Determination of the levels and possible associations of alpha2-macroglobulin with autoantibodies in the serum of patients with various forms of autoimmune thyroiditis.

Antibodies to thyroid peroxidase (AB-TPO), antibodies to thyroglobulin (AB-TG), and the content of α2-macroglobulin (α2-MG) have been studied in serum samples of patients with autoimmune thyroiditis (AIT). All the patients were divided into 3 groups depending on age: 25-35, 36-50, 51-65 years. We found a significant change in the thyroid panel parameters in AIT, but without significant changes in the average concentration of α2-MG in the age groups of patients. This may be due to the accumulation and retention of complexes of defective forms of α2-MG in the circulation associated with their decreased ability to bind to receptors.

Hypothyroidism and autoimmune thyroid disorders in rheumatoid arthritis: relationship with disease activity.

Background and aims: Thyroid function abnormalities and thyroid autoantibodies have previously been described in rheumatoid arthirits (RA) with limited data. In some studies, a relationship was found between thyroid autoantibodies and RA disease activity. However, there are not strong studies in the literature indicating the relationship between thyroid diseases and RA. The aim of this study was to determine the frequency of hypothyroidism and to investigate the relationship between thyroid hormone levels, autoantibodies and disease activity in patients with rheumatoid arthritis (RA). Methods : 1017 patients with the diagnosis of RA were recruited. This observational study was conducted between January 2014 and July 2015. Demographic variables were recorded. Anti-nuclear antibodies (ANA), anti-cyclic citrulli-nated peptide antibody (anti-CCP), Rheumatoid Factor (RF), C reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), anti-microsomal antibody (anti-TPO )and anti-thyroglobulin antibody (anti-TG) were determined. Visual analog score and Disease Activiy Score 28 (DAS-28) ESR and DAS-28 CRP were recorded. The relationship between thyroid hormone levels and thyroid antibodies and disease activity parameters were determined. Results: 98 (%9,7) patients had hypothyroidism and 61 (%6) patients had hyperthyroidism. 210 (20,7%) patients with RA was positive for TPOAb and 165(16,3%) for anti-TG. Positive correlation was detected between anti-TPO positivity and anti-CCP levels (p:0.005, r:0,274). In anti-TG antibody positive patients, there was a significant positive correlation of thyroid hormone levels with CRP and DAS 28-CRP (p:0.01, r:0,120; p:0.01, r:0,169). Conclusion: Thyroid autoantibodies were found to be positive in 16-21% of patients with RA. Though hypothyroidism is not very frequent in RA patients, autoimmune thyroid disease is quite common, which may be related to disease activity.

TPO antibody in euthyroid pregnant women and cognitive ability in the offspring: a focused review.

PURPOSE: A link between maternal thyroid dysfunction during pregnancy and the risk of cognitive and behavioral problems in the offspring has previously been established; however, the potential effects of maternal thyroid autoimmunity on neurodevelopment in the absence of maternal hypothyroidism are less clear. The present review aims to highlight the gaps in knowledge in this regard and provide a thorough assessment of relevant literature. METHOD: Related keywords searched in MEDLINE, Web of Science, and Scopus till January 2021. RESULTS: There is some evidence that neuropsychological and intellectual developments of offspring are adversely affected by maternal thyroid autoimmunity, although the results of available studies are not concordant. The tools and measurements that have been applied in different studies to assess neurodevelopment or IQ vary widely and the children born to mothers with thyroid autoimmunity have been assessed at different chronological stages of life. Such variations may explain some of the differences across studies. In addition, the definition of thyroid autoimmunity has been based on TPOAb cut points provided by manufacturers in most cases, but it is preferable to define these values based on age, trimester, and method-specific reference ranges. CONCLUSION: Well-designed studies are needed to assess verbal and non-verbal neurocognition of offspring born to mothers with autoimmune thyroid disease before or during pregnancy.

Thyroid autoimmunity and hypothyroidism are associated with deep molecular response in patients with chronic myeloid leukemia on tyrosine kinase inhibitors.

