Positive TgAb Research Articles

High Prevalences of Subclinical Hypothyroidism and Positive Thyroid Autoantibodies Recorded Among Women of Childbearing Age in China: National Cross-Sectional Study

Background: Iodine deficiency and thyroid disorders are associated with several obstetric and neonatal adverse outcomes. Mandatory universal salt iodization in China was implemented 20 years ago; however, the current iodine status and prevalence of thyroid disorders among women of childbearing age are unknown. Methods: A nationally representative cross-sectional study with 26166 enrolled participants aged 18 to 49 years from all 31 provincial regions of mainland China was performed. The participants were given a questionnaire and underwent B-mode ultrasonography of the thyroid. The serum concentrations of thyroid hormones and thyroid antibodies and the urine iodine concentration (UIC) were measured. Findings: The median UIC was 178.7 μg/L, which is indicative of adequate iodine status; however, 19.04% and 19.87% of the participants were classified as having iodine deficiency and excessive iodine, respectively. The weighted prevalences of thyroid disorders were as follows: 1.08% had overt hyperthyroidism, 0.58% had subclinical hyperthyroidism, 0.76% had Graves’ disease, 1.28% had overt hypothyroidism, 14.28% had subclinical hypothyroidism, 13.53% were positive for TPOAb, and 14.55% were positive for TgAb. Excessive iodine and overweight were associated with higher odds of subclinical hypothyroidism. A family history of thyroid disorders and an age between 40 and 49 years were significantly associated with higher odds of positivity for TPOAb and positive TgAb. At the provincial level, the prevalences of iodine deficiency, excessive iodine, subnormal TSH levels, and supranormal TSH levels varied widely. Gansu was identified as a region with high prevalences of both excessive iodine and supranormal TSH levels. Interpretation: Iodine deficiency, excessive iodine, subclinical hypothyroidism, and positivity for thyroid autoantibodies are still prevalent among women of childbearing age in China. Women of childbearing age who are relatively older, have excessive iodine, are overweight, or have a family history of thyroid disorders are encouraged to undergo active screening of their UIC and thyroid function when planning a pregnancy. Strategies for addressing iodine status and thyroid disorders require geographic targeting of this subpopulation. Funding Statement: National Health Commission of the People’s Republic of China and National Natural Science Foundation of China. Declaration of Interests: The authors declare no conflict of interests. Ethics Approval Statement: The research protocols were approved by the Medical Ethics Committee of China Medical University.

Prevalence of Thyroid Autoimmunity in Women with Recurrent Pregnancy Loss.

Background and objectives: Thyroid autoimmunity (TAI) has been associated with a significantly increased risk of miscarriage in women with recurrent pregnancy loss (RPL). The aim of this study was to determine the prevalence of TAI in women with RPL and compare the clinical characteristics of positive and negative TAI women. Materials and Methods: This is a retrospective cross-sectional study; 203 women with RPL were included. Thyroid profile, anti-thyroid peroxidase (TPO-Ab), and anti-thyroglobulin (TG-Ab) antibodies were measured in all participants. Clinical characteristics and causes of RPL were compared between positive and negative TAI. Results: Prevalence of TAI was 14.8%; prevalence of positive TPO-Ab and TG-Ab was 12.3% and 4.9%, respectively. Women with TAI had significantly higher concentrations of thyrotropin (TSH) compared to women without TAI (4.8 ± 3.8 versus 3.1 ± 1.1, p = 0.001). There was no significant difference in age, the number of gestations, miscarriages, state of antiphospholipid antibodies (aPL), or causes of RPL between women that were TAI-positive versus TAI-negative. Prevalence of positive TAI by cause of RPL was: endocrine 7/25 (28%), genetic 1/5 (20%), autoimmune 1/5 (20%), anatomic 8/55 (14.5%), and unexplained cause 13/112 (11.6%). Conclusions: The prevalence of TAI in women with RPL is 14.8%. Women with an endocrine cause have the highest prevalence of TAI.

Iodine nutrition status and thyroid function of women at different phases of gestation in an iodine sufficient rural area.

