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Concept: Thyroid peroxidase


Context:Maternal thyroid dysfunction, especially in early pregnancy, may lead to pregnancy complications and adverse birth outcomes. Few population-based prospective studies have evaluated these effects and results are discrepant.Objective:We examined the association of thyroid function and autoimmunity in early pregnancy with adverse pregnancy and birth outcomes.Setting and Participants:The study used data from the prospective mother-child cohort “Rhea” study in Crete, Greece. A total of 1170 women with singleton pregnancies participated in this analysis. Maternal serum samples in the first trimester of pregnancy were tested for thyroid hormones (TSH, free T(4), and free T(3)) and thyroid antibodies (thyroid peroxidase antibody and thyroglobulin antibody). Multivariable log-Poisson regression models were used adjusting for confounders.Main Outcome Measures:Outcomes included gestational diabetes, gestational hypertension/preeclampsia, cesarean section, preterm delivery, low birth weight, and small-for-gestational-age neonates.Results:The combination of high TSH and thyroid autoimmunity in early pregnancy was associated with a 4-fold increased risk for gestational diabetes [relative risk (RR) 4.3, 95% confidence interval (CI) 2.1-8.9)] and a 3-fold increased risk for low birth weight neonates (RR 3.1, 95% CI 1.2-8.0) after adjustment for several confounders. Women positive for thyroid antibodies without elevated TSH levels in early pregnancy were at high risk for spontaneous preterm delivery (RR 1.7, 95% CI 1.1-2.8), whereas the combined effect of high TSH and positive thyroid antibodies did not show an association with preterm birth.Conclusions:High TSH levels and thyroid autoimmunity in early pregnancy may detrimentally affect pregnancy and birth outcomes.

Concepts: Immune system, Pregnancy, Childbirth, Thyroid-stimulating hormone, Obstetrics, Thyroid, Thyroid hormone, Thyroid peroxidase


Background: The role of viruses as environmental triggers for Hashimoto’s thyroiditis (HT) is controversial. Thyroid epithelial cells express a variety of molecules involved in antiviral responses. This study combined histological, immunological and virological tests to describe changes in tissue from patients with newly diagnosed and untreated HT. To study the early events, patients with positive thyroid peroxidase antibodies (TPO-Ab) and normal thyroid function were also included. This stage was defined as “prethyroiditis”. Methods: Thyroid tissue was collected from 47 patients with high titers of TPO-Ab and from 24 controls. Seventeen patients had prethyroiditis, 17 had subclinical hypothyroidism, and 13 had overt hypothyroidism. IFN-α/β-inducible myxovirus resistance protein 1 (Myxovirus resistance protein A; MxA) was used as a surrogate marker for type I interferon (IFN) expression. Inflammation, expression of MxA, and the presence of the enteroviral capsid protein VP1 (VP1) were characterized by immunohistochemistry. The presence of enterovirus RNA was examined by in situ hybridization. Results: The density of CD4+ T cells was increased in all three patient groups, while CD8+ T cells were increased only in patients with overt hypothyroidism. The density of plasma cells increased as the disease progressed. The density of plasmacytoid dendritic cells (PDCs) and the expression of MxA were significantly increased in all patient groups compared with controls (p<0.01). Enterovirus RNA was present in 11% of HT patients but in none of the control subjects, whereas enteroviral protein was detected in 19% and 16%, respectively. Conclusion: The inflammatory reaction in the thyroid gland is a very early event in pathogenesis of HT. Increased expression of MxA in the inflamed tissue suggests that type I interferon plays a role in disease development. Whether this is virus-dependent needs to be explored in further studies.

Concepts: Immune system, Virus, Thyroid disease, Hypothyroidism, Hashimoto's thyroiditis, Hyperthyroidism, Thyroid, Thyroid peroxidase


