Impact of mildly evaluated thyroid-stimulating hormone levels on in vitro fertilization or intracytoplasmic sperm injection outcomes in women with the first fresh embryo transfer: a large study from China.

PURPOSE: This study aimed to investigate the association between mild elevation of thyroid-stimulating hormone (TSH) levels and pregnancy outcomes of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatments in women with the first fresh embryo transfer. METHODS: Large single-center retrospective cohort study of 15,728 patients from January 2018 to December 2022 were enrolled in the analyses. Clinical pregnancy rates, live birth rates, miscarriage rates, and ectopic pregnancy rates were compared between the TSH levels < 2.5 mIU/L group (N = 10,932) and TSH levels ≥ 2.5 mIU/L group (N = 4796). Subgroup analysis was performed for patients with TSH levels ≥ 2.5 mIU/L, dividing them into the thyroid peroxidase antibody (TPO)-negative group (N = 4524) and the TPO-positive group (N = 272). RESULTS: There were no significant differences in the aforementioned pregnancy outcomes between the TSH levels < 2.5 mIU/L group and TSH levels ≥ 2.5 mIU/L group. Similarly, no significant differences were observed in the pregnancy outcomes between the TPO-negative group and the TPO-positive group. CONCLUSION: Mildly elevated pre-conception TSH levels in thyroid-normal infertile patients did not have an impact on pregnancy outcomes of IVF/ICSI treatments.

Levothyroxine for subclinical hypothyroidism during pregnancy: an updated systematic review and meta-analysis of randomized controlled trials.

PURPOSE: We aimed to perform a systematic review and meta-analysis addressing the efficacy of levothyroxine therapy in pregnant women with subclinical hypothyroidism considering most recent evidence and subgroups of interest for clinical practice. METHODS: PubMed, Embase, and Cochrane Central were searched from inception for randomized controlled trials (RCTs) comparing levothyroxine with placebo or no intervention in pregnant women with subclinical hypothyroidism. We used a random-effects model and conducted subgroup analyses based on thyroid peroxidase antibody status, thyroid stimulating hormone levels, fertility treatment, and recurrent miscarriage. RESULTS: We included 11 RCTs comprising 2,749 pregnant women with subclinical hypothyroidism. Patients treated with levothyroxine (1,439; 52.3%) had significantly lower risk of pregnancy loss (risk ratio 0.69; 95% confidence interval 0.52-0.91; p < 0.01; 6 studies). However, there was no significant association between levothyroxine and live birth (risk ratio 1.01; 95% confidence interval 0.99-1.03; p = 0.29; 8 studies). No statistically significant interaction was observed across subgroups (p > 0.05). CONCLUSION: Levothyroxine replacement therapy for subclinical hypothyroidism during pregnancy may decrease pregnancy loss when early prescribed. Nevertheless, further investigation is needed in patients with thyroid stimulating hormone above four milliunits per liter, especially when associated with recurrent miscarriage or infertility.

Long-term stability of thyroid peroxidase antibody (anti-TPO) in serum in the Danish General Suburban Population Study.

OBJECTIVES: We evaluated the long-term stability of thyroid peroxidase antibody (anti-TPO). METHODS: In the Danish General Suburban Population Study (GESUS), serum samples were biobanked at -80 °C during 2010-2013. In a paired design with 70 subjects, we compared anti-TPO (30-198 U/mL) measured on fresh serum on Kryptor Classic in 2010-2011 (anti-TPOfresh) with anti-TPO remeasured on frozen serum (anti-TPOfrozen) on Kryptor Compact Plus in 2022. Both instruments used the same reagents and the anti-TPOn automated immunofluorescent assay, which was calibrated against the international standard NIBSC 66/387, based on the Time Resolved Amplified Cryptate Emission (TRACE) technology from BRAHMS. Values greater than 60 U/mL are regarded as positive in Denmark with this assay. Statistical comparisons included Bland-Altman, Passing-Bablok regression, and Kappa statistic. RESULTS: The mean follow-up time was 11.9 years (SD: 0.43). For anti-TPOfrozen vs. anti-TPOfresh, the line of equality was within the confidence interval of the absolute mean difference [5.71 (-0.32; 11.7) U/mL] and the average percentage deviation [+2.22% (-3.89%; +8.34%)]. The average percentage deviation of 2.22% did not exceed analytical variability. Passing-Bablok regression revealed both a statistically significant systematic and proportional difference: Anti-TPOfrozen=-22.6 + 1.22*(anti-TPOfresh). Frozen samples were correctly classified as positive in 64/70 (91.4%; Kappa=71.8%). CONCLUSIONS: Anti-TPO serum samples in the range 30-198 U/mL were stable after 12-years of storage at -80 °C with an estimated nonsignificant average percentage deviation of +2.22%. This comparison is based on Kryptor Classic and Kryptor Compact Plus, which used identical assays, reagents, and calibrator, but for which the agreement in the range 30-198 U/mL is unclarified.