PURPOSE: Thyroid alterations including de novo appearance of thyroid autoimmunity are adverse effects of tyrosine kinase inhibitors, used in solid and hematologic cancer therapy, but the relationship between thyroid alterations during this treatment and the outcome of chronic myeloid leukemia remains unclear. Aim of this study was to investigate whether the presence of thyroid alterations may affect the clinical outcome of chronic myeloid leukemia on tyrosine kinase inhibitors. METHODS: We evaluated thyroid function and autoimmunity in 69 chronic myeloid leukemia patients on long-term therapy looking at the association between thyroid abnormalities and disease molecular response. RESULTS: Overall, 24 of 69 (34.8%) had one or more thyroid abnormalities during therapy. A high percentage of patients (21/69, 30.4%) showed thyroid autoimmunity (positive thyroid autoantibodies with ultrasound hypoechogenicity), while clinical and subclinical hypothyroidism and subclinical hyperthyroidism were, respectively, found in 4 of 69 (5.8%) and 3 of 69 (4.3%) of cases. Second-generation tyrosine kinase inhibitors resulted significantly associated (14/32, 43.7%) with Hashimoto's thyroiditis, compared to first generation (7/37, 18.9%; p = 0.03). Interestingly, we also found a significant association between euthyroid (14/26, 53.8%) and hypothyroid Hashimoto's thyroiditis (4/26, 15.4%) in patients with deep molecular response, as compared to euthyroid (3/43, 7%; p = 0.0001) and hypothyroid (0/43, 0%; p = 0.02) Hashimoto's thyroiditis patients with major molecular response. CONCLUSIONS: Our study confirms and extends our knowledge on the tyrosine kinase inhibitors effects on thyroid, showing that thyroid autoimmunity is frequently observed in chronic myeloid leukemia patients on long-term therapy and is associated with a better oncological response.

A Prospective Observational Study of 42 Patients with COVID-19 infection and a History of Hepatitis C Virus Infection and Thyroid Disease with Follow-Up Thyroid Function and Autoantibody Testing.

BACKGROUND Thyroiditis is an important extrahepatic association in chronic hepatitis C virus (HCV) infection. There have been reports of an association between SARS-CoV-2 infection and the onset or re-activation of autoimmune hypothyroidism. Therefore, we performed this prospective observational study of 42 patients with COVID-19 infection and a history of hepatitis C virus infection and thyroid disease with follow-up thyroid function and autoantibody testing. MATERIAL AND METHODS From April 2020 to October 2020, we performed a prospective observational study of patients with cured hepatitis C virus (HCV) infection and documented thyroid disease who became infected with SARS-CoV-2 (confirmed by SARS-CoV-2 RNA detection via reverse-transcription polymerase chain reaction [RT-PCT] from the upper respiratory tract, both nasal and pharyngeal swabs). Evaluation at 1 and 3 months after SARS-CoV-2 infection included serum determination of antithyroid antibodies (anti-thyroglobulin [anti-Tg] and antithyroid peroxidase [ATPO]), thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), and evaluation of thyroid medication, with dose adjustment if required. RESULTS One-month follow-up showed that both patients with autoimmune thyroiditis as well as patients without antibodies had increased ATPO levels. Also, levels of TSH, fT3, and fT4 were significantly decreased. At 3-month follow-up, levels of ATPO were decreased in all patient groups and the levels of thyroid hormones increased to normal values. CONCLUSIONS This study supports previous reports of an association between SARS-CoV-2 infection and thyroid dysfunction associated with thyroid autoantibodies. Thyroid function tests may be considered as part of the laboratory work-up in patients with COVID-19.

The Roles of Exosomes in Immunoregulation and Autoimmune Thyroid Diseases.