Background: Thyroid autoimmunity (TAI) is frequent in infertile women but to what extend thyroglobulin antibodies (Tg-Abs) contribute to TAI is unclear in literature. The aims of the present study were to determine the prevalence of TAI in women consulting for fertility problems and to investigate the impact of isolated Tg-Abs, isolated thyroid peroxidase antibodies (TPO-Abs) and the presence of both Ab types on thyroid function. Furthermore, thyroid function was compared between women with - and without TAI and between infertile and fertile women. Methods: Cross-sectional data analysis nested within an ongoing prospective cohort study, to determine the prevalence of TAI in unselected women consulting our tertiary referral center for reproductive medicine (CRM). The women underwent a blood sample for the determination of serum TSH, FT4, TPO-Abs and Tg-Abs. Cause of infertility, age, BMI and smoking habits were recorded. Results: The prevalence of TAI was 16% (163/992); in 8% both types of antibodies were present, in 5% of women isolated positive Tg-Abs were found and 4% had isolated positive TPO-Abs (p=0.025 and p=0.003, respectively). The prevalence of TAI was significantly higher in infertile women as compared to that in fertile controls (19% versus 13%; p=0.047). The median serum TSH level was significantly higher in the women with TAI and with isolated positive Tg-Abs, compared to that in women without TAI (1.83 [1.44] and 1.90 [0.85] versus 1.47 [0.94] mIU/L; p<0.001 respectively). The median FT4, age, BMI and smoking habits, were comparable between the study groups. Conclusions: The prevalence of TAI was higher in infertile women as compared to fertile women consulting our CRM. Five percent of the women had isolated positive Tg-Abs and a significantly higher serum TSH compared to that in women without TAI.

Concepts: Pregnancy, Infertility, Fertility, Hashimoto's thyroiditis, Thyroid, Assisted reproductive technology, Thyroglobulin, Thyroid peroxidase


PURPOSE: The role of thyroid function in biochemical markers of first trimester screening has not been assessed. The aim of the present study was to investigate if there were any relation between maternal thyroid hormones and free-beta subunit of human chorionic gonadotropin (fβ-hCG) and pregnancy-associated plasma protein A (PAPP-A) levels as the biochemical markers of the combined first trimester aneuploidy screening. METHODS: 375 pregnant women between 11 and 14 weeks of gestation who were offered routine first trimester prenatal aneuploidy screening and whose thyroid hormone levels (Thyroid stimulating hormone (TSH), free and total thyroxine, free and total triiodothyronine, anti thyroid peroxidase antibody) were measured were assessed. Correlation of free-β-hCG and PAPP-A with maternal thyroid hormones was analyzed. RESULTS: There was no statistically significant correlation between maternal TSH, free and total thyroxine, free and total triiodothyronine, anti-thyroid peroxidase antibodies and free-β-hCG and PAPP-A as biochemical markers of first trimester aneuploidy screening. CONCLUSION: Maternal thyroid function does not seem to affect secretion of fβ-hCG and PAPP-A.

Concepts: Pregnancy, Hormone, Thyroid, Thyroid hormone, Human chorionic gonadotropin, Triiodothyronine, Thyroxine, Thyroid peroxidase


Context:Relatively little is known in euthyroid populations about the changes in maternal thyroid hormones during pregnancy, the nature of the relationship to cord thyroid hormone levels, and subsequent infant neurodevelopment.Objectives:The aim of the study was to describe the relationship between maternal and cord thyroid hormone parameters and to describe their associations with neurodevelopment at 5.5 years.Design:We conducted a follow-up of women and their children born at or over 37 weeks' gestation.Main Outcomes:We measured maternal levels of TSH, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), T(4), and free T(4) (FT(4)) at 10 and 34 weeks and at delivery, and cord levels of T(4), FT(4), TPOAb, and TgAb. The association of cord thyroid hormone parameters with McCarthy scale scores adjusted for the major confounders of neurodevelopment.Results:Fifteen percent of the women were TPOAb-positive, and 12% were TgAb-positive; the proportion of women with mildly elevated TSH levels increased during pregnancy with the maximum (14%) at delivery. Lower perceptual performance and motor scores were found with TgAb-positive women and lower perceptual performance scores with TgAb-positive cord levels; otherwise, unadjusted maternal levels of TPOAb, TgAb, and TSH and unadjusted cord levels of FT(4), TPOAb, and TgAb were not associated with neurodevelopment at 5.5 years. Low cord T(4) levels were associated with significant increments in four McCarthy scales: General Cognitive Index, Verbal, Quantitative, and Memory scales-increments that persisted after adjustment at 11.4, 7.8, 7.6, and 7.8 points, respectively.Conclusions:Lower levels of cord T(4) were associated with increments in the McCarthy scales in the domains that tested cognitive and verbal abilities at 5.5 years.

Concepts: Infant, Hormone, Thyroid-stimulating hormone, Thyroid, Thyroid hormone, Triiodothyronine, Thyroglobulin, Thyroid peroxidase


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).

