Unraveling the relationship between thyroid peroxidase antibodies and thyroid hormones: A partial correlation approach in autoimmune thyroid disease

Background:Rheumatoid arthritis is systemic autoimmune disease with progressive development leading to disabilities. The presence of thyroid autoantibodies and thyroid autoimmune disease has been known for more than six decades. The...

Whether iodized salt increases the risk of thyroid disease has been strongly debated in China, especially in the urban areas of coastal regions, in recent years. This study aimed to investigate the status of iodized salt in terms of urinary and serum iodine concentration in urban coastal areas, and to explore further whether consumption of iodized salt or non-iodized salt is associated with autoimmune thyroid disease (AITD). The data source was SPECT-China, a cross-sectional study in East China. A total of 1678 subjects were enrolled from 12 communities in downtown Shanghai. The type of salt consumed, the urinary iodine concentration (UIC), serum iodine, thyroid peroxidase antibodies (TPOAb), and thyroglobulin antibodies (TgAb) levels were obtained. AITD was defined as serum TPOAb and/or TgAb >60 kIU/L (TPO/TgAb [+]). The prevalence of AITD was 10.5% in men and 21.4% in women. The median UIC and serum iodine concentration were 106.4 μg/L and 60.9 μg/L, respectively. Among all the subjects, 46.4% consumed non-iodized salt; the prevalence of iodine deficiency among those subjects was significantly higher than that of the subjects who consumed iodized salt (54.2% vs. 40.1%; p < 0.001). Consumption of non-iodized salt was positively associated with AITD in all participants (odds ratio [OR] = 1.49 [confidence interval (CI) 1.15-1.95]; p = 0.003) and in women (OR = 1.63 [CI 1.20-2.21]; p < 0.01) after multivariable adjustment. Additionally, the association between low UIC and AITD was observed among all subjects (OR = 1.50 [CI 1.10-2.05]; p = 0.01) and in women (OR = 1.45 [CI 1.02-2.07]; p = 0.038). In coastal areas, which are believed to be rich in iodine, consuming non-iodized salt still led to lower UIC levels and a higher prevalence of iodine deficiency. The consumption of non-iodized salt and low UICs might be a risk factor for AITD, especially for women, which should be further confirmed by longitudinal studies.

The aggregation between AITD with rheumatologic, or dermatologic, autoimmune diseases

Background: One of the main cause of thyroid disease is autoimmune thyroid disease and anti thyroid peroxidase (TPO) antibodies is a major marker of the condition. There are very few studies in the country regarding the etiology of thyroid disorders and hence this study is being conducted for it.&#x0D; Methods: This is retrospective cross sectional study from 28 January 2019 to 29 July 2019 done at National Academy of Medical Sciences, Bir Hospital, Kathmandu. The laboratory serum sample data of all Anti TPO antibody results from patients seeking treatment at the instituition were analyzed for age and gender variation. Anti TPO antibody titre of equal or more than 34 IU/ml was considered as positive.&#x0D; Results: Out of 768 samples analysed for study, 79.9% were of women and 20.1 % were of men. A total of 205 (26.7%) were positive for anti TPO antibodies of which 83.4% were women and 16.6% were men . Women had more patients with anti TPO antibodies positive as compared men (27.9 vs 21.1%). Mean Anti TPO titre were also more in women as compared to men (61.01 vs 48.20 IU/ml).&#x0D; Conclusions: About one fourth of the patients had siginificant titers of anti TPO antibodies suggestive of thyroid autoimmunity. Both prevalence of positive anti TPO antibody titres and the mean anti TPO antibody titre values were more in women as compared to men. Further well designed larger community studies are required.

