Presence Of Thyroid Autoimmunity Research Articles

Exploring the bidirectional relationship between metabolic syndrome and thyroid autoimmunity: a Mendelian randomization study.

Observational studies have reported a possible association between metabolic syndrome (MetS) and thyroid autoimmunity. Nevertheless, the relationship between thyroid autoimmunity and MetS remains unclear. The objective of this research was to assess the causal impact of MetS on thyroid autoimmunity through the utilization of Mendelian randomization (MR) methodology. We performed bidirectional MR to elucidate the causal relationship between MetS and their components and thyroid autoimmunity (positivity of TPOAb). Single nucleotide polymorphisms (SNPs) of MetS and its components were obtained from the publicly available genetic variation summary database. The Thyroidomics Consortium conducted a genome-wide association analysis, which provided summary-level data pertaining to thyroid autoimmunity. The study included several statistical methods, including the inverse variance weighting method (IVW), weighted median, simple mode, weight mode, and MR-Egger methods, to assess the causal link. In addition, to ensure the stability of the results, a sensitivity analysis was conducted. IVW showed that MetS reduced the risk of developing thyroid autoimmunity (OR = 0.717, 95% CI = 0.584 - 0.88, P = 1.48E-03). The investigation into the causative association between components of MetS and thyroid autoimmune revealed a statistically significant link between triglycerides levels and the presence of thyroid autoimmunity (IVW analysis, OR = 0.603, 95%CI = 0.45 -0.807, P = 6.82E-04). The reverse analysis did not reveal any causal relationship between thyroid autoimmunity and MetS, including its five components. We have presented new genetic evidence demonstrating that MetS and its triglyceride components may serve as potential protective factors against thyroid autoimmunity.

Thyroid autoimmunity and autoimmune thyroid disease in Malaysian girls with Turner syndrome: An understudied population.

Knowledge on the spectrum of thyroid disorders amongst Turner syndrome (TS) patients in Southeast Asia is limited. This study aimed to evaluate the prevalence of thyroid autoimmunity, the spectrum of autoimmune thyroid disease and association with age and karyotype amongst Malaysian TS girls. A cross-sectional study was conducted at 11 paediatric endocrine units in Malaysia. Blood samples for antithyroglobulin antibodies, antithyroid peroxidase antibodies and thyroid function test were obtained. In patients with pre-existing thyroid disease, information on clinical and biochemical thyroid status was obtained from medical records. Ninety-seven TS patients with a mean age of 13.4 ± 4.8 years were recruited. Thyroid autoimmunity was found in 43.8% of TS patients. Nineteen per cent of those with thyroid autoimmunity had autoimmune thyroid disease (Hashimoto thyroiditis in 7.3% and hyperthyroidism in 1% of total population). Patients with isochromosome X and patients with 45,X mosaicism or other X chromosomal abnormalities were more prone to have thyroid autoimmunity compared to those with 45,X karyotype (OR 5.09, 95% CI 1.54-16.88, P = 0.008 and OR 3.41, 95% CI 1.32-8.82, P = 0.01 respectively). The prevalence of thyroid autoimmunity increased with age (33.3% for age 0-9.9 years; 46.8% for age 10-19.9 years and 57.1% age for 20-29.9 years) with autoimmune thyroid disease detected in 14.3% during adulthood. Thyroid autoimmunity was significantly associated with the non 45,X karyotype group, particularly isochromosome X. Annual screening of thyroid function should be carried out upon diagnosis of TS until adulthood with more frequent monitoring recommended in the presence of thyroid autoimmunity.

Impact of preconception thyrotrophin on obstetric outcomes in the fertile population