Exosomes are extracellular microvesicles (30-150 nm) released from cells that contain proteins, lipids, RNA and DNA. They can deliver bioactive molecules and serve as carriers facilitating cell-cell communication, such as antigen presentation, inflammatory activation, autoimmune diseases (AIDs) and tumor metastasis. Recently, much attention has been attracted to the biology and functions of exosomes in immune regulation and AIDs, including autoimmune thyroid diseases (AITDs). Some studies have shown that exosomes are involved in the occurrence and development of AITDs, but they are still in the preliminary stage of exploration. This review mainly introduces the association of exosomes with immune regulation and emphasizes the potential role of exosomes in AITDs, aiming to provide new research strategies and directions for the pathogenesis and early diagnosis of AITDs.

Autoimmune thyroid disease and thyroid function test fluctuations in patients with resistance to thyroid hormone.

OBJECTIVE: Resistance to thyroid hormone beta (RTHß) is an inherited syndrome caused by mutations in the thyroid hormone receptor ß (THRB) gene. Patients with RTHß typically have elevated thyroid hormone levels with non-suppressed serum thyroid-stimulating hormone (TSH). We aimed to elucidate the clinical, laboratory, and imaging findings of RTHß patients and further to explore their association with THRB gene mutations. DESIGN AND METHODS: We retrospectively reviewed the clinical charts and compared the clinical findings of 68 RTHß patients (45 probands and 23 relatives) and 30 unaffected relatives in Kuma Hospital. RESULTS: Genetic testing revealed 35 heterozygous THRB gene mutations. Among all RTHß patients, autoimmune thyroid disease (AITD) was detected in 42.1% of men and 40.9% of women, showing that the prevalence of AITD in affected males was significantly higher than in unaffected relatives (P = 0.019). During the follow-up of 44 patients, 13 patients (29.5%; 8 (42.1%) with AITD and 5 (20%) without AITD) temporarily showed thyroid function test results inconsistent with RTHß. Two patients with the R383H mutation, which has little dominant-negative effect, temporarily showed normal thyroid hormone and TSH levels without AITD. CONCLUSIONS: The frequency of AITD in male RTHß patients was significantly higher compared to unaffected relatives. More than 20% of RTHß patients temporarily showed laboratory findings atypical of RTHß during their follow-up, and patients with AITD and specific THRB mutations were prone to display such findings. Therefore, genetic testing should be performed even for patients with fluctuations in thyroid function test results to avoid misdiagnosis and inappropriate treatment.

Non-Conventional Clinical Uses of TSH Receptor Antibodies: The Case of Chronic Autoimmune Thyroiditis.

Anti TSH receptor antibodies (TSHrAb) are a family of antibodies with different activity, some of them stimulating thyroid function (TSAb), others with blocking properties (TBAb), it is a common finding that antibodies with different function might coexist in the same patient and can modulate the function of the thyroid. However, most of the labs routinely detect all antibodies binding to the TSH receptor (TRAb, i.e. TSH-receptor antibodies detected by binding assay without definition of functional property). Classical use of TSHr-Ab assay is in Graves' disease where they are tested for diagnostic and prognostic issues; however, they can be used in specific settings of chronic autoimmune thyroiditis (CAT) as well. Aim of the present paper is to highlight these conditions where detection of TSHr-Ab can be of clinical relevance. Prevalence of TSHrAb is different in in the 2 main form of CAT, i.e. classical Hashimoto's thyroiditis and in atrophic thyroiditis, where TBAb play a major role. Simultaneous presence of both TSAb and TBAb in the serum of the same patient might have clinical implication and cause the shift from hyperthyroidism to hypothyroidism and vice versa. Evaluation of TRAb is recommended in case of patients with Thyroid Associated Orbitopathy not associated with hyperthyroidism. At present, however, the most relevant recommendation for the use of TRAb assay is in patients with CAT secondary to a known agent; in particular, after treatment with alemtuzumab for multiple sclerosis. In conclusion, the routine use of anti-TSH receptor antibodies (either TRAb or TSAb/TBAb) assay cannot be suggested at the present for diagnosis/follow up of patients affected by CAT; there are, however, several conditions where their detection can be clinically relevant.

