Positive Thyroid Peroxidase Antibodies Research Articles

Impact of Abdominal Obesity on Thyroid Auto-Antibody Positivity: Abdominal Obesity Can Enhance the Risk of Thyroid Autoimmunity in Men.

Background The interrelation between obesity and autoimmune thyroid diseases is complex and has not been confirmed. The aim of the present study was to observe the relationship between thyroid autoimmunity and obesity, especially abdominal obesity, in a large population. Methods A total of 2253 residents who had lived in Xinjiang for more than 3 years were enrolled. Serum thyroid hormone concentration, thyroid autoantibodies, lipid parameters, Weight, height, and waist and hip circumference were measured. Results The prevalence of thyroid peroxidase antibody (TPOAb) and/or thyroglobulin antibody (TgAb) positive was 32.1% (21.2% in men and 37% in women, P < 0.01). Compared with women, men had significantly higher TG levels, waist circumference, and hip circumference levels (P < 0.01), while women showed higher TSH, TPOAb, and TgAb levels (P < 0.01). The prevalence of overweight and obesity was 71.1% in men and 63.5% in women. Men had a higher prevalence of abdominal obesity than women (56.6% in men and 47.6% in women, P < 0.01). TPOAb correlates positively with waist circumference (r = 0.100, P < 0.05) in men. Binary logistic analysis showed that TPOAb positivity had increased risks of abdominal obesity in men, and the OR was 1.1044 (95% CI 1.035, 1.151, P < 0.05). Conclusion Our results indicate that men had higher lipid levels, thicker waist circumference, and higher prevalence of overweight, obesity, and abdominal obesity. Abdominal obesity is a risk factor for TPOAb positivity in men, suggesting that abdominal obesity can enhance the risk of thyroid autoimmunity in men.

Thyroid Peroxidase Antibody (TPO) as a Predictor of Radiation Induced Thyroid Dysfunction Among Nurses and Technicians Working in Mansoura Specialized Medical Hospital: Cross Sectional Study

Thyroid gland is a probable goal tissue for radiation-related injury. Occupational exposure to ionizing radiation leads to thyroid dysfunction and exposure to high dose may lead to thyroid carcinoma. Evaluation of the role of Thyroid peroxidase antibody as a predictor for thyroid dysfunction among nurses and technicians in the radiology department in Mansoura Specialized Medical hospital (MSMH). Subjects were Nurses and technicians who are working in (MSMH) with persistent daily duty in the last 3 years and fulfilling the inclusion and exclusion criteria. All subjects included in the study were recruited in one month and divided into two groups; Group 1: 50 subjects who were working in radiology, coronary angiography and ERCP unit, Radiation -exposed group. Group 2: 33 subjects who were working in In-patient departments and in out- patient clinics and not exposed to any type of radiation. Non fasting blood sample was taken from all enrolled subjects for measurement of TSH and Anti-TPO. TPO was positively and significantly correlated to age, TSH, duration of radiology/ y (r=0.388, 0.364, 0.342respectively) p value <0.05. Roc curve was done to detect the sensitivity and specificity of TSH in relation to TPO that revealed the cutoff value of TSH > 1.69 with Sensitivity and Specificity. PPV, NPV and accuracy at cutoff >1.69 were 70.6%, 51.5%, 42.8%, 77.3% and 58%. Working personnel with positive anti TPO and their TSH levels are more than 1.69 associated with symptoms of hypothyroidism, a trial of treatment is mandatory to relieve symptoms.

Maternal urinary bisphenol A concentration and thyroid hormone levels of Chinese mothers and newborns by maternal body mass index.