IntroductionThere is evidence that subclinical hypothyroidism is associated with infertility, miscarriage and obstetric complications. However, there is controversy regarding the optimal TSH value in women seeking pregnancy.Current guidelines recommend that hypothyroid women with levothyroxine replacement who are planning pregnancy should optimise the dose of levothyroxine to achieve thyrotrophin (TSH) levels <2.5 mU/l, since these requirements increase in pregnancy, thus reducing the risk of TSH elevation during the first trimester.In women with infertility, who undergo highly complex treatments and have positive thyroid autoimmunity, values of TSH <2.5 mU/l prior to fertility treatment are suggested.Although this is a different population, these «optimal» TSH levels were also extended to euthyroid women without evidence of infertility, who are seeking pregnancy. ObjectivesDetermine whether preconception TSH levels between 2.5 and 4.64 mIU/l are associated with adverse obstetric outcomes in euthyroid women. Materials and methodsRetrospective cohort study. We evaluated 3265 medical records of pregnant women aged 18–40 years, euthyroid (TSH 0.5–4.64 mU/ml), with TSH measurement at least one year before gestation. 1779 met inclusion criteria. The population was divided according to categories: TSH 0.5–2.4 mU/l (optimal) and TSH 2.5–4.6 mU/l (suboptimal). Information on maternal and fetal obstetric outcomes was collected from each group. ResultsWe found no statistical difference in the occurrence of adverse obstetric events between the two groups. There was also no difference when adjusting for thyroid autoimmunity, age, body mass index, previous diabetes and previous arterial hypertension. ConclusionOur results suggest that the reference range of TSH used in the general population could be used in women seeking pregnancy, even in the presence of thyroid autoimmunity. Treatment with levothyroxine should be considered only in patients with special situations.

Impacto de la tirotrofina preconcepcional en los resultados obstétricos en población fértil

IntroductionThere is evidence that subclinical hypothyroidism is associated with infertility, miscarriage and obstetric complications. However, there is controversy regarding the optimal TSH value in women seeking pregnancy.Current guidelines recommend that hypothyroid women with levothyroxine replacement who are planning pregnancy should optimise the dose of levothyroxine to achieve thyrotrophin (TSH) levels < 2.5 mU/L, since these requirements increase in pregnancy, thus reducing the risk of TSH elevation during the first trimester.In women with infertility, who undergo highly complex treatments and have positive thyroid autoimmunity, values of TSH < 2.5 mU/L prior to fertility treatment are suggested.Although this is a different population, these «optimal» TSH levels were also extended to euthyroid women without evidence of infertility, who are seeking pregnancy. ObjectivesDetermine whether preconception TSH levels between 2.5 and 4.64 mIU/L are associated with adverse obstetric outcomes in euthyroid women. Materials and methodsRetrospective cohort study. We evaluated 3,265 medical records of pregnant women aged 18 to 40 years, euthyroid (TSH 0.5-4.64 mU/ml), with TSH measurement at least one year before gestation. 1,779 met inclusion criteria. The population was divided according to categories: TSH 0.5- 2.4 mU/L (optimal) and TSH 2.5-4.6 mU/L (suboptimal). Information on maternal and fetal obstetric outcomes was collected from each group. ResultsWe found no statistical difference in the occurrence of adverse obstetric events between the two groups. There was also no difference when adjusting for thyroid autoimmunity, age, body mass index, previous diabetes and previous arterial hypertension. ConclusionOur results suggest that the reference range of TSH used in the general population could be used in women seeking pregnancy, even in the presence of thyroid autoimmunity. Treatment with levothyroxine should be considered only in patients with special situations.

Impact of Thyroid Autoimmunity on Assisted Reproductive Technology Outcomes and Ovarian Reserve Markers: An Updated Systematic Review and Meta-Analysis

Background: Thyroid autoimmunity (TAI) has a high prevalence among women of reproductive age. Investigating its possible impact on ovarian function and fertility is, thus, of utmost relevance. The aim of this systematic review and meta-analysis was to elucidate the effect of TAI on both assisted reproductive technology (ART) outcomes and ovarian reserve. Methods: This systematic review and meta-analysis was restricted to two groups of research articles investigating the association between TAI and: (1) autologous ART outcomes (i.e., fertilization rate [FR], implantation rate, clinical pregnancy rate [CPR], miscarriage rate, and live birth rate), (2) markers of ovarian reserve (i.e., anti-Müllerian hormone, basal follicle stimulating hormone, antral follicle count, and number of oocytes retrieved). Studies including women affected by overt hypo/hyperthyroidism were excluded. Relevant studies were identified by a systematic search in PubMed, MEDLINE, ClinicalTrials.gov, Embase, and Scopus, from database inception to May 1, 2022. Results: From a total of 432 identified publications, 22 studies were included in Group 1 and 26 studies in Group 2. The presence of TAI was associated with a higher risk of miscarriage (7606 participants, odds ratio [OR] 1.52, confidence interval [CI 1.14-2.01], p = 0.004, I2 = 53%), lower chance of embryo implantation (7118 participants, OR 0.72, [CI 0.59-0.88], p = 0.001, I2 = 36%), and live birth (11417 participants, OR 0.73, [CI 0.56-0.94], p = 0.02, I2 = 71%). These associations were no longer observed in a subgroup analysis of patients who exclusively underwent intracytoplasmic sperm injection (ICSI). The FR and CPR as well as the mean values of surrogate markers of oocyte quantity appeared not to be affected by TAI. Conclusions: This data synthesis suggest a higher risk of adverse ART outcomes in women with positive TAI. However, the reliability of these findings is hampered by the relatively low quality of the evidence and significant heterogeneity in many of the meta-analyses. The possible protective effect of ICSI is promising but should be confirmed in controlled prospective clinical trials. PROSPERO Registration ID: CRD42021236529.

