Protective effect of thyroid and restores of ovarian function of Buzhong Yiqi granule on experimental autoimmune thyroiditis in female rats.

OBJECTIVE: To observe the effects of Buzhong Yiqi granule on thyroid function and ovarian function in rats with experimental autoimmune thyroiditis (EAT). METHODS: EAT model was replicate by using the method of mixing and injecting porcine thyroglobulin with Freund's adjuvant and high iodine. Rats were randomly divided into normal control (NC) group, EAT model (EAT) group, selenium yeast (PC) group, low dose Buzhong Yiqi (BZYQ-L) group, medium dose Buzhong Yiqi (BZYQ-M) group and high dose Buzhong Yiqi (BZYQ-H) group. After two months of drug intervention according to dosage, enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), anti-thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb) in peripheral blood of rats. The pathological changes of rat thyroid tissues were observed under light microscope with HE staining; ELISA was used to determine estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), anti-müllerian hormone (AMH), and the pathological changes of rat ovarian tissues were observed under light microscope with hematoxylin and eosin staining. RESULTS: Compared with the NC group, BZYQ granule improved the thyroid and ovarian tissue morphology, and the levels of TPOAb, TGAb and TSH in the model group rats significantly increased (P < 0.05), the thyroid tissue was severely destroyed, the levels of E2, FSH, LH, T, AMH significantly increased (P < 0.05), and the ovary exhibited polycystic changes; Compared with the model group, TSH level in the BZYQ-L group rats decreased (P < 0.05), FSH, T, AMH levels decreased (P < 0.05), in the BZYQ-M group TPOAb, TSH levels decreased (P < 0.05), FSH, LH, T, AMH levels significantly decreased (P < 0.05), BZYQ-H group TPOAb, TGAb, TSH levels significantly decreased (P < 0.05), FSH, LH, T, AMH levels significantly decreased (P < 0.05), with the greatest improvement and significantly better than selenium yeast group (P < 0.05). CONCLUSIONS: BZYQ granule could regulate the thyroid function of EAT rats, reduce thyroid antibody titers, then act on the ovarian function, regulate hormone disorders, and alleviate the pathological damage of rat's ovarian tissues. The effect of high dose Buzhong Yiqi granule is the best.

Thyroid disturbances after COVID-19 and the effect of vaccination in children: a prospective tri-center registry analysis.

Rapidly evolving clinical data suggest that the novel coronavirus (SARS-CoV-2) and vaccination against COVID-19 might be associated with thyroid disturbances. However, studies remain limited among the pediatric population. Our aim was to assess the prevalence and permanence of thyroid autoimmunity (TA) and dysfunction in children after an acute infection and its potential association with vaccination. A prospective, multicenter registry analysis was performed among 458 children (mean age: 12.4 ± 3,8 years, 45.4% male) with preceding COVID-19. Patient inclusion lasted from 24th March, 2021 to 23rd March, 2022 at three pediatric outpatient facilities at Semmelweis University, Budapest. Primary outcomes were the rate of thyroid disturbances assessed by laboratory parameters (thyroid function tests, antithyroglobulin [ATG] and anti-thyroid peroxidase [ATPO] antibodies) and thyroid ultrasound. TA rate among vaccinated and unvaccinated children was determined. Children with newly diagnosed thyroid alterations were followed up for 12.7 ± 4.3 months. Six children had previous thyroid disease. Out of 452 children, 30 cases (6.6%) of newly diagnosed TA (six of them had abnormal thyroid-stimulating hormone [TSH] levels) and eight cases (1.8%) of isolated TSH elevation were observed. Ultrasound-proven autoimmune thyroiditis (AIT) was 4.0%. No association was found between COVID-19 vaccination and thyroid autoimmunity (χ2(1,N = 452) = 0.138, p = 0.815). Among children with TA, 73.3% had long-lasting alterations.  Conclusion: Vaccination had no effect on the prevalence of TA. Until further controlled studies state otherwise, children with preceding COVID-19 might benefit from thyroid screening. What is Known: • Numerous case reports implicate that coronavirus disease-2019 (COVID-19) and vaccination against SARS-CoV-2 can be responsible for thyroid disturbances. • Thyroid alterations discovered during acute COVID-19 tend to cease by time and only incidental thyroid autoimmunity (TA) is diagnosed after COVID-19. In adults, no increase in vaccine-related hyper- or hypothyroidism was found. What is New: • TA rate after COVID-19 vaccination among children was not increased. TA had no role in long COVID syndrome. • We discovered a considerable rate of TA (6.6%) and ultrasound-proven autoimmune thyroiditis (AIT) (4.0%) after SARS-CoV-2 infection, and the majority of these alterations remained positive after 6 months.

Helicobacter pylori Infection Is Associated With Thyroid Dysfunction in Children With Congenital Hypothyroidism.