Association between levothyroxine treatment for maternal subclinical hypothyroidism with negative TPOAb and early child neurodevelopment: A prospective real-world clinical trial.

INTRODUCTION: Subclinical hypothyroidism (SCH) during pregnancy is reported to have detrimental impact on pregnancy and child development. However, its treatment indications require further investigation in different thyroid peroxidase antibody (TPOAb) status. MATERIAL AND METHODS: This was a secondary analysis of a Chinese prospective cohort in a real-world setting. Pregnant women with gestational SCH were enrolled at the first antenatal visit and grouped by TPOAb positivity. Child neurodevelopment was assessed by the Gesell development diagnosis scale (GDDS) at one, three, six, 12, and 24 months of age. Subgroup analyses and sensitivity analyses were also conducted. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01744743. RESULTS: From January 2012 to December 2013, a total of 171 participants were enrolled, including 116 of SCH with TPOAb negative (SCH-TPOAb [-]) and 55 of SCH with TPOAb positive (SCH-TPOAb [+]). Compared to women in the SCH-TPOAb (+) group, those in the SCH-TPOAb (-) group had lower thyroid-stimulating hormone (TSH) levels at enrollment and 12-16+6 gestational weeks, and unexpectedly higher TSH levels at 30-34+6 gestational weeks and delivery, with a correspondingly lower levothyroxine dosage throughout pregnancy (all p < 0.05). Offspring in the SCH-TPOAb (-) group displayed lower GDDS scores at one year old than did their counterparts (adjusted p < 0.05), which was possibly related to the worse thyroid function control of maternal SCH-TPOAb (-). No statistically significant difference was found in the GDDS assessments of children at one, three, six, and 24 months of age. These results were also confirmed in subgroup analyses stratified by maternal thyroid characteristics at enrollment, namely TSH levels, free levothyroxine (T4 ) levels, and anti-thyroglobulin antibody (TgAb) status, as well as in sensitivity analyses excluding participants with no levothyroxine treatment at enrollment. CONCLUSIONS: In the current clinical practice, infants born to mothers with SCH-TPOAb (-) displayed slightly lower neurodevelopmental scores at one year old than did those born to mothers with SCH-TPOAb (+) but this difference was not seen at two years.

A first-trimester serum TSH in the 4-10 mIU/L range is associated with obstetric complications in thyroid peroxidase antibody-negative women.

PURPOSE: The impact of mild subclinical hypothyroidism on pregnancy outcomes in TPOAb-negative women is poorly explored. The aim of the present study was the evaluation in a wide cohort of TPOAb-negative pregnant women the role of subclinical hypothyroidism (SCH) on several pregnancy outcomes. METHODS: The study included women aged ≥ 18 years with a singleton pregnancy without known thyroid disease with serum TSH concentration between 0.4 and 10 mIU/L and TPOAb negative. Data about clinical and demographic features were collected. A blood sample was drown to test TSH, TPOAb, ANA and ENA concentration. The mean uterine artery pulsatility index was measured. Risk of adverse obstetric and fetal outcomes was collected. RESULTS: The cohort included 2135 pregnant women. Pregnant women with TSH 4-10 mUI/L had a significantly higher frequency of family history of thyroid diseases, and personal history of celiac disease diseases, type 1 diabetes mellitus, rheumatic disease, antinuclear antibody (ANA) and anti-extractable nuclear antigen (ENA) positive tests. The risk for pre-eclampsia and small for gestational age (SGA) was significantly higher in pregnant women with first-trimester TSH 4-10 mIU/L. A first-trimester TSH serum level greater than 4 mIU/L was associated with a significant increase in the occurrence of abnormal uterine artery pulsatility index, with a more than threefold increase in the risk of developing pre-eclampsia and with the risk of SGA. CONCLUSIONS: In TPOAb-negative pregnant women, a first-trimester serum TSH level ranging from 4 to 10 mIU/L is significantly and independently linked to an increased uterine artery pulsatility index as well as to negative pregnancy outcomes such as pre-eclampsia, SGA and gestational diabetes.

The association between dietary selenium intake and Hashimoto's thyroiditis among US adults: National Health and Nutrition Examination Survey (NHANES), 2007-2012.