Animal studies indicated that bisphenol A (BPA) exposure during pregnancy may disrupt thyroid function which is critical for fetal development. However, few epidemiological studies have examined this topic and the results were inconsistent. We aimed to evaluate whether prenatal BPA exposure is associated with thyroid hormone levels in Chinese mothers and newborns with stratification by maternal body mass index (BMI). BPA concentration were measured in urine samples collected from 555 women at late pregnancy. Maternal serum free thyroxin (FT4), thyroid-stimulating hormone (TSH) and thyroid peroxidase antibody (TPO-Ab) concentrations at the third trimester were abstracted from medical records. Cord serum-free triiodothyronine (FT3), FT4, TSH, and TPO-Ab levels were measured in 398 newborns. Prenatal urinary BPA was detected in 98.5% of mothers with a geometric mean of 1.32ng/mL (95% CI 1.17-1.49ng/mL). With each 10-fold increase in BPA concentrations, maternal log10_(TSH) mIU/L was 0.10 lowered (95% CI - 0.20, - 0.005, p < 0.05) among pre-pregnancy BMI>23kg/m2, with adjustment for maternal age, maternal education, gestation diabetes mellitus (GDM), husband smoking during pregnancy, parity, and gestational age at thyroid parameters measured, but no association was observed in pre-pregnancy BMI < 18.5, or 18.5-22.9kg/m2 stratum. No BPA-associated changes were observed in maternal FT4 level or odds of positive TPO-Ab in all BMI stratum. Also, no associations were observed between prenatal urinary BPA concentration and cord serum FT4, FT3, TSH levels, and odds of positive TPO-Ab in both male and female newborns among pre-pregnancy BMI < 18.5, 18.5-22.9 or>23kg/m2 stratum. In this study, prenatal urinary BPA concentration was associated with lower maternal TSH among women with overweight, but not associated with other maternal thyroid parameters or cord serum thyroid parameters across maternal BMI categories. More research on pregnant women and newborns cohort with BPA exposure are warranted.

The impact of positive thyroid peroxidase antibody in patients with unexplained recurrent miscarriage

BackgroundMiscarriage is considered the most common adverse outcome in early pregnancy. Thyroid auto antibodies are involved in both these areas and are associated with major alterations in the course of pregnancy affecting the mother, the fetus, and the neonate.MethodsThe present study included 140 women who were already diagnosed with recurrent miscarriage. Following complete clinical workup, including history, examination and investigations, enrolled women were classified into two main subgroups, explained group (<italic>n</italic> = 85) and unexplained group (<italic>n</italic> = 55). Then they were classified according to Thyroid peroxidase antibody: positively group (n=28) and negatively group (n=112) and then they are treated with thyroxine and follow up for 14 weeks.ResultsRecurrent miscarriage rate increased in women with positive anti-phospholipids where Women with only Anti-APS antibody positive results accounted for 72 (51.4%). Where the remaining represent the other causes such as bicornuate uterus and thyroid abnormality. Thyroid peroxidase antibody represent important cause of abortion, in addition successful pregnancy was encountered in 26 out of 28 women treated with low doses thyroxin accounting for 92.9% successful rate; however, there was no significant difference in successful pregnancy rate between explained and unexplained groups, 9 (81.8%) versus 17 (100.0%), respectively.Women with positive thyroid peroxidase antibody can be mean cause of pregnant loss and treatment with thyroxine can lead to increasing the live-birth rate in recurrent miscarriage women with positive thyroid peroxidase antibody.

Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: A Systematic Review and Meta-analysis

(Abstracted from JAMA 2019;322(7):632–641) Preterm birth complicates 5% to 15% of births worldwide, and although it is the most important direct cause of morbidity and mortality in children younger than 5 years, no known risk factors can be identified in the majority of cases. However, overt hypothyroidism and hyperthyroidism during pregnancy are well-known risk factors for preterm birth, and as such, the purpose of this study was to assess whether thyroid function test abnormalities and thyroid peroxidase (TPO) antibody positivity were associated with preterm birth.

The influence of thyroid autoimmunity on pregnancy outcome in infertile women: a prospective study.

Thyroid dysfunction and thyroid autoimmunity (TAI) have been reported to be linked to infertility, pregnancy loss and preterm birth. Infertile women undergoing assisted reproductive technology are recommended to maintain thyroid stimulating hormone (TSH) levels below 2.5 μIU/mL. It is unclear, however, whether levothyroxine (L-T4) treatment decreases the effects of TAI on fertility and pregnancy outcome in infertile women. We therefore aimed to clarify the influence of TAI on pregnancy undergoing L-T4 treatment for hypothyroidism. Prospectively recruited to this study were the 595 infertile women who visited the Utsunomiya Ladies Clinic between January 2013 and December 2015. Five patients with Graves' disease were excluded. Clinical profiles of 590 women were as follows: proportion of SCH = 19.6%, thyroid peroxidase antibody (TPOAb) positivity = 10.4%, and thyroglobulin antibody (TgAb) positivity = 15.1%. Fertility was not affected by any thyroid-associated factors. Regarding pregnancy outcomes, TPOAb titers were significantly higher in women who had miscarriage than in those progressed to delivery (46.4 ± 114.1 vs. 18.9 ± 54.6 IU/mL, p = 0.039), notably in those undergoing intrauterine insemination (p = 0.046) and in vitro fertilization (p = 0.023). Multivariate logistic regression analysis revealed that higher age (odds ratio 26.4, p < 0.001) and higher TPOAb titer (odds ratio 11.8, p = 0.043) were risk factors for miscarriage. Higher TPOAb titer should be considered as one of the risk factors for miscarriage in infertile women, even if they have been treated with L-T4 for hypothyroidism.