Helicobacter pylori (H. pylori) infection leads to a systemic low-grade inflammatory state and has been associated causally with a diverse spectrum of extra-gastric disorders. Among them, the infection has been involved in the pathogenesis of autoimmune thyroid disease (ATD), but only one study had evaluated children. Therefore, a cross-sectional study was conducted in a cohort of 142 children and adolescents, randomly assessed among those followed up for thyroid diseases in a university pediatric endocrinology service: 106 with congenital hypothyroidism (CH) and 36 with ATD. All children were asymptomatic, under strict control on levothyroxine replacement, and reported no other diseases or use of drugs. Helicobacter pylori status was evaluated by the 13C-Urea Breath Test (13C-UBT). Antithyroid antibodies (ATPO, antiTg, and TRAb) and serum thyroid hormones (TSH, free T4, and T3) were assessed by standard assays. Data were analyzed in logistic models by the SPSS statistical software package, and a p-value ≤ 0.05 was considered statistically significant. The prevalence of H. pylori infection was 19.44% in children with ATD. Neither the gender nor the serum levels of thyroid hormones and antithyroid antibodies were associated with the H. pylori-positive status. Thirty-seven (34.90%) children with CH were infected with H. pylori. The mean T3 serum level (3.59 ± 0.84) was significantly lower (p = 0.001) in the infected children than in those free from the infection (3.95 ± 0.89), association that remained after adjustment for the other variables in the multivariate analysis. Because no difference was observed in the levels of TSH and T4, the results indicate that the infection may lead to impairment in the thyroid hormonal balance, but not in the hypothalamic-pituitary-thyroid axis function. In as much as H. pylori infection is highly widespread and the prevalence of CH is also not negligible, additional studies are required to confirm our results and to identify the involved mechanisms.

Effects of herbal cake-partitioned moxibustion on the expression of thyroid autophagy-related factors LC3B and Beclin-1 in rats with autoimmune thyroiditis / 针灸推拿医学（英文版）

Objective: To observe the anti-inflammatory effect, as well as the effect on the expression of microtubule-associated protein light chain 3B (LC3B) and Beclin-1 of herbal cake-partitioned moxibustion in rats with experimental autoimmune thyroiditis (EAT). Methods: Female Sprague-Dawley rats were randomly divided into a normal group and a modeling group. The EAT rat model was prepared by a combination of antigen immunization plus iodine agent induction. After the model was prepared, rats in the modeling group were randomly and equally divided into a model group and a herbal cake-partitioned moxibustion group. In the herbal cake-partitioned moxibustion group, moxibustion was alternately applied to two groups of points [Dazhui (GV14)-Mingmen (GV4) and Tiantu (CV22)-Guanyuan (CV4)], and the treatment continued for 30 d. Rats in the normal and model groups were only fixed identically without intervention. Histopathological manifestations of thyroid glands were observed by hematoxylin-eosin staining; the concentrations of thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TGAb), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay; real-time fluorescence quantitative polymerase chain reaction and immunohistochemistry were used to detect the mRNA and protein expression of autophagy-related factors LC3B and Beclin-1 in thyroid tissue. Results: There were massive follicular destruction, lymphocytic infiltration, and interstitial fibrous tissue hyperplasia of the thyroid glands in the model group. Some follicles of the thyroid glands were destroyed with few lymphocyte infiltrations and fibrous tissue hyperplasia in the moxibustion group. Compared with the normal group, the concentrations of serum TPOAb, TGAb, IL-1β, IL-6, and TNF-α were increased in the model rats (P<0.05); the mRNA and protein expression levels of LC3B and Beclin-1 in thyroid tissue were reduced in the model group (P<0.05). Compared with the model group, the concentrations of serum TPOAb, TGAb, IL-1β, IL-6, and TNF-α were reduced in the herbal cake-partitioned moxibustion group (P<0.05); the mRNA and protein expression levels of LC3B and Beclin-1 in thyroid tissue were increased in the herbal cake-partitioned moxibustion group (P<0.05). The mRNA and protein expression of LC3B and Beclin-1 in thyroid tissue was negatively correlated with the serum levels of TPOAb and TGAb.Conclusion: Herbal cake-partitioned moxibustion reduces the inflammatory response in the thyroid glands of EAT rats and lowers the levels of serum TPOAb and TGAb. This may be related to the regulation of mRNA and protein expression of the autophagy-associated factors LC3B and Beclin-1 in rat thyroid tissue.