BACKGROUND: Selenium has been shown to influence the pathological processes and physiological functions of thyroid. Although growing evidence has shown that selenium can improve the treatment of Hashimoto's thyroiditis (HT), there is a need to evaluate the association between dietary selenium intake and HT in a large cross-sectional study. This study explored the association between dietary selenium intake and HT based on the National Health reand Nutrition Examination Survey (NHANES) database (2007-2012). METHODS: A total of 8756 of 30,442 participants were included in the study. Dietary selenium intake was the independent variable, while HT was the dependent variable. In addition, the relative importance of the selected variables was determined using the XGBoost model. A smooth curve was constructed based on the fully adjusted model to investigate the potential linear relationship between dietary selenium intake and HT. Smooth curves were also constructed to explore the linear/non-linear relationship between dietary selenium intake and thyroid peroxidase antibody (TPOAb)/ thyroglobulin antibody (TgAb). RESULTS: The mean age of the enrolled participants was 44.35 years (± 20.92). The risk of HT was significantly reduced by a 35% per-unit increase in dietary selenium intake after fully adjusting for covariates according to the model (log2-transformed data; OR 0.65; 95% CI 0.51, 0.83). The XGBoost model revealed that dietary selenium intake was the most important variable associated with Hashimoto's thyroiditis. Dietary selenium intake (Log2-transformed) was negatively correlated with TPOAb levels [- 16.42 (- 22.18, - 10.65), P < 0.0001], while a non-linear relationship was observed between dietary selenium intake and TgAb with an inflection point of 6.58 (95.67 µg, Log2-transformed). CONCLUSION: Dietary selenium intake is independently and inversely associated with HT risk. Moreover, dietary selenium intake is negatively correlated with TPOAb levels and non-linearly correlated with TGAb levels. Therefore, dietary selenium intake may be a safe and low-cost alternative for the prevention and treatment of HT.

TPOAb positivity can impact ovarian reserve, embryo quality, and IVF/ICSI outcomes in euthyroid infertile women.

The aim of this study was to investigate the effects of positive anti-thyroid peroxidase (TPO) antibodies on fertility, embryo quality, and pregnancy outcomes in women with normal thyroid function. A cross-sectional study of 1223 infertile women who received assisted reproductive technology (ART) treatment for the first time was conducted at our hospital from January 2019 to March 2022. Overall, 263 infertile women were included, comprising 263 cycles and 1813 embryos, and were divided into a positive group and a control group based on TPO antibody levels. The positive group was further divided into two subgroups according to the median antibody titer, and the therapeutic indices and pregnancy outcomes for each group were compared. The results showed that the AMH level in the positive group was significantly lower than that in the control group (2.37 (1.26-3.63) ng/ml vs. 3.54 (1.74-5.41) ng/ml, p < 0.001). The high-quality embryo rate (40.04% vs. 45.49%, p = 0.034) and live birth rate (23.26% vs. 36.16, p = 0.035) of the positive group were lower than those of the control group; the miscarriage rate was higher than that of the control group (37.50% vs. 17.95%, p = 0.035). The live birth rate in the low-titer group was significantly higher than that in the high-titer group (32.56% vs. 13.95%, p = 0.041). Studies have shown that positive anti-thyroid peroxidase antibodies are associated with a decreased ovarian reserve and decreased embryo quality. High titers of anti-thyroid peroxidase antibodies can reduce the live birth rate.

Fetal cardiac left ventricle functional changes in pregnancies with maternal hypothyroidism.

OBJECTIVES: To evaluate fetal cardiac function in cases with overt and subclinical hypothyroidism and to determine the effect of levothyroxine (LT4) treatment and Anti-thyroid peroxidase (Anti-TPO) antibody status on fetal cardiac functions in cases with subclinical hypothyroidism. METHODS: Within the scope of the study, fetuses of 23 overt hypothyroid, 52 subclinical hypothyroid and 250 control group pregnant women were evaluated. Fetal cardiac function was assessed via cardiac Doppler. RESULTS: Isovolumetric relaxation time (IRT) and myocardial performance index (MPI) values in the overt hypothyroid group were significantly higher than both the subclinical hypothyroid group (p: .006, p: .000, respectively) and the control group (p: .000, p: .000, respectively). In addition, both IRT and MPI were significantly higher in the subclinical hypothyroid group than in the control group (p: .000, p: .000, respectively). In the subclinical hypothyroid group, there was no significant difference in terms of cardiac function parameters in the fetuses of pregnant women who received LT4 therapy and those who did not. When pregnant women with subclinical hypothyroidism were evaluated according to their Anti-TPO antibody status, IRT and MPI values were found to be significantly higher in fetuses of Anti-TPO (+) pregnant women (respectively, p: .005, p: .019). CONCLUSION: In the presence of maternal overt or subclinical hypothyroidism, fetal cardiac functions may be affected as early as the second trimester. Anti-TPO antibody positivity in cases with subclinical hypothyroidism seems to negatively affect fetal cardiac functions.