The Association Between Three Adipocytokines (Adiponectin, Resistin and Visfatin) And Thyroid Status in Patients With Type 2 Diabetes Mellitus and Autoimmune Thyroiditis.

Autoimmune thyroiditis (AIT) and type 2 diabetes mellitus (DM2) are the most common endocrinological diseases worldwide. Relation between these diseases explains several hypotheses. One of them is influence of some adipocytokines. This study evaluated association between three adipocytokines (adiponectin, resistin and visfatin) and thyroid and glycid status in patients with DM2 and AIT compared to the control group (CG). The group consisted of four subgroups: patients with DM2 without thyreopathies, patients with AIT on substitution therapy without diabetes and prediabetes, patients with DM2 and AIT on substitution therapy and healthy subjects as the CG. We investigated parameters of thyroid and glucose metabolism and serum levels of three adipocytokines. The mean level of resistin in the group of patients with diabetes and thyroiditis was significantly higher than in patients with thyroiditis without diabetes and than in the CG. We found a weak negative correlation between visfatin and fasting glucose levels in patients with thyroiditis without diabetes. We detected a weak negative correlation between resistin and glycated haemoglobin and a weak negative correlation between visfatin and thyroid gland volume in patients with diabetes without thyroiditis. In the CG we determined a weak positive correlation between visfatin and free thyroxin. Our results are consistent with several studies, which confirmed association between AIT and adipocytokines.

The impact of levothyroxine on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in men with autoimmune hypothyroidism and early-onset androgenetic alopecia.

INTRODUCTION: Administration of testosterone or dehydroepiandrosterone to subjects with low levels of these hormones was found to reduce thyroid antibody titres. Male-pattern baldness is accompanied by mildly increased androgen levels. The present study was aimed at investigating whether early-onset androgenetic alopecia determines the impact of exogenous levothyroxine on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in young men with autoimmune hypothyroidism. MATERIAL AND METHODS: The study included 2 thyroid-antibody-matched groups of men with autoimmune hypothyroidism: subjects with early-onset androgenetic alopecia (group 1; n = 24) and subjects with no evidence of hair loss (group 2; n = 24). All patients were treated with exogenous levothyroxine. Circulating titres of thyroid peroxidase and thyroglobulin antibodies, as well as levels of thyrotropin, free thyroxine, free triiodothyronine, prolactin, total testosterone, calculated bioavailable testosterone, dehydroepiandrosterone-sulphate, and oestradiol were measured before levothyroxine treatment and 6 months later. RESULTS: In both study groups, levothyroxine decreased thyroid antibody titres, reduced thyrotropin levels and increased free thyroid hormone levels. However, these effects were less pronounced in the men with early-onset male-pattern baldness than in the control men. The degree of reduction in antibody titres and thyrotropin levels correlated with baseline levels of total and calculated bioavailable testosterone, as well with baseline insulin sensitivity and treatment-induced improvement in insulin sensitivity. Concentrations of the remaining variables remained unchanged throughout the study period. CONCLUSIONS: The results of the current study suggest that the benefits of levothyroxine therapy in men with autoimmune hypothyroidism are less pronounced in individuals with early-onset androgenetic alopecia.

Changes in thyroid antibody and T lymphocyte subsets after radiofrequency ablation of thyroid nodules in patients with autoimmune thyroiditis.