This study whose purpose was to examine the prevalence and pattern of autoimmune disease of the thyroid gland (TG) in young patients with type I diabetes mellitus (DM1) involved 288 individuals with DM1 whose age was 5.5 to 30years; the average duration of DM1 was 5.5+4.7 years. In all the patients, thyroid ultrasonography was performed, thyroid antibodies (Abs) [thyroid peroxidase antibodies (TPO-Abs) and thyroglobulin antibodies (TG-Abs)] were determined, thyroid function was evaluated by measuring the level of thyroid-stimulating hormone (TSH) and free reactions of thyroid hormones were assessed. The detection rates of TPO-Abs and TG-Abs were 22.2 and 20.5%, respectively, which was substantially greater than those in apparently healthy individuals matched by age and gender. The frequency of positive thyroid Abs was significantly higher in females. Age at the moment of examination and the duration of DM1 were not found to have an impact on the detection rate of thyroid Abs. The ultrasound signs of autoimmune thyroid diseases were revealed in 19.1% of the cases. 10.0% of the patients with DM1 were found to have these or those TG dysfunctions the most common of which was subclinical hypothyroidism (6.60%). A comprehensive TG assessment in the young patients with DM1 demonstrated the typical signs of autoimmune thyroid disease in 14.2% of the examinees. In the patients with autoimmune thyroid disease, the thyroid was significantly larger and the levels of TSH, TPO-Abs, and TG-Abs were higher than the patients without autoimmune thyroid disease and those at risk for the latter. The proportion of females was significantly higher among the patients 19 with concomitant autoimmune thyroid disease than that among those without the signs of this condition. It has been concluded that the high incidence of autoimmune thyroid disease in young patients with DM1 permits the authors to recommend a screening for its early detection, which involves the measurement of the serum level of TPO-Abs and TG ultrasonography in all females with first detected DM1.

Vulvar lichen sclerosus (VLS) is defined as a chronic inflammatory skin disease that most often involves lesions on the mucous membranes of the vulva with a tendency to progress to the anal skin. The etiopathogenesis of VLS remains unknown and is likely multifactorial. Data emphasize the role of immunological factors - more than 25% of VLS cases coexist with autoimmune diseases. The purpose of the present study was to determine the correlation of the prevalence of anti-thyroid antibodies - IgG class antibodies against thyroid peroxidase and IgG class antibodies against thyroglobulin in women with vulvar lichen sclerosus, and the appropriateness of screening tests for autoimmune thyroid diseases in women with vulvar lichen sclerosus. Fifty women with vulvar lichen sclerosus were enrolled in the study. The control group consisted of 41 healthy women. A detailed medical history was taken with all patients, followed by laboratory determinations - anti-thyroid antibodies - IgG class antibodies against thyroid peroxidase and IgG class antibodies against thyroglobulin. Antibodies to thyroid peroxidase were present in 12% of the study group with vulvar lichen sclerosus and 4.88% of the control group, and this difference was not statistically significant (p = 0.41). Anti-thyroglobulin antibodies were detected in 4% of the patients with vulvar lichen sclerosus and 4.88% of the control group, and this difference was not statistically significant either (p = 0.76). The study did not confirm the association of VLS with autoimmune thyroid diseases. Undoubtedly, based on the data available in the literature, further studies are needed to determine the mechanisms behind the association between vulvar lichen sclerosus and autoimmune thyroid diseases.

Iodine is the main component in the synthesis of thyroid hormones. Therefore,adequate iodine consumption is important for thyroid hormone production. Iodineinterference with TSH system can be as the limiting factor for thyroid hormonesproduction. Magelang district knows as IDD area had program to supply intakeiodine from iodine capsule and iodinated salt. In endemic Iodine Deficiencydisorders (IDD) area, intake iodine was taken from iodine capsule and iodinatedsalt. Iodine stored at thyroglobulin. Post-translational modification of thyroglobulinby iodine has immunological consequences such that increased AutoimmuneThyroid Disease (AITD). Tiroglobulin and Thyroidperoxidase antibodies arethe main factor of production of AITD. A study was to asses the descriptionbetween iodine intake and tiroglobulin and thyroidperoxidase antibodies causedAITD. The study was conducted at Magelang district and the respondents arechildbearing age woman. Samples were collected to measured TPO antibody andThyroglobulin antibody. Magelang district is one of the IDD areas received capsuleiodine distributed to prevent new IDD cases. Most all of respondent consumediodine capsule 1-2 capsule/year. The result showed that all respondent haveTPO and Thyroglobulin antibodies. 23% respondent has positive thyroglobulinand 47% positive TPO antibody. Statistical analysis showed that Iodine capsuleintake is one of predesposition factor of AITD. The results showed that intake ofhigh concentration iodine capsule had immunological consequences. Over doseof iodine can increased incident of AITD. Thyroglobulin and TPO antibodies thatfound in all respondents with consume high concentration iodine capsule.