Mechanism research of the modified Xiaoyao Powder on inflammatory response of rats with syndrome of stagnation of liver qi and spleen deficiency of experimental autoimmune thyroiditis based on mirRNA326 regulating Th17 cells / 国际中医中药杂志

Objective:To explore the mechanism of modified Xiaoyao Powder on inflammatory response of rats with syndrome of stagnation of liver qi and spleen deficiency of experimental autoimmune thyroiditis (EAT) from the perspective of differentiation of microrna 326 (miR326) regulating Th17 cell.Methods:48 rats were randomly divided into normal group (12 rats) and model group (36 rats) respectively and they were immunized twice a week with high iodine water combined with subcutaneous injection of thyroglobulin. From the fifth to eighth weeks, 36 rats were immunized once a week. From the fifth week, the model group with liver depression and spleen deficiency syndrome of Traditional Chinese Medicine was reproduced with chronic restraint stress, excessive fatigue and eating incoherence methods. The modelrats were randomly divided into model group, Xiaoyao Powder group and Jinshuibao group. Rats in Xiaoyao Powder group were gavaged with 13.63 g/(kg·d) Xiaoyao Powder modified granule suspension, and rats in Jinshuibao group were gavaged with 477 mg/(kg·d) Jinshuibao suspension, twice a day, for 8 weeks.The levels of serum FT3, FT4, TSH, TGAb and TPOAb were detected by ELISA; the expression of miR326, IL-17 mRNA, IL-4 mRNA and IFN-γ mRNA were detected by PCR. The expression of Ets-1 protein in thyroid tissue was detected by Wes method, and the proportion of CD4 + IFNγ + T cells, CD4 + IL-4 + T cells and CD4 + IL-17 + T cells were detected by flow cytometry, HE staining was used to detect the pathological manifestations of thyroid tissue in each group. Results:Compared with the model group, the serum TSH [(3 328.88±724.45) pg/ml vs. (1 900.25±203.91) pg/ml] in Xiaoyao Powder group increased ( P<0.01), TGAb [(63.60±9.01) IU/ml vs. (96.19±10.74) IU/ml] and TPOAb [(6.84±1.45) IU/ml vs. (11.62±2.06) IU/ml] decreased ( P<0.01), and the expression of miR326 (3.57±0.57 vs. 7.63±0.90),IL-17 mRNA (6.71±0.97 vs. 13.02±1.18) significantly decreased ( P<0.01), the expression of Ets-1 (0.71±0.40 vs. 0.39±0.02) significantly increased ( P<0.01), the ratio of CD4 +IFN-γ + T cell [(13.10±2.23)% vs. (20.7±2.07)%], CD4 +IL-17 + T cell ratio [(18.90±1.31)% vs. (25.1±1.03)%] significantly decreased ( P<0.01), and thyroid histopathology changed significantly. Conclusion:Modified Xiaoyao Powder could regulate the expression of target protein Ets-1 upward, inhibit the differentiation of Th17 cells and further reduce the expression of IL-17 mRNA by regulating the expression of mir-326 downward in the thyroid tissue of EAT rats, so as to improve the inflammatory response of rats with liver depression and spleen deficiency.

Clinicopathological and prognostic analysis of medullary thyroid carcinoma co-existent with Hashimoto's thyroiditis / 中华普通外科杂志

Objective:To investigate the clinicopathological features and prognosis of medullary thyroid carcinoma (MTC) co-existent with Hashimoto's thyroiditis (HT).Methods:Seven cases of MTC co-existent with HT were collected from Fujian Cancer Hospital between Jan 2007 and May 2021. Its clinicopathological features were analyzed.Results:All patients were adult female with a median age of 49 years, and 6 of them were unilateral MTC. The tumor diameter ranged from 0.4 to 7.0 cm. The thyroid tissue surrounding the tumor showed HT. The follow-up time was 16 to 152 months, with a median time of 61 months, 5 patients (tumor diameter <1 cm) were biochemically cured, 1 patient (tumor diameter >1 cm) was anatomically cured. The another patient died due to tumor progression 30 months after surgery, the tumor cells in which were highly atypia and more mitoses (5~8/10HPF) necrosis and vascular invasion were also observed.Conclusion:MTC with HT are mostly sporadic cases, and most of them have a fair prognosis.

COVID-19 Vaccination for Endocrine Patients: A Position Statement from the Korean Endocrine Society.

Since the first outbreak of coronavirus disease 2019 (COVID-19), ongoing efforts have been made to discover an efficacious vaccine against COVID-19 to combat the pandemic. In most countries, both mRNA and DNA vaccines have been administered, and their side effects have also been reported. The clinical course of COVID-19 and the effects of vaccination against COVID-19 are both influenced by patients' health status and involve a systemic physiological response. In view of the systemic function of endocrine hormones, endocrine disorders themselves and the therapeutics used to treat them can influence the outcomes of vaccination for COVID-19. However, there are very limited data to support the development of clinical guidelines for patients with specific medical backgrounds based on large clinical trials. In the current severe circumstances of the COVID-19 pandemic, position statements made by clinical specialists are essential to provide appropriate recommendations based on both medical evidence and clinical experiences. As endocrinologists, we would like to present the medical background of COVID-19 vaccination, as well as precautions to prevent the side effects of COVID-19 vaccination in patients with specific endocrine disorders, including adrenal insufficiency, diabetes mellitus, osteoporosis, autoimmune thyroid disease, hypogonadism, and pituitary disorders.

