H-2h4 mice. Furthermore, an in vivo study demonstrated that blocking S1PR1 by FTY720 administration could reduce the incidence and severity of thyroiditis and goiter in SAT mice in a time-dependent manner. The proportions of STAT3-related and inflammation-related cell subtypes, such as T helper 1, T helper 17, and follicular T helper cells, were elevated in the SAT group when compared to the control group, and these cell subtypes decreased after FTY720 administration. Furthermore, the downstream inflammatory cytokines of STAT3 were also downregulated after FTY720 administration. Conclusion: The present study shows that blocking Sphk1/S1P/S1PR1 signaling can ameliorate the severity of AIT, providing evidence of a promising therapeutic target for AIT.

Association between thyroglobulin polymorphisms and autoimmune thyroid disease: a systematic review and meta-analysis of case-control studies.

Emerging evidence revealed that thyroglobulin (TG) contributes to the development of autoimmune disease, and the relationship between TG and autoimmune thyroid disease (AITD) is still controversial. The aim of this study was to quantify the association between rs2076740, rs853326, rs180223, and rs2069550 TG polymorphisms and risk of AITD using a meta-analysis approach. We identified all studies that assessed the association between TG polymorphisms and AITD from PubMed, Embase, and Web of Science databases. A total of 3013 cases and 1812 controls from ten case-control studies were included. There was no significant associations found between rs2069550, rs180223, and rs853326 polymorphisms and AITD risk. The association between the rs2076740 polymorphism and AITD risk was significant in the codominant model (P = 0.005), suggesting the CC rs2076740 genotype might be a protective factor for AITD. Sensitivity analysis by removing one or two study changed the results in dominant rs2076740 and rs853326 and rs2069550 allele models (P = 0.016, 0.024, 0.027). Latitude and ethnicity significantly affected the association between rs2076740 and rs2069550 polymorphisms and AITD, indicating their protective effects in allele or dominant model (P = 0.012, 0.012, 0.012, 0.009, 0.009). The association between rs2076740, rs2069550, and rs853326 polymorphisms and AITD risk is significantly affected by study characteristics.

Endocrine disorders associated with hepatitis C virus chronic infection.

The term "HCV syndrome" encompasses several organ- and systemic pathophysiological states, which often recognize autoimmunity or neoplastic evolution in their pathophysiology, as well as chronic HCV infection as trigger. The clinical features of HCV patients are heterogenous, and may include endocrine or metabolic disorders, namely autoimmune thyroiditis, type 2 diabetes mellitus, and erectile/sexual dysfunctions. In this review, we summarize current knowledge on the endocrine/metabolic diseases associated with chronic HCV infection, focusing on the main concepts emerged in the recent literature in this field. The application of this knowledge in everyday clinical practice may be relevant, in order to reinforce a holistic vision of the patient with chronic HCV infection, stimulating in turn a multi-disciplinary approach, thus increasing the probability of early diagnosis, more effective treatments, and a better prognostic outcome.