Type 1 diabetes mellitus (T1DM) is frequently associated with other autoimmune disorders that are characterized by the presence of organ-specific autoantibodies. Autoimmune thyroid disease (AIT) is the most frequent autoimmune disorder associated with T1DM. Thyroid peroxidase antibodies (TPOAb) serve as a marker for diagnosing AIT. Prior research indicates that thyroid dysfunction can negatively impact linear growth and glycemic control in subjects with T1DM. The present study was done to determine the impact of thyroid autoimmunity on the clinical and biochemical characteristics of patients with newly diagnosed T1DM. In this single-center, hospital-based, observational cross-sectional study, we enrolled 70 patients with newly diagnosed T1DM ≤18 years of age. Type 1 diabetes mellitus was diagnosed based on the acute onset of osmotic symptoms with or without diabetic ketoacidosis (DKA), severe hyperglycemia (blood glucose >13.9 mmol/l (>250 mg/dl)), and insulin requirement from the onset of diabetes. Secondary diabetes, pancreatic diabetes (Type 3c), and maturity-onset diabetes of the young (MODY) were excluded. Participants were screened for AIT disease using TPOAb testing. Based on the presence or absence of TPOAb, the participants were categorized into two groups: Group A comprised individuals with T1DM who tested positive for TPOAb, while Group B consisted of those who tested negative for TPOAb. Out of 70 patients, 41.4% were girls and 58.6% were boys, with a mean age of 9.8±4.4 years. The prevalence of TPOAb among the cohort was 18.6%. A significant majority of patients (71.4%), presented with DKA. Group A showed significantly lower mean height standard deviation scores (SDS) compared to Group B (-0.3±0.6 vs. -0.8±0.5, p = 0.004), but no differences in weight SDS or BMI SDS. Hemoglobin A1C (HbA1c) levels, C-peptide levels, and frequency of DKA did not differ between groups. Group A had higher mean thyroid-stimulating hormone (TSH) levels (4.8±3.7 µU/ml vs. 2.6±1.5 µU/ml, p = 0.001) and a greater proportion of patients with TSH levels above the upper limit of normal compared to Group B (38.4% vs. 7.1%, p = 0.008). Additionally, Group A exhibited a higher frequency of glutamic acid decarboxylase antibody (GADA) positivity compared to Group B (46.1% vs. 17.5%, p = 0.04). Patients positive for TPOAb exhibited significantly lower height SDS compared to TPOAb-negative patients. Additionally, T1DM patients with TPOAb positivity showed an increased frequency of GADA compared to those without TPOAb. However, no significant differences were found in HbA1c levels, C-peptide levels, or hematological parameters between TPOAb-positive and TPOAb-negative patients. These findings emphasize the impact of TPOAb on growth parameters in T1DM and advocate for routine screening of TPOAb in all T1DM patients, starting at the time of diabetes diagnosis.

Introduction: Hashimoto's Thyroiditis (HT) and Graves' Disease (GD) reflect two extremes in the spectrum of autoimmune thyroid diseases. In HT, there are anti-thyroid peroxidase antibodies thought, but not proven, to be destructive to thyroid follicles as well as thyroid stimulating hormone (TSH) stimulation-blocking antibodies which block the action of TSH and cause damage and atrophy of the thyroid gland leading to hypothyroidism. On the other hand, GD is characterized by primary hyperthyroidism due to stimulating autoantibodies against TSH receptors. While some of the patients with GD can develop spontaneous hypothyroidism due to HT, development of GD with hyperthyroidism following HT is unusual (1). We report a case of development of GD in a case of long standing HT. Case Report: A 55-year-old woman with a 20-year history of HT on stable doses of levothyroxine was found to be hyperthyroid on routine follow up. She presented with clinical signs of hyperthyroidism including weight loss of 40 pounds over 1 year and periorbital edema. The dose of levothyroxine was tapered and ultimately stopped over six months. Despite discontinuation of thyroid hormone, she continued to remain hyperthyroid. Labs were significant for elevated free T4 2.28 (0.82-1.77 ng/dL), elevated free T3 9.2, (2.0-4.4 pg/mL) and suppressed TSH, 0.006 (0.0-0.55 IU/L). Further testing revealed elevated thyroid antibodies including TSI of 10.4 (0.0-0.55 IU/L), Thyroglobulin Ab of 50.6 (0.0-0.9 IU/mL), TSH receptor Ab of 6.1 (>1.5 U/L positive) and TPO Ab of > 600 (0.0-34 IU/mL). Thyroid ultrasound disclosed an enlarged, heterogenous and hyperemic thyroid parenchyma. The 24-hour radioactive iodine uptake was elevated at 52% (8-35%) indicative of hyperthyroidism, most likely from GD. She was treated with methimazole and atenolol, followed by total thyroidectomy. Surgical pathologyrevealed diffuse chronic lymphocytic thyroiditis with lymphoid aggregates, fibrosis, adenomatous nodules with oncocytic changes and reactive nuclear atypia. Conclusion: Although development of GD following HT is rare, it can occur suggesting that HT does not always result in irreversible destruction of the thyroid gland. Patients with thyroid autoimmune disease have both thyroid hormone receptor stimulating and thyroid hormone receptor blocking antibodies and clinical manifestations depend upon the level of these antibodies and the state of the thyroid gland. Because patients with HT can transform to GD at any point due to a change of blocking to stimulating antibodies, clinicians should be aware of the potential for this transformation.