Effect of Zuojin Pill on HIF-1α expression and apoptosis of thyroid cells in rats with autoimmune thyroiditis / 国际中医中药杂志

Objective:To investigate the effect of Zuojin Pill on the expression of hypoxia inducible factor-1α (HIF-1α) and apoptosis of thyroid cells in rats with autoimmune thyroiditis (AIT). Methods:Ninetysix rats were divided into control group, model group, standarlized protocol and low, medium and high dose Zuojin Pill groups. Except the control group, the rats in other groups were produced as AIT model. After successful modeling, rats in low-, medium-, and high-dose groups were intragastrically administered with 0.63, 1.26, and 2.52 g/kg Zuojin Pill respectively, standarlized protocol was given 6.25 mg/kg Tripterygium wilfordii polyglycoside, and the control group and model group were given the same amount of normal saline. The levels of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) were detected by enzyme-linked immunosorbent assay (ELISA); the activity of SOD and the content of MDA in thyroid tissue were detected by kit; the pathological changes of thyroid tissue were observed by HE staining; the apoptosis of thyroid cells was detected by TUNEL; the expression of HIF-1α, B-cell lymphoma-2 (Bcl-2), Bcl-2-related X protein (Bax) and Cleaved caspase-3 in thyroid tissues was detected by Western blot. Results:Compared with the model group, the content of TNF-α, TPOAb and TGAb in serum of rats in the low, medium and high dose Zuojin Pill groups significantly decreased, the content of IL-10 in serum significantly increased ( P<0.05). The SOD activity significantly increased, and the MDA content significantly decreased in the low, medium and high dose Zuojin Pill groups ( P<0.05). The apoptosis rate significantly decreased in the low, medium and high dose Zuojin Pill groups ( P<0.05). The expression of HIF-1α (0.48 ± 0.05, 0.63 ± 0.06, 0.86 ± 0.06 vs. 0.33 ± 0.03), Bcl-2 (0.48 ± 0.04, 0.59 ± 0.05, 0.68 ± 0.04 vs. 0.37 ± 0.04) significantly increased, the expression of Bax (0.67 ± 0.05, 0.53 ± 0.05, 0.40 ± 0.05 vs. 0.80 ± 0.06), Cleaved caspase-3 (0.64 ± 0.06, 0.51 ± 0.03, 0.36 ± 0.03 vs. 0.77 ± 0.05) significantly decreased in the low, medium and high dose Zuojin Pill groups ( P<0.05). Conclusion:Zuojin Pill could enhance the expression of HIF-1α, regulate the secretion of inflammatory factors, reduce the level of oxidative stress and thyroid autoantibody, and inhibit the apoptosis of thyroid cells.

Chronic urticaria and thyroid pathology.

Urticaria is defined as the sudden appearance of erythematous, itchy wheals of variable size, with or without angioedema (AE) (swelling of the deeper layers of the skin). Its classification depends on time course of symptoms and the presence of eliciting factors. When it lasts less than 6 weeks it is classified as acute urticaria (AU), and if the symptoms persist for more than 6 weeks, it is classified as chronic urticaria (CU). Current International Guidelines also classify CU as chronic spontaneous urticaria (CSU) and inducible urticarial, according to the absence or presence of environmental triggering factors. CSU is defined as urticaria and/or angioedema in which there is no evidence of a specific eliciting factor. CSU is associated with autoimmunity in 30-45% of the cases, sharing some immunological mechanisms with other autoimmune diseases, and is associated with autoimmune thyroid disease (ATD) in about 4.3%-57.4% patients. Several studies suggest that adequate therapy with anti-thyroid drugs or levothyroxine in early stages of ATD and CSU, may help to remit the latter; but there is still a lack of double-blind, placebo-controlled studies that support this hypothesis in patients without abnormal thyroid hormone levels. The objective of this review is to describe the pathophysiology of chronic spontaneous urticaria and its association with autoimmune thyroid disease.

[Application of the superior thyroid artery peak systolic velocity in differentiating Graves' disease from autoimmune thyroiditis].

