Thyroperoxidase Antibody Positivity Research Articles

A Novel Nomogram for Predicting the Risk of Premature Delivery Based on the Thyroid Function in Pregnant Women.

BackgroundMaternal thyroid dysfunction and autoantibodies were associated with preterm delivery. However, recommendations for cutoff values of thyroperoxidase antibody (TPOAb) positivity and thyroid-stimulating homone (TSH) associated with premature delivery are lacking.ObjectiveTo identify the pregnancy-specific cutoff values for TPOAb positivity and TSH associated with preterm delivery. To develop a nomogram for the risk prediction of premature delivery based on maternal thyroid function in singleton pregnant women without pre-pregnancy complications.MethodsThis study included data from the International Peace Maternity and Child Care Health Hospital (IPMCH) in Shanghai, China, between January 2013 and December 2016. Added data between September 2019 and November 2019 as the test cohort. Youden’s index calculated the pregnancy-specific cutoff values for TPOAb positivity and TSH concentration. Univariate and multivariable logistic regression analysis were used to screen the risk factors of premature delivery. The nomogram was developed according to the regression coefficient of relevant variables. Discrimination and calibration of the model were assessed using the C-index, Hosmer-Lemeshow test, calibration curve and decision curve analysis.Results45,467 pregnant women were divided into the training and validation cohorts according to the ratio of 7: 3. The testing cohort included 727 participants. The pregnancy-specific cutoff values associated with the risk of premature delivery during the first trimester were 5.14 IU/mL for TPOAb positivity and 1.33 mU/L for TSH concentration. Multivariable logistic regression analysis showed that maternal age, history of premature delivery, elevated TSH concentration and TPOAb positivity in the early pregnancy, preeclampsia and gestational diabetes mellitus were risk factors of premature delivery. The C-index was 0.62 of the nomogram. Hosmer-Lemeshow test showed that the Chi-square value was 2.64 (P = 0.955 > 0.05). Decision curve analysis showed a positive net benefit. The calibration curves of three cohorts were shown to be in good agreement.ConclusionsWe identified the pregnancy-specific cutoff values for TPOAb positivity and TSH concentration associated with preterm delivery in singleton pregnant women without pre-pregnancy complications. We developed a nomogram to predict the occurrence of premature delivery based on thyroid function and other risk factors as a clinical decision-making tool.

Association of breastfeeding with thyroid function and autoimmunity in postmenopausal women.

Whether breastfeeding influences thyroid function and autoimmunity is not elucidated. We examined the association of history of breastfeeding with thyroid hormones and thyroperoxidase antibody (TPOAb). Cross-sectional study of data from the 2013-2015 Korea National Health and Nutrition Examination Survey. A total of 816 postmenopausal women were stratified into three groups according to the duration of breastfeeding and number of breastfed children. Thyroid hormones levels, TPOAb titers, and the prevalence of hypothyroidism and TPOAb positivity were evaluated in each group. Subjects with a history of prolonged breastfeeding had lower levels of thyrotropin (TSH) and TPOAb than the others. After adjusting for multiple confounding factors, the estimated means of TSH and TPOAb were associated with cumulative duration of breastfeeding. Duration of breastfeeding per child was associated with TSH levels, and number of breastfed children was associated with TPOAb titers. The odds ratio (OR) of hypothyroidism was significantly lower in group for ≥36 months of cumulative duration of breastfeeding, and the OR of TPOAb positivity was significantly lower in group with ≥3 breastfed children. In addition, duration of breastfeeding and the number of breastfed children were linearly correlated with log TSH and TPOAb each other in the multivariate model. The present study showed that prolonged breastfeeding was inversely associated with TSH and the prevalence of hypothyroidism. Moreover, TPOAb and the prevalence of TPOAb positivity were inversely associated with number of breastfed children. These results indicate that breastfeeding may exert a protective effect on thyroid function and autoimmunity.