Association between thyroid autoimmunity and gestational diabetes mellitus in euthyroid women.

ObjectivePregnant women with autoimmune (subclinical) hypothyroidism have an increased risk of developing gestational diabetes mellitus (GDM). However, this association remains controversial in euthyroid women with thyroid autoimmunity (TAI). Therefore, the aim of the study was to determine the association between TAI and GDM in euthyroid women in a logistic regression analysis with adjustments for baseline/demographic parameters.MethodsCross-sectional study in 1447 euthyroid women who performed their entire clinical/biological workup and oral glucose tolerance test (OGTT) in our center. At median 13 (11–17) weeks of gestation, thyroid-stimulating hormone, free T4, and thyroid peroxidase antibodies (TPOAb) were measured, baseline characteristics were recorded, and an OGTT was performed between 24 and 28 weeks of pregnancy. Exclusion criteria were pre-pregnancy diabetes, assisted pregnancies, and women with (treated) thyroid dysfunction before or after screening. The diagnosis of GDM was based on 2013 World Health Organization criteria, and TAI was defined as TPOAb levels ≥60 kIU/L.ResultsTwo hundred eighty women were diagnosed with GDM (19.4%), 26.1% in women with TAI, and 18.9% in women without TAI (P = 0.096). In the logistic regression analysis, TAI was associated with GDM in women older than 30 years (adjusted odds ratio 1.68 (95% CI, 1.01–2.78); P = 0.048). Maternal age >30 years, pre-pregnancy BMI ≥30 kg/m2, and other than Caucasian background were also associated with GDM; aOR 1.93 (95% CI, 1.46–2.56); P < 0.001, 2.03 (95% CI, 1.46–2.81); P < 0.001 and 1.46 (95% CI, 1.03–2.06); P = 0.034, respectively.ConclusionsIn older pregnant women, the presence of TAI in euthyroid women was associated with GDM. In line with the literature data, (higher) age and BMI were strongly associated with GDM. Future investigations should focus on treatments that might prevent the development of GDM in euthyroid women with TAI.

More Live Births in Primary Subfertile Intracytoplasmic Sperm Injection-Treated Women with High Normal TSH Levels

Objectives: The aim of this study was to analyze the fertility outcome in intracytoplasmic sperm injection (ICSI)-treated women across normal range thyroid-stimulating hormone (TSH) levels. Published results are inconclusive about optimal TSH levels and fertility. Design: This is a retrospective cohort study in 752 ICSI-treated women with predominantly severe male factor subfertility, starting treatment between the first of January 2008 and the first of March 2012 with a follow-up until 2014. Participants/Materials, Setting, Methods: Women aged 22–45 years with TSH 0.3–4.5 mIU/L without thyroid hormone substitution were included in Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands, an iodine-sufficient area. Demographic and baseline characteristics were compared between groups of patients based on TSH, using one-way ANOVA, Kruskal-Wallis ANOVA, and χ² test. The patient was the unit of analysis: all cumulative cycles per patient were analyzed up to and including the first ongoing pregnancy. The primary outcome was a cumulative live birth rate. Clinical pregnancy rate, pregnancy loss, and ongoing pregnancy rate were secondary outcomes. The χ² test and logistic regression were used to compare interquartile groups while adjusting for confounders. Logistic regression was used with the natural logarithm of TSH as a continuous predictor. Primary and secondary subfertile women were analyzed separately. Results: Analysis of the total cohort (n = 752) showed no difference in fertility outcomes across the normal TSH range. The cumulative live birth rate for the 4 groups of primary subfertile women (n = 455) was 76% in the upper TSH quartile compared to 56%, 60%, and 59% in the lower TSH quartiles. Limitations: Levels of thyroxine and presence of thyroid autoimmunity were not measured in this retrospective cohort study. Conclusions: The observation that a higher live birth rate was found in primary subfertile ICSI-treated women with high but allegedly normal TSH levels contributes to the hypothesis that in certain subfertile women in addition to a male factor, female factors such as subtle hypothyroidism and/or thyroid autoimmunity may play a role in keeping them from conception, which can be overcome by the process of ICSI.