SETTINGS AND DESIGN: The aim was to study the changes in thyroid antibody and T lymphocyte subsets after radiofrequency ablation (RFA) of thyroid nodules in patients with autoimmune thyroiditis. SUBJECTS AND METHODS: Patients (n = 135) with autoimmune thyroiditis and thyroid nodules were treated by RFA. The indices of thyroid function and thyroid antibody and T lymphocyte subsets were examined preoperation and on the 1st day and the 1st month after ablation. Any complications were recorded. STATISTICAL ANALYSIS: The software SPSS 17.0.0 (version: 2008-8-23) running under Windows 8 was used for statistical analysis. The measurement data were expressed as x ± s, with P < 0.01 indicating a significant difference in the statistical data. RESULTS: Levels of free triiodothyronine, free thyroxine, and thyroid-stimulating hormone were in the normal range before ablation, and no significant changes occurred on the 1st day or in the 1st month after ablation. The change in the percentage of CD8+T cells and the absolute value of B cells were not statistically significant (P > 0.01), and the values were in the normal range. Compared with values recorded preoperation, the value of TG-Ab, TPO-Ab, CD4+/CD8+, the percentage of CD4+T cells, the absolute values of lymphocytes, T cells, CD4+T cells, and CD8+T cells decreased significantly at the 1st day after ablation (P < 0.01) and then recovered to preoperative levels during the first 30 days after ablation (P > 0.01). Within 1 month after ablation, none of the patients had complications such as active bleeding, infection, recurrent laryngeal nerve injury, parathyroid gland injury, skin scald, and so on. CONCLUSIONS: After RFA of thyroid nodules in patients with autoimmune thyroiditis, thyroid function is not affected and no serious complications occurred. TG-Ab and TPO-Ab levels can be significantly decreased, and the distribution of T lymphocyte subsets can be changed in the short term after ablation.

Screening of Organ-Specific Autoantibodies in a Large Cohort of Patients with Autoimmune Thyroid Diseases.

Background: Autoimmune diseases tend to cluster in the same individual or in families. Four types of autoimmune polyglandular syndromes (APS) have been described based on the combination of endocrine and/or non-endocrine autoimmune diseases. In particular, type-3 APS is defined by the association of an autoimmune thyroid disease (ATD) and other autoimmune diseases and has a multifactorial etiology. The natural history of autoimmune diseases is characterized by three stages: potential, subclinical, and clinical. Methods: To determine the prevalence of organ-specific autoantibodies (anti-adrenal, anti-ovary [StCA], anti-pituitary [APA], anti-parietal cells [PCA], anti-tissue transglutaminase [tTGAb], anti-mitochondrial [AMA], anti-glutamic acid decarboxylase [GADA], anti-nicotinic acetylcholine receptor) in patients with ATD and to define the stage of the disease in patients with positive autoantibodies. From January 2016 to November 2018, 1502 patients (1302 female; age 52.7 ± 14.7 [mean ± standard deviation] years, range 18-86 years) with ATD (1285/1502 [85.6%] with chronic autoimmune thyroiditis and 217/1502 [14.4%] with Graves' disease) were prospectively enrolled. Results: The most common organ-specific autoantibodies were PCA (6.99%) and GADA (2.83%), while the prevalence of the remaining autoantibodies was ≤1%. All autoimmune diseases, but celiac disease, were predominant at the potential stage. Sex, ATD type, smoking habit, and coexistence of other autoimmune diseases correlated with the susceptibility to develop chronic atrophic gastritis (CAG) or autoimmune diabetes mellitus. Conclusions: The association between ATD and CAG was the most common manifestation of type-3 APS, mainly at the potential stage, that could lead to appropriate follow-up for early detection and timely treatment of the disease.

Celiac Disease and the Thyroid: Highlighting the Roles of Vitamin D and Iron.

Celiac disease (CD) and autoimmune thyroid diseases (AITD) like Hashimoto's thyroiditis (HT) and Graves' disease (GD) frequently coexist, entailing numerous potential impacts on diagnostic and therapeutic approaches. Possible correlations might exist through gut microbiota, regulating the immune system and inflammatory responses, promoting autoimmune diseases, as well as shared cytokines in pathogenesis pathways, cross-reacting antibodies or malabsorption of micronutrients that are essential for the thyroid like iron or vitamin D. Vitamin D deficiency is a common finding in patients with AITD, but might protect from autoimmunity by wielding immunoregulatory and tolerogenic impacts. Additionally, vitamin D is assumed to be involved in the onset and progression of CD, presumably plays a substantial protective role for intestinal mucosa and affects the thyroid via its immunomodulatory effects. Iron is an essential micronutrient for the thyroid gland needed for effective iodine utilization by the iron-dependent enzyme thyroid iodine peroxidase (TPO). Despite being crucial for thyroid hormone synthesis, iron deficiency (ID) is a common finding in patients with hypothyroidism like HT and is frequently found in patients with CD. A literature research was conducted to examine the interplay between CD, AITD, vitamin D and iron deficiency. This narrative review highlights the relevant correlation of the two disease entities CD and AITD, their reciprocal impact and possible therapeutic options that should be further explored by future studies.