Thyroid autoimmunity and future pregnancy outcome in women of recurrent pregnancy loss: a meta-analysis.

BACKGROUND: Thyroid autoimmunity (TAI) has been associated with the risk of recurrent pregnancy loss (RPL). This systematic review and meta-analysis was conducted to evaluate the influence of TAI on subsequent pregnancy outcome of women with RPL. METHODS: A systematic search of Medline, Web of Science, and Embase was conducted to identify studies evaluating the influence of TAI on subsequent risk of pregnancy loss (PL) in women with RPL. Study quality was evaluated via the Newcastle-Ottawa Scale. A random-effects model was utilized to pool the results, accounting for heterogeneity. RESULTS: Ten observational studies were included. Compared to women without thyroid autoantibodies, RPL women with TAI had a higher risk of PL in their subsequent pregnancy (risk ratio [RR]: 1.46. 95% confidence interval [CI]: 1.20 to 1.78, p < 0.001; I2 = 35%). Sensitivity analyses showed consistent results in studies with thyroid peroxidase antibody positivity (RR: 1.50, 95% CI: 1.23 to 1.82) and in studies with TAI assessed before pregnancy (RR: 1.28, 95% CI: 1.07 to 1.53). Subgroup analyses showed that the results were not significantly different in prospective and retrospective studies, in RPL defined as at least two or three PL, in euthyroid women and women with euthyroidism or subclinical hypothyroidism, in women with and without levothyroxine treatment, in studies reporting first-trimester or overall PL, and in studies with different quality scores (p for subgroup difference all > 0.05). CONCLUSIONS: In women with RPL, positive for TAI may be related to a higher risk of PL in subsequent pregnancy.

Correlation between serum beta-human chorionic gonadotropin levels and thyroid metabolic function in pregnant women with hyperemesis gravidarum.

As previously demonstrated, serum beta-human chorionic gonadotropin (ß-hCG) is linked to identifying early gestational abnormalities. This research was aimed at investigating the correlation between serum ß-hCG levels and thyroid metabolic function in pregnant women with hyperemesis gravidarum (HG). Ninety-one pregnant women with HG were selected as the study group and divided into early pregnancy (EP), mid-pregnancy (MP), and late pregnancy (LP) groups according to their gestational weeks, while 84 normal pregnant women were selected as the control group. Venous blood was collected from pregnant women in both groups and serum ß-hCG levels were measured by chemiluminescent immunoassay. The levels of free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), thyroid-stimulating hormone receptor antibody (TRAb), and thyroglobulin antibody (TgAb) were tested by chemiluminescent microparticle immunoassay. Visual analog scale (VAS) scores were utilized to assess the degree of HG. Pearson analysis was implemented to measure the correlations between serum ß-hCG levels and serum FT3, FT4, TSH, TPOAb, TRAb, TgAb, as well as VAS scores and the correlations between ß-hCG, FT3, FT4, TSH, TPOAb, TRAb, TgAb, as well as VAS scores and gestation period. The receiver operating characteristic (ROC) curve was plotted to analyze the diagnostic values of thyroid hormones, thyroid-related antibodies, and ß-hCG levels for HG. Versus those in the control group, ß-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores were higher and TSH levels were lower in the study group. Versus those in the EP group, ß-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores of pregnant women in the MP and LP groups were decreased, and TSH levels were increased. Serum ß-hCG levels of pregnant women with HG were positively correlated with FT3, FT4, TPOAb, TRAb, TgAb, and VAS scores and negatively correlated with TSH levels. Serum ß-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores of pregnant women with HG had a negative correlation with the gestation period, while TSH levels had a positive correlation with the gestation period. The ROC curve analysis showed that ß-hCG and thyroid function-related indicators were of high clinical values in the diagnosis of HG. Collectively, our article suggests that serum ß-hCG expression of pregnant women with HG is abnormally elevated and closely related to the degree of HG and hyperthyroidism. In addition, ß-hCG and thyroid function-related indicators have certain diagnostic efficacy for HG.

[Association of maternal isolated thyroid peroxidase antibody positive in the first trimester with fetal growth].