This study was undertaken to evaluate the status of iodine nutrition and thyroid function of women at different phases of gestation in an iodine sufficient rural area. 215 pregnant women in different trimesters were consecutively enrolled in iodine sufficient rural areas of Yongjing county of Gansu province, China. The blood samples and random urine samples were collected from them, and serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxin (FT4), thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb) and urinary iodine were measured. Median Urinary Iodine (MUI) of three groups of pregnant women (first, second and third trimester) were 190 μg/L, 153 μg/L and 145 μg/L respectively. With the increase of gestational age, the level of FT3 decreased. And the FT3 level in the first trimester was higher than those in the second and third trimester. There was a U-shaped curve seen between the TSH levels and the gestational age. The medians of TgAb and TPOAb appeared the lowest in the first trimester．Significant difference was seen in TgAb and TPOAb levels of the three groups of pregnant women. The incidence of thyroid function disorder was 1.86%, including subclinical hypothyroidism accounted for 1.40% and hypothyroidism accounted for 0.47%. The incidence of thyroid function disorder mainly appeared in the early pregnancy. Abnormal FT3, TSH, positive TgAb and TPOAb were mainly seen during early pregnancy. The levels of serum TSH and thyroid hormones fluctuate at the different phases of pregnancy. With the increase of gestational age, the incidence of iodine deficiency also increased. Abnormal thyroid hormones, TSH, positive TgAb and TPOAb were mainly existed in the early pregnancy.

Test Utilization for Thyroglobulin and Anti-Thyroglobulin Antibody Assays in Korea.

When measuring thyroglobulin (Tg), simultaneous measurement of Tg autoantibodies (Ab) is recommended by clinical guidelines for follow-up of patients with differentiated thyroid cancers after thyroidectomy and radioactive iodine ablation. We aimed to investigate test utilization of Tg and Tg Ab assays in local clinics and hospitals in Korea. We retrospectively reviewed data from the laboratory information system between November 6, 2017 and December 31, 2019. During the study period, 10,551 Tg tests were performed on 2,592 Korean adults from 97 local clinics and hospitals. Among them, 3,924 (37.2%) test results lacked concurrent Tg Ab assays, while 6,627 test results had concurrently measured Tg Ab, and 528 (8.0%) showed positive Tg Ab results, which could interfere with measurement of Tg concentration. The results of this study provide basic information regarding test utilization of Tg Ab assays to improve test utilization for accurate Tg measurement in Korean patients.

Positive Thyroid Peroxidase Antibody and Thyroglobulin Antibody are Associated With Better Clinicopathologic Features of Papillary Thyroid Cancer

ObjectiveTo compare the thyroid autoantibody status of patients with papillary thyroid cancer (PTC) and benign nodular goiter as well as possible associations between thyroid autoantibodies and clinicopathologic features of PTC. MethodsA total of 3934 participants who underwent thyroidectomy were enrolled in this retrospective study. Patients were divided into PTC and benign nodule groups according to pathological diagnosis. Based on the preoperative serum antibody results, PTC patients were divided into thyroid peroxidase antibody (TPOAb)-positive, thyroglobulin antibody (TgAb)-positive, dual TPOAb- and TgAb-positive, or antibody-negative groups. ResultsOf the 3934 enrolled patients, 2926 (74.4%) were diagnosed with PTC. Multivariate regression analyses suggested that high thyroid-stimulating hormone levels (adjusted odds ratio [OR] = 1.732, 95% CI [1.485-2.021], P < .001), positive TgAb (adjusted OR = 1.768, 95% CI [1.436-2.178], P < .001), and positive TPOAb (adjusted OR = 1.452, 95% CI [1.148-1.836], P = .002) were independent risk factors for predicting malignancy of thyroid nodules. Multinomial multiple logistic regression analyses indicated that positive TPOAb alone was an independent predictor of less central lymph node metastasis in PTC patients (adjusted OR = 0.643, 95% CI [0.448-0.923], P = .017), whereas positive TgAb alone was significantly associated with less extrathyroidal extension (adjusted OR = 0.778, 95% CI [0.622-0.974], P = .028). PTC patients with dual-positive TPOAb and TgAb displayed a decreased incidence of extrathyroidal extension (adjusted OR = 0.767, 95% CI [0.623-0.944], P = .012) and central lymph node metastasis (adjusted OR = 0.784, 95% CI [0.624-0.986], P = .037). ConclusionAlthough preoperative positive TPOAb and TgAb are independent predictive markers for PTC, they are also associated with better clinicopathologic features of PTC.

