Autoimmune Thyroiditis Patients Research Articles

Researching of the relationship between the numberof t regulatory cells and serum arachidonic acid level in autoimmune thyroiditis patients

Researching of the relationship between the numberof t regulatory cells and serum arachidonic acid level in autoimmune thyroiditis patients

Cytokine-determined mechanisms of the pathomorphological realization of gastroesophageal reflux disease against the background of autoimmune thyroiditis in young persons

The aim: to study the features of proinflammatory cytokine status and pathomorphological realization of gastroesophageal reflux disease (GERD) against the background of autoimmune thyroiditis (AIT) in young people.
 Materials and methods. Examinations involved 120 patients with GERD and AIT and 45 people with isolated GERD. The control group consisted of 20 volunteers matched by age, gender, and social status. All patients underwent esophagogastroduodenoscopy, histological study, comparative morphometry of the esophageal mucosa, and determination of proinflammatory cytokines’ levels: interleukin‑1β (IL‑1β), IL‑18, tumor necrosis factor‑α (TNF‑α).
 Results. The frequency of erosive GERD in the examined groups of patients did not statistically differ. At the same time, analysis of the structure of erosive GERD forms revealed a significant redistribution of esophagitis grades towards its enhancement in patients with comorbid pathology. The histological study showed that in patients with nonerosive GERD and AIT all the studied morphometric parameters had significantly deeper changes and exceeded similar indicators of the group with isolated GERD: epithelium total thickness 319.3±9.1 µm against 286.1±8.2 µm (p <0.01), epithelium basal layer thickness 79.6±3.2 µm versus 49.7±2.1 µm (p <0.01), connective tissue papillae height 224.8±7.3 µm against 172.7±4.6 µm (p <0.01), intercellular space 1.55±0.11 µm versus 1.12±0.09 µm (p <0.01). The presence of concomitant AIT was associated with a significant redistribution towards increased degrees of hyperplasia of the basal layer of the epithelium, elongation of the papillae, and leukocyte infiltration. The comorbidity of GERD and AIT in young people was associated with significant increase in the blood serum levels of proinflammatory cytokines in compared to isolated GERD: IL‑1β — 29.6 pg/ml versus 17.7 pg/ml (p <0.01), IL‑18—1763.4 pg/ml versus 614.6 pg/ml (p <0.01), TNF‑α — 7.6 pg/ml versus 5.2 pg/ml (p <0.01). Correlation analysis of the cytokine content and expressivity of certain morphometric parameters of the esophageal mucosa revealed the direct correlations.
 Conclusions. GERD and euthyroid AIT comorbidity in the student population is accompanied by significant redistribution of esophagitis grades towards its aggravation. The presence of concomitant AIT in patients with non‑erosive GERD leads to the significant intensification of the degree of epithelium basal layer hyperplasia, connective tissue papillae elongation, and polymorphic cellular inflammatory infiltration in comparison with isolated GERD, while these deviations demonstrate direct correlations with the levels of IL‑1β, IL‑18, and TNF‑α.

Circadian clock disruption in autoimmune thyroiditis.

A vicious cycle between circadian disruption and escalating immune responses has been described in diverse inflammatory disease. The current study aimed to explore the role of circadian clock disruption in autoimmune thyroiditis (AIT). Thirty AIT patients and 30 controls were enrolled and biopsied for thyroid tissues. Alterations of core clock genes expression in AIT thyroid tissues, and its association with serum and tissue inflammatory biomarkers were assessed. For animal studies, C57BL/6J mice administered with porcine thyroglobulin or PBS (as control) combined with adjuvants were sacrificed at four time points to investigate the circadian characteristic of experimental autoimmune thyroiditis (EAT). Light shift (LS) conditions were used to explore the influence of external circadian disturbance on EAT. The expression of clock genes BMAL1 and PER2 was significantly reduced in thyroid tissues from AIT patients and was negatively correlated to levels of thyroid peroxidase antibodies. In mouse models, diurnal fluctuations of proinflammatory cytokines were demonstrated, and further exposing mice to LS led to overproduction of TNF-α, IFN-γ, and anti-thyroglobulin antibodies. Circadian analysis revealed significant oscillations of Bmal1, Clock, Per2, Cry1, Ror, and Rev-erb, which was broadly disturbed in EAT, LS, and EAT + LS groups. This study demonstrates that expression pattern of clock genes was disrupted in AIT thyroid, and chronic circadian disruption may aggravate the inflammatory responses in AIT. Whether maintaining a regular circadian rhythm can alleviate autoimmune thyroid diseases warrants further research.

Pharmacological suppression of NLRP3 inflammasome attenuated the development of autoimmune thyroiditis.

