Positive Thyroid Peroxidase Antibodies Research Articles

Iodine Nutritional Status and Thyroid Autoimmunity in Chinese Children and Adolescents Aged 6-17 Years.

Background: Thyroid autoimmunity (TAI), marked by thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb), affects over 10% of the general population, with children and adolescents experiencing significant impacts on growth and quality of life despite lower prevalence rates compared to adults. Methods: In the context of over 20 years of universal salt iodization (USI) in China, this study investigated the relationship between iodine nutritional status and TAI in children and adolescents aged 6-17. Results: Our findings suggest that while iodine levels are generally sufficient (median urinary iodine concentration [UIC] was 205.2 µg/L), TAI remains a significant concern due to its potential impact on growth and development. TAI was significantly associated with age, sex, and urban-rural residency (p < 0.05). Positive TPOAb and TgAb were identified as risk factors for subclinical hypothyroidism (OR = 2.274, 95% CI: 1.171-1.916). Although some literature suggests that excessive iodine may exacerbate TAI and others propose iodine deficiency as a risk factor, this study did not find a significant overall association between iodine status and TAI. Notably, a low urinary iodine-to-creatinine ratio (UI/Cr) level was linked to an increased risk of TgAb positivity in males (OR = 3.470, 95% CI: 1.200-10.036). In individuals with negative thyroid antibodies, increased BMI (OR = 1.062, 95% CI: 1.032-1.093) and high UI/Cr levels (OR = 1.510, 95% CI: 1.175-1.941) were risk factors for subclinical hypothyroidism, whereas older age (OR = 0.710, 95% CI: 0.555-0.908 for the age 9-11 group; OR = 0.681, 95% CI = 0.484-0.959 for the age 12-17 group) and high UIC levels (OR = 0.739, 95% CI: 0.554-0.985) were associated with reduced risk. No significant associations were observed in the thyroid antibody-positive group. Conclusions: These results highlight the importance of considering individual TAI status when devising iodine supplementation policies.

Female Reproductive System and Thyroid Dysfunction: Findings from a 12-Year Follow-Up in the Tehran Thyroid Study.

Background: The impact of thyroid dysfunction (TD) on the female reproductive system has been extensively documented. While there is evidence suggesting that alteration in female reproductive status may affect thyroid function, conflicting results have prevented definitive conclusions. This study aimed to investigate the associations of parity, spontaneous abortion (mentioned as abortion throughout this study), and menopause status with the prevalence and incidence of TD. Methods: From the Tehran thyroid study population, 2711 participants were included in the cross-sectional analysis to explore associations between female reproductive status and TD. Overall, 2191 participants with euthyroid were included in the survival study and followed up in 3-year intervals. Multinomial logistic regression was adopted in cross-sectional analysis and multivariable Cox proportional hazard model was used to determine associations between the incidence of TD with parity, abortion, and menopause status, adjusting for age, smoking, body mass index, and thyroid peroxidase antibodies positivity. Results: At the baseline, multiple parities (≥4) were significantly associated with overt hypothyroidism (odds ratio [OR] = 1.12; confidence interval [CI] 1.0-1.26) and subclinical hyperthyroidism (OR = 1.11 [CI 1.03-1.21]). Furthermore, multiple abortions were associated with overt hyperthyroidism (OR = 2.09 [CI 1.02-4.26]). Over the course of the study, multiple parities were significantly associated with the incident subclinical and clinical hypothyroidism. Conversely, a history of abortion was associated with a reduced risk of incident overt hypothyroidism. We found no significant association between menopause status and the prevalence or incidence of either hypothyroidism or hyperthyroidism. Conclusions: Our results suggest that the female reproductive system may be associated with thyroid function. Parity and abortion are associated with the occurrence of TD. A deeper understanding of the underlying mechanisms of the cellular and molecular alterations in signaling cascades during pregnancy is necessary to fully elucidate these associations.

The Relationships among the Urinary Iodine Concentration, Selenium Intake, and Thyroid Antibodies in Adults, Including the Interaction between Iodine and Selenium: National Health and Nutrition Examination Survey 2007-2012.