Relationship between autoimmune liver disease and autoimmune thyroid disease: a cross-sectional study

Background: A high prevalence of autoimmune thyroid disease (AITD) has been observed in patients with autoimmune liver disease (AILD); however, data on the clinical relationship between AILD and AITD remain scant. We aimed to evaluate the relationship between AILD and AITD.Methods: We performed a retrospective study using medical records from 324 patients with AILD, 113 of whom had concurrent AITD.Results: Patients with autoimmune hepatitis (AIH) were more likely to develop AITD (45.8%), followed by autoimmune hepatitis-primary biliary cholangitis overlap syndrome (AIH-PBC OS) (39.5%) and PBC (22.6%). Patients with concurrent AILD and AITD showed higher levels of immunoglobulin G (IgG) (21.5 g/L vs 16.3 g/L, p < .0001) and gamma globulin (γ-globulin) (27.1% vs 21.9%, p < .0001). IgG was positively correlated with thyroid antibodies [thymoglobulin antibody (TGAb) and thyroperoxidase antibody (TPOAb)] (r = 0.396, 0.322; p < .0001, p = .002, respectively). TPOAb positivity was highest in PBC patients with concurrent AITD (83.9%). Patients with concurrent PBC and AITD were significantly older than those with PBC alone (p = .0004). Patients with concurrent AIH and AITD had a higher homogenous nuclear pattern of antinuclear antibody positivity compared to those with AIH alone (p = .019). Thyroid dysfunction in AILD patients with concurrent AITD was principally characterized by Hashimoto’s thyroiditis (65.5%), and diffuse lesions were mainly found by thyroid ultrasound (53.1%).Conclusions: The high incidence of AILD concomitant with AITD, the higher levels of serum IgG and γ-globulin, and the strong correlation between thyroid antibodies and IgG suggest that close screening for AITD and accurate physical examinations should be performed for all patients with AILD.

The Association of Maternal Thyroid Autoimmunity During Pregnancy With Child IQ.

Thyroperoxidase antibody (TPOAb) positivity is a major risk factor for gestational thyroid dysfunction. During the first 18 to 20 weeks of pregnancy, high concentrations of human chorionic gonadotropin (hCG) stimulate the thyroid to ensure adequate thyroid hormone availability for the developing fetus. However, TPOAb-positive women have an impaired thyroidal response to hCG stimulation. To study the association of maternal TPOAb positivity during pregnancy with child IQ. This study was embedded in two prospective birth cohorts: Generation R (Rotterdam, the Netherlands) and Avon Longitudinal Study of Parents and Children (ALSPAC; United Kingdom). Mother-child pairs with available data on early pregnancy TPOAb (≤18 weeks of gestation) and offspring IQ were included (n = 3637 for Generation R and n = 2396 for ALSPAC). Child IQ at 5 to 10 years of age. In Generation R, TPOAb positivity was associated with a 2.0 ± 0.9-point lower mean child IQ (P = 0.03). Sensitivity analyses showed negative effect estimates already from TPOAb concentrations considerably lower than currently used manufacturer cutoffs. In ALSPAC, neither TPOAb positivity nor TPOAb concentrations below manufacturer cutoffs were associated with child IQ (TPOAb positivity: 0.7 ± 1.0; P = 0.45). Adjustment for maternal TSH or free T4 concentrations or urinary iodine/creatinine ratio did not change the results. TPOAb positivity during pregnancy was associated with lower child IQ in Generation R but not in ALSPAC. Further studies are needed to elucidate whether differences between the study populations, such as maternal iodine status, could be the underlying cause for these differences.

Dose Dependency and a Functional Cutoff for TPO-Antibody Positivity During Pregnancy.

To investigate a dose dependency of thyroperoxidase antibody (TPOAb) concentrations in relation to thyroid function and premature delivery and define a population-based, pregnancy-specific, functional cutoff for TPOAb positivity. Individual participant meta-analysis of three prospective birth cohorts: the Amsterdam Born Children and their Development study, and the Holistic Approach to Pregnancy. Population-based studies in the Netherlands (2002 to 2014). A total of 11,212 pregnant women (<20 weeks' gestation). Thyrotropin (TSH) and FT4 concentrations, premature delivery. In all cohorts, there was a dose-dependent positive association of TPOAb concentrations with TSH concentrations, as well as a dose-dependent negative association with FT4 concentrations during early pregnancy (all P < 0.0001). There was a dose-dependent association of TPOAb concentrations with the risk of premature delivery, which was also modified by TSH concentrations. Women with TPOAb concentrations from the 92nd percentile upward had a higher TSH and a higher risk of a TSH >2.5 mU/L (range, 19.4% to 51.3%). Stratified analyses showed that women with TPOAb concentrations below manufacturer cutoffs already had a higher risk of premature delivery, especially when TSH concentrations were high or in the high-normal range. This study demonstrated a dose-dependent relationship between TPOAbs and thyroid function as well as the risk of premature delivery. Furthermore, our results indicate that the currently used cutoffs for TPOAb positivity may be too high. Furthermore, the use of a population-based cutoff for TPOAbs may identify women with a clinically relevant extent of thyroid autoimmunity and a higher risk of premature delivery but that would not be considered TPOAb positive or eligible for treatment otherwise.