Autoimmune thyroiditis (AIT), characterized by an endless inflammatory process of self-destruction, ultimately leads to chronic swelling of the thyroid gland and its dysfunction. Here, we investigated the involvement of the NLR pyrin domain-containing 3 (NLRP3) inflammasome in AIT development. We found that NLRP3 is significantly upregulated in the thyroid of AIT patients and mice with experimental autoimmune thyroiditis (EAT). Pharmacological suppression of NLRP3 using its inhibitor MCC950 suppressed the progression of EAT in vivo. Furthermore, MCC950 treatment significantly reduced the numbers of infiltrating CD4+ and CD8+ T cells in the thyroid. Moreover, MCC950 significantly lowered the amounts of T helper 1 cells, T helper 17 cells, interferon gamma, and interleukin-17A; however, it significantly increased regulatory-T-cell numbers and interleukin-10 levels. These results suggest that suppression of NLRP3 inflammasome activation reverses AIT by inhibiting Th1- and Th17-cell responses and promoting Treg cell responses. Hence, the NLRP3 inflammasome is a promising therapeutic and theragnostic target in AIT. inhibits Th1- and Th17-cell responses and promotes Treg cell responses.

Can anti-thyroglobulin antibody (anti-Tg) be a tumor marker for recurrence in papillary thyroid carcinoma (PTC) in patients without autoimmune thyroiditis (AIT)?: A case report

Abstract Introduction Thyroid carcinoma is the most common malignancy of the endocrine system, accounting for 1% of all newly diagnosed cancers. Thyroglobulin (Tg) is a tumor marker for papillary thyroid carcinoma (PTC) if the anti-thyroglobulin antibody (anti-Tg) is negative. In autoimmune thyroiditis (AIT) patients with positive anti-Tg, the level of this antibody can be a marker in the follow-up of PTC, since the anti-Tg concentration depends on the amount of Tg-secreting tissue. However, there is no clear data on whether the development of anti-Tg positivity during follow-up is an indicator of recurrence in a patient who has neither AIT nor anti-Tg positivity before surgery. Clinical Case 21-year-old male admitted to our hospital with a complaint of a palpable mass on the neck. The patient was euthyroid and thyroid autoantibodies were negative. In neck ultrasonography (US), 10 mm EU-TIRADS 5 nodule in right lobe and pathologic lymphs nodes in right cervical compartments were detected, and FNABs were done. Results were consistent with PTC. Total thyroidectomy, central and right neck dissection were performed. Histopathology report resulted in classic variant 2 cm PTC in right lobe, one central and 10 lateral pathologic lymph nodes among a total of 41. While 150 mCi RAI was given as adjuvant therapy; TSH level was 109 µIU/ml, Tg was 11 ng/mL and anti-Tg was negative. No involvement was detected in the post-RAI whole body scan except microscopic residual RAI avid foci in the thyroid bed and upper mediastinum. No pathologic focus was observed in the upper mediastinum in thorax CT. During one year, he was followed with an excellent response. At the end of the first year after surgery, anti-Tg antibody was detected as positive with 6.63 IU/mL (0–4 normal range) when neck ultrasonography and thyroglobulin were negative (<0.1 ng/mL). At the end of the second year that the patient was under close follow-up, the anti-Tg titer increased to 8 IU/mL and neck US revealed a single suspicious 7×6mm, round lymph node, with loss of normal hilum, in the central compartment (level VI-VII). Central lymph node dissection was performed when Tg washout was positive in this lymph node. Histopathological examination resulted in two metastatic (2 and 3 mm) lymph nodes out of four lymph nodes removed. In postoperative third months, Tg and anti-Tg were negative. Conclusion This case shows that anti-Tg can be used as a tumor marker for PTC in patients without AIT. It was thought that the autoimmunity that developed afterwards against the thyroglobulin antigen might have been triggered by the thyroglobulin that passed into the serum after the adjuvant rai treatment, and it might have turned into a tumor marker in this way for this patient. Therefore, we recommend that anti-Tg testing should be continued in the follow-up of patients with PTC whose anti-Tg were not positive before surgery.