The objective of this study was to examine the urinary iodine concentration (UIC)-thyroid autoimmunity (TAI) association and UIC-selenium intake interaction in U.S. adults. We analyzed 2007-2012 National Health and Nutrition Examination Survey (NHANES) data on ≥20-year-old adults (n = 6612). Their food and supplemental selenium intake was measured. The associations of the UIC and selenium intake with thyroid peroxidase antibody (TPOAb) positivity, thyroglobulin antibody (TgAb) positivity, and TAI were assessed via weighted multivariable logistic regression. Interaction and subgroup analyses were conducted. Nonlinear relationships were explored and visualized via restricted cubic splines (RCSs). Compared with a UIC 100~200 μg/L, a UIC 500~800 μg/L was associated with a 57% increased TPOAb positivity risk (OR = 1.57 [CI = 1.07-2.30]; p = 0.022), a one-fold greater TgAb positivity risk (OR = 2.00 [CI = 1.10-3.65]; p = 0.025), and a 62% increased TAI risk (OR = 1.62 [CI = 1.07-2.45]; p = 0.024). Nonlinear relationships between the UIC and thyroid antibody positivity were observed. According to the univariate models, each 1 μg increase in selenium intake was associated with a 0.049 IU/mL decrease in the TPOAb levels (β [95% CI] = -0.049 [-0.092--0.005]; p = 0.028). In the low-selenium group, a UIC of 200~300 μg/L was a risk factor for TPOAb positivity (p = 0.046). At a moderate level of selenium intake, a UIC of 300~800 μg/L significantly increased the TPOAb positivity risk (all p < 0.05). At a high level of selenium intake, the UIC and TPOAb positivity risks were not significantly associated (all p > 0.05). A UIC of 500~800 μg/L is an independent TAI risk factor. The selenium intake modifies the UIC-thyroid antibody positivity relationship, with the association disappearing at high selenium levels.

Investigating Associations between Subclinical Hypothyroidism and Pregnancy Outcomes and Effects of Levothyroxine Therapy on Improving Maternal and Infant Prognosis

Background: Current evidence shows subclinical hypothyroidism (SCH) is associated with increased risk of adverse pregnancy outcomes, though some controversies exist. However, little is known on the impacts and effectiveness of levothyroxine (LT4) therapy on pregnancy outcomes in women with SCH. Present study aims to investigate the associations between SCH and adverse pregnancy outcomes and clinical effects of levothyroxine (LT4) replacement therapy in patients with SCH. Methods: The clinical data of pregnant women (n = 635) with SCH who referred to Huai'an Maternal and Child Health Care Hospital, Huaian, China from June 2018 to December 2018 were retrospectively analyzed. Among them, 147 cases received standard thyroxine replacement therapy, 292 cases did not receive treatment and 150 cases who received irregular treatment or did not achieve the target or were lost to follow-up. 46 cases whose thyroid peroxidase antibody (TPOAb) was not checked during pregnancy were not included in the study. According to the TPOAb test results patients were divided into positive treatment (n = 14), negative treatment (n = 133), positive untreated (n = 19), or negative untreated (n = 273) subgroups. A total of 1876 pregnant women with normal thyroid function (TPOAb positive = 59; TPOAb negative = 1817) who delivered during the same period were selected as the control group. Pregnancy outcomes were assessed and compared between treated and control group, untreated and control group, TPOAb positive treatment subgroup and TPOAb positive and untreated subgroup, TPOAb negative treatment subgroup and TPOAb negative subgroup, and TPOAb positive and TPOAb negative subgroup. Results: Our data showed that the incidences of hypertensive disease, premature delivery, fetal growth restriction and fetal death during pregnancy in the untreated group were significantly higher than in the control group (p &lt; 0.05). The incidence of preterm delivery in the treatment group was significantly lower compared to the untreated group and the control group (p &lt; 0.05). Moreover, the incidence of premature birth in TPOAb positive treatment subgroup was significantly lower than their peers in TPOAb positive and untreated subgroup. The incidence of premature delivery in TPOAb negative treatment subgroup was significantly lower than TPOAb negative untreated subgroup and the difference was statistically significant (p &lt; 0.05). There was no significant difference in the incidence of adverse pregnancy outcomes between TPOAb positive subgroup and TPOAb negative subgroup in the control group (p &gt; 0.05). Conclusions: SCH during pregnancy is a risk factor for hypertensive disease during pregnancy, fetal growth restriction, premature delivery and fetal death. L-T4 replacement therapy improves maternal and infant outcomes in patients with SCH during pregnancy, regardless of whether or not TPOAb is positive.