Objective: To evaluate the clinical value of the superior thyroid artery peak systolic velocity (STA-PSV) for the differential diagnosis of autoimmune thyrotoxicosis. Methods: A total of 301 patients with newly diagnosed thyrotoxicosis and without any anti-thyroid drug intervention were collected from the Department of Endocrinology and Metabolism, Peking University People's Hospital from Jan. 2015 to Oct. 2018. Among them, 241 patients were with Graves' disease (GD) and 60 patients were with autoimmune thyroiditis (AIT). STA-PSV, thyroid function and thyrotropin receptor antibody (TRAb) were determined. A multiple linear regression was used to identify factors associated with STA-PSV. A receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the discriminating ability of STA-PSV to GD. Results: STA-PSV leves in GD group were significantly higher than those in AIT group [61.00 (41.00, 86.50) cm/s vs. 34.50 (25.25, 46.00) cm/s, P<0.001]. The ROC curve analysis showed that the AUC was 0.790 (95%CI 0.734-0.845), and 49.5cm/s was the optimal cutoff point for the diagnosis of GD, in which the sensitivity was 64.3% and the specificity was 83.3%. In all patients with thyrotoxicosis, multiple linear regression analyses showed free thyroxine (FT(4)) (ß=0.371, 95%CI 0.005-0.010, P<0.001) and TRAb (ß=0.138, 95%CI 0.001-0.014, P=0.035) were positively associated with STA-PSV. Conclusions: The STA-PSV is positively associated with FT(4) and TRAb levels, and it is a helpful marker in differential diagnosis between GD and AIT.

Hepatitis C Virus Infection of Human Thyrocytes: Metabolic, Hormonal, and Immunological Implications.

CONTEXT: Hepatitis C virus (HCV) infection is a prevalent disease worldwide. Thyroid dysfunction is one of the most common extrahepatic manifestations of HCV infection. We hypothesized that HCV can directly infect human thyrocytes thereby causing thyroid dysfunction. SETTING: Human thyrocytes in primary cell culture, ML-1 human thyroid cell line, and Huh7.5 human hepatocyte cell line were infected with HCV using the Huh7.5JFH1 cell line that releases infectious HCV virions. After infection, the release of new virions, production of proinflammatory cytokines, and expression of miR-122 were evaluated. Ribonucleic acid (RNA) extracted from HCV-infected cells and mock-infected cells was subjected to RNA sequencing and transcriptomic analysis. Ingenuity pathway analysis was used to detect up- and down-regulated pathways. RESULTS: Human thyrocytes express major HCV entry factors including CD81, occludin, claudin-1, and scavenger receptor class B1. Viral infection of thyroid cells was confirmed by detection of HCV core protein in supernatants and negative-sense HCV RNA in cell lysates. HCV infection of thyrocytes induced the production of the chemokine CXCL-8 and the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and significantly increased the expression of miR-122. Moreover, HCV infection of thyrocytes decreased expression of the thyroid peroxidase and thyroglobulin genes and increased expression of the deiodinase 2 gene. The top upregulated pathways in HCV-infected thyrocytes were immune pathways and metabolic pathways, while infected hepatocytes upregulated lipid and glucose metabolism pathways as previously reported. CONCLUSIONS: HCV infection may induce thyroid dysfunction by different mechanisms including direct infection of thyrocytes leading to activation of inflammatory pathways and upregulation of miR-122. These findings support a general mechanism for viral induction of autoimmunity through direct infection of target tissues.

Application of the superior thyroid artery peak systolic velocity in differentiating Graves′ disease from autoimmune thyroiditis / 中华内科杂志

Objective@#To evaluate the clinical value of the superior thyroid artery peak systolic velocity (STA-PSV) for the differential diagnosis of autoimmune thyrotoxicosis.@*Methods@#A total of 301 patients with newly diagnosed thyrotoxicosis and without any anti-thyroid drug intervention were collected from the Department of Endocrinology and Metabolism, Peking University People′s Hospital from Jan. 2015 to Oct. 2018. Among them, 241 patients were with Graves′ disease (GD) and 60 patients were with autoimmune thyroiditis (AIT). STA-PSV, thyroid function and thyrotropin receptor antibody (TRAb) were determined. A multiple linear regression was used to identify factors associated with STA-PSV. A receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the discriminating ability of STA-PSV to GD.@*Results@#STA-PSV leves in GD group were significantly higher than those in AIT group [61.00 (41.00, 86.50) cm/s vs. 34.50 (25.25, 46.00) cm/s, P<0.001]. The ROC curve analysis showed that the AUC was 0.790 (95%CI 0.734-0.845), and 49.5cm/s was the optimal cutoff point for the diagnosis of GD, in which the sensitivity was 64.3% and the specificity was 83.3%. In all patients with thyrotoxicosis, multiple linear regression analyses showed free thyroxine (FT4) (β=0.371, 95%CI 0.005-0.010, P<0.001) and TRAb (β=0.138, 95%CI 0.001-0.014, P=0.035) were positively associated with STA-PSV.@*Conclusions@#The STA-PSV is positively associated with FT4 and TRAb levels, and it is a helpful marker in differential diagnosis between GD and AIT.

[Hypothyroidism-when and how to treat?] / Hypothyreose ­ wann und wie behandeln?