Nivoi vitamina D i genetski variant VDR rs2228570 u autoimunom tireoditisu

Autoimmune Thyroiditis (AIT) is a prevalent autoimmune disorder characterized by an immune response targeting the thyroid gland. Genetic factors play a significant role in AIT susceptibility, with immune-related genes, especially the vitamin D receptor (VDR) gene, potentially influencing AIT development. This comprehensive review delves into the intricate association between VDR gene polymorphisms, particularly rs2228570 (FokI), and AIT susceptibility, exploring various populations. Research has unveiled contrasting outcomes regarding the link between the VDR rs2228570 polymorphism and AIT risk across diverse ethnic groups. Certain populations have exhibited a noteworthy correlation, suggesting that population-specific genetic factors contribute to AIT risk. A recurring observation of vitamin D deficiency in AIT patients has correlated with elevated anti-thyroid antibodies, abnormal thyroid function , and thyroid volume. The results emphasize the possible role of vitamin D in the development of AIT, suggesting the importance of vitamin D supplementation to address deficiencies associated with AIT. In addition to VDR rs2228570, other genetic variants have also shown associations with AIT susceptibility, displaying varying results across different populations. Ethnicity emerges as a pivotal factor influencing these associations, underscoring the need to consider genetic variations in diverse populations. We emphasize the intricate interplay between VDR gene polymorphisms, vitamin D, and AIT susceptibility. Extensive research is essential to unveil the clinical significance of these genetic variations, offering prospects for enhanced diagnostic and therapeutic strategies for individuals with AIT.

Expression of Cytokines and Cytokine Receptors-Genes in Patients with Different Forms of Thyroid Pathology in Ukrainian Population

Abstract Multiple susceptibility genes can be involved in the development of Hashimoto’s thyroiditis. Some of these genes are implicated in other autoimmune diseases, while others are specific to thyroid autoimmune response. 153 patients with thyroid pathology were enrolled in the study (152 women and 1 man, the average age was 46,02±14,3). They were divided into 3 groups: 16 patients with postoperative hypothyroidism; 65 patients with hypothyroidism resulting from autoimmune thyroiditis, and 72 patients with both AIT and elevated serum an anti-thyroglobulin and anti-thyroid peroxidase antibodies. We used a pathway-specific real-time Polymerase chain reaction array to identify and verify cytokines and receptor pathway-associated gene expression in peripheral white blood cells in randomly selected 12 individuals from each group. In the patients with postoperative hypothyroidism and those with hypothyroidism resulting from autoimmune thyroiditis, the expression of Chemokine (C-X3-C motif) receptor 1, Chemokine (C-X-C motif) receptor 4, Interleukin 6, and Interleukin 6 receptor significantly decreased, while the expression of IL6ST and IL10RA increased. In contrast, mRNA levels of Chemokine (C-X3-C motif) receptor 1, Chemokine (C-XC motif) receptor 4, Interleukin 6, and Interleukin 6 receptor increased in the autoimmune thyroiditis patients with elevated serum anti-thyroglobulin and anti-thyroid peroxidase antibodies, while the expression of Interleukin 6 signal transducer and Interleukin 10 receptor, alpha decreased in this group of patients. The patients with hypothyroidism resulting from autoimmune thyroiditis and patients with elevated serum anti-thyroglobulin and anti-thyroid peroxidase antibodies had significantly lowered expression of Interleukin 10, while the expression of Interleukin 1, beta and Interleukin 1 receptor, type I was elevated. autoimmune thyroiditis and hypothyroidism affect the mRNA-level expression of cytokines and cytokine receptor genes in a gene-specific manner, and these changes to gene expression can be among the triggers of autoimmune inflammation progression in the thyroid gland. Transcriptional activity of cytokines, inducer, and receptor genes in the peripheral white blood cells can be used as an important minimally invasive prognostic marker of the autoimmune thyroid disease severity.

The substantiation of differentiated therapy of the combined disgormonal pathology of reproductive organs in women of reproductive age with comorbid conditions

The objective: substantiation of differentiated therapeutic approaches to the treatment of combined dyshormonal pathology of the reproductive organs, taking into account the comorbidity of patients.Materials and methods. 300 women of reproductive age (20–42 years, mean age – 29.9±5.6 years) with dyshormonal pathology of reproductive organs were examined: the main group included 180 patients who were prescribed complex differentiated pharmacotherapy for the treatment of combined dyshormonal pathology of the reproductive organs with correction of comorbid conditions, and the comparison group included 120 patients who received a standard set of measures. The control group included 50 healthy women without somatic and gynecological pathology. All women had ultrasound examination of the pelvic organs, mamma glands, thyroid gland, determination of the levels of pituitary tropic hormones and steroid ovary hormones, thyroid hormones, antibodies to thyroperoxidase, and the level of 25 (OH) D in blood serum. Results. Obesity of various degrees was observed in 31.0% of examined patients with dyshormonal pathology of the reproductive system, the prevalence of autoimmune thyroiditis in patients was 36.0%, and subclinical hypothyroidism was diagnosed in 21.3%. Among women with autoimmune thyroiditis, the frequency of subclinical hypothyroidism was 59.3% with 3.7% of manifest hypothyroidism. Vitamin D insufficiency was found in 34.0% of patients with dyshormonal pathology, vitamin D deficiency – in 44.3%, severe deficiency – in 21.7%. Treatment of patients in the main group led to the normalization of the menstrual cycle in 97.2% of cases, in the comparison group – in 73.3%, to a reduction of pain syndrome severity – in 94.7% and 60.6%, respectively, cyclic mastodynia – in 93.9% and 43.9%, manifestations of vegetative-vascular and non-specific symptoms – in 94.8±3.9% and 24.3±16.7% of cases, contributed to achieving the desired pregnancy – in 64.1% and 30.6% of patients, respectively, and also there was a reducing the frequency of relapses during 6 months of observation from 14.5% to 4.1%.Conclusions. The use of complex differentiated pharmacotherapy for the treatment of combined dyshormonal pathology of the reproductive organs with the correction of comorbid conditions makes possible to achieve higher efficiency, which is manifested in a greater reduction in the frequency of clinical symptoms and disease relapses compared to the usual practice.