8471 A Rare Case of Graves' Disease in a Three-Year-Old

Abstract Disclosure: A. Rajesh: None. A. Ravari: None. L.E. Kimball-Ravari: None. H. Roan: None. Graves’ Disease (GD) is an autoimmune disease that causes hyperfunctioning of the thyroid gland which may be triggered by environmental factors such as infection or stress. Though the leading cause of hyperthyroidism in both adult and pediatric populations is GD, it is extremely rare in children under the age of four years old. Some studies show the incidence to be 1 per 1,000,000 cases[1],2. Detecting GD in children early is very important as untreated GD poses a risk for failure to thrive. There have also been cases of young children suffering from psychomotor delays, craniosynostosis, and language delays because their suspected diagnosis of GD had not been detected for one to two years. In this article, we report the case of a previously healthy three-year-old Caucasian female who presented to the pediatric endocrinologist after collapsing from an episode of hypoglycemia; plasma glucose 47 mg/dL (71-180) . The patient was diagnosed with Graves’ Disease due to her significantly elevated free T3 and T4, decreased TSH, positive thyroid peroxidase (TPO) antibodies, and elevated TSIg. She was started on methimazole treatment; however, she did not respond after six months of ATD and underwent total thyroidectomy. Her hypoglycemia was attributed to abnormal proinsulin processing and glucose metabolism, which has been associated with hyperthyroidism; thyroid hormones can produce increased GLUT2 transporters3. This case report demonstrates the importance of recognizing the signs and symptoms of GD early, as well as discuss the importance of increasing the recognition of autoimmune diseases in the pediatric population.

Updates on the Association Between Vitiligo and Thyroid Diseases: A Systematic Review.

The main objective of this study is to estimate the prevalence of thyroid diseases in patients with vitiligo and investigate the potential shared autoimmune mechanisms underlying the co-occurrence of vitiligo and thyroid diseases. To locate research that met the inclusion criteria, a thorough computerized search of relevant databases was carried out. A comprehensive search was carried out on PubMed, SCOPUS, Science Direct, and Web of Science to locate relevant material. Our data included 13 trials with 82,230 participants, and 40,116 (48.8%) of them were males. The prevalence of thyroid disorders ranged from 3.2% to 32.1%, with a total prevalence of 2,906 (3.5%). Vitiligo patients are more likely to have a number of immunological comorbidities, underscoring the serious effects of the illness on overall health, especially thyroid disorders. The correlation between vitiligo and positive thyroid peroxidase antibodies, hypothyroidism, and autoimmune thyroiditis is notably high. We found a strong association between vitiligo and the incidence of thyroid disorders, particularly autoimmune thyroid disorders. The findings emphasize the necessity of identifying and treating thyroid dysfunction in vitiligo patients, as it might affect the clinical course of the skin condition and overall patient health. Future research is required to standardize study methodology, investigate underlying mechanisms, and create integrated therapy and screening regimens.

Association Between Long-Term Exposure to Environmental Fine Particulate Matter and the Prevalence of Thyroid Disorders: A National Cross-Sectional Study in China.

Background: Exposure to particles with an aerodynamic diameter of ≤2.5 μm (PM2.5) is associated with the occurrence of thyroid dysfunction among pregnant women and neonates, but it is not known if this association occurs in the general population. We aimed to determine the association of prolonged exposure to PM2.5 with the prevalence of thyroid disorders among adults in China. Methods: A nationally representative cross-sectional study of thyroid disorders, iodine status, and diabetes status was carried out in all 31 provinces across China from 2015 to 2017. In total, 73,900 adults aged 18 years and older were included. Serum concentrations of thyroid hormones, thyrotropin, and thyroid antibodies and the urine iodine concentration were measured. The environmental concentration of PM2.5 for each participant's residential address at a spatial resolution of 1 × 1 km was estimated. Results: The average long-term exposure to PM2.5 at residential addresses was 66.41 μg/m3, ranging from 17.58 μg/m3 to 120.40 μg/m3. Compared with that of individuals with lower exposure levels, the prevalence of thyroid diseases such as autoimmune thyroiditis and subclinical hypothyroidism was greater in those with PM2.5 concentrations within the third quartile range (60.18 to 73.78 μg/m3). Compared with those in the first quartile (17.58 to 46.38 μg/m3), participants in the highest PM2.5 quartile (73.78 to 120.40 μg/m3) presented an increased risk of overt hypothyroidism (OR 1.23 [CI 0.94-1.61]), subclinical hypothyroidism (1.10 [1.01-1.21]), autoimmune thyroiditis (1.09 [1.00-1.18]), and thyroglobulin antibody positivity (1.17 [1.07-1.29]). However, there was no association between PM2.5 exposure and overt hyperthyroidism, subclinical hyperthyroidism, Graves' disease, or thyroid peroxidase antibody positivity (p > 0.05). Each 10 μg/m³ increase in the PM2.5 concentration was associated with an increased risk of overt hypothyroidism (OR 1.05 [1.00-1.11]), subclinical hypothyroidism (1.02 [1.00-1.03]), and thyroglobulin antibody positivity (1.02 [1.00-1.04]). Furthermore, a nearly linear exposure-response relationship was observed between long-term PM2.5 exposure and thyroglobulin antibody positivity. Conclusions: PM2.5 exposure was associated with thyroid disorders among Chinese adults. A dose-response relationship between PM2.5 exposure and autoimmune thyroiditis, as well as thyroglobulin antibody positivity, was also observed.