Objective: The association between thyroid hormones, thyroid autoantibodies, and thyroid nodules are still not clear. The cross-sectional study, conducted in Hangzhou, China in 2010, aimed to identify the relationship of thyroid hormones and autoantibodies with thyroid nodules. Methods: Information regarding social demography was collected by a questionnaire. Thyroid hormones (triiodothyronine, thyroxin, free triiodothyronine, free thyroxin, thyrotropin), thyroid autoantibodies (thyroid peroxidase antibody, antithyroglobulin antibody), and thyroid nodules (diagnosed by ultrasonography) was measured in 1271 adults. The association of thyroid hormones and thyroid autoantibodies with thyroid nodules was evaluated using multiple logistic regression models. Results: The prevalence of thyroid nodules among males and females was 29.49% and 33.15%, respectively. The thyroid hormone level in the thyroid nodules group was significantly higher than the non-nodules group (all p values < 0.05), except reversely in TSH (thyroid stimulating hormone) (p = 0.0532) and TGAb (thyroglobulin antibody) (p = 0.0004). High levels of TPOAb (thyroid peroxidase antibody) (OR (Odds Ratio) = 1.51, 95% CI (confidence interval): 0.99–2.30) and TGAb (OR = 2.86, 95% CI: 1.49–5.51) were associated with increased risk of thyroid nodules, compared with corresponding low levels. However, following sub-analyses in two genders, the similar associations were only observed in females (TPOAb: OR = 1.63, 95% CI: 0.99–2.68; TGAb: OR = 3.13, 95% CI: 1.53–6.40). Conclusions: The present study indicated that thyroid autoantibodies were positively associated with the risk of thyroid nodules in Chinese coastal adults.

Objective To explore the correlation of the gene polymorphism of the two single nucleotide polymorphisms(SNPs)rs1443434 and rs925489 on forkhead box El(FOXE1)with the high normal thyroid stimulating hormone(TSH)level in Chinese Han population. Methods 1 400 subjects with normal serum TSH and thyroid peroxidase antibody(TPOAb)levels were included. According to TSH or TPOAb levels, the subjects were divided into high normal TSH group(H-TSH group, n=195)and normal TSH control group(TSH control group, n=1 205)or high normal TPOAb group(H-TPOAb group, n=711)and low normal TPOAb group(L-TPOAb group, n=689), respectively. The genotypes on the two SNPs of all the subjects were performed by whole-genome genotyping chips. Results There were significant differences in rs925489 genotypic distributions and allele frequencies between H-TSH group and TSH control group(both P<0.05). The genotype TT and allele T in H-TSH group were significantly higher than those in TSH control group(89.75% vs 83.15%, 94.62% vs 91.29%). The normal TSH levels were positively associated with rs925489 genotypic distributions after adjustment for sex, age, and high density lipoprotein cholesterol(P<0.01). There were no significant differences in rs1443434 genotypic distributions and allele frequencies between two TSH groups or two TPOAb groups. Conclusion FOXE1 rs925489 gene polymorphism may be correlated with the high normal TSH level in Chinese Han population. Key words: Forkhead box El; rs925489; Polymorphism, single nucleotide; TSH