OBJECTIVE: To investigate the association of isolated thyroid peroxidase antibody (TPOAb) positive in the first trimester with fetal growth. METHODS: A total of 16 446 pregnant women were included in the birth cohort study, whose last menstrual period was between May 2016 and April 2019 and with singleton pregnancy. Maternal serum samples were collected when they firstly came for prenatal care in the first trimester. The pregnant women were consecutively seen and followed in the hospital and the information of pregnant women was extracted from the electronic medical information system. The pregnant women were divided into isolated TPOAb positive group (n=1 654) and euthyroid group (n=14 792). Three fetal ultrasound examinations were scheduled during the routine prenatal visits at the hospital and were performed by trained sonographers. All fetal growth indicators were quantified as gestational age- and gender- adjusted standard deviation score (Z-score) using the generalized additive models for location, scale and shape (GAMLSS). Fetal growth indicators included estimated fetal weight (EFW), abdominal circumference (AC), biparietal diameter (BPD), femur length (FL) and head circumference (HC). Fetal growth restriction (FGR) was defined as AC or EFW Z-score＜3rd centile based on clinical consensus. Generalized estimating equation (GEE) analysis was applied to assess the association of maternal isolated TPOAb positive with fetal growth. The generalized linear model was further used to analyze the association between isolated TPOAb positive and fetal growth indicator at different gestational ages when the fetal growth indicator was significantly associated with isolated TPOAb positive in the GEE mo-del. RESULTS: The median gestational age at three ultrasound measurements was 23.6 (23.3, 24.1), 30.3 (29.7, 30.9), 37.3 (37.0, 37.7) weeks, respectively. The BPD Z-score was higher in isolated TPOAb positive women, compared with the euthyroid pregnant women after adjustment (ß=0.057, 95%CI: 0.014-0.100, P=0.009). The generalized linear model showed the BPD Z-score was higher in the isolated TPOAb positive women at the end of 21-25 weeks (ß=0.052, 95%CI: 0.001-0.103, P=0.044), 29-32 weeks (ß=0.055, 95%CI: 0.004-0.107, P=0.035) and 36-40 weeks (ß=0.068, 95%CI: 0.011-0.125, P=0.020), compared with the euthyroid pregnant women. There was no difference in other fetal growth indicators (EFW, AC, FL and HC) and FGR between the isolated TPOAb positive and euthyroid pregnant women. CONCLUSION: The BPD Z-score was slightly increased in the isolated TPOAb positive pregnant women in the first trimester, while other fetal growth indicators were not changed. The reproducibility and practical significance of this result need to be confirmed.

Association between serum levels of TSH and free T4 and per- and polyfluoroalkyl compounds concentrations in pregnant women.

Many per- and polyfluoralkyl substances (PFASs) may disrupt maternal thyroid hormone homeostasis in pregnancy. Concerns should be raised regarding the PFASs exposure in pregnant women because thyroid hormones are involved in the early development of the fetus. In this study, we measured the concentrations of 13 PFASs, including five novel short-chain PFASs, in serum from 123 pregnant women in Beijing, China. Linear regression models were used to investigate the association between thyroid-stimulating hormone (TSH) or free thyroxine (FT4) levels and PFASs concentrations under consideration of the impacts of pregnancy-induced physiological factors. We found that perfluorobutanoic acid (PFBA) (ß=0.189, 95%CI=-0.039, 0.417, p=0.10) and perfluorodecanoic acid (PFDA) (ß=-0.554, 95%CI=-1.16, 0.049, p=0.071) were suggestive of significant association with TSH in thyroid peroxidase antibody (TPOAb) negative women. No association was observed between all PFASs and FT4 levels after controlling for these confounding factors, such as BMI, gestational weight gain and maternal age. These findings suggest that it should pay more attention to the association between thyroid hormone levels and short-chain PFASs concentrations. Future studies could consider a greater sample and the inclusion of other clinical indicators of thyroid function, such as free T3 and total T3.

Association between thyroid autoimmunity and the decline of ovarian reserve in euthyroid women.

RESEARCH QUESTION: Is thyroid autoimmunity (TAI) associated with the decline of ovarian reserve in euthyroid women? DESIGN: Case-control study. Data from 4302 euthyroid women with normal ovarian reserve (NOR) and low ovarian reserve (LOR), including biochemical premature ovarian insufficiency (POI) and overt POI, were retrospectively analysed. The prevalence and effect of TAI on ovarian reserve was evaluated between women with NOR and LOR. Status of ovarian insufficiency and TSH levels was further stratified for analysis. The correlation between anti-thyroid peroxidase antibody (TPOAb), anti-thyroglobulin antibody (TgAb) titres and ovarian reserve markers was also determined. RESULTS: The prevalence of positive TAI and TgAb was equally distributed between women with NOR and LOR (P = 0.080, P = 0.172); the prevalence of TPOAb positivity was higher in the LOR group (P = 0.005). After stratifying ovarian reserve and TSH, positive TAI, TPOAb and TGAb were significantly associated with overt POI when TSH was >2.5 µIU/ml (all P < 0.001); no association was observed with biochemical POI or overt POI when TSH was ≤2.5 µIU/ml. No correlation was found between TPOAb, TGAb titres and AMH (P = 0.218, P = 0.368, respectively), and bilateral AFC (P = 0.184, P = 0.315, respectively) in patients with LOR; only TPOAb titre was positively correlated with FSH (P = 0.039). CONCLUSIONS: Among the whole population of euthyroid women, TAI was not associated with low ovarian reserve but was significantly associated with overt POI in women with TSH>2.5 µIU/ml. Further basic studies on underlying mechanisms are needed.