Pregnancy outcome in subclinical hypothyroidism with and without thyroid peroxidase antibodies-a prospective cohort study.

Subclinical hypothyroidism (SCH) in pregnancy is associated with adverse foetomaternal outcomes. The literature is scarce with respect to maternal and perinatal outcomes in women with mild SCH (TSH levels between 2.5-4 mIU/L). The primary objective of the study was to compare the pregnancy outcome between SCH and euthyroid women. The secondary objectives were to find out the proportion of women with SCH having thyroid peroxidase antibodies (TPOAb) and to see the effect of TPOAb positivity on foetomaternal outcomes. A total of 178 pregnant women were recruited in the first trimester, and those with TSH between 0.1 and 2.4 mIU/L were considered as euthyroid and 2.5-4mIU/L were labelled as SCH. Women with SCH underwent testing for TPOAb. All women were followed until delivery, and foetomaternal outcomes were assessed. Amongst SCH group, there was a significantly higher proportion of overweight and obese women (76/91 (83.51%) vs 59/87 (68%), p = 0.031). The neonatal intensive care unit (NICU) admission was higher with adjusted odds ratio of 3.24 (1.41-7.43) in women with SCH as compared to euthyroid women. Otherwise, there was no difference in foetomaternal outcomes between the two groups. The proportion of gestational diabetes mellitus, intrauterine growth retardation and still birth were higher in SCH women with TPOAb as compared to euthyroid. Amongst SCH women, the proportion of induced labour was lower (aOR:0.27 (0.08-0.93) whereas the proportion of stillbirth and low APGAR scores were higher in TPOAb-positive women with a statistically significant difference and adjusted odds ratio (aOR:20.18 (1.84-220.83)) and (aOR:4.77 (1.06-21.3)), respectively, when compared to TPOAb-negative women. There appears to be no difference in pregnancy outcomes between women with SCH and euthyroid women except higher NICU admission in SCH group. Future multi-centre large prospective studies are required to understand better about the pregnancy outcomes in these women.

What is causing this patient's urticaria?

This article describes a teenage patient who was referred to a pediatric endocrinologist after her workup for recurring urticaria revealed a suppressed thyroid-stimulating hormone level and positive microsomal thyroid peroxidase antibodies. The patient's laboratory results revealed an autoimmune cause for the urticaria as a result of new-onset autoimmune thyroid disease.

Correlation between estradiol-to-testosterone ratio and thyroid peroxidase antibody positivity in men with treatment-naïve primary hypothyroidism or euthyroidism.

Thyroid diseases pose a substantial socioeconomic burden globally. The aim of this study was to evaluate the correlation between estradiol-to-testosterone (E2/T) ratio and thyroid peroxidase antibody (TPOAb) positivity in male patients with hypothyroidism or euthyroidism. Cross-sectional observational study including 115 male patients with hypothyroidism or euthyroidism. The patients were divided into two groups based on positive or negative TPOAb results, with TPOAb positivity defined by a serum TPOAb value ≥ 35 IU/mL. Patients with positive TPOAbs, compared with those with negative TPOAbs, had a higher prevalence of goiter and obesity and higher levels of total cholesterol, triglycerides, and low-density lipoprotein (LDL) cholesterol. The median estradiol level was higher, and the median total testosterone and sex-hormone binding globulin (SHBG) levels were lower in the TPOAb-positive versus the TPOAb-negative group (p < 0.001). In subgroup analysis including only patients with hypothyroidism (n = 80), the median E2/T ratio was higher in the TPOAb-positive group (p = 0.016). The prevalence of TPOAb positivity increased with the increase in E2/T ratio quartiles, from 37.9% in the lowest quartile to 96.2% in the highest quartile (p value for trend across all quartiles < 0.001). On adjusted multivariate analysis, the E2/T ratio emerged as an independent predictor of TPOAb positivity. An E2/T ratio cutoff value of 6.565 x10-3 demonstrated the best diagnostic accuracy, with a sensitivity of 78.2% and specificity of 67.6%. The present study provides insights into the role of the E2/T ratio as a predictor of thyroid disorders.