Impact of Thyroid Autoimmunity on In Vitro Fertilization/Intracytoplasmic Sperm Injection Outcomes and Fetal Weight.

Several studies have reported the association between thyroid autoimmunity (TAI) and in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcomes. However, the findings remain controversial. We performed a large-scale retrospective cohort study to verify the effect of the presence of thyroid antibodies on IVF/ICSI outcomes and fetal growth and to evaluate the association between the types and titers of thyroid antibodies and adverse IVF/ICSI outcomes. A total of 16481 patients with infertility were referred to the Reproductive Center of Peking University Third Hospital for their first IVF/ICSI treatment between January 2018 and June 2019.Patients who sought IVF/ICSI treatment due to tubal or male factors infertility and who achieved fresh embryo transfer were included in our study. Finally, 778 patients with thyroid antibody positivity were selected as the TAI group, and 778 age-matched patients were included in the control group. The number of oocytes retrieved and high-graded embryos and the rates of clinical pregnancy, miscarriage, live birth, and preterm delivery were compared between the TAI and control groups. In addition, subgroup analysis was performed to demonstrate whether different types and titers of thyroid antibodies had different effects on IVF/ICSI outcomes. After adjusting for thyroid function, anti-Müllerian hormone levels, basal follicle stimulating hormone levels, basal estradiol levels and antral follicle count, the number of oocytes retrieved in the TAI group was significantly lower than that in the control group. No significant differences were observed between the two groups in the rates of clinical pregnancy, miscarriage, preterm delivery, live birth, and birth weight in singletons; however, the birth weight in twin pregnancy was significantly lower in the TAI group than in the control group. Subgroup analysis showed no association between the types or titers of thyroid antibodies and adverse IVF/ICSI outcomes. In conclusion, the presence of TAI in patients with infertility did not impair embryo quality or affect pregnancy outcomes, including clinical pregnancy, miscarriage, preterm delivery, and live birth. However, it decreased the number of oocytes retrieved and birth weight in twin pregnancy.

The prevalence of thyroid autoantibodies in autoimmune connective tissue diseases: a systematic review and meta-analysis

ABSTRACT Aim Patients with autoimmune connective tissue disease (ACTD) may have anti-thyroid peroxidase antibody (TPOAb) and anti-thyroglobulin antibody (TgAb). This study aimed to compare the prevalence of thyroid autoantibodies in ACTD patients and controls. Methods All case-control studies published between 1980 and 2019 in English were searched from Medline, Embase, Web of Science, PubMed databases for meta-analysis and subgroup analyses. Results Total 10,321 ACTD cases and 12,949 healthy controls were included, and the prevalence of thyroid autoantibody positivity was higher in ACTD patients than in controls. Subgroup analysis revealed positive association between TgAb and ACTD in populations from all continents including European, Asian, African, and American. In addition, we found positive association between TgAb positivity and most ACTD cases including RA, SLE, pSS, and UCTD, positive association between TPOAb positivity and all ACTD cases including RA, SLE, pSS, SSc, and UCTD, and positive association between TPOAb positivity and ACTD in European, Asian, and African but not in American populations. Conclusion Thyroid autoantibodies are more prevalent in ACTD patients than in healthy controls. It is important to screen patients with ACTD for the presence of thyroid autoimmunity, and perform thyroid function tests in clinical evaluation of ACTD patients.

Valores de referencia de hormonas tiroideas en la población de gestantes en Lugo

Background and objectiveThe complex physiology of thyroid function during pregnancy requires a hormonal evaluation according to reference values for each trimester, each area, and with the techniques of each laboratory. The objectives of this study were to analyse thyroid function in the three trimesters of pregnancy and to establish the reference values of hormones in pregnant women in this health area (Lugo). MethodsA total of 831 pregnant women were included in the study (median age: 33years, age range: 16-47years). Once the exclusion criteria were applied, the sample consisted of 641 pregnant women, a size that can be considered representative of the reference population. ResultsThe reference intervals were as follows: TSH first trimester, 0.10-3.74mIU/L; second trimester, 0.45-3.77mIU/L; and third trimester, 0.36-4.15mIU/L. For Free T4 in the first trimester, 0.87-1.34ng/dL; second trimester, 0.78-1.20ng/dL; and third trimester, 0.78-1.23ng/dL. For Free T3 in the first trimester, 2.52-3.78pg/mL; second trimester, 2.22-3.21pg/mL; and third trimester, 2.17-3.14pg/mL. The presence of thyroid autoimmunity was confirmed in 109 women (13.1%), who presented with higher TSH values than pregnant women without thyroid autoimmunity. ConclusionThe reference intervals for TSH, Free T4, and Free T3 obtained in this study are below those used in the non-pregnant adult population in this laboratory. This should help to identify more accurately a possible thyroid dysfunction in pregnant women in the study area, avoiding an underdiagnosis of subclinical hypothyroidism and reducing the possible associated perinatal complications.