Analysis of the transcriptional activity of genes of neuropeptides and their receptors in the blood of patients with thyroid pathology.

The thyroid hormone plays a vital role in the development and maturation of the nervous system not only during prenatal and perinatal age but also in adults. "Peripheral marker hypothesis" revealed that gene expression changes in some regions of the brain are reflected into the peripheral blood lymphocytes. The objective of the study was to investigate changes in the gene expression profile of neuropeptides and their receptors in patients with different forms of thyroid pathology. One hundred fifty-three patients with thyroid pathology were enrolled in the study. They were divided into three groups: group 1 included 16 patients with postoperative hypothyroidism, group 2 included 65 patients with hypothyroidism resulting from autoimmune thyroiditis (AIT), and group 3 included 72 patients with AIT and elevated levels of anti-thyroglobulin (anti-Tg) and anti-thyroid peroxidase (anti-TPO) antibodies in the serum. We used a pathway-specific polymerase chain reaction (PCR) array (RT2 Profiler™ PCR Array Human Neurotrophins & Receptors, QIAGEN, Germany) to identify and verify neuropeptides and receptors pathway-focused gene expression in 12 individuals that were randomly selected from each group using real-time PCR. Our research identified that patients with postoperative hypothyroidism had a considerably increased expression of NPY1R, NTSR1, and NPY4R. The patients with hypothyroidism caused by autoimmune thyroiditis had considerably lower expression of NTSR1, while the expression of NPY1R increased. The mRNA levels of NPY2R and PNOC increased in the patients with elevated levels of autoantibodies anti-Tg and anti-TPO in the serum, and mRNA levels of NPY1R and NTSR1 decreased in this group of patients.

Relationship between autoimmune thyroid disease and nephropathy: A clinicopathological study.

ABSTRACT: The association of nephropathy with autoimmune thyroid disease (AITD) has been reported previously. However, there is limited information on the relationship between thyroid autoantibodies and nephropathy. A retrospective study was conducted using the medical records of 246 patients with nephropathy, 82 of whom had concurrent AITD. General characteristics, thyroid function, autoantibodies, and the pathological types of nephropathy were analyzed. Immunohistochemistry was used to detect the thyroglobulin antibody (TG-Ab) and thyroid peroxidase antibody (TPO-Ab) in the kidneys. We found nephropathy patients with AITD exhibited higher serum levels of TPO-Ab, TG-Ab, thyroid-stimulating hormone receptor antibody (TR-Ab), and immunoglobulin G (IgG) (P < .05). Compared with the nephropathy without AITD group, the nephropathy with AITD group exhibited higher proportions of membranous nephropathy (MN) and focal segmental glomerulosclerosis (FSGS), and relatively lower proportions of mesangial proliferative glomerulonephritis (MsPGN) and minimal change nephropathy (MCN) (P = .005). TPO-Ab and TG-Ab levels in the kidney were more prevalent in nephropathy patients with AITD than those without AITD (P = .015 and P = .026, respectively). Subgroup analysis demonstrated that serum levels of thyroid stimulating hormone (TSH), TG-Ab, TPO-Ab, immunoglobulin M (IgM), and IgG in the MN group were significantly higher, whereas the levels of free thyroxine (FT4) and estimated glomerular filtration rate (eGFR) were lower, as compared with MN with Hashimoto thyroiditis (HT) group (P < .05). TPO-Ab and TG-Ab expression levels in the kidneys were more prevalent in the MN group than in the MN with HT group (P = .034). The expression levels of FT4, TG-Ab, TPO-Ab, and thyroid-stimulating hormone receptor antibody (TSHR-Ab) in the serum were significantly higher in the MN group than in the MN with Graves disease (GD) group (P < .05). The expression of TPO-Ab in the kidneys was more prevalent in the MN group than in the MN with GD group (P = .011). In sum, the expressions of TPO-Ab and TG-Ab were more prevalent in the kidneys of patients with nephropathy and AITD. Our findings indicate that TPO-Ab and TG-Ab may play a role in the development of AITD-related nephropathy.