The diagnosis of hypothyroidism is primarily based on clinical signs and symptoms as well as measurement of thyroid-stimulating hormone (TSH) concentration. Subclinical hypothyroidism is characterized by elevated TSH with normal serum free thyroxine (fT4) and triiodothyronine (fT3) levels, while in manifest hypothyroidism serum fT4 and fT3 levels are reduced. Common causes of primary hypothyroidism are autoimmune thyroiditis as well as therapeutic interventions, such as thyroid surgery or radioiodine therapy. Signs and symptoms of hypothyroidism include fatigue, bradycardia, constipation and cold intolerance. In subclinical hypothyroidism, symptoms may be absent. Initiation of levothyroxine (T4) therapy not only depends on the level of TSH elevation, but also on other factors, such as patient age, presence of pregnancy or comorbidities. Treatment of patients with subclinical hypothyroidism is still a controversial topic. In general, thyroid hormone replacement therapy in non-pregnant adults ≤ 70 years is clearly indicated if the TSH concentration is >10 mU/l. Standard of care for treatment of hypothyroidism is T4 monotherapy. The biochemical treatment goal for T4 replacement in primary hypothyroidism is a TSH level within the reference range (0.4-4.0 mU/l). In contrast, in secondary hypothyroidism, serum fT4 levels are the basis for adjusting thyroid hormone dosage. Inadequate replacement of T4 resulting in subclinical or even manifest hyperthyroidism should urgently be avoided. T4/liothyronine (T3) combination therapy is still a matter of debate and not recommended as standard therapy, but may be considered in patients with persistence of symptoms, despite optimal T4 treatment, based on expert opinion.

Protective effects of Jiayan Kangtai granules on autoimmune thyroiditis in a rat model by modulating Th17/Treg cell balance.

OBJECTIVE: To investigate the protective effects of Jiayan Kangtai (JYKT) granules, consisting of 9 Chinese herbs, in a rat model of autoimmune thyroiditis (AIT), and the possible underlying mechanism. METHODS: Female Lewis rats (6-8 weeks) were randomly apportioned to 5 groups of 10, including a normal control. AIT was induced in the untreated AIT-model group, and rats treated subsequently with daily low, medium, or high dose JYKT granules. After 12 weeks, plasma levels of thyroid autoantibodies and morphological changes in the thyroid were detected by enzyme-linked immunosorbent assay and histological examination, respectively. The presence of interleukin (IL)-6, IL23p19, and IL-2 in thyroid tissue was assessed by immunohistochemical staining. The percentages of T helper (Th)17 cells and regulatory T cells (Tregs) in the peripheral blood were analyzed by flow cytometry. Relevant levels of cytokines and proteins were examined via bead-based multiplex flow cytometry and ELISA, respectively. Expressions of genes and proteins regulated by Th17 cells and Tregs were shown by real-time PCR and Western blot. RESULTS: Compared to the control, AIT-model rats had higher plasma concentrations of thyroid autoantibodies. The high-dose JYKT rats showed significantly lower levels of thyroid autoantibodies compared with the AIT model group. Rats in the AIT-JYKT groups also had fewer thyroid lesions and less lymphocytic infiltration, a lower percentage of Th17 cells, and a higher percentage of Tregs, compared with the AIT-model. Rats given high-dose JYKT had a significantly lower Th17/Treg ratio compared with the AIT model. Differences in plasma cytokine concentrations and relevant gene and protein expressions in the spleens of JYKT-treated rats and the AIT group suggested an association between JYKT treatment and lower Th17 cell percentage and higher Treg activity. CONCLUSION: JYKT treatment appeared to be protective against AIT in rats, possibly via the regulation of the Th17 cell/Treg imbalance in AIT.

Hemostasis in Hypothyroidism and Autoimmune Thyroid Disorders.

CONTEXT: There are contradictory results on the effect of hypothyroidism on the changes in hemostasis. Inadequate population-based studies limited their clinical implications, mainly on the risk of venous thromboembolism (VTE). This paper reviews the studies on laboratory and population-based findings regarding hemostatic changes and risk of VTE in hypothyroidism and autoimmune thyroid disorders. EVIDENCE ACQUISITION: A comprehensive literature search was conducted employing MEDLINE database. The following words were used for the search: Hypothyroidism; thyroiditis, autoimmune; blood coagulation factors; blood coagulation tests; hemostasis, blood coagulation disorders; thyroid hormones; myxedema; venous thromboembolism; fibrinolysis, receptors thyroid hormone. The papers that were related to hypothyroidism and autoimmune thyroid disorder and hemostasis are used in this review. RESULTS: Overt hypothyroidism is more associated with a hypocoagulable state. Decreased platelet count, aggregation and agglutination, von Willebrand factor antigen and activity, several coagulation factors such as factor VIII, IX, XI, VII, and plasminogen activator-1 are detected in overt hypothyrodism. Increased fibrinogen has been detected in subclinical hypothyroidism and autoimmune thyroid disease rendering a tendency towards a hypercoagulability state. Increased factor VII and its activity, and plasminogen activator inhibitor-1 are among several findings contributing to a prothrombotic state in subclinical hypothyroidism. CONCLUSIONS: Overt hypothyroidism is associated with a hypocoagulable state and subclinical hypothyroidism and autoimmune thyroid disorders may induce a prothrombotic state. However, there are contradictory findings for the abovementioned thyroid disorders. Prospective studies on the risk of VTE in various levels of hypofunctioning of the thyroid and autoimmune thyroid disorders are warranted.