Concepts: Pregnancy, Childbirth, Thyroid, Progesterone, Human chorionic gonadotropin, Glycoprotein, Pregnancy test, Thyroid peroxidase


Purpose: The association between autoimmune thyroid diseases (AITDs) and vitamin D deficiency is controversial. We aimed to evaluate the relationship between serum 25-hydroxy-vitamin D3 [25(OH)D3] and anti-thyroid antibody levels. Materials and Methods: 25(OH)D3, anti-thyroid antibodies, and thyroid function measured in 304 patients who visited the endocrinology clinic were analyzed. The patients were subgrouped into the AITDs or non-AITDs category according to the presence or absence of anti-thyroid antibodies. The relationship between anti-thyroid peroxidase antibody (TPOAb) and 25(OH)D3 was evaluated. Results: The patients with elevated anti-thyroid antibodies had lower levels of serum 25(OH)D3 than those who did not (12.6±5.5 ng/mL vs. 14.5±7.3 ng/mL, respectively, p<0.001). Importantly, after adjusting for age, sex, and body mass index, a negative correlation (r=-0.252, p<0.001) was recognized between 25(OH)D3 and TPOAb levels in the AITDs group, but this correlation did not exist in the non-AITDs group (r=0.117, p=0.127). 25(OH)D3 level was confirmed as an independent factor after adjusting for co-factors that may affect the presence of TPOAb in the AITDs group. Conclusion: 25(OH)D3 level is an independent factor affecting the presence of TPOAb in AITDs. The causal effect of 25(OH)D3 deficiency to AITDs is to be elucidated.

Concepts: Immune system, Vitamin D, Hashimoto's thyroiditis, Hyperthyroidism, Thyroid, Graves' disease, Endocrine system, Thyroid peroxidase


Context: 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. Objective: The objective of the study was to examine the association between normal-range thyroid function and the risk of depression. Design, Setting, and Participants: This was a cohort study in 1503 Dutch men and women, aged 70.6 (7.3) 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). Results: 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. Conclusions: 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.

Concepts: Cohort study, Epidemiology, Hashimoto's thyroiditis, Thyroid, Normal distribution, Major depressive disorder, Dysthymia, Thyroid peroxidase


Context:Hashimoto’s thyroiditis is less prevalent in tobacco smokers. Anatabine, an alkaloid found in Solanaceae plants including tobacco, has been reported to ameliorate a mouse model of Hashimoto’s thyroiditis.Objective:The effects of anatabine in patients with Hashimoto’s thyroiditis.Design, Setting, Patients, and Intervention:Double-blind, randomized, placebo-controlled multi-site study. A total of 146 patients (70 treated with anatabine, and 76 placebo) completed the study. Approximately 50% of patients in each group were on levothyroxine medication. Anatabine lozenges (9-24 mg/day) or placebo, each containing vitamins A and D3, were administered orally 3 times a day for three months.Main Outcome Measures:Assessment of serum thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb). Safety was assessed though adverse events (AEs), clinical laboratory evaluations, and vital sign measurements.Results:Anatabine treated patients had a significant reduction in absolute serum TgAb levels from baseline by study end relative to those on placebo (p=0.027); however, there were no significant changes or differences in treatment group means for TPOAb or TgAb. Mean (±SD) TgAb values decreased by 46.2 (±101.1) and 3.9 (±83.9) WHO units for the anatabine and placebo groups, respectively. Significantly more patients had a >20% drop in TgAb in the anatabine than placebo group (p=0.023). Overall the anatabine supplement was safe and well tolerated, although significantly (p<0.05) more patients in the anatabine group reported AEs.Conclusions:These results demonstrate an immunological effect of anatabine on TgAb levels. Further studies are warranted to dissect longer-term effects and possible actions of anatabine on the course of Hashimoto's thyroiditis.

Concepts: Clinical trial, Hypothyroidism, Hashimoto's thyroiditis, Hyperthyroidism, Thyroid, Placebo, Thyroglobulin, Thyroid peroxidase


Autoimmune disruption may contribute to risk for autism; however, since previous studies relied upon clinical diagnoses, exposure misclassification and recall bias are limitations. Thyroid peroxidase antibody (TPO-Ab) is an autoantibody involved in autoimmune thyroiditis. We aimed to test the a priori hypothesis that positivity to maternal serum TPO-Ab (TPO-Ab+) (defined as >156 IU/ml) during pregnancy is related to childhood autism.

Concepts: Immune system, Cohort study, Coeliac disease, Thyroid peroxidase