Gestational hypertension (GH) and preeclampsia (PE) are two important complications of pregnancy. Considering the U-shaped association between thyroidstimulating hormone (TSH) and hypertensive disorders of pregnancy in some reports, we decided to investigate the effect of levothyroxine treatment on GH and PE in pregnant women with subclinical hypothyroidism (SCH) overt hypothyroidism (OH), and autoimmune thyroid diseases. Google Scholar and databases, such as ProQuest, Medline, Cochrane Library, ScienceDirect, and Scopus were searched electronically for clinical trials and observational studies using the following search terms: (("levothyroxine" OR "LT4" OR "thyroxine supplementation") AND ("subclinical hypothyroidism" OR "SCH" OR "thyroid peroxidase antibodies" OR "autoimmune thyroid disease") AND ("pregnancy outcomes" OR "preeclampsia" OR "gestational hypertension" OR "PIH")). Further, we investigated the impact of levothyroxine on the incidence of GH and/or PE compared with control or placebo groups from April 4 to November 1, 2022. After treatment with levothyroxine, the odd ratios (ORs) of GH and PE in subclinical [OR = 1.03, 95% CI: (0.85, 1.25), I2 = 35.25%, P =0.78, OR = 1.02, 95% CI: (0.66,1.58), I2 = 46.86%, P =0.94, respectively] and overt hypothyroidism [OR=1.10, 95% CI: (0.70,1.71), I2=38.44%, P =0.69, OR=1.32, 95% CI: (0.83, 2.09), I2=0.00%, P =0.24, respectively] were not different from controls. Furthermore, this result was observed in studies that recruited women with SCH and OH [OR=1.12, 95% CI: (0.58, 2.14), I2=92.74%, P =0.74, OR=0.51, 95% CI: (0.15, 1.72), I2=97.30%, P =0.28, respectively]. Additionally, the odds ratios of GH and PE were statistically similar in women who were TPOAb-positive compared to those who were TPOAbnegative (OR=1.01,95% CI: (0.80, 1.28), (I2 =0.00%, P =0.00). However, LT4 reduced the risk of GH in treated TPOAb+ women compared with untreated TPOAb+ (OR=0.43, 95% CI: (0.30, 0.62), I2=0.00%, P =0.00). Following LT4 therapy, the incidence rates of GH and PE in all forms of hypothyroidism showed no significant difference compared to the control group. However, the decrease in GH was noteworthy for TPOAb+ women using levothyroxine compared to those not using it.

AB0343 Thyroid Autoantibodies in Seropositive Versus Seronegative Rheumatoid Arthritis: Is There a Link?

Thyroid peroxidase antibody titers, thyroid function, and iodine nutrition status of pregnant normotensive and preeclamptic women in Eastern Cape South Africa

Increasing evidence supports the genetic susceptibility for thyroid antibody (TAb) production in patients with autoimmune thyroid disease, and recently, it has been shown that the cytotoxic T lymphocyte antigen 4 (CTLA-4) gene is most likely a major TAb susceptibility gene. To assess the relationship between exon 1 CTLA-4 gene polymorphism and TAb production, we genotyped 67 patients with newly diagnosed Graves' disease. Free thyroid hormones and TAb were measured, including thyroglobulin antibodies (TgAb), thyroid peroxidase antibodies (TPOAb), and thyroid-stimulating antibodies (TSAb). AA genotype was found in 25 patients, AG genotype in 34 patients, and GG genotype in 8 patients. G allele carrying genotypes showed significantly higher frequency of positive TPOAb (p < 0.005) and TgAb (p < 0.05) compared to AA genotype. Furthermore, the median values of TPOAb were significantly higher in the group with G allele (p < 0.002). However, the median values of TgAb and TSAb did not differ significantly between both groups and similarly, CTLA-4 genotype showed no association with serum free thyroxine (T(4)) and Graves' ophthalmopathy. In conclusion, our findings suggest that G allele carrying genotype of the CTLA-4 gene influences higher production of TPOAb and TgAb, and therefore, support the hypothesis that CTLA-4 gene plays a major role in TAb production.