Thyroid Hormone Changes in Early Pregnancy Along With the COVID-19 Pandemic.

PurposeCOVID-19 (Coronavirus Disease 2019) was first reported in December 2019 and quickly swept across China and around the world. Levels of anxiety and depression were increased among pregnant women during this infectious pandemic. Thyroid function is altered during stressful experiences, and any abnormality during early pregnancy may significantly affect fetal development and pregnancy outcomes. This study aimed to determine whether the COVID-19 pandemic induces thyroid hormone changes in early pregnant women.MethodsThis study comprised two groups of pregnant women in Shanghai in their first trimester – those pregnant women before the COVID-19 outbreak from January 20, 2019, to March 31, 2019 (Group 1) and those pregnant during the COVID-19 outbreak from January 20, 2020, to March 31, 2020 (Group 2). All women were included if they had early pregnancy thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4), total triiodothyronine (TT3), and total thyroxine (TT4) concentrations, thyroid peroxidase (TPO) antibody or thyroglobulin antibody (TgAb) available and did not have a history of thyroid diseases or received thyroid treatment before or during pregnancy. We used propensity score matching to form a cohort in which patients had similar baseline characteristics.ResultsAmong 3338 eligible pregnant women, 727 women in Group 1 and 727 in Group 2 had similar propensity scores and were included in the analyses. Pregnant women in Group 2 had significantly higher FT3 (5.7 vs. 5.2 pmol/L, P<0.001) and lower FT4 (12.8 vs. 13.2 pmol/L, P<0.001) concentrations compared with those in Group 1. Pregnant women in Group 2 were more likely to develop isolated hypothyroxinemia (11.6% vs. 6.9%, OR, 1.75 [95% CI, 1.20–2.53], P=0.003) than those in Group 1 but had a significantly lower risk of TgAb positivity (12.0% vs. 19.0%, OR, 0.58 [95% CI, 0.43–0.78], P<0.001).ConclusionPregnant women in their first trimester in Shanghai during the COVID-19 outbreak were at an increased risk of having higher FT3 concentrations, lower FT4 concentrations, and isolated hypothyroxinemia. The association between thyroid hormones, pregnancy outcomes, and the COVID-19 outbreak should be explored further.

Prognostic value and dynamics of antithyroglobulin antibodies for differentiated thyroid carcinoma.

Background: The clinical value of antithyroglobulin antibodies (TgAb) as a tumor marker for differentiated thyroid cancer (DTC) is still controversial. Materials & methods: We studied 110 TgAb positive DTC patients who underwent total thyroidectomy and 131I therapies. Multivariate logistic regression was conducted to analyze the association between prognostic factors and disease outcomes. Results & conclusion: Pre-ablation TgAb levels and the changes of TgAb in 6-12 months after the first 131I therapy were risk factors for disease outcome in patients younger than 55, while extrathyroid extensionwas a risk factor in patients older than 55. The median TgAb half-life was 7.7monthsand the median time for TgAb positivity to become negative was 15.8months. The dynamics of TgAb within the first year after remnant ablation could predict disease outcome for DTC patients.

SERUM THYROGLOBULIN AND ANTI THYROGLOBULIN LEVELS IN PATIENTS WITH THYROID NODULES

Objectives: To compare the levels and pathological values of serum Tg and TgAb between the patients with benign and malignant thyroid nodules and evaluate the relationship between serum Tg and TgAb levels with the rim characteristic and elasticity score of the nodule by thyroid elasto-echography. Subjects: 30 patients with thyroid nodules, Serum Tg and TgAb levels and thyroid elasto-echography are examen before operation. Results: The ratio of the positive Tg level of malignant thyroid nodules was higher than the benign thyroid nodules (16.7% vs 8.3%) but the serum Tg level was not significantly different (33.48 ± 38.67 ng/ml vs 27.32 ± 28.44 ng/ml, p &gt; 0.05) and The ratio of positive TgAb level of malignant thyroid nodules was higher than that of benign thyroid nodules (22.2% vs 0%) but serum TgAb level was not different (64.15 ± 14.91 UI/ml vs 16.9 ± 14.48 UI/ml, p &gt; 0.05). The combination of the ratio of positive Tg and positive TgAb level did not show any difference in the ratio of pathological value between benign and malignant thyroid nodules (5.6% vs 0%). Serum Tg levels in patients with irregular rim thyroid nodules were higher than those in patients with regular rim thyroid nodules but the serum Tg level was not different when evaluated with the elastic score. Conclusions: The mean level and ratio of the pathological value of serum Tg and TgAb did not differ between malignant and benign thyroid nodules. There is a relationship between serum Tg level and irregular rim characteristic of thyroid nodule (p &lt; 0.05). Key words: serum thyroglobulin level, serum anti thyroglobulin level, thyroid nodule.