The effects of vitamin D and gene polymorphisms on susceptibility to thyroid peroxidase antibody positivity

BackgroundThe etiology of Hashimoto's thyroiditis (HT) involves genetic and environmental factors. There is a lack of clarity regarding the relationship between Vitamin D and HT. This study aimed to investigate the effect of Vitamin D and gene polymorphisms on thyroid peroxidase antibody (TPOAb) positivity. MethodsA total of 9,966 participants were included from a survey conducted in East China from 2014 to 2016. We measured the levels of 25(OH)D, thyroid hormones and autoimmune antibodies. rs11675434, rs9277555, and rs301799 were genotyped. Based on these 3 SNPs, a weighted genetic risk score was calculated for TPOAb. ResultsThe proportion of females in the TPOAb-positive group was greater than that in the TPOAb-negative group (74.2% vs. 57.2%, P<0.001). Vitamin D levels were lower in the TPOAb-positive group than in the TPOAb-negative group (40.07±11.87 vs. 40.80±12.84, P=0.01). The GG genotype of rs9277555 and the TT genotype of rs11675434 were correlated with the risk of TPOAb positivity (OR=1.34, 95% CI 1.13-1.59, P=0.001; OR=1.29, 95% CI 1.06-1.58, P=0.01). TPOAb-GRS was associated with TPOAb positivity (OR=3.17, 95% CI 1.72-5.84; P<0.001). When stratified by Vitamin D group, the association between TPOAb-GRS and TPOAb positivity existed only in the Vitamin D deficiency group (OR=3.41, 95% CI 1.73-6.70 P<0.001) but not in the control group (OR=2.45, 95% CI 0.59-10.19, P=0.22). ConclusionsThis study suggested that TPOAb-GRS was associated with TPOAb positivity in the Han Chinese population, mainly due to rs9277555 and rs11675434. The hereditary effect of TPOAb positivity differed depending on Vitamin D status.

Use of levothyroxine for euthyroid, thyroid antibody positive women with infertility: Analyses of aggregate data from a survey of European thyroid specialists (Treatment of Hypothyroidism in Europe by Specialists: An International Survey).

The use of levothyroxine (LT4) treatment aiming to improve fertility in euthyroid women with positive thyroid peroxidase antibodies (TPOAb) is not supported by the available evidence. The aim of the study was to document the use of LT4 by European thyroid specialists in such patients. The data presented derive from Treatment of Hypothyroidism in Europe by Specialists, an International Survey (THESIS), a questionnaire conducted between 2019 and 2021 to document the management of hypothyroidism by European thyroid specialists. Here, we report the aggregate results on the use of LT4 in infertile, euthyroid women with positive TPOAb. A total of 2316/5406 (42.8%) respondents stated that LT4 may be indicated in TPOAb positive euthyroid women with infertility. The proportion of those replying positively to this question varied widely across different countries (median 39.4, range 22.9%-83.7%). In multivariate analyses males (OR: 0.8; CI: 0.7-0.9) and respondents >60 years (OR: 0.7; 0.6-0.8) were the least inclined to consider LT4 for this indication. Conversely, respondents managing many thyroid patients ("weekly" [OR: 1.4; CI: 1.0-1.9], "daily" [OR: 1.8; CI: 1.3-2.4]) and practicing in Eastern Europe (OR: 1.5; CI: 1.3-1.9) were most likely to consider LT4. A remarkably high number of respondents surveyed between 2019 and 2021, would consider LT4 treatment in TPOAb positive euthyroid women with infertility. This view varied widely across countries and correlated with sex, ageand workload, potentially influencing patient management. These results raise concerns about potential risks of overtreatment.

Sex-Specific Associations between Maternal Thyroid Peroxidase Antibodies and Cognitive Development in Preschool Children: A Prospective Cohort Study.