Assessment of subclinical hypothyroidism for a clinical score and thyroid peroxidase antibody: a comparison with euthyroidism grouped by different thyroid-stimulating hormone levels

Abstract Background Subclinical hypothyroidism (SCH) might have many symptoms of hypothyroidism. The controversy appears to lower the level of thyroid-stimulating hormone (TSH) and group subjects with TSH of more than 3 or even 2.5 mIU/L as SCH subjects. Objectives To assess SCH subjects both clinically using Zulewski clinical score and biochemically and to evaluate whether the euthyroid subjects with high-normal TSH (HNT) have any clinical symptom or subnormal biochemical finding. Methods A prospective cross-sectional study of 233 subjects, 67 with SCH and 166 euthyroidism, was conducted. Euthyroid subjects were divided according to the level of TSH as HNT (&gt;2.5 mIU/L) and low-normal TSH (0.5–2.5 mIU/L). The subjects were examined for clinical feature including Zulewski clinical score and biochemical evaluations including thyroid peroxidase antibody (TPO-Ab) titer. The comparisons between groups were assessed using independent sample t test, and correlations between variables were evaluated using Pearson correlation. Results A significantly higher clinical score and higher frequencies of symptoms were found in the SCH group compared to the euthyroid group. The most frequent symptom was fatigue. Euthyroid subjects with HNT were found to have higher TPO-Ab titers than those with low-normal TSH, P &lt; 0.05. The Zulewski clinical score was positively correlated with TSH and TPO-Ab titer but negatively correlated with the FT4 level, P &lt; 0.05. Conclusions Zulewski clinical score is higher in SCH subjects compared to euthyroid subjects and can aid in assessing SCH subjects. A significant correlation exists between Zulewski clinical score and each of the TSH, FT4, and TPO-Ab titer levels. The frequency of TPO-Ab positivity is high in SCH. Additionally, euthyroid with higher TSH levels has higher level of TPO-Ab titer but not higher clinical score.

An Evaluation of the Results of the Steroid and Non-steroidal Anti-inflammatory Drug Treatments in Subacute Thyroiditis in relation to Persistent Hypothyroidism and Recurrence

Subacute thyroiditis (SAT) is an inflammatory thyroid disease. The main purpose of the treatment is to relieve pain and control the inflammatory process. The aim of the present study was to evaluate the therapeutic effects of steroid and non-steroidal anti-inflammatory drugs (NSAIDs) in SAT. Initial laboratory data, treatment response, and long-term results of 295 SAT patients treated with ibuprofen or methylprednisolone were evaluated. After the exclusion of 78 patients, evaluation was made of 126 patients treated with 1800 mg ibuprofen and 91 patients treated with 48 mg methylprednisolone. In 59.5% of 126 patients treated with ibuprofen, there was no adequate clinical response at the first control visit. In 54% of patients, the treatment was changed to steroids in mean 9.5 days. Symptomatic remission was achieved within two weeks in all patients treated with methylprednisolone. The total recurrence rate was 19.8%, and recurrences were observed more frequently in patients receiving only steroid therapy than in patients treated with NSAID only (23% vs. 10.5% p:0.04). Persistent hypothyroidism developed in 22.8% of patients treated only with ibuprofen and in 6.6% of patients treated with methylprednisolone only. Treatment with only ibuprofen (p:0.039) and positive thyroid peroxidase antibody (anti-TPO) (p:0.029) were determined as the main risk factors for permanent hypothyroidism. NSAID treatment is not as effective as steroid treatment in early clinical remission. Steroid treatment was detected as a protective factor against permanent hypothyroidism. Therefore, steroid therapy may be considered especially in anti-TPO positive SAT patients and patients with high-level acute phase reactants.

The Impact of Obesity on Thyroid Autoimmunity and Dysfunction: A Systematic Review and Meta-Analysis