The role of a new polyclonal competitive thyroglobulin assay in the follow-up of patients with differentiated thyroid cancer with structural disease but low levels of serum thyroglobulin by immunometric and LC-MS/MS methods.

The aims of this study were to assess the role of an in-house competitive thyroglobulin assay (Tg-c) in the follow-up of metastatic differentiated thyroid carcinoma (DTC) patients who presented underestimated Tg measurements by immunometric assays (Tg-IMA) and to compare the results with IMA and LC-MS/MS Tg methods. This prospective study included 40 patients. Twenty-one with metastatic disease: 14 had Tg-IMA levels inappropriately low or undetectable (eight patients with positive and six with borderline TgAb) and seven had high Tg-IMA levels. Nineteen had an excellent response to therapy. The competitive assay employs a polyclonal antibody produced in rabbits immunized with human Tg, Tg labeled with biotin, and for the solid phase separation, a monoclonal anti-rabbit IgG antibody adsorbed to microtiter plates. All 14 patients with structural disease and underestimated levels of Tg-IMA presented detectable Tg-c levels. The median Tg-c level in the group with positive TgAb was 183 µg/L (range: 22-710 µg/L), and 58 µg/L (range 23-148 µg/L) in the borderline TgAb group. The levels of Tg-LC-MS/MS were detectable in some patients (range < 0.5-18 µg/L). All seven patients with high Tg-IMA presented also high levels of Tg-c. Only 2/19 patients with excellent response had Tg-c levels above the functional sensitivity. The competitive assay was able to detect Tg in all patients, even in the presence of serum TgAb, and may be an option in patients with underestimated Tg-IMA and relevant structural disease.

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.

Determination of thyroglobulin levels by radioimmunoassay method in anti thyroglobulin positive differentiated thyroid patients: One center clinical experience

It is very crucial to determine Tg accurately and precisely in thyroid cancer cases. Although there are many studies on the detection of Tg in thyroid cases in the literature, there are no sufficient clinical studies examining many cases with different features by using RIA methodology. Here, a radiometric and chromatographic method has been studied for the first time to eliminate the interference from anti-Tg positive patients. In this paper, radioimmunoassay (RIA) and immunoradiometric (IRMA) techniques were used for the analysis of 302 sera collected from patients for Tg and TgAb quantification. By the RIA technique, a reliable result was obtained by calculating the real Tg value quantitatively in 41 patients showing TgAb positivity out of 208 patients. Our findings show that the RIA assay is the most suitable approach for detection of changeable (low or undetectable) Tg value and metastases detected by post-therapeutic imaging in early-stage DTC cases showing preoperative and postoperative TgAb positivity. The new immunoradiometric method allows the real (%) Tg value to be reached in a part of TgAb-positive DTC. Even if TgAb positive in the metastatic and nonmetastatic DTC patient group. This allows the accurate clinical follow-up of patients.

Correlation between thyroid autoantibodies and the risk of thyroid papillary carcinoma.

To investigate the correlation of thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) with the risk of papillary thyroid carcinoma (PTC). The clinical data of 322 patients with pathologically confirmed thyroid nodules who underwent surgical treatment in Lishui Hospital of Zhejiang University from January 2018 to December 2019 were enrolled in this study. The enrolled patients were divided into a benign nodule group and a PTC group according their pathological results. Comparison was drawn based around the difference of thyroid autoantibody distribution between groups and its correlation with the risk of PTC. The positive rate of TgAb in the PTC group was significantly higher than that in the benign nodule group (P<0.05). The incidence of PTC was significantly higher in TgAb positive patients in the presence of negative TPOAb (P<0.05). Further regression analysis revealed positive TgAb to be a risk factor of PTC (OR =3.097, P<0.05), while age ≥55 years old (OR =0.188, P<0.05) and nodule diameter ≥10 mm (OR =0.064, P<0.05) reduced the risk of PTC. Simultaneously, positive TgAb was also a risk factor for PTC in females (OR =3.532, P<0.05), but not in males (P>0.05). The risk of PTC in females was not associated with further increase in the titer of TgAb. TgAb may be associated with an increased risk of PTC in females, but there is no clear correlation between the risk of PTC and higher antibody titer in these patients.