Background: An association between maternal thyroid dysfunction throughout pregnancy and the subsequent risk of neurodevelopmental abnormalities in offspring has been demonstrated. However, the potential effects of maternal thyroid autoimmunity on neurodevelopment in the absence of maternal hypothyroidism remain unclear. Therefore, in this study, we explored the association between maternal thyroid peroxidase antibody (TPOAb) positivity and cognitive development in preschool children. Methods: A total of 1849 mother-child pairs were recruited from the Ma'anshan Birth Cohort (MABC) Study. During the follow-up period, an electrochemiluminescence immunoassay was used to retrospectively measure serum TPOAb levels in pregnant women. The cognitive development of preschool children was evaluated by using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV). A growth mixture model was used to fit the trajectory of TPOAb. Multiple linear regression and logistic regression models were used to explore the associations between the developmental trajectory of TPOAb-positivity at different gestational periods and the cognitive development of preschool children by sex. Results: A total of 1849 mother-child pairs (mean [SD] age: 26.7 [3.6] years) were enrolled in the final study. Maternal TPOAb positivity in the first trimester was associated with a risk of below-average processing speed index in girls (OR: 2.07; 95% CI 1.06 to 4.01) and below-average full-scale intelligence quotient (FSIQ) in boys (OR: 2.36; 95% CI: 1.10 to 5.05). Maternal TPOAb positivity in the third trimester (T3) was associated with below-average working memory index (WMI) (OR: 2.51; 95% CI: 1.02 to 6.20) in girls. In girls, the WMI (β = -3.17, 95% CI: -5.82 to -0.52), fluid reasoning index (FRI) (β = -4.49, 95% CI: -7.18 to -1.80), and FSIQ score (β = -2.43, 95% CI: -4.77 to -0.08) decreased, whereas in mothers, the level of log-transformed thyroid peroxidase antibody (lgTPOAb) increased during pregnancy. Conclusions: Positive maternal TPOAb levels during pregnancy may be associated with poorer cognitive development in preschool children. These findings require independent confirmation in other populations.

Impact of Thyroid Autoimmunity on the Clinical and Biochemical Characteristics of Type 1 Diabetes Mellitus Patients.

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.

The Effect of Mediterranean Diet on Thyroid Gland Activity.

The main goal of this research was to determine whether there is a correlation between adherence to the Mediterranean diet (assessed by the Mediterranean Diet Serving Score (MDSS)) and parameters indicating thyroid gland activity, such as concentration of thyroid-stimulating hormone (TSH), thyroid hormones (free triiodothyronine (fT3), free thyroxine (fT4)), thyroglobulin (Tg), antibodies to thyroid proteins (thyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb)), and calcitonin (CT) in plasma and serum samples. An additional objective was to investigate whether there are differences in the values of the MDSS among clinical groups (euthyroid individuals, euthyroid individuals with positive TgAb and/or TPOAb, and hypothyroid and hyperthyroid participants). This cross-sectional study included 4620 participants over 18 years of age from the islands of Korčula and Vis, and the mainland city of Split. The MDSS was assessed from a food frequency questionnaire (FFQ). MDSS values were significantly higher in females compared to males and showed a positive association with the age of the participants. There was no significant difference in the MDSS values among the examined clinical groups. In the group of subjects with euthyroidism, a significant positive association was found between fT3 and the MDSS, while in the group of subjects with subclinical hypothyroidism, a significant positive association was observed between the MDSS and both fT3 and fT4. CT levels were also positively associated with the MDSS. Considering the significant positive association of the MDSS and both fT3 and fT4 levels in patients with subclinical hypothyroidism, the results of this study could be used to create guidelines for selecting an appropriate, potentially protective diet for these patients.

Levothyroxine Treatment in Pregnant Women with Thyrotropin Levels Ranging Between 2.5 and 10 mIU/L: A Propensity Score Matched Analysis.