Effect of different iodine levels on the DNA methylation of PRKAA2, ITGA6, THEM4 and PRL genes in PI3K-AKT signaling pathway and population-based validation from autoimmune thyroiditis patients.

Autoimmune thyroiditis (AIT) is one of the most common autoimmune endocrine diseases. The currently recognized causes are genetic susceptibility, environmental factors and immune disorders. It is important to clarify the pathogenesis for the prevention, diagnosis, treatment of AIT and scientific iodine supplementation. This study analyzed the DNA methylation levels of PRKAA2, ITGA6, PRL and THEM4 genes related to PI3K-AKT signaling pathway, compared the DNA methylation levels between cases and controls from different water iodine levels in Shandong Province of China, and evaluated the contribution of PI3K-AKT signaling pathway-related genes in AIT. A total of 176 adult AIT patients were included from three different water iodine areas, and 176 healthy controls were included according to gender, age and BMI. According to the results of the Illumina Methylation 850K BeadChip in our previous research, the significant methylation differences of genes on the PI3K-AKT signaling pathway related to AIT were determined. The MethylTarget™ assay was used to detect the methylation levels of the target genes, and real-time PCR experiments were used to verify the mRNA expression levels. Compared with the control group, PRKAA2_3 and 15 CpG sites were hyper-methylated. ITGA6 gene and 2 CpG sites were hypo-methylated in AIT cases. The mRNA expression of ITGA6 gene was negatively correlated with the DNA methylation levels of ITGA6 gene and 2 CpG sites. Compared with cases and controls in areas with different water iodine levels, methylation differences were mainly in PRKAA2 and ITGA6 genes. The methylation levels of PRKAA2_1 and PRKAA2_3 were positively correlated with age. The methylation levels of PRL and THEM4 genes were negatively correlated with age. The methylation level of PRKAA2_3 was positively correlated with FT4. In summary, we identified aberrant DNA methylation levels of PRKAA2 and ITGA6 genes related to PI3K-AKT signaling pathway in the blood of AIT patients. Both iodine supplementation after long-term iodine deficiency and iodine excess can affect the DNA methylation levels of PRKAA2 and ITGA6 genes, and the former affects more obviously. In ITGA6 gene, this aberrant epigenetic modification is associated with the increased mRNA expression.

Autoimmune thyroiditis in patients with sudden sensorineural hearing loss.

ObjectiveThis study aims to evaluate the association between autoimmune thyroiditis and Sudden Sensorineural Hearing Loss (SSNHL).MethodsHundred and five patients with SSNHL were enrolled. Audiometric tests, serum thyroid autoantibodies (TPOAb, TgAb) were studied. Based on the thyroid autoantibody results, patients were divided into two groups: thyroid autoantibody‐positive and negative. The relationship between thyroid autoimmunity and audiological characteristics was analyzed.ResultsTwenty‐six patients (24.8%) of the SSNHL had thyroid autoantibody elevated. The pure tone average (PTA) of patients with and without thyroid autoantibody is 60 ± 38.51 and 54.99 ± 33.87 dBHL, respectively. The PTA was significantly improved in both groups after treatment (p < 0.001), but the hearing gains were similar in both groups (p = 0.205). Hearing loss of 2000–8000 Hz was worse than 125–1000 Hz among thyroid autoantibody‐positive patients (p < 0.05), but the hearing improvement of both groups have no significant difference. The hearing improvement of 125–1000 Hz is significantly better than 2000–8000 Hz among patients with thyroid autoantibody negative (p < 0.05).ConclusionsWe speculate that a potential association between thyroid autoimmunity and SSNHL. Thyroid autoimmunity may be a pathogenesis factor of SSNHL and associated with more severe hearing loss of high‐frequency hearing.