The Correlation Between Metabolic Disorders And Tpoab/Tgab: A Cross-Sectional Population-Based Study

Studies have shown that metabolic abnormalities influence the immune system. Because the prevalence of metabolic and autoimmune thyroid diseases has increased synchronously, the correlation between them was worth exploring. The study objective was to investigate the relationship between metabolic disorders and thyroid auto-antibodies in euthyroid subjects. Data were obtained from the Thyroid Diseases and Diabetes Mellitus project survey of 55,891 subjects from 31 provinces in China. The body mass index (BMI), waist circumference (WC), blood pressure, thyroid peroxidase antibodies (TPOAbs), thyroglobulin antibodies (TgAbs), thyroid-stimulating hormone (TSH), urinary iodine concentration, blood glucose, lipid profile, and uric acid levels were evaluated. Free thyroxine and free triiodothyronine levels were measured in patients with abnormal serum TSH levels. In males, the BMI, WC, systolic blood pressure (SBP), diastolic blood pressure (DBP), and 2-hour post-glucose oral glucose tolerance test results of the TPOAb-/TgAb-positive group were significantly higher than those of the TPOAb-/TgAb-negative group. In females, the BMI, WC, SBP, DBP, total cholesterol, and low-density-lipoprotein cholesterol (LDL-C) in the TPOAb-/TgAb-positive group were significantly increased compared to the TPOAb-/TgAb-negative group. Multivariate analysis showed that in males, the odds ratio (OR) of positive TgAbs in the abdominal obesity group was 1.175 (95% confidence interval [CI], 1.016 to 1.359; P = .03), and the OR of positive TPOAbs in the hyperuricemia group was 1.195 (95% CI, 1.041 to 1.372; P = .011). In females, the OR of positive TgAbs was 1.19 (95% CI, 1.068 to 1.326; P = .002) in the high LDL-C group. Obesity, high LDL-C, and hyperuricemia were positively correlated with the prevalence of positive thyroid autoantibodies in euthyroid subjects in a gender-dependent manner. This cross-sectional survey showed that metabolic disorders are associated with increased positive thyroid autoantibody levels in euthyroid subjects in a gender-dependent manner. AIT = autoimmune thyroiditis; BMI = body mass index; CI = confidence interval; DBP = diastolic blood pressure; FPG = fasting plasma glucose; FT3 = free triiodothyronine; FT4 = free thyroxine; HbA1c = glycated hemoglobin; HDL-C = high-density-lipoprotein cholesterol; LDL-C = low-density-lipoprotein cholesterol; OGTT2hPG = oral glucose tolerance test 2-hours post-glucose; OR = odds ratio; SBP = systolic blood pressure; TC = total cholesterol; TG = triglycerides; TgAb = thyroglobulin antibody; TPOAb = thyroid peroxidase antibody; TSH = thyroid-stimulating hormone; UA = uric acid; WC = waist circumference.