Objective: To clarify the association between levothyroxine (LT4) treatment and various adverse pregnancy outcomes in pregnant women with thyrotropin (TSH) levels ranging between 2.5 and 10.0 mIU/L in the first trimester, stratified according to thyroid peroxidase antibody (TPOAb) positivity and TSH level. Methods: This retrospective analysis of retrospectively and prospectively collected cohort data included Chinese pregnant women with TSH levels of 2.5-10 mIU/L and normal free thyroxine levels (11.8-18.4 pmol/L) in the first trimester. All participants were followed up until the completion of pregnancy, and information on LT4 treatment, pregnancy complications, and pregnancy outcomes was recorded. A 1:1 nearest-neighbor propensity score matching (PSM) between the LT4-treated and - untreated groups with a caliper distance of 0.02 was performed using a multivariable logistic regression model. Multivariable-adjusted modified Poisson regression was used to estimate the relative risk (RR) and 95% confidence interval (CI) of LT4 treatment for adverse pregnancy outcomes. Subgroup analyses were also performed in four subgroups simultaneously stratified by TPOAb status (negative or positive) and TSH levels (2.5-4.0 mIU/L as high-normal group and 4.0-10.0 mIU/L as SCH group). The study was registered in the Chinese Clinical Trial Registry (ChiCTR2100047394). Results: Among the 4,370 pregnant women in the study, 1,342 received LT4 treatment and 3,028 did not. The 1:1 PSM yielded 668 pairs of individuals and revealed that LT4 treatment was significantly associated with a decreased risk of pregnancy loss (RR = 0.528, 95% CI: 0.344-0.812) and an increased risk of small-for-gestational-age infants (RR = 1.595, 95% CI: 1.023-2.485). Subgroup analyses suggested that the above effects of LT4 treatment were mainly from TPOAb-negative participants. LT4 treatment was associated with an increased risk of preterm birth (RR = 2.214, 95% CI: 1.016-4.825) in TPOAb-positive pregnant women with high-normal TSH levels. Conclusion: LT4 treatment was significantly associated with a lower risk of pregnancy loss and a higher risk of small-for-gestational-age infants in pregnant women with TSH levels of 2.5-10 mIU/L. An increased risk of preterm birth was observed in the LT4-treated group among TPOAb-positive participants with TSH levels of 2.5-4.0 mIU/L.

Early-pregnancy sex steroid and thyroid function hormones, thyroid autoimmunity, and maternal papillary thyroid cancer incidence in the Finnish Maternity Cohort.

Thyroid cancer more commonly affects women than men and is the third most frequently diagnosed cancer among women of reproductive age. We conducted a nested case-control study within the Finnish Maternity Cohort to evaluate pre-diagnostic sex steroid and thyroid function markers in relation to subsequent maternal papillary thyroid cancer. Cases (n = 605) were women ages 18-44 years, who provided an early-pregnancy (<20 weeks gestation) blood sample and were diagnosed with papillary thyroid cancer up to 11 years afterward. Controls (n = 1185) were matched to cases 2:1 by gestational age, mother's age, and date at blood draw. Odds ratios (ORs) for the associations of serum thyroid peroxidase antibodies (TPO-Ab), thyroglobulin antibodies (Tg-Ab), thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), progesterone, and estradiol with papillary thyroid cancer were estimated using conditional logistic regression. TPO-Ab and Tg-Ab positivity (>95th percentile among controls) were associated with more than 3-fold (OR = 3.32, 95% confidence interval [CI] 2.33-4.72) and 2-fold (OR = 2.03, 95% CI 1.41-2.93) increased odds of papillary thyroid cancer, respectively. These associations were similar by time since blood draw, parity, gestational age, smoking status, and age and stage at diagnosis. In models excluding TPO-Ab or Tg-Ab positivity, TPO-Ab (quartile 4 vs. 1: OR = 1.66, 95% CI 1.17-2.37, p-trend = .002) and Tg-Ab (quartile 4 vs. 1: OR = 1.74, 95% CI 1.22-2.49, p-trend = .01) levels were positively associated with papillary thyroid cancer. No associations were observed for estradiol, progesterone, TSH, fT3, or fT4 overall. Our results suggest that thyroid autoimmunity in early pregnancy may increase the risk of maternal papillary thyroid cancer.

Thyroid autoimmunity in euthyroid pregnant women is associated with slower productive language acquisition: the Odense child cohort study.

Maternal thyroid autoimmunity and thyroid function in early pregnancy may impact fetal neurodevelopment. We aimed to investigate how thyroid autoimmunity and thyroid function in early pregnancy were associated with language acquisition in offspring at 12-36 months of age. This study was embedded in the prospective Odense child cohort. Mother-child dyads were excluded in case of maternal intake of thyroid medication during pregnancy. The parents completed MacArthur-Bates Communicative Development Inventories (MB-CDI) every third month to assess their offspring's productive vocabulary. All completed reports for each child were included in the analyses. Logistic growth curve models evaluated associations between MB-CDI scores and levels of maternal thyroid peroxidase antibodies (TPOAb), free thyroxine (FT4), and thyrotropin, respectively, measured in early pregnancy (median gestational week 12). All models were stratified by offspring sex and adjusted for maternal age, education, pre-pregnancy body mass index, parity, breastfeeding, and offspring age. The study included 735 mother-child dyads. Children born to mothers with TPOAb ≥11 kIU/L, opposed to TPOAb <11 kIU/L, had a lower probability of producing words at age 18-36 months for girls (OR = 0.78, P < 0.001) and 33-36 months for boys (OR = 0.83, P < 0.001). The probability of producing words was higher in girls at 30-36 months of age with low-normal maternal FT4 vs high-normal FT4 (OR = 0.60, P < 0.001), and a similar trend was seen in boys. Results were ambiguous for thyrotropin. In women without known thyroid disease, TPOAb positivity in early pregnancy was negatively associated with productive vocabulary acquisition in girls and boys. This association was not mediated by a decreased thyroid function, as low-normal maternal FT4, unexpectedly, indicated better vocabulary acquisition. Our results support that maternal thyroid autoimmunity per se may affect fetal neurodevelopment.