Associations between thyroid function and gestational diabetes mellitus in Chinese pregnant women: a retrospective cohort study.

BACKGROUND: Thyroid function is known to be closely linked with type 2 diabetes, but data on the association between thyroid function and gestational diabetes mellitus (GDM) are inconsistent. METHODS: A total of 2849 pregnant women were included in this retrospective study. Serum concentrations of thyroid indicators (free tetraiodothyronine, FT4; thyroid-stimulating hormone, TSH; and thyroid peroxidase antibody, TPO Ab) were obtained from a clinical laboratory. The presence of GDM were drawn from medical records. The clinical subtypes of thyroid function (euthyroidism, subclinical hypothyroidism, hyperthyroidism, and isolated hypothyroxinemia) were categorized according to the thresholds of the 2.5th/97.5th and 10th/90th percentiles of TSH and FT4 concentrations. A concentration of > 34 IU/L was defined as indicating TPO Ab-positivity. RESULTS: Two hundred and thirty-five (8.25%) of the 2849 women were TPO Ab-positive. Higher serum concentrations of FT4 (top vs. bottom tertiles) was found to be negatively associated with the risk of GDM. The corresponding odds (OR) values (top tertile vs. bottom tertile) were 0.71 [95% confidence interval (CI): 0.54, 0.93]. No significant associations were observed between the extremely 2.5th/97.5th or 10th/90th percentiles of FT4 concentration, TSH concentration, thyroid function subtypes (vs. euthyroidism), TPO Ab-positivity (vs. -negativity), and the GDM risk. The corresponding results remained similar when TPO Ab-positive subjects were excluded. CONCLUSIONS: A negative association with the risk of GDM was observed for the highest FT4 concentrations tertile. No significant associations were found between the TSH concentration, thyroid function subtypes, TPO Ab positivity, and the GDM risk.

Dynamics of gut microbiota during pregnancy in women with TPOAb-positive subclinical hypothyroidism: a prospective cohort study.

BACKGROUND: Anti-thyroid peroxidase antibody (TPOAb) positivity can contribute to inhibit thyroxine synthesis. Gut microbiota can interact with metabolic or immune diseases. However, dynamics of gut microbiota from the second (T2) to the third trimester (T3) in women with TPOAb-positive/negative subclinical hypothyroidism (TPOAb+/TPOAb- SCH) have not been reported. Therefore, we aimed to evaluate whether gut microbiota can be potential therapeutic targets for managing TPOAb+ SCH. METHODS: In this single-center prospective cohort study, we observed gut microbiota dynamics by sequencing 16S rRNA from fecal samples collected in T2 (20-23+ 6 weeks) and T3 (28-33+ 6 weeks). TPOAb+/TPOAb- SCH were stratified depending on whether or not they used levothyroxine (LT4) during the pregnancy (LT4+/LT4-). Microbiome bioinformatics analyses were performed using QIIME2. The linear discriminant analysis effect size (LEfSe) was used for the quantitative analysis of biomarkers. Functional profiling was performed with PICRUSt2. RESULTS: Distinct gut microbiota dynamics from T2 to T3 were noted in the TPOAb- (n = 68) and TPOAb+ (n = 64) SCH groups. The TPOAb+ LT4- group was characterized by enriched bacterial amplicon sequence variants (ASVs) of Prevotella in T2 and Bacteria, Lachnospirales, Lachnospiraceae, Blautia, and Agathobacter in T3 and by depleted ASVs of Gammaproteobacteria, Enterobacterales, and Enterobacteriaceae in T2 and Actinobacteriota, Coriobacteriia, Actinobacteria, Coriobacteriales, Bifidobacteriales, Bifidobacteriaceae, Bifidobacterium, Dorea formicigenerans, and Bifidobacterium longum in T3. The TPOAb+ LT4+ group was characterized by enriched bacterial ASVs of Blautia, Streptococcus salivarius, and Bifidobacterium longum in T3 and by depleted ASVs of Bacteroidota, Bacteroidia, Bacteroidales, and Prevotella in T2 and Agathobacter in T3. Moreover, we identified 53 kinds of metabolic functions that were mainly involved in sugar, lipid, and amino acid metabolism. CONCLUSIONS: Our results indicated that low dynamics of gut microbiota composition and high dynamics of its metabolic function from T2 to T3 were associated with TPOAb+ SCH. We concluded that gut microbiota could be new targets for treatment of TPOAb+ SCH during pregnancy. TRIAL REGISTRATION: This study was retrospectively registered at the Chinese Clinical Trial Registry (registration number ChiCTR2100047175 ) on June 10, 2021.