Cordyceps sinensis-derived fungus Isaria felina ameliorates experimental autoimmune thyroiditis in mice.

AIMS: This study aimed to investigate the therapeutic effect of Cordyceps sinensis-derived fungus Isaria felina on experimental autoimmune thyroiditis (EAT). METHODS: A NaI-induced EAT mouse model was established. The mice received oral administration of vehicle, low-dose Isaria felina (300 mg/kg), or high-dose Isaria felina (600 mg/kg) once a day for four weeks before euthanasia. Enzyme-linked immunosorbent assays (ELISA) was performed to measure serum thyroid-stimulating hormone (TSH) levels, thyroid antibodies, and cytokines. Hematoxylin and eosin (H&E) staining was conducted to assess histopathological changes in the thyroid tissue samples of mice. TUNEL and Bcl-2 immunohistochemistry (IHC) were performed to evaluate cell apoptosis, and cleaved caspase-3 IHC was performed to detect the relative expression in the thyroid tissue samples. RESULTS: Compared with KIO3 and KI water, NaI water consumption successfully induced EAT in mice, as evidenced by significantly increased circulating TSH and thyroid antibody levels, along with typical histopathological abnormalities of autoimmune thyroiditis (AIT) in the thyroid tissue samples. Compared with vehicle or low-dose Isaria felina, high-dose Isaria felina treatment resulted in significant reductions in white cell counts and circulating TSH, thyroid antibody, and cytokine levels of EAT mice. High-dose Isaria felina also alleviated histopathological abnormalities and attenuated TUNEL staining, Bcl-2 protein expression, and cleaved caspase-3 expression in the thyroid tissue samples. CONCLUSION: High-dose Isaria felina treatment alleviates thyroid inflammation and cell apoptosis in EAT, serving as a novel, promising therapeutic agent for AIT.

Glucocorticoid supplementation improves reproductive outcomes in infertile women with antithyroid autoimmunity undergoing ART: A meta-analysis.

BACKGROUND: Thyroid autoimmune disease (TAI) has been verified to be related to multiple adverse pregnancy outcomes. A growing number of evidences highlight the protective roles of glucocorticoid on the treatments of TAI. This meta-analysis aimed to study whether it is beneficial to add glucocorticoid treatment in infertile women with TAI when they are undergoing assisted reproductive technology (ART). METHODS: We conducted a systematic search in PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), WanFang database, Weipu China Science and Technology Journal Databases (VIP database) up to September 10, 2020. The Revman 5.3 software was utilized for data statistics. We used a random-effects model to analyze data and the odds ratio (OR) combining with 95% confidence interval (95% CI) were employed to reveal the results. RESULTS: Three publications with 237 antithyroid antibody (ATA)-positive and 384 ATA-negative women were included in the final analysis. Overall, glucocorticoid therapy showed satisfying effects on improving clinical pregnancy rate (OR = 4.63, 95% CI [2.23, 9.58], I2 = 0.0%, P < .0001) and live birth rate (OR = 3.19, 95% CI [1.13, 9.04], I2 = 0.0%, P = .03) of ATA-positive women compared with control group. However, it seems that glucocorticoid showed no significant difference in the abortion rate (OR = 0.62, 95% CI [0.09, 4.32], I2 = 35%, P = .64) and oocyte recovery (OR = 2.26, 95% CI [-1.46, 5.99], I2 = 79%, P < .0001) between the 2 groups. CONCLUSIONS: Glucocorticoid may improve the pregnancy outcomes of ART women with ATA positive, but there is no significant reduction in the risk of miscarriage. Due to the limited enrolled references, glucocorticoid adjuvant therapy should be applied after more randomized controlled trials.