Subclinical hypothyroidism in childhood, treatment or only follow-up?

BackgroundSubclinical hypothyroidism (SH) is defined as serum levels of thyroid-stimulating hormone (TSH) above the upper limit with normal concentrations of free T4 (fT4). Its management remains challenging. The aim of the study was to evaluate clinical and laboratory findings as well as the clinical course of children with SH followed in a third level hospital. Sixty-five patients aged between 2 and 18 years old were retrospectively studied.MethodsThe patients were followed for a median period of 9 months (range 6 months to 24 months). Those who normalized TSH levels were discharged (Group 1). If TSH persisted mildly elevated (5-10μUI/mL) with normal fT4 and negative TPOAb/TgAb, they were classified as Group 2 and followed semi-annually without treatment. Those patients whose TSH raised ≥10μUI/mL or who maintained TSH 5-10μUI/mL and positive TPOAb/TgAb were considered suitable for thyroxin therapy (Group 3, G3).ResultsIn 89% of our patients, TSH concentrations spontaneously reverted to normality or remained stable without treatment (Groups 1 and 2), whereas less than 11% progressed to clinical hypothyroidism (Group 3). Baseline TSH was significantly lower in group 1 than in group 3. In group 3 the prevalence of female sex (71%) was higher and TPO antibodies were present in 85% of patients. The risk of developing overt hypothyroidism in patients with positive anti-thyroid antibodies respect to those who normalized TSH was 45 (95%CI 6.5–312.5).ConclusionBaseline TSH, female sex and the presence of thyroid autoimmunity were the best predictors of the evolution to SH over time.

Higher TSH Is Not Associated With Thyroid Cancer Risk in the Presence of Thyroid Autoimmunity.

Higher-but-within-normal thyrotropin (thyroid-stimulating hormone, TSH) is associated with higher risk for differentiated thyroid cancer (DTC) in surgical series. Our recent clinical observations suggest that this is not the case in the presence of autoimmune thyroid disease (AITD). We designed the present study to clarify this controversy. We analyzed our prospectively collected database of patients referred for thyroid surgery at 2 tertiary care referral centers in Greece and the United States. We collected data for preoperative TSH, postoperative pathology, and thyroid peroxidase (TPO) antibodies titers. Subjects were subdivided into 2 groups, those with AITD (i.e., lymphocytic thyroiditis) and non-AITD. We excluded subjects with Graves disease, abnormal TSH (< 0.40 or > 4.50 mIU/mL), or recent use of levothyroxine. We compared the serum TSH among different groups using the Mann-Whitney test. A total of 3973 subjects were screened; 1357 met exclusion criteria. After all exclusions, data from 1731 non-AITD subjects and 329 AITD subjects were included in the analysis. AITD subjects had higher TSH than non-AITD subjects (2.09 vs 1.48; P < 0.0001). TSH values were higher in DTC compared with benign histology only in non-AITD subjects (1.65 vs 1.40; P < 0.0001). Progressively higher TSH was associated with higher incidence of DTC only in non-AITD subjects (P < 0.0001). In AITD subjects, TSH was similar between groups with or without DTC (2.02 vs 2.14; P = 0.21). TSH concentrations are not associated with the risk of developing DTC in the presence of thyroid autoimmunity, even though this seems to be the case for all other patients.

Interaction effect of obesity and thyroid autoimmunity on the prevalence of hyperthyrotropinaemia.