Anaemia in hypothyroidism

Background: Anaemia is very common in hypothyroid patient. The results of the type of anaemia in hypothyroid patient studied outside may not be similar on Bangladeshi population. So far, there is no such study regarding the types of anaemia in hypothyroid patients in Bangladeshi population.&#x0D; Methods: This was a cross sectional study in patients with hypothyroidism who was attending in the thyroid and endocrine clinic of Bangabandhu Sheikh Mujib Medical University, Dhaka over a period of one year. All newly diagnosed cases were selected considering inclusion and exclusion criteria. A structured questionnaire was used for data collection.&#x0D; Results: Fifty newly detected hypothy sroid patients were studied among the study population, 52.0% was between 05 to 35 years and another 48.0% were in 36 to 65 years. 76.0% were female. Bradycardia was found in 20.0% cases. Puffiness of face, peripheral oedema and cold intoleran ce were found in 78.0%, 68.0% and 82.0% cases respectively. Hoarseness of voice, delayed relaxation of tendon reflexes and paraesthesia were found in about 80.0% cases. Myxoedema and vitiligo were found in 54.0% and 6% cases. FT4 level was reduced in 100.0% cases (Normal range of FT4-9.14-23.81 pmol/L). The mean of FT4 was 5.10 pmol/L. On the other hand TSH level increased in all cases (Normal range of TSH-0.47-5.0l mIU/L). The mean of TSH was 109.88 mIU/L. 50 cases were positive anti TG-Ab and also anti PO­-Ab was positive in Fifty cases. Hemoglobin concentration was reduced in 70.0% cases. The mean of haemoglobin concentration was 10.67 gm/dl. In this present study, association of serum anti TG Ab and anti PO Ab of the patients with hypothyroidism and their corresponding hemoglobin concentration were found significant (p&lt;0.05) but on the other hand there was no association between serum FT4 of the patients with hypothyroidism and their corresponding haemoglobin concentration (p&gt; 0.05). Normocytic normochromic anaemia were found in 64.0% cases, and Microcytic hypochromic anaemia in 32% and Macrocytic anaemia in 4.0% of the cases. Iron deficiency was found in 90.0% and chronic blood loss in 44.0% of the cases.&#x0D; Conclusion: Anaemia is frequently found in hypothyroid patients. So, hypothyroidism should be excluded in anaemia of nonspecific origin.&#x0D; Bangladesh Med Res Counc Bull 2020; 46(1): 55-60

2249-PUB: Clustering Analysis as a Tool to Define Endotypes in Type 1 Diabetes (T1D)

Due to heterogeneity in pediatric T1D, uniform treatment strategies are unlikely to benefit all patients equally. T1D endotypes, or subgroups with distinct characteristics amenable to particular interventions, are a potential solution, but defining endotypes remains a challenge. We used electronic medical records (EMR) to define clusters of distinct presentations of pediatric T1D in a diverse population with a high prevalence of obesity. We analyzed data collected through an EMR Population Health Diabetes Registry of 604 children newly diagnosed with T1D at a large academic hospital in southwestern USA. Using PROC Cluster (SAS 9.4), we applied the Centroid Clustering method to find the optimal number of clusters that minimized the sum of squared distance, then used SAS PROC Tree to identify subjects in each cluster. Variables used were age, DKA at diagnosis, weight, sex, race/ethnicity, c-peptide, hemoglobin A1c (A1c), thyroglobulin antibody (TgAb), and thyroid peroxidase antibody (TPO). Due to multiple testing, p-values &amp;lt;0.01 were statistically significant. This yielded 6 clusters: Cluster 1 (n=424), was characterized by low C-peptide, normal weight, negative TgAb and TPO, intermediate or high A1C; Cluster 2 (n=73) by obesity, low or intermediate C-peptide, and negative TgAb and TPO; Cluster 3 (n=42) by positive TgAb; Cluster 4 (n=33), by positive TPO and negative TgAb; Cluster 5 (n=19) by high or intermediate C-peptide without obesity or intermediate C-Peptide with obesity and negative TgAb and TPO; Cluster 6 (n=13) by obesity, high C-peptide and negative TgAb and TPO. After adjusting for age, BMI Z-score and race/ethnicity, clusters were statistically different for A1c, C-peptide and TPO and TgAb status (all p&amp;lt;0.01), but not for glucose or DKA. This strategy identifies distinct groups in T1D based on objective criteria. Endotypes from clustering analysis of more EMR data could be used for targeting therapeutic strategies to groups with similar characteristics and help personalize T1D treatment and care. Disclosure A.F. Siller: None. X. Gu: None. M. Tosur: None. M. Astudillo: None. A. Balasubramanyam: None. M. Bondy: None. M.J. Redondo: None. Funding Baylor College of Medicine

Urinary Concentrations of Phthalate Metabolite Mixtures in Relation to Serum Biomarkers of Thyroid Function and Autoimmunity among Women from a Fertility Center.