Evaluation of the therapeutic efficacy of different doses of LT4 in pregnant women with high-normal TSH levels and TPOAb positivity in the first half of pregnancy.

The objective was to investigate the efficacy of different doses of levothyroxine therapy among pregnant women exhibiting high-normal thyroid stimulating hormone levels and positive thyroid peroxidase antibodies throughout the first half of pregnancy. Pregnant women exhibiting high-normal thyroid stimulating hormone levels and thyroid peroxidase antibodies positivity throughout the initial half of pregnancy were selected from January 2021 to September 2023. Based on the different doses of levothyroxine, the pregnant women were categorized into the nonintervention group (G0, 122 women), 25µg levothyroxine intervention group (G25, 69 women), and 50µg levothyroxine intervention group (G50, 58 women). Serum parameters, gastrointestinal symptoms, small intestinal bacterial overgrowth (SIBO), maternal and neonatal outcomes were compared after the intervention among the three groups. After the intervention, in the G25 and G50 groups, the thyroid stimulating hormone, triglyceride and low-density lipoprotein levels were notably less in contrast to those in the G0 group (P < 0.05). The rates of abdominal distension and SIBO in the G25 and G50 groups were notably lower in contrast to the G0 group (P = 0.043 and 0.040, respectively). The G50 group had a lower rate of spontaneous abortion and premature membrane rupture than the G0 group (P = 0.01 and 0.015, respectively). Before 11+ 2 weeks of gestation and at thyroid peroxidase antibodies levels ≥ 117 IU/mL, in contrast to the G0 group, the G50 group experienced a decreased rate of spontaneous abortion (P = 0.008). The G50 group had significantly higher newborn weight than the G0 group (P = 0.014), as well as a notably longer newborn length than the G0 and G25 groups (P = 0.005). For pregnant women with high-normal thyroid stimulating hormone levels and thyroid peroxidase antibodies positive during the first half of pregnancy, supplementation with 50µg levothyroxine was more effective in improving their blood lipid status and gastrointestinal symptoms, reducing the incidence of SIBO and premature rupture of membranes, and before 11+2 weeks, TPOAb ≥ 117IU/mL proved more beneficial in mitigating the risk of spontaneous abortion.

The impact of gut microbiota on autoimmune thyroiditis and relationship with pregnancy outcomes: a review.

Autoimmune thyroiditis (AITD) is a T-cell-mediated, organ- specific autoimmune disease caused by interactions between genetic and environmental factors. Patients with AITD show thyroid lymphocyte infiltration and an increase in the titer of thyroid autoimmune antibodies, thereby altering the integrity of thyroid follicle epithelial cells and dysregulating their metabolism and immune function, leading to a decrease in multi-tissue metabolic activity. Research has shown that patients with AITD have a significantly higher risk of adverse pregnancy outcomes, such as infertility and miscarriage. Levothyroxine(LT4) treatment can improve the pregnancy outcomes of normal pregnant women with thyroid peroxidase antibodies(TPOAb) positivity, but it is not effective for invitro fertilization embryo transfer (IVF-ET) in women with normal thyroid function and positive TPOAb. Other factors may also influence pregnancy outcomes of patients with AITD. Recent studies have revealed that the gut microbiota participates in the occurrence and development of AITD by influencing the gut-thyroid axis. The bacterial abundance and diversity of patients with Hashimoto thyroiditis (HT) were significantly reduced, and the relative abundances of Bacteroides, fecal Bacillus, Prevotella, and Lactobacillus also decreased. The confirmation of whether adjusting the composition of the gut microbiota can improve pregnancy outcomes in patients with AITD is still pending. This article reviews the characteristics of the gut microbiota in patients with AITD and the current research on its impact in pregnancy.