A novel data-driven workflow combining literature and electronic health records to estimate comorbidities burden for a specific disease: a case study on autoimmune comorbidities in patients with celiac disease.

BACKGROUND: Data collected in EHRs have been widely used to identifying specific conditions; however there is still a need for methods to define comorbidities and sources to identify comorbidities burden. We propose an approach to assess comorbidities burden for a specific disease using the literature and EHR data sources in the case of autoimmune diseases in celiac disease (CD). METHODS: We generated a restricted set of comorbidities using the literature (via the MeSH® co-occurrence file). We extracted the 15 most co-occurring autoimmune diseases of the CD. We used mappings of the comorbidities to EHR terminologies: ICD-10 (billing codes), ATC (drugs) and UMLS (clinical reports). Finally, we extracted the concepts from the different data sources. We evaluated our approach using the correlation between prevalence estimates in our cohort and co-occurrence ranking in the literature. RESULTS: We retrieved the comorbidities for 741 patients with CD. 18.1% of patients had at least one of the 15 studied autoimmune disorders. Overall, 79.3% of the mapped concepts were detected only in text, 5.3% only in ICD codes and/or drugs prescriptions, and 15.4% could be found in both sources. Prevalence in our cohort were correlated with literature (Spearman's coefficient 0.789, p = 0.0005). The three most prevalent comorbidities were thyroiditis 12.6% (95% CI 10.1-14.9), type 1 diabetes 2.3% (95% CI 1.2-3.4) and dermatitis herpetiformis 2.0% (95% CI 1.0-3.0). CONCLUSION: We introduced a process that leveraged the MeSH terminology to identify relevant autoimmune comorbidities of the CD and several data sources from EHRs to phenotype a large population of CD patients. We achieved prevalence estimates comparable to the literature.

Relationship between vitiligo and Hashimoto's thyroiditis / Relação entre vitiligo e tireoidite de Hashimoto

Introduction: vitiligo is a multifactorial acquired depigmenting disorder, characterized by a spontaneous loss of functional melanocytes from the epidermis. Vitiligo and Hashimoto's thyroiditis (HT) often occur in association and seem to be characterized by an autoimmune process. The vitiligo associated with HT suggests genetic homologies between them. Objective: to identify protein sequence homology between melanocyte protein (Pmel) and thyroid peroxidase (TPO), using bioinformatics tools, to propose an initial mechanism which could explain the production of cross-reacting autoantibodies to melanocyte and TPO. Methods: we performed a comparison between Pmel and TPO amino acids (AA) sequences, available on the National Center for Biotechnology Information (NCBI) database by BLAST (Basic Local Alignment Search Tool) in order to find local homology regions between the AA sequences. Results: the homology sequence between the Pmel and TPO ranged from 21.0 % (19 identical residues out of 90 AA in the sequence) to 55.0% (6 identical residues out of 11 AA in the sequence). The identical alignments presented relatively high E values due to presence of short alignment. Conclusion: bioinformatics data suggest a possible pathological link between Pmel and TPO. Sequence homology between Pmel and TPO may present a molecular mimicry suggesting the possibility of antigen crossover between Pmel and TPO that might represent an immunological basis for vitiligo associated with HT.

Introdução: o vitiligo é uma doença de despimentação adquirida multifatorial, caracterizada por uma perda espontânea de melanócitos funcionais da epiderme. Vitiligo e tiroidite de Hashimoto (TH) ocorrem frequentemente em associação e parecem ser caracterizados por um processo autoimune. O vitiligo associado à TH sugere homologias genéticas entre eles. Objetivo: identificar homologia das sequências de proteína entre a proteína do melanócito (Pmel) e peroxidase da tiróide (TPO), usando ferramentas de bioinformática, para propor um mecanismo inicial que poderia explicar a produção de autoanticorpos de reação cruzada entre o melanócito e a TPO. Metodologia: foi realizada uma comparação entre a sequência de aminoácidos (AA) da Pmel e da TPO, disponível no banco de dados Basic Local Alignment Search Tool (BLAST) do National Center for Biotechnology Information (NCBI), a fim de encontrar regiões de homologia locais entre as sequências de AA. Resultados: a sequência de homologia entre a Pmel e a TPO variou de 21,0% (19 resíduos idênticos na sequência de cada 90 AA na sequência) a 55,0% (6 resíduos idênticos na sequência de 11 AA). Os alinhamentos idênticos apresentaram valores relativamente altos (E) devido à presença de alinhamentos curtos. Conclusão: os dados de Bioinformática sugerem uma possível ligação patológica entre Pmel e a TPO. A sequência de homologia entre Pmel e a TPO pode apresentar um mimetismo molecular sugerindo a possibilidade de cruzamento entre antígeno da Pmel e da TPO que pode representar uma base imunológica para a associação entre o vitiligo e a TH.