Background: To help inform decision making in the clinical setting, we carried out a systematic review and meta-analysis to estimate the association of thyroid disease risks with obesity.Methods: Pubmed, Embase, Web of Science, Cochrane database and Google Scholar electronic databases were searched from inception to October 31, 2018 without language restrictions to explore the relationship between thyroid disorders and obesity. The relative risk (RR) or odds risk (OR) for thyroid disorders were pooled using the SPSS and STATA software.Results: A total of 22 studies were included in the study. (1) Meta-analysis showed that obesity was significantly associated with an increased risk of hypothyroidism (RR = 1.86, 95% CI 1.63–2.11, P < 0.001). Meta-analyses after stratification further showed that obese population had increased risks of overt hypothyroidism (RR = 3.21, 95% CI 2.12–4.86, P < 0.001) and subclinical hypothyroidism (RR = 1.70, 95% CI 1.42–2.03, P < 0.001). (2) Further meta-analysis also showed obesity was clearly associated with Hashimoto's thyroiditis (RR = 1.91, 95% CI 1.10–3.32, P = 0.022), but not with Graves' disease. (3) In the meta-analysis of antibodies, obesity was correlated with positive thyroid peroxidase antibody (TPOAb) (RR = 1.93, 95% CI 1.31–2.85, P = 0.001), but not with positive thyroglobulin antibody (TGAb).Conclusions: Obesity was significantly related to hypothyroidism, HT, and TPOAb, implying that prevention of obesity is crucial for thyroid disorders.Systematic Review Registration: PROSPERO: CRD42018096897.

Thyroid Peroxidase Antibodies and Prospective Live Birth Rate: A Cohort Study of Women with Recurrent Pregnancy Loss.

Background: Thyroid autoimmunity has been associated with pregnancy loss. Suggested mechanisms include thyroid function aberrations or an underlying breach of immunotolerance. We hypothesized that thyroid autoimmunity is a marker of the latter in women with recurrent pregnancy loss. This study investigated thyroid peroxidase antibody (TPOAb) status as a predictor of live birth in women with unexplained recurrent pregnancy loss. Methods: Cohort study of 825 consecutive women with recurrent pregnancy loss followed at the tertiary referral center for Recurrent Pregnancy Loss, Copenhagen University Hospital (Rigshospitalet), from 2011 to 2017. Recurrent pregnancy loss was defined as ≥3 consecutive losses, and as unexplained by absence of antiphospholipid syndrome, parental chromosome abnormality, or uterus malformation. Upon first visit, all women were screened for thyrotropin (TSH) and TPOAbs (TPOAb positivity: ≥60 kIU/L). Adjusted logistic regression analyses included as covariates the following: maternal age, TSH, previous number of losses, body mass index, smoking, pregnancy achieved by assisted reproductive technology, and thyroxine replacement (T4) treatment. Results: We included 825 women with a total of 3246 previous losses, of whom 139 (16.8%) were TPOAb positive. TPOAb positivity was not associated with the previous number of losses (p = 0.41). Women with unexplained recurrent pregnancy loss had a live birth rate in the first pregnancy after referral of 62.8% (285 of 454). TPOAb positivity was found in 78 of 454 (17.2%) women and was associated with a reduced live birth rate (51.3% vs. 65.2%, p = 0.02, adjusted odds ratio [aOR] 0.2 [0.1-0.6] p = 0.001). Treatment with T4 increased live birth rate significantly (aOR 3.7 [1.4-9.8], p = 0.007), and TPOAb-positive women receiving T4 had a live birth rate similar to that of TPOAb-negative women not receiving T4 (p = 0.70). Only 30% of TPOAb-positive women and 39% of women treated with T4 during pregnancy had known thyroid disease at referral. Conclusion: In a large cohort of women with unexplained recurrent pregnancy loss, TPOAb positivity was predictive of a reduced live birth rate. However, T4 treatment improved odds of live birth. The study supports screening for TPOAbs as a risk factor in women with unexplained recurrent pregnancy loss. The beneficial effect of T4 treatment in this high-risk group needs confirmation by randomized controlled trials. Close collaboration between fertility experts and endocrinologists is paramount.

Maternal prenatal thyroid function and trajectories of offspring emotional and behavioural problems: findings from the ALSPAC cohort.

Maternal thyroid hormone may have impact on fetal brain development and consequently lead to offspring mental health problems. This study examined the roleof maternal prenatal thyroid function on trajectories of offspring emotional and behavioural problems. Data were taken from the Avon Longitudinal Study of Parents and Children. A total of 4839 mother-child pairs were included. Thyroid-stimulating hormone (TSH) levels, free thyroxine (FT4), and thyroid peroxidase antibodies (TPO-Ab) were assessed during the first trimester of pregnancy. Childhood emotional and behavioural problems were assessed using the Strengths and difficulties questionnaire. A group-based modelling approach was used to identify the different trajectories of offspring emotional and behavioural problems reported by parents over four waves of measurement at age 3.5 (42months), 6.75 (81months), 9 and 11years. Multinomial logistic regression was then used to test for an association between hormone levels and class membership. We identified four trajectories of offspring emotional and behavioural problems; normative-decreasing (49.7%), moderate-decreasing (35.7%), moderate-static (8.4%), and high-decreasing (6.2%) trajectory. There were no significant differences in the mean values of mother's FT4, TSH, and the proportion of mothers with positive TPO-Ab between trajectories. Univariable and multivariable multinomial logistic models showed no association between maternal thyroid function (FT4, TSH, and TPO-Ab) and the trajectories of offspring emotional and behavioural problems. The results of our study show that maternal thyroid parameters in a community population are not associated with trajectories of offspring emotional and behavioural problems.

Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth

Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth. To study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth. Studies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT4] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded. The primary authors provided individual participant data that were analyzed using mixed-effects models. The primary outcome was preterm birth (<37 weeks' gestational age). From 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47 045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1%) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT4 concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT4 concentration with normal thyrotropin concentration), and 3043 (7.5%) were TPO antibody positive; 2357 (5.0%) had a preterm birth. The risk of preterm birth was higher for women with subclinical hypothyroidism than euthyroid women (6.1% vs 5.0%, respectively; absolute risk difference, 1.4% [95% CI, 0%-3.2%]; odds ratio [OR], 1.29 [95% CI, 1.01-1.64]). Among women with isolated hypothyroxinemia, the risk of preterm birth was 7.1% vs 5.0% in euthyroid women (absolute risk difference, 2.3% [95% CI, 0.6%-4.5%]; OR, 1.46 [95% CI, 1.12-1.90]). In continuous analyses, each 1-SD higher maternal thyrotropin concentration was associated with a higher risk of preterm birth (absolute risk difference, 0.2% [95% CI, 0%-0.4%] per 1 SD; OR, 1.04 [95% CI, 1.00-1.09] per 1 SD). Thyroid peroxidase antibody-positive women had a higher risk of preterm birth vs TPO antibody-negative women (6.6% vs 4.9%, respectively; absolute risk difference, 1.6% [95% CI, 0.7%-2.8%]; OR, 1.33 [95% CI, 1.15-1.56]). Among pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth. These results provide insights toward optimizing clinical decision-making strategies that should consider the potential harms and benefits of screening programs and levothyroxine treatment during pregnancy.

Maternal TSH levels at first trimester and subsequent spontaneous miscarriage: a nested case-control study.

Thyroid dysfunction is a frequently found endocrine disorder among reproductively aged women. Subclinical hypothyroidism is the most common condition of thyroid disorders during pregnancy and is defined as manifesting a thyroid-stimulating hormone concentration exceeding the trimester-specific reference value, with a normal free thyroxine concentration. Here, we evaluated the prospective association between spontaneous miscarriage and first-trimester thyroid function. We conducted a case–control study (421 cases and 1684 controls) that was nested. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), thyroid-peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) status were measured. We found that higher TSH was related to spontaneous miscarriage (OR 1.21; 95% CI, 1.13–1.30, P < 0.001). Compared with women with TSH levels of 0.4–<2.5 mIU/L, the risk of miscarriage was increased in women with TSH levels of 2.5–<4.87 mIU/L (OR 1.47; 95% CI, 1.16–1.87) and TSH greater than 4.87 mIU/L (OR 1.97; 95% CI, 1.22–3.18). After controlling for the confounding factor, TPOAb positivity status and FT4, the results were similar. The present study showed that higher TSH was associated with miscarriage in early pregnancy. In fact, TSH levels between 2.5 and 4.87 mIU/L increased the risk for miscarriage, with TSH greater than 4.87 mIU/L increasing the risk even further.

Association between iodine intake and thyroid autoantibodies: a cross-sectional study of 7073 early pregnant women in an iodine-adequate region.

The association between iodine intake and thyroid autoimmunity has been debated, especially in pregnant women. This study aimed to investigate thyroid autoantibodies and their association with iodine intake and hypothyroidism in early pregnancy. 7073 early pregnant women from an iodine-sufficient region participated in this study. Urinary iodine concentrations (UICs) were measured using an ammonium persulfate method. Serum thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), thyroid-stimulating hormone (TSH), free thyroxine (FT4), and Tg were determined using an electrochemiluminescence immunoassay. Iodine deficiency (UIC < 100μg/L) was associated with higher risks of TPOAb positivity [adjusted odds ratio (aOR) = 1.64, 95% confidence interval [CI] (1.29-2.08)] and TgAb positivity [aOR = 1.44, 95% CI (1.16-1.80)]. Women with isolated TPOAb positivity, isolated TgAb positivity, or both TPOAb and TgAb positivity had a 14.64-fold, 7.83-fold, and 44.69-fold increased risk of overt hypothyroidism, and a 4.36-fold, 2.86-fold, and 6.26-fold increased risk of subclinical hypothyroidism, respectively. Moreover, the risks of overt and subclinical hypothyroidism in women with a high TPOAb titer were 16.99 and 4.80 times that in TPOAb-negative women, respectively. The risk of overt hypothyroidism in women with a high TgAb titer was 6.97 times that in TgAb-negative women. Our work demonstrates that iodine deficiency during early pregnancy is an independent risk factor for both TPOAb positivity and TgAb positivity. Furthermore, positivity for both autoantibodies and a high thyroid autoantibody titer are associated with significantly higher risks of overt and subclinical hypothyroidism.