Background:Although previous epidemiological studies have explored associations of phthalate metabolites with thyroid function, no studies to date have assessed associations of mixtures with thyroid function and autoimmunity among potentially susceptible subgroups such as subfertile women.Objective:We aimed to explore associations of mixtures of urinary phthalate metabolites with serum markers of thyroid function and autoimmunity.Methods:This cross-sectional study included 558 women attending a fertility center who provided one spot urine and one blood sample at enrollment (2005–2015). We quantified urinary concentrations of eight phthalate metabolites using mass spectrometry, and biomarkers of thyroid function [thyroid-stimulating hormone (TSH), free and total thyroxine (, ) and triiodothyronine (, ), and autoimmunity [thyroid peroxidase and thyroglobulin antibodies (TPOAb and TgAb, respectively)] in serum using electrochemiluminescence assays. We applied principal component analysis (PCA) and Bayesian kernel machine regression (BKMR) to identify the main patterns of urinary phthalate metabolites. We used linear mixed models to assess the association between PCA-derived factor scores in quintiles and serum thyroid function and autoimmunity, adjusting for age, body mass index (BMI), specific gravity (SG), and, for the PCA, other factor scores.Results:We observed two factors using PCA, one representing the di(2-ethylhexyl) (DEHP) and another non-DEHP metabolites. Compared to women in the lowest quintile of the DEHP factor scores, women in the highest quintile had significantly lower serum concentrations of , , , and [absolute difference: ; 95% confidence interval (CI): , ; ; absolute difference: ; 95% CI: , ; ; absolute difference: ; 95% CI: 0.54, ; ; and absolute difference: ; 95% CI: , ; , respectively]. Using BKMR, we observed that mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was the primary contributor to these negative associations. DEHP and non-DEHP factor scores were not associated with serum TSH, TgAb, or TPOAb.Conclusions:Mixtures of urinary DEHP metabolites were inversely associated with serum biomarkers of thyroid function but not with autoimmunity, which were within normal ranges for healthy adult women. https://doi.org/10.1289/EHP6740

Prognostic Significance of Thyroglobulin Antibodies in Differentiated Thyroid Cancer

Objective To investigate whether variations in thyroglobulin autoantibodies (TgAb) are related to the recurrence or persistence of differentiated thyroid carcinoma (DTC) and may therefore be useful as surrogate tumor markers. Design and Methods. We retrospectively studied 98 subjects (83 women, 47 ± 15 years old) from an initial cohort of 1017 patients treated for DTC in five hospitals, with positive TgAb at any time during the follow-up. Patients presented five different patterns of evolution of serum TgAb concentrations: (1) stable positive TgAb, (2) de novo appearance, (3) an increase of more than 50%, (4) TgAb levels from positive to negative, and (5) a decrease of more than 50%. Results In the group of 11 patients with stable TgAb, four cases presented persistence of the disease with structural incomplete response. In the group of 22 patients with sustained increasing trend rising more than 50% or de novo detectable TgAb levels, three patients were diagnosed with structural incomplete response. There was no evidence of recurrence or persistence of the disease in any of the 65 patients who showed a significant decrease in (n = 35) or disappearance of (n = 30) TgAb. Conclusions Our results suggest that not only the appearance of a significant increase in TgAb but also stable concentrations of TgAb should be regarded as a sufficient risk condition for an active search for recurrent or persistent disease. Conversely, a significant decrease in TgAb levels can represent a good prognostic sign.

Thyroid Parameters and Kidney Disorder in Type 2 Diabetes: Results from the METAL Study.

Objective Diabetic kidney disease is one of the most common microvascular complications of diabetes mellitus. We aimed to analyze the association of thyroid parameters with kidney disorders, especially in euthyroid participants. Methods The data were obtained from a cross-sectional study, the METAL study. Thyroid parameters, including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), triiodothyronine (T3), thyroxin (T4), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb), of 4136 participants with type 2 diabetes were measured. Two structure parameters of thyroid homeostasis, including the sum activity of step-up deiodinases (SPINA-GD) and thyroid secretory capacity (SPINA-GT), and two pituitary thyrotropic function indices, including Jostel's TSH index (TSHI) and the thyrotroph thyroid hormone resistance index (TTSI), were also calculated. Kidney disorders were described according to the presence of reduced estimated glomerular filtration rate (eGFR) and/or higher urinary albumin to creatinine ratio (UACR). Results The prevalence of kidney disorders increased with decreasing FT3 or T3 and increasing FT4 or T4 quartile levels (all P < 0.05). After full adjustment, linear regression showed that UACR levels were negatively associated with FT3 and T3 (P < 0.001). In addition, eGFR was positively associated with FT3 and T3 and was negatively associated with TSH and FT4 levels and TgAb positivity (all P < 0.05). By using binary logistic regression, higher TSH and FT4 and lower FT3 and T3 were associated with kidney disorders (all P < 0.05). Similar results were seen in sensitivity analyses, which were performed in 3035 euthyroid diabetic participants; however, TSH was no longer related to them. The area under the receiver operating characteristic curve (AUROC) of lower FT3 for existing kidney disorder was greater than that for any other thyroid hormones (all P < 0.001). The cutoff value of FT3 for reduced eGFR was 4.39 pmol/L. Regarding thyroid homeostasis parameters, SPINA-GD was negatively associated with three statuses of kidney disorders, and TSHI and TTSI were positively associated with reduced eGFR (all P < 0.05). Conclusions Among patients with type 2 diabetes, elevated TSH and FT4 (or T4), lower FT3 (or T3), TgAb positivity, lower SPINA-GD, and higher TSHI and TTSI were associated with kidney disorders. The lower FT3, even within the normal range (<4.38 pmol/L), may be the factor most related to reduced eGFR compared with other thyroid hormones in diabetic patients.