Ultrasonographic assessment of thyroid volume in oldest-old individuals

ABSTRACT Objective The aim of this study was to describe the relationship between thyroid volume and age, gender, anthropometric characteristics, and echogenicity in oldest-old subjects in an iodine-sufficient area. Subjects and methods The study included 81 independent elderly individuals aged ≥ 80 years (65 [80.2%] women). We determined these individuals' anthropometric characteristics, body mass index (BMI), and lean body mass, as well as thyroid volume and echogenicity by ultrasonography. Results We observed that octogenarians and nonagenarians had different profiles of thyroid echogenicity. The volume of the thyroid was smaller in nonagenarians than octogenarians (p = 0.012, r = 0.176), and subjects aged 80-89 years had more often hypoechoic glands than those aged ≥ 90 years (p = 0.01 versus 0.602). Conclusion The identification of ultrasonographic differences in oldest-old individuals will contribute to establishing preclinical markers, such as echogenicity, to identify individuals at risk of developing autoimmune thyroid disease. Future prospective studies should identify if 80-89-year-old individuals with hypoechoic glands progress to hypothyroidism, and if the absence of changes in echogenicity (i.e. a normal thyroid parenchyma) would have a positive impact on longevity among nonagenarians.

Excessive iodine and autoimmune thyroid disease / 中华地方病学杂志

Autoimmune thyroid disease (AITD) is an archetypal organ-specific autoimmune disorder that is characterized by the production of thyroid autoantibodies and lymphocytic infiltration into the thyroid.Excessive iodine can increase the incidence of AITD.During trapping,oxidation and organification of excessive iodine in thyroid cells,excessive reactive oxygen species (ROS) were generated,which induces apoptosis of thyroid cells,accelerates thyroglobulin autoantigen presentation,promotes lymphocytes infiltration and cytokine expression.Excessive iodine is an environmental risk factor which promotes the people with stealth autoimmune thyroid disease to get sick.In this article,we discussed the relationship between excessive iodine and AITD and its mechanism.

Effect of Xiaoying Decoction on Changes of Regulatory T Cells and Th17 Cells in Experimental Autoimmune Thyroiditis Rats / 医药导报

Objective To explore the mechanism of Xiaoying decoction on experimental autoimmune thyroiditis (EAT) rats in view of regulatory T cells and Th17 cells.Methods SD rats were divided into five groups,normal control group,model control group,tripterygium glycoside group,Xiaoying decoction low and high dose groups.Except for normal control group,the other groups were established the model of EAT.Rats in the Xiaoying decoction low,and high dose groups were given Xiaoying decoction of 17.24 and 68.95 g·kg-1;rats in the tripterygium glycoside group were given tripterygium glycoside 6.25 mg·kg-1.The serum free triiodothyronine(FT3),free thyrocyte(FT4) and thyroglobulin antibody were detected by RIA method.Thyrocyte morphology was observed under optical microscope.The expression levels of Foxp3 mRNA and IL-17 mRNA were detected by real-time PCR.The changes of Treg cells and Th17 cells were analyzed by flow cytometry.Results Compared with the normal control group,FT3,FT4 and TgAb were increased in the model control group (P ＜0.01,P ＜0.01,P ＜0.05).Compared with the model control group,FT3,FT4 and TgAb were decreased in tripterygium glycoside group and Xiaoying decoction high dose group (P ＜ 0.05).The infiltration score in the normal control group,model control group,tripterygium glycoside group,Xiaoying decoction low and high dose groups were 0,4,4,3.5,2.Compared with model control group,the infiltration was improved (P ＜0.01).Foxp3 mRNA expression was decreased while IL-17 mRNA increased in the model control group as compared with the normal control group(P ＜ 0.01).In contrast,the expression of Foxp3 mRNA was increased and IL-17 mRNA expression was decreased in Xiaoying decoction low and high dose groups,tripterygium glycoside group as compared with the model control group (P ＜0.05).Compared with the normal control group,rats in the model control group had fewer Treg cells and more Th17 cells (P ＜0.01).Compared with the model control group,the percentage of Treg cells was elevated and Th17 cells was reduced in tripterygium glycoside group and Xiaoying decoction high dose groups (P ＜ 0.01).Conclusion The therapeutic mechanism of Xiaoying decoction on EAT rats may be related to changing the percentage of regulatory T cells and Th17 cells with up-regulating the expression of Foxp3 mRNA and down-regulating the expression of IL17mRNA.