Effect of occupational cadmium exposure on the thyroid gland and associated inflammatory markers among workers of the electroplating industry.

Cadmium (Cd) is widespread throughout the environment and is used in the electroplating industry. It has been found to have an effect on the endocrine system. However, its effects and their underlying mechanisms are still not clear. The aim of this study was to evaluate how cadmium exposure at work affected the levels of thyroid hormones and the associated inflammatory and oxidative markers. This study was conducted in an electroplating industry in Cairo, Egypt. Ninety male cadmium-exposed workers were matched with 90 male unexposed participants. A detailed questionnaire was designed and given to every participant in the study, and full clinical examinations were carried out. Blood samples were collected from all participants for determination of levels of serum cadmium, thyroid hormones, anti-thyroid peroxidase antibody (anti-TPO), interleukin-6 (IL-6), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-α). Morning midstream urine samples were obtained to measure urine cadmium levels. Results showed that the total blood and urinary cadmium levels were significantly higher in the exposed group (2.38 ± 0.94 µg/L and 5.45 ± 1.92 µg/g creatinine, respectively) than in the unexposed group. The serum levels of anti-TPO antibody, TSH, MDA, IL-6, and TNF-α also were significantly higher in the cadmium-exposed group than in the unexposed group. Significant direct relationships were seen between the biological indices of cadmium exposure and anti-TPO antibodies, TSH, IL-6, TNF-α, and MDA. It was concluded that there is a link between occupational cadmium exposure and autoimmune hypothyroidism, inflammatory, and oxidative stress markers.

[Expression of thyroglobulin antibody and thyroid peroxidase antibody in children with immune thrombocytopenia]. / ç”²çŠ¶è ºçƒè›‹ç™½æŠ—ä½“å’Œç”²çŠ¶è ºè¿‡æ°§åŒ–ç‰©é ¶æŠ—ä½“åœ¨å„¿ç«¥å ç–«æ€§è¡€å°æ¿å‡å°‘ç—‡ä¸­çš„è¡¨è¾¾åŠä¸´åºŠæ„ä¹‰.

OBJECTIVES: To examine the expression of serum thyroglobulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb) in children with immune thrombocytopenia (ITP). METHODS: A total of 120 children with ITP who were admitted from October 2019 to October 2021 were enrolled as the ITP group. A total of 60 children without ITP were enrolled as the non-ITP group. According to the clinical classification of ITP, the children in the ITP group were further divided into a newly diagnosed ITP group, a persistent ITP group, and a chronic ITP group. The clinical data were compared between the ITP group and the non-ITP group and between the children with different clinical classifications of ITP. The expression levels of serum TGAb and TPOAb in children with ITP were measured and their association with the clinical classification of ITP was analyzed. RESULTS: Compared with the non-ITP group, the ITP group had significantly lower levels of CD3+, CD4+, and platelet count (PLT) and significantly higher levels of CD8+, TGAb, and TPOAb (P<0.05). The children with chronic ITP had significantly lower levels of CD3+, CD4+, and PLT and significantly higher levels of CD8+, TGAb, and TPOAb than those with newly diagnosed ITP or persistent ITP (P<0.05). The logistic regression analysis showed that CD3+, CD4+, CD8+, TGAb, and TPOAb were the influencing factors for chronic ITP (P<0.05). A decision curve was plotted, and the results showed that TGAb combined with TPOAb within the high-risk threshold range of 0.0-1.0 had a net benefit rate of >0 in evaluating the clinical classification of ITP in children. CONCLUSIONS: TGAb and TPOAb are abnormally expressed in children with ITP and are associated with the clinical classification of ITP in children.

Autoimmune thyroid disease in children with diabetes and adolescents: A single center study from south Punjab.