Features of ultrasound and dopplerometric endometry examination in autoimmune thyroiditis patients with abnormal uterine bleeding

Abnormal uterine bleeding occurs in 10–30% of reproductive age women. Ultrasound examination is one of the most effective methods of diagnosing lesions of the pelvic organs while it has high sensitivity (96%), but low specificity (13.8%) in relation to endometrial lesions, the informativeness of ultrasound in the diagnosis of abnormal uterine bleeding ranges from 60 to 93.3%. It had been revealed revealed that the imbalance of thyroid hormones can have a direct effect on the endometrium. Thus, the analysis of ultrasound examinations data together with dopplerometric assessment of the blood flow of the internal genital organs in autoimmune thyroiditis patients with abnormal uterine bleeding is an urgent task of modern gynecology. The purpose is to determine the features of ultrasound exanimation with Doppler assessment of the endometrium in autoimmune thyroiditis patients with abnormal uterine bleeding. Materials and methods. The patients’ examinations were carried out from 2019 to 2022 We examined 120 patients, of whom 90 (75%) suffered from abnormal uterine bleeding and 30 (25%) did not have signs of gynecological and somatic pathology (control group). Abnormal bleeding patients average age was 36.3±3.2 years. The average age of bleeding and thyroid pathology women was 34.8±2.6 years, the control group average age was 30.7±2.9 years. Results. Echographic signs of endometrium structural changes were detected in 83 (92.2%) of abnormal nautoimmune bleeding women and in 7 (7.8%) women ultrasound signs of pathology were not detected. Significant differences were found when analyzing the results of ultrasonographic examination of patients with bleeding and bleeding + thyroid pathology. Conclusion. Ultrasound is an important method that contributes to a significant improvement in the diagnosis of isolated or combined benign uterine diseases in women with abnormal autoimmune bleeding at the background of thyroid pathology, and in most cases corresponds to the histological diagnosis.

Association of autoimmune thyroiditis with latent autoimmune diabetes of adults (LADA): A study from North India

Objective: The aim of this work was to study the association of autoimmune thyroiditis (AIT) in the patients of latent autoimmune diabetes of adult (LADA). Materials and Methods: The subjects included were more than 30 years of age, presenting with the deranged glycemic profile. After GAD65 autoantibody testing, they were grouped into LADA positive and LADA negative groups. Simultaneously, a thyroid workup for the presence of AIT was done. Statistical Analysis: The Student’s unpaired t test and chi-square test (χ2 test) were used to test for the significance of the difference in AIT between LADA and type 2 diabetes mellitus (T2DM) subjects as applicable. A value of P < 0.05 was taken as significant. Results: A total of 77 patients were included in the study. The mean age was 48 ± 13 years and M:F ratio was 1:3. A high frequency of AIT was found in the LADA group (80%) when compared to the true T2DM group (35%). Mean values of both anti-thyroid peroxidase antibody (anti-TPO) and anti-thyroglobulin antibody (anti-TG) antibodies were found to be significantly different between LADA and T2DM. Percentage positivity for anti-TPO, anti-TG, as well as combined anti-TPO and anti-TG were also found to be significantly different. Conclusion: Based on the significant association of AIT with LADA found in our study, we recommend all AIT patients to undergo simultaneous screening for LADA for a multimodal treatment.

Autoimmune thyroiditis: organizational and medical measures for early detection in the Republic of Belarus

Objective. To evaluate the effectiveness of conducted organizational and medical measures for early detection and medical examination of patients with autoimmune thyroiditis (AIT) in the regions of the Republic of Belarus and to develop measures to enhance them.Materials and methods. Data on the incidence rates of AIT and primary hypothyroidism (PGT) in the Republic of Belarus from 1997 to 2017 were analyzed, data of a sociological study were presented and patients` records were analyzed. Epidemiological and sociological methods were used.Results. In the Republic of Belarus, two organizational and medical approaches to early diagnosis of AIT have been developed. The study has found a low competence level among therapists (general practitioners) of the Brest and Gomel regions and showed the absence of patients with AIT at Gomel Regional Endocrinological Dispensary even if there is a pathognomonic ultrasound picture and a high level of AT-TPO titer, which indicates that the incidence is undercounted.Conclusion. As a result of the performed study, the algorithm for organizational and medical measures has been developed and implemented for early detection and clinical examination of AIT patients aimed at PGT prevention.

DNA Methylation Patterns in the HLA-DPB1 and PDCD1LG2 Gene Regions in Patients with Autoimmune Thyroiditis from Different Water Iodine Areas.