The potential benefit of levothyroxine treatment during pregnancy: another step forward

Thyroid hypofunction during pregnancy is associated with a wide range of adverse pregnancy and child outcomes such as miscarriage, premature delivery, abnormal birth weight and suboptimal offspring neurodevelopment. Thyroid autoimmunity, reflected by thyroperoxidase antibody (TPOAb) positivity, is the most important risk factor for thyroid hypofunction. During pregnancy, TPOAb-positive women have higher TSH and lower FT4 concentrations and a higher risk of overt and subclinical hypothyroidism than TPOAb-negative women (1, 2). Intriguingly, TPOAb positivity is associated in several observational studies with a higher risk of adverse outcomes including miscarriage, premature delivery and gestational diabetes, even in euthyroid women (2, 3, 4, 5, 6, 7). Such studies suggest potential adverse effects of thyroid autoimmunity on pregnancy outcome. However, the mechanisms underlying these associations, as well as causality of the associations, remain to be elucidated. In this context, the study by Nazarpour et al. in the current issue of the European Journal of Endocrinology is a very valuable contribution.

Thyroid Autoimmunity Impairs the Thyroidal Response to Human Chorionic Gonadotropin: Two Population-Based Prospective Cohort Studies.

Thyroperoxidase antibody (TPOAb) positivity is the main risk factor for thyroid dysfunction during pregnancy and is consistently associated with premature delivery. However, the underlying mechanism is currently unknown. We hypothesized that TPOAb positivity may interfere with gestational thyroid stimulation induced by the pregnancy hormone human chorionic gonadotropin (hCG). Thyrotropin (TSH), free thyroxine (FT4), TPOAbs, and/or hCG concentrations were measured in early and late pregnancy of 7587 pregnant women from 2 Dutch population-based prospective cohorts (n = 5924, Generation R study; n = 1663, Holistic Approach to Pregnancy and the First Postpartum Year study). None. Thyroidal response to hCG stimulation, premature delivery. In TPOAb-negative women, hCG was positively associated with FT4 and negatively with TSH in both cohorts (P < 0.0001). In contrast, in TPOAb-positive women, hCG was not associated with FT4 or TSH in either cohort (all P > 0.40; P for interaction TPOAb positive vs negative ≤ 0.05). Overall, TPOAb positivity was associated with a 1.7-fold higher risk of premature delivery. TPOAb-positive women with an adequate response of FT4 to hCG (high FT4 concentration with high hCG concentration) did not have a higher risk of premature delivery. In contrast, TPOAb-positive women with an inadequate FT4 response to hCG (low FT4 concentration with high hCG concentration) had a 2.2- to 2.8-fold higher risk of premature delivery. TPOAb-positive women display an impaired thyroidal response to hCG and this may explain the higher risk of premature delivery in these women. This abnormal response in TPOAb-positive women might suggest that these women require a different treatment approach than TPOAb-negative women.

Thyroid Function Within the Normal Range and the Risk of Depression: A Population-Based Cohort Study

Overt hypo- and hyperthyroidism are associated with an increased risk of depression. Little is known about the effects of variation in thyroid function within the normal range on the risk of depression. The objective of the study was to examine the association between normal-range thyroid function and the risk of depression. This was a cohort study in 1503 Dutch men and women, aged 70.6 (7.3) (mean [SD]) years. At baseline, serum TSH, thyroperoxidase antibody levels, and depressive symptoms [Center for Epidemiologic Studies Depression Scale (CES-D)] were assessed. A CES-D of 16 or greater is indicative of a depressive disorder. During follow-up (mean 8.0 y), participants were continuously monitored for the occurrence of incident depressive syndromes (n = 156). Cross-sectionally, persons in the lowest TSH tertile (0.3-1.0 mU/L) had more depressive symptoms [CES-D score (mean): 7.95 vs 6.63, P = .014] as well as an increased risk of a CES-D of 16 or greater [10.7% vs 5.0%, odds ratio (95% confidence interval) 2.22 (1.18-4.17)], compared with persons in the highest normal range TSH tertile (1.6-4.0 mU/L). In the prospective analyses, persons in the lowest TSH tertile who were depression free at baseline had a higher risk of incident depressive syndromes [12.3% vs 7.6%, odds ratio (95% confidence interval) 1.85 (1.10-3.11)]. Thyroid autoimmunity (thyroperoxidase antibody positivity) was not associated with CES-D scores or incident depressive syndromes. Elderly persons with low-normal TSH levels have more concurrent depressive symptoms as well as a substantially increased risk of developing a depressive syndrome in the subsequent years. This study identifies low-normal TSH as an important risk factor for depression in the elderly.