Maternal thyroid function during pregnancy and child brain morphology: a time window-specific analysis of a prospective cohort

Adequate thyroid hormone availability during pregnancy is necessary for optimal fetal brain development. During the first 18-20 weeks of gestation, fetal thyroid hormone availability largely depends on the placental transfer of maternal thyroxine. Although various studies have shown that maternal thyroid dysfunction is associated with suboptimal child neurodevelopmental outcomes, the most vulnerable time window remains to be identified. The aim of this study is to examine the association of maternal thyroid function with child brain morphology and to study whether any association depends on the timing of thyroid assessment. This prospective cohort study was part of the Generation R Study in Rotterdam, Netherlands, with a prospective population-based birth cohort. Pregnant women living in Rotterdam with an expected delivery date between April 1, 2002, and Jan 1, 2006, were eligible. Other inclusion criteria were maternal serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) measurement in early or mid-pregnancy (≤18 weeks) and available brain MRI data for child at age 10 years. Exclusion criteria were pre-existing thyroid disorder, thyroid disorder treatment, twin pregnancy, in-vitro fertilisation-induced pregnancy, and suboptimal-quality MRI data or major incidental finding on MRI. The main outcome was the association between maternal TSH and FT4 concentrations with brain MRI outcomes of children. Regression analyses accounted for gestational age at blood sampling, maternal age, ethnicity, education level, smoking, thyroid peroxidase antibody positivity, child sex, age at MRI, and total intracranial volume. Effect modification by gestational age at blood sampling was also investigated. Between Dec 1, 2001, and June 30, 2005, 7069 women were enrolled during early or mid-pregnancy (≤18 weeks of gestation), of whom 5088 were not included because they did not have available data on maternal serum TSH or FT4 concentrations (n=1175), their child did not have brain MRI done (n=3377), or they met exclusion criteria (n=536). Thus, 1981 mother-child pairs were included in the study, with TSH and FT4 concentrations measured during pregnancy at a median of 13·1 weeks of gestation (IQR 12·1-14·5) and offspring brain morphology assessed by MRI at a median age of 9·9 years (9·7-10·2). Maternal TSH had an inverted U-shaped association with offspring total grey matter volume (p=0·007) and with cortical grey matter volume (p=0·022). The association of maternal TSH with child total grey matter volume (pinteraction=0·053) and cortical volume (pinteraction=0·086) differed by the duration of gestation. Analyses stratified for gestational age at blood sampling showed an inverted U-shaped association of maternal TSH with child total grey matter volume and cortical grey matter volume, which was most evident at 8 weeks gestation. After about 14 weeks of gestation, TSH was no longer associated with child brain morphology. Maternal FT4 concentrations were not associated with child total grey matter volume after adjusting for total intracranial volume (p=0·75). Here, we show that both low and high maternal thyroid function are associated with smaller child total grey matter and cortical volume. To the best of our knowledge, this study is the first to show that an association with a neurodevelopmental outcome is most evident when maternal thyroid function is measured early in pregnancy. These novel findings suggest that embryonic brain development is particularly vulnerable to altered maternal thyroid function. Netherlands Organisation for Health Research and Development and the Sophia Children's Hospital Foundation.

Positive thyroid antibodies and risk of thyroid cancer: A systematic review and meta-analysis.