Detecting Recurrence Following Lobectomy for Thyroid Cancer: Role of Thyroglobulin and Thyroglobulin Antibodies.

The use of thyroglobulin (Tg) and thyroglobulin antibodies (TgAb) for detecting disease recurrence is well validated following total thyroidectomy and radioiodine ablation. However, limited data are available for patients treated with thyroid lobectomy. Patients who had lobectomy for papillary thyroid cancer followed for >1 year, with sufficient data on Tg and TgAb, including subgroup analysis for Hashimoto's thyroiditis and contralateral nodules. One-hundred sixty-seven patients met the inclusion criteria. Average tumor size was 9.5 ± 6 mm. Following lobectomy, Tg was 12.1 ± 14.8 ng/mL. Of 52 patients with Hashimoto's thyroiditis, 38% had positive TgAb with titers of 438 ± 528 IU/mL, and in patients without TgAb the mean Tg level was 14.7 ± 19.0 ng/mL. In 34 patients with contralateral nodules ≥1 cm, Tg was 15.3 ± 17 ng/mL. During the first 2 years of follow-up, Tg declined ≥1 ng/mL in 42% of patients (by 5.1 ± 3.7 ng/mL), remained stable in 22%, and increased in 36% (by 4.9 ± 5.7 ng/mL). During a mean follow-up of 6.5 years (78 ± 43.5 months), 18 patients had completion thyroidectomy and 12 were diagnosed with contralateral cancer (n = 8) or lymph node metastases (n = 4). In patients with recurrence followed for >2 years, there was a rise in Tg in 3 cases, Tg was stable in 2 cases, and in 1 TgAb decreased from 1534 to 276 IU/mL despite metastatic lymph nodes. Basal Tg and Tg dynamics did not predict disease recurrence. Serum thyroglobulin used independently is of limited value for predicting or detecting disease recurrence following thyroid lobectomy. Other potential roles of Tg, such as detecting distant metastases following lobectomy, should be further studied.

Serum antithyroglobulin antibody levels are not a good predictive factor on detection of disease activity in patients with papillary thyroid carcinoma.

Thyroglobulin antibodies (TgAb) are detected in thyroid cancer patients up to 25%. We investigated the prognostic value of TgAb positivity in patients with papillary thyroid carcinoma (PTC) after initial therapy. A database of 109 consecutive patients who underwent total thyroidectomy and therapeutic lateral neck dissection followed by remnant ablation for PTC between January 1989 and December 2014 was reviewed We recorded the patients' all serum Tg and TgAb levels over time to establish changing trends. Patients were classified as either positive or negative according to serum TgAb levels. The recurrence or persistence rates in both groups were compared. Of the 109 patients enrolled 14 patients had TgAb positivity. Thirty-two (29.3%) showed disease recurrence or persistent disease during 101 months of follow-up. Twenty-seven of 95 patients (28.4%) with negative TgAb had persistent or recurrent disease, whereas 5 of 14 patients (35.7%) with positive TgAb had persistence or recurrence (P = 0.57). No significant difference in disease-free survival (115.3 ± 10.8 vs. 224.1 ± 16.6 months, P = 0.78) and overall survival (P = 0.59) was observed between TgAb positive and TgAb negative patients. TgAb status is not useful as a prognostic and predictive factor for clinical outcomes in patients with PTC in our experience.