Background: Epigenetic disorders play an important role in the pathogenesis of autoimmune thyroiditis (AIT). Therefore, the study of the possible role of DNA methylation in AIT is of great significance to explore the pathogenesis of AIT. Methods: From May 2019 to June 2019, whole blood samples were collected from 176 AIT patients and 176 controls from different water iodine levels in Shandong Province, China. We used the Illumina Methylation 850K BeadChip to determine significant differences in methylation status of genes and used the MethylTarget™ assay to verify the methylation level in 176 cases and 176 controls. The relative mRNA levels of genes were detected by quantitative real-time-polymerase chain reaction. Results: There were multiple differential methylation sites in the HLA-DPB1 and PDCD1LG2 genes between the case and control population with different water iodine levels. Some target regions of HLA-DPB1 and PDCD1LG2 genes were negatively correlated with relative mRNA expression in the case and control populations and with different water iodine levels. Conclusions: There is differential methylation status in genomic DNA in patients with AIT. The methylation patterns of HLA-DPB1 and PDCD1LG2 genes related to cell adhesion molecule pathway may be different based on different water iodine levels. HLA-DPB1 and PDCD1LG2 genes related to the cell adhesion molecules pathway may play a role in the development of AIT. This study is registered with Chinese Clinical Trial Registry, www.chictr.org.cn, number ChiCTR2000039105.

Morbus Basedow

The diagnosis of Graves' disease is mainly based on ultrasonography and laboratory diagnostics. This includes the determination of the TSH value and the peripheral thyroid hormones. TSH receptor antibody (TRAb) measurement is highly sensitive and specific for the detection of Graves' disease (GD) and helps to distinguish from autoimmune thyroiditis (AIT). However, as recent studies show, some may AIT patients may also reveal TRAb. Current guidelines recommend primarily the use of thiamazol/carbimazole in GD. Due to the comparatively higher hepatotoxicity, propylthiouracil is not recommended as first line therapy. In case of relapse during 12 up to 18 months of antithyroid drug therapy or after a frustrating attempt at cessation, definitive therapy should be considered. Alternatively, in accordance with the current recommendations of the European Thyroid Association, drug therapy may be continued for up to 12 months after initial diagnosis. The treatment of active GD during pregnancy is problematic due to diaplacental crossing of peripheral thyroid hormones, TSH receptor stimulating antibodies and antithyroid drugs. According to current guidelines, PTU is recommended during the first 16 weeks of pregnancy, whereas for the 2nd and 3 rd trimester no special recommendations are given. After that, you can choose which antithyroid drug might be used. The aim of antithyroid drug therapy during pregnancy is to achieve a suppressed TSH value together with normal or slightly increased fT4 while using lowest effective dose of antithyroid drug. The most common endocrine side effect with this therapy is thyroid dysfunction. Hyperthyroidism; occur most frequently in combination therapy (CTLA-4 / anti-PD-1 therapy) ICI mainly causes destructive thyroiditis with lymphocytic infiltration; GD is absolutely rare in this context and only few cases are described.

Associative relationships between vitamin D levels,immunological characteristics and thyroid volume in patients with hypothyroidism due to autoimmune thyroiditis

Background. The leading factor of hypothyroidism in patients with autoimmune thyroiditis is destruction of the thyroid gland under the influence of the autoimmune process. Therefore, the essence of pathogenetic therapy for autoimmune thyroiditis is the prescription of immunomodulators. Understanding the features of autoimmune disorders in autoimmune thyroiditis will allow justifying the requirements for such drugs. Aim: to determine if there is an association between thyroid volume, vitamin D level, and immunological parameters in hypothyroidism due to autoimmune thyroiditis. Materials and methods. A comparative analysis of thyroid status in terms of thyroid-stimulating hormone and free thyroxine content, blood vitamin D levels and immune homeostasis indicators (CD3, CD4, CD8, CD16, CD22, thyroid pe­roxidase antibo­dies and thyroglobulin antibodies) was performed in 55 women with drug-compensated hypothyroidism due to autoimmune thyroiditis. The first group consisted of 29 women with autoimmune thyroi­ditis who for at least one year received indivi­dually selected thyroid replacement therapy, with thyroid volume of 11.05 ± 1.86 cm3, the second group — of 26 women, at least a year ago operated for benign thyroid nodules against the background of autoimmune thyroiditis, with thyroid volume of 4.26 ± 1.89 cm3 (p &lt; 0.05 between groups). The control group included 12 women without autoimmune thyroiditis and hypothyroidism, thyroid volume was 8.7 ± 0.6 cm3. Results. While the thyroid status indicators in autoimmune thyroiditis patients were within the reference norms, the vitamin D level in the general group of women with autoimmune thyroidi­tis and hypothyroidism was significantly (p &lt; 0.02) lower than in the control group, despite the fact that in the control group it corresponded to deficiency status (22.7 ng/ml), and against the background of autoimmune thyroiditis — to vitamin D deficiency (18.3 ng/ml). In patients with a smaller thyroid volume (group 2), the content of vitamin D was significantly (p &lt; 0.05) lower than in group 1. Indicators of cellular immunity were within the re­ference standards, but the level of natural killers in group 2 was significantly (p &lt; 0.05) lower. The levels of antithyroid antibo­dies in both groups were high, indicating the activity of the autoimmune process. Conclusions. In patients with hypothyroidism on the background of autoimmune thyroiditis in a state of drug compensation, smaller thyroid glands are associated with a more pronounced vitamin D deficiency. Thyroid volumes in patients with autoimmune thyroiditis are not associated with pronounced changes in cellular immunity, except for a decrease in the level of natural killers in smaller thyroid volume. The persistent activity of the autoimmune process in patients with hypothyroidism due to autoimmune thyroiditis against the background of prolonged and successful thyroid replacement therapy necessitates the addition of adequate immunomodulators to it, including vitamin D.