The role of thyroid autoimmunity in the association between obesity and hyperthyrotropinaemia remains unclear. We aimed to assess the relationship between obesity, autoimmunity, and hyperthyrotropinaemia. In this population-based cross-sectional study, 12531 Chinese individuals (18-80 years) with thyroid function test were categorized into three groups by body mass index (BMI) and were categorized into three layers by thyroid autoantibodies. Multivariate logistic regression was employed to assess the correlation and interaction effect. There was no significant difference in prevalence of hyperthyrotropinaemia (P = 0.637) among three BMI groups. After stratification, the difference of serum thyrotropin (P < 0.01) and prevalence of hyperthyrotropinaemia (P < 0.01) between the three groups have significant linear trends at the positive levels of thyroid peroxidase antibody (TPOAb) or/and thyroglobulin antibody (TgAb). When TPOAb and TgAb were positive, the risk of hyperthyrotropinaemia increased 1.857-fold in overweight group and 2.201-fold in obese group compared with normal group. Compared with negative TPOAb and TgAb, the risk of hyperthyrotropinaemia for individuals with two positive antibodies increased 3.310-fold, 4.969-fold, and 5.122-fold in the three BMI groups. The adjusted OR (95% CI) for interaction were 1.033 (0.752-1.419) for overweight and one positive antibodies, 1.935 (1.252-2.990) for overweight and two positive antibodies, 1.435 (0.978-2.105) for obesity and one positive antibodies and 2.191 (1.252-3.832) for obesity and two positive antibodies. Overweight and obesity were associated with hyperthyrotropinaemia only in presence of thyroid autoimmunity, and obesity might aggravate the pathogenic effect of autoimmunity on hyperthyrotropinaemia. There was an interaction effect between obesity and autoimmunity on the prevalence of hyperthyrotropinaemia.

Short-Term Weight Changes in Treated Primary Hypothyroid Subjects

Weight loss due to diuresis is an early clinical response of treatment with levothyroxine in primary hypothyroidism. The objective of this study was to evaluate weight changes in patients with primary hypothyroidism after 6 weeks of initiation of treatment with levothyroxine. This prospective observational follow up study included 99 newly diagnosed primary hypothyroid patients of 18-60 years of age of both sexes. The weight and height of each patient were measured and body mass index (BMI) was calculated both at the time of enrollment and at the end of 6 weeks of treatment with levothyroxine, and variables at the baseline and at follow up were compared. 93 patients out of 99 completed follow-up at 6±1 weeks. There were significant reduction in TSH level (85.1±51.6 vs. 1.87±0.9 µIU/mL, mean±SD) and increase in FT4 level (0.49±0.19 vs. 1.4±0.78 ng/dL, mean±SD) at follow up in comparison to their baseline values. Among the participants, 90.3% lost body weight while 5.4% gained weight and 4.3% of subjects didn’t show any change in their weight at the end of the study. The mean body weight and mean BMI after levothyroxine replacement were significantly lower (weight 62.2±13.7 vs. 59.0±12.1 kg, BMI 25.1±4.6 vs. 23.8±4.1 Kg/M2, mean±SD) than the pretreatment values. The mean changes in body weight and BMI were 3.19±0.32 Kg (mean±SEM) and 1.31±0.14 Kg/M2 (mean±SEM) respectively. The mean changes in body weight and BMI did not differ significantly among subjects with different TSH categories. No statistically significant effect of any individual predictors like age, gender, and socioeconomic status, weight at baseline, baseline TSH, baseline FT4 and presence of thyroid autoimmunity was observed on weight change. Levothyroxine replacement was associated with a significant reduction of mean body weight and BMI at short-term follow up in our study, though not all patients experienced weight loss.

Breg Cells in Celiac Disease Isolated or Associated to Hashimoto's Thyroiditis.

Hashimoto's thyroiditis (HT) may occur associated with celiac disease (CD). Regulatory B cells (Breg) subsets have been shown to play a significant role in autoimmune processes. Therefore, we have characterized their distribution in the peripheral blood obtained from 10 patients with isolated HT, 10 patients with HT + CD, 9 patients with isolated CD, and 9 healthy donors (HD). Th17 cells were significantly increased in patients with HT and in patients bearing both HT and CD, while patients with isolated CD exhibited a lower percentage of Th17, as compared with healthy donors. CD24hiCD38hi Breg cells were significantly higher in patients with HT + CD and in patients with isolated CD as compared to both HD patients and patients with isolated HT (p = 0.0010). On the contrary, Breg memory phenotypes (CD24hiCD38− and CD24hiCD27+) significantly decreased in patients with HT + CD as compared with the isolated disorders. Following CpG oligodeoxynucleotide stimulation, IL-10+ CD24hiCD38hi Breg cells were similar in all groups of patients, despite these cells would have been higher in CD patients. In conclusion, celiac disease, isolated and even more when associated with HT, determines a peculiar behavior of Breg cells which are increased in number but possibly functionally defective. Furthermore, the association CD + HT was characterized by a reduction of Breg memory subsets as compared with the isolated disorders. The behavior of Th17 subset in patients with celiac disease associated with HT might have been sensitive to the effect of long-lasting GFD, and it is essentially determined by the presence of thyroid autoimmunity.