OBJECTIVE: To evaluate the prevalence of autoimmune thyroid disease in children with diabetes. METHODS: The descriptive cross-sectional study was conducted from January to December 2019 at the Children Hospital and the Institute of Child Health, Multan, Pakistan, and comprised paediatric type 1 diabetes mellitus patients of both genders. Blood samples were obtained for detailed testing of thyroid functions tests. Data was analysed using SPSS 20. RESULTS: Of the 161 paediatric subjects, 83(51.6%) were boys. The overall mean age was 9.7±4.3 years. Thyroid peroxidase antibody was positive in 34(21.1%) patients and thyroglobulin antibody in 27(16.7%). Both antibodies were positive in 17(10.5%) patients. Six (3.7%) patients had evidence of subclinical hypothyroidism, 8(4.9%) had overt hypothyroidism and 1(0.62%) had hyperthyroidism. CONCLUSIONS: The prevalence of autoimmune thyroid disease among children and adolescents with type 1 diabetes mellitus was 21%, with hypothyroidism being more prevalent compared to hyperthyroidism.

What is the impact of thyroidectomy on autoimmune features associated with Hashimoto's thyroiditis?-Institutional experience.

BACKGROUND: Hashimoto's thyroiditis (HT) is one of the commonest endocrine disorders, globally. Often, HT presents a protean range of associated autoimmune features (AAI) such as vitiligo, rheumatoid arthritis, pernicious anemia, skin allergy/atopy, thrombocytopenia, Addison's disease, type 1 diabetes, celiac disease, eosinophilia, etc., The usual treatment of HT is symptomatic with no curative option. In this context, we report our experience on the impact of surgical thyroidectomy on remission of AAI in HT. AIMS: To report our experience on the impact of surgical thyroidectomy on remission of AAI in patients with HT. MATERIAL AND METHODS: This is a retrospective study conducted in the Endocrine Surgery department of a tertiary care hospital. A total of 61 patients with HT and various AAI combinations were included in this study. All the clinicoinvestigative and operative data were systematically analyzed. The most frequent indication for surgery was nodular goiter followed by associated malignancy, persistent goiter, and painful thyroiditis. Others were cosmetic/pressure symptoms and not AAI per se. The mean follow-up after surgery was 55.6 ± 11.8 months. RESULTS: The gender ratio was 5.8:1 in favor of women and the mean age was 41.5 ± 5.4 years. The mean preoperative and postoperative serum anti-thyroperoxidase antibody (Anti-TPO Ab) levels were 339 ± 98.2 and 58.75 ± 25 IU/L at the last follow-up visit. A total of 60% AAI manifestations had resolution or significant alleviation. The major improvements in AAI were skin allergy, eosinophilia, rheumatoid arthritis, vitiligo, thrombocytopenia, celiac disease symptomatic episodes; but, type 1 diabetes and Addison's disease showed static response. CONCLUSIONS: Surgical total thyroidectomy and anti-TPO Ab-related autoimmunity appear to play a beneficial role and definitive role in the remission of AAI in HT.

Anti-thyroid peroxidase antibody and thyroid cysts among the general Japanese population: a cross-sectional study.

BACKGROUND: Anti-thyroid peroxidase antibody (TPO-Ab) has been shown to cause autoimmune thyroiditis by inducing a deleterious influence on thyroid hormone synthesis. Further, thyroglobulin, which has an important role in thyroid hormone synthesis, is reported to be high in the fluid from thyroid cysts. Therefore, TPO-Ab could be associated with the presence of thyroid cyst, partly by affecting the activity of thyroid hormone synthesis. METHODS: To investigate the association between TPO-Ab and thyroid cysts, we conducted a cross-sectional study of 1432 Japanese with normal thyroid function [i.e., normal range of free triiodothyronine (free T3) and free thyroxine (free T4)] between the ages of 40 and 74 years, who participated in an annual health check-up. RESULTS: In men, the statistical power did not reach a statistical significance value. Additionally, subjects with TPO-Ab showed lower odds ratios (ORs) of thyroid cysts than those without TPO-Ab. In women, subjects with TPO-Ab showed significantly lower ORs of thyroid cysts than those without TPO-Ab. The fully adjusted ORs were 0.68 (0.40, 1.18) for men and 0.40 (0.27, 0.60) for women. When evaluating the association between logarithmic values of TPO-Ab titer and thyroid cysts in both men and women, a notable inverse correlation was observed. The fully adjusted ORs were 0.68 (0.50, 0.92) for men and 0.68 (0.57, 0.81) for women. CONCLUSION: TPO-Ab titer revealed to be inversely associated with thyroid cysts among Japanese with normal thyroid function. The presence of a thyroid cyst could indicate a lower risk of having TPO-Ab among the general population with normal thyroid function.