The incidence of thyroid function abnormalities and natural course of subclinical thyroid disorders, Tehran, I.R. Iran.

Despite the high prevalence of thyroid dysfunction, the epidemiology and natural course of these disorders have not been identified yet. The present survey was conducted to determine the incidence of thyroid dysfunction and natural course of subclinical thyroid disorders in an urban community of Tehran, I.R. Iran. Serum TSH and thyroperoxidase antibody (TPOAb) were measured at baseline and after 6.7 yr from a sample of 1999 randomly selected subjects aged≥20 yr, participants of the Tehran Lipid and Glucose Study (TLGS). Median TSH value and 2.5, 5, 95, and 97.5 TSH percentiles were determined at baseline using data obtained from 808 negative TPOAb subjects with no history of any thyroid disease or surgery, goiter, nodule, taking thyroid hormone preparations or anti-thyroid drugs. In those with abnormal TSH level, total T4 and T3 uptake were measured and free T4 index was calculated. Normal TSH reference range was 0.4-5.8 μU/ml according to the 2.5 and 97.5 TSH percentiles. The incidence rates of thyroid function abnormalities in 1000 subjects per year were as follows: clinical hypothyroidism: 0.28 in women and 0.21 in men; subclinical hypothyroidism: 11.59 in women and 4.69 in men; clinical hyperthyroidism: 1.4 in women and 0.21 in men; and subclinical hyperthyroidism: 5.72 in women and 3.62 in men. A significant increase was found in the frequency of positive TPOAb in women from 15.9 to 17.7% (p=0.006). Of 8 women with subclinical hypothyroidism at baseline, 5 remained unchanged, 1 became normal, and 1 developed clinical hypothyroidism at followup. Two women with subclinical hyperthyroidism normalized at follow-up. Of 2 men with subclinical hypothyroidism at baseline, 1 remained unchanged, whereas the other progressed to clinical hypothyroidism. After a 6.7 yr follow-up significant increase in the incidence of subclinical thyroid disorders was observed in both men and women, as compared to overt thyroid dysfunction. Increase in the prevalence of TPOAb positivity was observed only in women.

Serum Pepsinogen I: An Early Marker of Pernicious Anemia in Patients with Type 1 Diabetes

Pernicious anemia (PA) is an autoimmune organ disease much more common in type 1 diabetic patients (DM1) than in nondiabetic subjects, but it is clinically silent until its end stage. This study aimed to determine biochemical markers of latent PA in a population of DM1 patients attending the endocrinology outpatient clinic of a university hospital. The population studied consisted of 186 unselected patients (32.4 +/- 8.7 yr) and 118 healthy controls (30.9 +/- 9.4 yr). Plasma gastrin and pepsinogen I were determined in patients and controls, whereas hemoglobin A1c, serum cobalamin, hemoglobin, and organ-specific antibodies were determined only in patients. Latent PA was defined as serum pepsinogen I less than 30 microg/liter. In patients with low pepsinogen I concentrations and hypergastrinemia, esophagogastroduodenoscopy (EGD) was performed. DM1 patients showed significantly lower pepsinogen I concentrations (P < 0.001) and higher gastrinemia than controls. Latent PA was present in 12.4% of patients vs. 0.9% of controls. Among patients, more women than men showed low plasma pepsinogen I concentrations (P = 0.002) and thyroperoxidase antibody positivity (P < 0.001). Only the highest parietal cell antibody titers (> or =1:640) identified patients with significantly higher levels of plasma gastrin (P < 0.001) and lower levels of pepsinogen I (P < 0.001). The histopathological EGD findings confirmed different degrees of gastric body mucosa atrophy in all cases. The high prevalence of latent PA found in our DM1 patients leads us to recommend its screening using serum pepsinogen I concentrations. In patients with hypergastrinemia and high parietal cell antibody titers, EGD should be considered to confirm gastric mucosa atrophy.