Mild subclinical hypothyroidism is associated with paediatric dyslipidaemia.

There is a lack of consensus on the cardiometabolic consequences of mild subclinical hypothyroidism (SCH) among children. The objective of the current study was to compare lipid profiles in children with mild SCH with those of euthyroid children. Retrospective medical record review. Children (ages 2-18years) who had undergone simultaneous measurement of TSH, free thyroxine (T4) and lipids. Lipids in children with mild SCH (TSH 5-<10 mIU/L and normal free T4, n=228) were compared with those in euthyroid children (n=1215). TSH level was positively associated with total cholesterol and nonhigh density lipoprotein (non-HDL) cholesterol [β 0.05(0.03-0.08), P<.0001 and β 0.05(0.03-0.08), P<.0001, respectively]. Total cholesterol was significantly higher in children and adolescents with mild SCH compared with euthyroid children (4.43±1.14mmol/L vs 4.2±0.85mmol/L, P=.0005). Similarly, non-HDL cholesterol level was also higher in children with mild SCH relative to euthyroid children (3.08±1.14mmol/L vs 2.91±0.8mmol/L, P=.001). The adjusted odds ratio of having elevated total cholesterol and elevated non-HDL cholesterol was greater in children with mild SCH compared with euthyroid children (OR 1.88, 95% CI; 1.28-2.73; P=.001 and 1.72, 95% CI 1.2-2.5; P=.003, respectively). The presence of thyroid autoimmunity was not associated with higher rates of dyslipidaemia. Mild SCH in children and adolescents was associated with higher rates of elevated total cholesterol and elevated non-HDL cholesterol. Randomized placebo controlled studies are warranted to determine if treatment of mild SCH in children leads to improvement in lipid profile.

Insulin resistance is associated with larger thyroid volume in adults with type 1 diabetes independently from presence of thyroid autoimmunity

To investigate the effect of insulin resistance (IR) on thyroid function, thyroid autoimmunity (AIT) and thyroid volume in type 1 diabetes (T1DM). 100 consecutive patients with T1DM aged 29 (±6) years with diabetes duration 13 (±6) years were included. Exclusion criteria were: history of thyroid disease, current treatment with L-thyroxin or anti-thyroid drugs. Evaluation of thyroid stimulating hormone (TSH), free thyroid hormones and anti-thyroid antibodies was performed. Thyroid volume was measured by ultrasonography. IR was assessed using the estimated glucose disposal rate (eGDR) formula. In the study group 22% of subjects had insulin resistance defined as eGDR lower or equal to 7.5 mg/kg/min. The prevalence of thyroid autoimmunity (positivity for ATPO or ATg or TRAb) in the study group was 37%. There were no significant differences in the concentration of TSH, FT3, FT4, the prevalence of AIT and hypothyroidism between IR and insulin sensitive (IS) group. Mean (±SD) thyroid volume was 15.6 (±6.2) mL in patients with IR and 11.7 (±4.7) mL in IS subjects (p = .002). Thyroid volume correlated inversely with eGDR (r = –0.35, p < .001). In a multivariate linear regression model the association between thyroid volume and eGDR was independent of sex, age, duration of diabetes, daily insulin dose, BMI, cigarette smoking, TSH value and presence of thyroid autoimmunity (beta: –0.29, p = .012). Insulin resisance is associated with larger thyroid volume in patients with type 1 diabetes independently of sex, body mass index, TSH value and presence of autoimmune thyroid disease.

Systemic Lupus Erythematosus and Thyroid Autoimmunity.