Clinical efficacy of thyroid-stimulating immunoglobulin detection for diagnosing Graves’ disease and predictors of responsiveness to methimazole

BackgroundAs thyroid-stimulating immunoglobulins (TSI) are a sign of Graves' disease (GD), measuring TSI titers is becoming increasingly important for GD diagnosis. This study evaluated the diagnostic accuracy of a new fully automated TSI immunoassay (Immulite™ TSI assay) in GD patients and compared it to the third generation thyroid-stimulating hormone receptor antibody (TRAb) electrochemiluminescence assay (Elecsys Anti-TSHR assay). Additionally, clinical characteristics associated with responsiveness to methimazole in patients with newly diagnosed GD were preliminarily explored. MethodsThis study involved 324 subjects, comprising patients with untreated GD (GD-UT), Graves’ ophthalmopathy (GO) patients, GD patients who had been treated for > 12 months (GD-T), autoimmune thyroiditis (AIT) patients, and healthy subjects (HS). The Immulite™ TSI and Elecsys Anti-TSHR assay were performed on all samples. According to their responsiveness to methimazole, the GD-UT patients were divided into rapid and slow responder groups, and their clinical characteristics were compared. ResultsA receiver operating characteristic (ROC) curve analysis of GD-UT patients showed that the optimal TSI cut-off value was 0.57 IU/L. Logistic regression revealed that age and initial FT4 and TSI levels in the middle-dose methimazole group were related to a rapid response, while the initial FT4 level, but not TSI, in the high-dose group was also associated with a rapid response. ConclusionsThe clinical diagnostic performance of the Immulite™ TSI assay for diagnosing GD was comparable to that of the Elecsys Anti-TSHR assay. The initial FT4 and TSI levels can be used as predictors of the responsiveness to methimazole in patients with newly diagnosed GD.

TNF-α May Exert Different Antitumor Effects in Response to Radioactive Iodine Therapy in Papillary Thyroid Cancer with/without Autoimmune Thyroiditis.

Simple SummaryRecent evidence shows that autoimmune thyroiditis (AIT) may impair the uptake of radioiodine (131I), altering the success of attempted remnant ablation in papillary thyroid cancer (PTC), but the cause is not clear. Finding the mechanisms that govern immune cells during the 131I therapy of PTC with concomitant AIT (PTC + AIT) could provide a rationale for these reports. Our study was conducted on female patients admitted for 131I therapy. In the PTC group, 131I therapy modulates the production of cytokines in situ, increasing the antitumor immune response accordingly. On the contrary, in the presence of chronic inflammation due to AIT, 131I therapy amplifies innate immunity, leading to a weaker development of adaptive, specific immunity.Autoimmune thyroiditis (AIT) may impair radioiodine (131I) uptake in papillary thyroid cancer (PTC). Finding the mechanisms that govern immune cells during 131I therapy of PTC with concomitant AIT (PTC + AIT) could provide a rationale. Our study aimed to evaluate the effects of 131I on anti-thyroglobulin antibodies (TgAb), matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor TIMP-1 and tumor necrosis factor-α (TNF-α) and its receptors TNFR1 and TNFR2, in PTC and PTC + AIT patients. Peripheral blood was collected from 56 female patients with PTC and 32 with PTC + AIT before and 4 days after 131I (3.7 GBq). The serum levels of TgAb, MMP-9, TIMP-1, TNF-α, TNFR1 and TNFR2 were measured by ELISA. The mean radioactivity of blood samples collected after 131I intake was higher in the PTC + AIT group than in PTC (p < 0.001). In the PTC + AIT group, TNF-α/TNFR1 and TNF-α/TNFR2 ratios decreased by 0.38-fold and 0.32-fold after 131I and were positively correlated with the MMP-9/TIMP-1 ratio (r = 0.48, p = 0.005, and r = 0.46, p = 0.007). In the PTC group, TNF-α/TNFR1 and TNF-α/TNFR2 ratios increased by 3.17-fold and 3.33-fold and were negatively correlated with the MMP-9/TIMP-1 ratio (r = −0.62, p < 0.001 and r = −0.58, p < 0.001). Our results demonstrate that TNF-α may exert different antitumor effects in response to 131I therapy depending on the patient’s immune profile.