Previous studies assessing the association between thyroid antibodies and the risk of thyroid cancer (TC) have produced inconsistent results. The present study therefore conducted a meta-analysis of the available data. PubMed, Embase and the Cochrane Library were searched for the retrieval of relevant studies and a meta-analysis was conducted to systematically evaluate the association between positive thyroid antibodies and the risk of TC. This search identified 16 articles containing 17 studies on thyroglobulin antibodies (TgAb), which involved a total of 34,488 patients. Positive TgAb was associated with an increased risk of TC [odds ratio (OR)=1.93, 95% confidence interval (CI)=1.64–2.27, I2=67.2%]. Whether to adjust for confounding factors (gender and thyroid nodule number) was the main cause of heterogeneity. A stronger association between positive TgAb and an increased risk of TC was identified in the studies with an unadjusted thyroid nodule number (OR=2.14, 95% CI=1.82–2.52), as compared to those with an adjusted thyroid nodule number (OR=1.61, 95% CI=1.29–2.00; P=0.04). In addition, 12 studies on thyroid peroxidase antibodies (TPOAb) involving 30,007 patients were included. Positive TPOAb was associated with an increased risk of TC (OR=1.50, 95%CI=1.16–1.95, I2=83.0%). No significant heterogeneity was observed in the PTC group. Positive TgAb is an independent risk factor for TC. The association between positive TPOAb and increased risk of TC needs to be further studied.

Long-Term Variations of Antithyroperoxidase Antibodies and its Clinical Significance.

Various cut-offs have been proposed for thyroid peroxidase antibodies (TPOAb) positivity. Considering that the long-term trend of TPOAb levels and its positivity incidence is not clearly understood, we conducted the current study to determine the longitudinal variations of TPOAb in a population-based cohort study. We followed 5783 individuals of Tehran Thyroid cohort Study (TTS) for 10 years (4 phases). After exclusions, data of 3493 euthyroid participants remained for analyses. The baseline prevalence rates of TPOAb positivity were 19.8, 17, and 11.4% and the annual incidence rates (95% CI) of TPOAb positivity were 8.53 (8.29-8.77), 7.59 (7.37-7.80) and 6.79 (6.60-6.98) per 1000 persons for the 3 proposed cut-offs of 14.77, 18.38, and 40 U/l; respectively. Although a slightly increasing trend was observed for TPOAb levels (p=0.001) and its conventional positivity (TPOAb>40U/l), the recently proposed cut-offs of 14.77 and 18.38 U/l showed constant TPOAb positivity over 10 years. The time trends of the TPOAb levels among younger participants were significantly different from older participants (time×age effect p=0.004), with the former having an increasing trend and the latter, a relatively decreasing trend. Although the prevalence of TPOAb positivity was significantly (p<0.001) higher among women as compared to men, the longitudinal changes of TPOAb were similar in men and women. TPOAb positivity along with TSH values between 2.5 and 5.0 mU/l or free T4 values between 0.93 and 1.7 ng/dl exerted a significantly increased risk of subclinical or overt hypothyroidism. In an iodine sufficient population, an increasing trend in TPOAb levels was observed in line with the increasing incidence of subclinical and overt hypothyroidism.

SAT-583 Expanding the Clinical Spectrum of Hashimoto's Thyroiditis: Acute Presentation of a Chronic Illness

BACKGROUND: Hashimoto’s encephalopathy is an entity poorly defined in the pediatric literature , with widely variable presentations ranging from acute to chronic symptoms. Most cases described are of older adults, with female predominance and generally with previously diagnosed autoimmune thyroiditis. We describe a previously healthy adolescent male who presented in an acute encephalopathic state and was found to be frankly hypothyroid with positive thyroid peroxidase antibodies consistent with Hashimoto’s encephalopathy. CASE DESCRIPTION: A 16 year old previously healthy male presented with unresponsiveness to the emergency room. He underwent an extensive metabolic and infectious work up which was negative. Vital signs were normal throughout his hospital course. A TSH was ordered as part of the work up for altered mental status and was found to be significantly elevated at 492 mcIU/ml . Free T4 and free T3 levels were also low at 0.5 ng/dl (0.8-1.8 ng/dl) and 1.5 pg/ml (2.3 - 4.2 pg/ml) respectively. TPO antibody titer was >1000 IU/mL. Family reported no previous signs or symptoms suggestive of hypothyroidism. CSF autoimmune/paraneoplastic panel was negative. He was initiated on Levothyroxine with an intravenous loading dose. The following day, he also received methylprednisolone 150 mg I.V daily for 3 days. Clinically, he was back to baseline 48 hrs after initiating levothyroxine. He was discharged home on levothyroxine supplementation. CONCLUSION: Hashimoto’s encephalopathy is a controversial entity, with some authors recommending that the term ‘steroid responsive encephalopathy’ be used to describe patients presenting in an encephalopathic state, found to have positive thyroid peroxidase antibodies and respond to high dose steroids. Our patient showed clinical improvement within 24 hours of initiating levothyroxine. Although autoimmune thyroiditis with hypothyroidism typically has a gradual onset with long standing symptoms, it should be ruled out even in acute encephalopathic presentations. While the role of autoantibodies in the pathophysiology of Hashimoto’s or steroid responsive encephalopathy remains uncertain, this case highlights the importance of a high index of suspicion for thyroid dysfunction when evaluating patients with acute mental status changes.