Most of the studies present in the literature show a high prevalence, and incidence, of new cases of hypothyroidism and autoimmune thyroiditis (AT) in systemic lupus erythematosus (SLE) patients, overall in female gender. A limited number of cases of Graves’ disease have been also reported in SLE patients, in agreement with the higher prevalence of thyroid autoimmunity. It has been also demonstrated that a Th1 predominance is associated with AT in SLE patients. Furthermore, a higher prevalence of papillary thyroid cancer has been recently reported in SLE, in particular in the presence of thyroid autoimmunity. However, studies in larger number of SLE patients are needed to confirm findings about thyroid cancer. On the whole, data from literature strongly suggest that female SLE patients, with a high risk (a normal but at the higher limit thyroid-stimulating hormone value, positive antithyroid peroxidase antibodies, a hypoechoic pattern, and small thyroid), should undergo periodic thyroid function follow-up, and appropriate treatments when needed. A careful thyroid monitoring would be opportune during the follow-up of these patients.

CD4+ FOXP3+ Regulatory T Cells Exhibit Impaired Ability to Suppress Effector T Cell Proliferation in Patients with Turner Syndrome.

ObjectiveWe investigated whether the frequency, phenotype, and suppressive function of CD4+FOXP3+ regulatory T cells (Tregs) are altered in young TS patients with the 45,X karyotype compared to age-matched controls.Design and MethodsPeripheral blood mononuclear cells from young TS patients (n = 24, 17.4–35.9 years) and healthy controls (n = 16) were stained with various Treg markers to characterize their phenotypes. Based on the presence of thyroid autoimmunity, patients were categorized into TS (–) (n = 7) and TS (+) (n = 17). Tregs sorted for CD4+CD25bright were co-cultured with autologous CD4+CD25− target cells in the presence of anti-CD3 and -CD28 antibodies to assess their suppressive function.ResultsDespite a lower frequency of CD4+ T cells in the TS (-) and TS (+) patients (mean 30.8% and 31.7%, vs. 41.2%; P = 0.003 and P < 0.001, respectively), both groups exhibited a higher frequency of FOXP3+ Tregs among CD4+ T cells compared with controls (means 1.99% and 2.05%, vs. 1.33%; P = 0.029 and P = 0.004, respectively). There were no differences in the expression of CTLA-4 and the frequency of Tregs expressing CXCR3+, and CCR4+CCR6+ among the three groups. However, the ability of Tregs to suppress the in vitro proliferation of autologous CD4+CD25− T cells was significantly impaired in the TS (–) and TS (+) patients compared to controls (P = 0.003 and P = 0.041). Meanwhile, both the TS (–) and TS (+) groups had lower frequencies of naïve cells (P = 0.001 for both) but higher frequencies of effector memory cells (P = 0.004 and P = 0.002) than did the healthy control group.ConclusionsThe Tregs of the TS patients could not efficiently suppress the proliferation of autologous effector T cells, despite their increased frequency in peripheral CD4+ T cells.

Peripheral blood natural killer cells and mild thyroid abnormalities in women with reproductive failure.

Abnormalities in peripheral blood natural killer (NK) cells have been reported in women with primary infertility and recurrent spontaneous abortion (RSA) and several studies have been presented to define cutoff values for abnormal peripheral blood NK cell levels in this context. Elevated levels of NK cells were observed in infertile/RSA women in the presence of thyroid autoimmunity (TAI), while no studies have been carried out, to date, on NK cells in infertile/RSA women with non-autoimmune thyroid diseases. The contribution of this study is two-fold: (1) the evaluation of peripheral blood NK cell levels in a cohort of infertile/RSA women, in order to confirm related data from the literature; and (2) the assessment of NK cell levels in the presence of both TAI and subclinical hypothyroidism (SCH) in order to explore the possibility that the association between NK cells and thyroid function is not only restricted to TAI but also to SCH. In a retrospective study, 259 age-matched women (primary infertility [n = 49], primary RSA [n = 145], and secondary RSA [n = 65]) were evaluated for CD56+CD16+NK cells by flow cytometry. Women were stratified according to thyroid status: TAI, SCH, and without thyroid diseases (ET). Fertile women (n = 45) were used as controls. Infertile/RSA women showed higher mean NK cell levels than controls. The cutoff value determining the abnormal NK cell levels resulted ⩾15% in all the groups of women. Among the infertile/RSA women, SCH resulted the most frequently associated thyroid disorder while no difference resulted in the prevalence of TAI and ET women between patients and controls. A higher prevalence of women with NK cell levels ⩾15% was observed in infertile/RSA women with SCH when compared to TAI/ET women. According to our data, NK cell assessment could be used as a diagnostic tool in women with reproductive failure and we suggest that the possible association between NK cell levels and thyroid function can be described not only in the presence of TAI but also in the presence of non-autoimmune thyroid disorders.