Associations of GWAS-Supported Non-MHC Genes with Autoimmune Thyroiditis in Patients with Type 1 Diabetes.

PurposeA genome-wide association study (GWAS) in Caucasian population identified five non-MHC genes (PHTF1, PTPN22, MAGI3, BCL2L15, and QRFPR) associated with risk of the co-occurrence of autoimmune thyroid diseases (AITD) and type 1 diabetes (T1D). The aim of this study is to replicate these associations with AITD in patients with T1D in Chinese Han population.Patients and MethodsA case–control study was designed. Five single-nucleotide polymorphisms (SNPs) PHTF1 rs1111695, PTPN22 rs1217407, MAGI3 rs2153977, BCL2L15 rs2358994, and QRFPR rs7679475 were genotyped in 489 patients with T1D. Associations between genotypes and AITD risk were analyzed with logistic regression model.ResultsAITD occurred in 159 (32.5%) patients. When adjusting multiple factors by logistic regression, QRFPR rs7679475 was significantly associated with an increased risk of AITD in T1D patients in codominant model (G/G vs A/A, OR 2.93; 95% CI 1.44–5.96; P = 0.003), dominant model (G/A-G/G vs A/A, OR 1.81; 95% CI 1.17–2.79; P = 0.007) and recessive model (G/G vs A/A-G/A, OR 2.28; 95% CI 1.17–4.43; P = 0.015). Furthermore, we found a significant interaction between rs7679475 and female (P interaction = 0.005). In silico analysis indicated that rs7679475 is located in histone modification marked region and can change the binding of regulatory motifs.ConclusionOur results suggested that QRFPR rs7679475 may influence the risk of AITD in patients with T1D in Chinese Han population, and this effect may be modulated by sex.

The rationale for selenium supplementation in patients with autoimmune thyroiditis, according to the current state of knowledge.

Selenium (Se) supplements are commonly prescribed to autoimmune thyroiditis (AIT) patients by European endocrinologists, despite the lack of official guidelines. The majority of Europe is depleted of natural Se sources, and the daily population intake does not comply with recommended values. Optimal individual plasma Se concentration is reached when the selenoproteins (selenoprotein P, glutathione peroxidase) are fully saturated. However, Se intake has to be regulated because both Se shortage and overdose negatively impact health. In the case of AIT, Se may alleviate symptoms or prevent progression to hypothyroidism and postpartum hypothyroidism. Se supplementation in euthyroid, subclinical, or overt hypothyroid AIT patients decreased thyroid autoantibodies, lowered or maintained the TSH level, decreased the fT4/fT3 ratio, reduced the body's oxidative stress and inflammatory status, and amended quality of life and thyroid ultrasound structure and volume. In pregnant females, adequate Se intake protected them against miscarriages, preeclampsia/hypertension, preterm birth, small-for-gestational-age infants' birth, and improved child's neuropsychological development. In the elderly population, adequate Se supplementation decreased cardiovascular diseases and hypertension risk, but prolonged intake of excessive doses increased the all-cause mortality rate. Routine Se supplementation implementation requires from researchers and clinicians consideration of specific populational differences in natural Se and iodine supply, the patient's clinical situation (supplementation simultaneously or before levothyroxine treatment, AIT/non-AIT hypothyroidism), individual response to supplementation (Se and selenoprotein P assessment), predisposition (genetic testing), the status of other trace elements, and the interplay between those micronutrients. Moreover, the safety of commercially available Se formulations, doses, and duration of treatment should be determined. Proper guidelines are warranted to standardise the medical approach to Se supplementation. This article presents a comprehensive review of recent randomised-controlled trials, meta-analyses, and clinical trials concerning the risks and benefits of Se supplementation in different clinical settings and specific populations with particular emphasis on AIT in a practical manner.