False-positive very long-chain fatty acids in a case of autoimmune adrenal insufficiency.

BACKGROUND: X-linked adrenoleukodystrophy (ALD) affects up to 25% of boys diagnosed with adrenal insufficiency in childhood. Because early identification of these individuals can be lifesaving, all boys with new-onset primary adrenal insufficiency should be tested for ALD with a plasma very long-chain fatty acid (VLCFA) level. While plasma VLCFA is a diagnostic test with high sensitivity and specificity, false-positive results have been reported in individuals on a ketogenic diet. CASE PRESENTATION: We present a case of an 11-year-old boy with new-onset primary adrenal insufficiency due to autoimmune adrenalitis who was initially found to have elevated VLCFA levels, suggestive of ALD, that normalized on repeat testing. CONCLUSIONS: As advances in gene therapy and newborn screening for ALD expand, VLCFA testing may increase, and clinicians should be aware that testing during the initial presentation of primary adrenal insufficiency may lead to false-positive results and associated psychosocial distress.

Transcriptome analysis of the effect of diosgenin on autoimmune thyroiditis in a rat model.

In a mouse model of Graves' disease (GD), diosgenin has been shown to have a therapeutic effect on GD by alleviating goitre. However, research on the effect of diosgenin on autoimmune thyroiditis (AIT) is lacking. In this study, transcriptomics was used to comprehensively analyse the protective effect of diosgenin against AIT in rats and the possible mechanism. The results showed that in the diosgenin-intervention group, compared to the model group, the expression of serum triiodothyronine, thyroxine, free triiodothyronine, and free thyroxine was decreased and that of thyroid-stimulating hormone was increased; these changes were accompanied by the downregulation of thyroglobulin, TSH receptor antibody and thyroid peroxidase expression in serum. Furthermore, transcriptome detection, RT-qPCR and immunohistochemistry verification revealed that in thyroid tissue, the relative mRNA and protein expression of cyclic adenosine 3',5'-monophosphate (cAMP), protein kinase A (PKA) and cAMP response element-binding protein (Creb) were increased and the mRNA expression of S100 calcium-binding protein A9 (S100A9) was decreased in the diosgenin groups. In summary, diosgenin alleviates the development of AIT, possibly via the activation of the cAMP/PKA/Creb pathway and downregulation of S100A9 gene expression.

Severe primary hypothyroidism in an apparently asymptomatic 19-year-old woman: a case report.

BACKGROUND: Hypothyroidism is diagnosed on the basis of laboratory tests because of the lack of specificity of the typical clinical manifestations. There is conflicting evidence on screening for hypothyroidism. CASE PRESENTATION: We report a case of an apparently healthy 19-year-old Kuwaiti woman referred to our clinic with an incidental finding of extremely high thyroid-stimulating hormone (TSH), tested at the patient's insistence as she had a strong family history of hypothyroidism. Despite no stated complaints, the patient presented typical symptoms and signs of hypothyroidism on evaluation. Thyroid function testing was repeated by using different assays, with similar results; ultrasound imaging of the thyroid showed a typical picture of thyroiditis. Treatment with levothyroxine alleviated symptoms and the patient later became biochemically euthyroid on treatment. CONCLUSION: There is controversy regarding screening asymptomatic individuals for hypothyroidism; therefore, it is important to maintain a high index of suspicion when presented with mild signs and symptoms of hypothyroidism especially with certain ethnic groups, as they may be free of the classical symptoms of disease.