SUN-622 Graves Disease Triggered by Lobectomy for Thyroid Cancer

Background: The incidence of Hashimoto thyroiditis as well as Graves disease in patients with thyroid cancer has been observed however molecular and pathophysiological basis of this association has only been hypothesized. Cases of new onset severe thyrotoxicosis and Graves ophthalmopathy shortly after lobectomy for thyroid cancer have not been described to our knowledge. Case: The patient is a 46-year-old woman who had a 2.5cm thyroid nodule. Fine needle aspiration showed atypia of undetermined significance and subsequent thyroid genomic classifier test Thyroseq confirmed positive for fusions involving THADA and IGF2BP3. Since THADA positive nodules are usually associated with low risk thyroid carcinoma and non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), thyroid lobectomy was advised. Prior to surgery the patient had positive thyroid peroxidase antibodies and was treated with low dose levothyroxine only during two pregnancies. Surgical pathology confirmed 2.5 cm NIFTP and 2 foci of papillary thyroid microcarcinoma of 0.5mm and 1mm with the background of chronic lymphocytic thyroiditis (Hashimoto). No further therapy was advised. At 6 weeks after left thyroid lobectomy the patient presented for a follow up clinically euthyroid with thyroid stimulating hormone (TSH) of 3 mcIU/mL. Two weeks after this regular follow up visit she started having severe periorbital swelling, double vision and bulging of her eyes that was followed by shortness of breath, palpitations, anxiety, sweating and weight loss. She presented to emergency room and was found to have suppressed TSH and positive TSI and TBII antibodies with high titer. After stabilization of hyperthyroidism with methimazole completion thyroidectomy was performed on patient request. Surgical pathology of the right thyroid lobe showed scattered papillary hyperplasia, chronic inflammation, focal atrophy and lymphoid follicles. Six weeks after completion thyroidectomy the patient is clinically euthyroid on levothyroxine and with significantly improved ophthalmopathy. TSI and TBII antibodies remain positive and continue to downtrend. Conclusion: As partial thyroidectomy for low-risk thyroid carcinoma is becoming increasingly convenient method of therapy we may encounter more surgically triggered autoimmune thyroid disorders in the future.

Comorbidity and health-related quality of life in Somali women living in Sweden

Objective: To explore the relationship between low serum vitamin D levels and comorbidity in Somali women, immigrants to Sweden.Design and setting: Cohort study in a Primary Health Care Center and a University Hospital.Subjects: Somali women skin type V, n = 114, aged 18–56 years, from latitude 0–10○ N, living in Sweden, latitude 57○ N > 2 years were compared with women from a population sample, skin type II-III, n = 69, aged 38–56 years, the WHO MONICA study, Gothenburg, Sweden.Main outcome measures: Serum (S)-25(OH)D, S-parathyroid hormone (PTH), comorbidity and Health-Related Quality of Life (HRQoL) using the Short Form-36 (SF-36) and part of the EQ-5D questionnaires. All calculations were corrected for age.Results: Vitamin D deficiency (S-25(OH)D < 25 nmol/l) was found in 73% of the Somali women and in 1% of the controls (p < .0001). S-PTH was elevated (>6.9 pmol/l) in 26% and 9%, respectively (p < .004). Somali women used less medication, 16% vs. 55%, p < .0001) but more allergy medication, 11% vs. 7% (p = .006), had fewer fractures, 2% vs. 28% (p < .0001) and lower HRQoL in 7 out of 9 scales (p < .05–.001), than native controls. There were no differences in the prevalence of diabetes mellitus, hypothyroidism, positive thyroid peroxidase antibodies, vitamin B12 deficiency, celiac disease or hypertension.Conclusions: Vitamin D deficiency was common in Somali women living in Sweden, 73%, but comorbidity was low. Both mental, and especially physical HRQoL scores were lower in the Somali women. The effects of long-lasting deficiency are unknown.Key pointsThe aim was to explore the relationship between vitamin D deficiency (S-25(OH)D < 25 nmol/l) and comorbidity in immigrants.Vitamin D deficiency was common in Somali women living in Sweden, 73%, but comorbidity of hypothyroidism, diabetes mellitus, hypertension, fractures and use of medications was low.Both mental, and especially physical, Health-Related Quality of Life were lower in the Somali women than in native Swedish women.The effects of long-lasting deficiency are unknown.