Negative Thyroid Peroxidase Antibody Research Articles

Difficulties in the Diagnostics and Treatment of Hashimoto's Encephalopathy-A Systematic and Critical Review.

Hashimoto's encephalopathy (HE) has been a poorly understood disease. It has been described in all age group, yet, there is no specific HE marker. Additionally, the treatment data in the available studies are frequently divergent and contradictory. Therefore, the aim of our systematic and critical review is to evaluate the diagnosis and treatment of HE in view of the latest findings. The databases browsed comprised PubMed, Scopus, and Google Scholar as well as Cochrane Library, and the search strategy included controlled vocabulary and keywords. A total of 2443 manuscripts were found, published since the beginning of HE research until February 2024. In order to determine validity of the data collected from studies, bias assessment was performed using RoB 2 tool. Ultimately, six studies were included in our study. HE should be considered in the differential diagnosis in patients with psychiatric and neurological symptoms. According to our findings, negative thyroid peroxidase antibodies (anti-TPOs) may represent a valuable parameter in ruling out HE. Nonetheless, this result cannot be used to confirm HE. Furthermore, the proposed anti NH2-terminal-α-enolase (anti-NAE) is non-specific for HE. The effectiveness of glucocorticoid therapy is 60.94%, although relapse occurs in 31.67% of patients following the treatment. Our review emphasizes the significance of conducting further large-scale research and the need to take into account the potential genetic factor.

Association between levothyroxine treatment for maternal subclinical hypothyroidism with negative TPOAb and early child neurodevelopment: A prospective real-world clinical trial.

Subclinical hypothyroidism (SCH) during pregnancy is reported to have detrimental impact on pregnancy and child development. However, its treatment indications require further investigation in different thyroid peroxidase antibody (TPOAb) status. This was a secondary analysis of a Chinese prospective cohort in a real-world setting. Pregnant women with gestational SCH were enrolled at the first antenatal visit and grouped by TPOAb positivity. Child neurodevelopment was assessed by the Gesell development diagnosis scale (GDDS) at one, three, six, 12, and 24 months of age. Subgroup analyses and sensitivity analyses were also conducted. ClinicalTrials.gov NCT01744743. From January 2012 to December 2013, a total of 171 participants were enrolled, including 116 of SCH with TPOAb negative (SCH-TPOAb [-]) and 55 of SCH with TPOAb positive (SCH-TPOAb [+]). Compared to women in the SCH-TPOAb (+) group, those in the SCH-TPOAb (-) group had lower thyroid-stimulating hormone (TSH) levels at enrollment and 12-16+6 gestational weeks, and unexpectedly higher TSH levels at 30-34+6 gestational weeks and delivery, with a correspondingly lower levothyroxine dosage throughout pregnancy (all p < 0.05). Offspring in the SCH-TPOAb (-) group displayed lower GDDS scores at one year old than did their counterparts (adjusted p < 0.05), which was possibly related to the worse thyroid function control of maternal SCH-TPOAb (-). No statistically significant difference was found in the GDDS assessments of children at one, three, six, and 24 months of age. These results were also confirmed in subgroup analyses stratified by maternal thyroid characteristics at enrollment, namely TSH levels, free levothyroxine (T4 ) levels, and anti-thyroglobulin antibody (TgAb) status, as well as in sensitivity analyses excluding participants with no levothyroxine treatment at enrollment. In the current clinical practice, infants born to mothers with SCH-TPOAb (-) displayed slightly lower neurodevelopmental scores at one year old than did those born to mothers with SCH-TPOAb (+) but this difference was not seen at two years.

ASSESSING THE UTILITY OF SIMULTANEOUS CO-TESTING APPROACH WITH THYROID STIMULATING HORMONE (TSH) AND THYROID PEROXIDASE (TPO) ANTIBODY TESTING IN INFERTILE WOMEN

Thyroid stimulating hormone (TSH) levels >2.5 mIU/L in the presence of thyroid peroxidase (TPO) antibodies have been associated with adverse pregnancy outcomes but treatment with levothyroxine has been shown to improve outcomes. Many fertility centers initiate treatment when TSH is >2.5 without evaluating TPO antibodies though benefits are unclear when TPO antibodies are negative. By forgoing TPO antibody testing, patients with elevated TSH but negative TPO antibodies are not identified. Therefore, we sought to identify the number of patients needing to undergo co-testing (NNT) with TSH and TPO antibodies to identify 1 patient with TSH >2.5 and negative TPO antibodies.

Ambient air pollution and thyroid function in Spanish adults. A nationwide population-based study (Di@bet.es study)

BackgroundRecent reports have suggested that air pollution may impact thyroid function, although the evidence is still scarce and inconclusive. In this study we evaluated the association of exposure to air pollutants to thyroid function parameters in a nationwide sample representative of the adult population of Spain.MethodsThe Di@bet.es study is a national, cross-sectional, population-based survey which was conducted in 2008-2010 using a random cluster sampling of the Spanish population. The present analyses included 3859 individuals, without a previous thyroid disease diagnosis, and with negative thyroid peroxidase antibodies (TPO Abs) and thyroid-stimulating hormone (TSH) levels of 0.1-20 mIU/L. Participants were assigned air pollution concentrations for particulate matter <2.5μm (PM2.5) and Nitrogen Dioxide (NO2), corresponding to the health examination year, obtained by means of modeling combined with measurements taken at air quality stations (CHIMERE chemistry-transport model). TSH, free thyroxine (FT4), free triiodothyronine (FT3) and TPO Abs concentrations were analyzed using an electrochemiluminescence immunoassay (Modular Analytics E170 Roche).ResultsIn multivariate linear regression models, there was a highly significant negative correlation between PM2.5 concentrations and both FT4 (p<0.001), and FT3 levels (p<0.001). In multivariate logistic regression, there was a significant association between PM2.5 concentrations and the odds of presenting high TSH [OR 1.24 (1.01-1.52) p=0.043], lower FT4 [OR 1.25 (1.02-1.54) p=0.032] and low FT3 levels [1.48 (1.19-1.84) p=<0.001] per each IQR increase in PM2.5 (4.86 μg/m3). There was no association between NO2 concentrations and thyroid hormone levels. No significant heterogeneity was seen in the results between groups of men, pre-menopausal and post-menopausal women.ConclusionsExposures to PM2.5 in the general population were associated with mild alterations in thyroid function.

Relationship Between Thyroid Autoantibodies and Recurrence of Papillary Thyroid Carcinoma in Children and Adolescents.

BackgroundNumerous studies reported connection between papillary thyroid carcinoma (PTC) and thyroid autoantibody in adults, but few of them have investigated whether there is a similar link in children and adolescents. The purpose of this research was to explore the relationship between clinicopathological features, prognosis and preoperative thyroid peroxidase antibody (TPOAb) as well as thyroglobulin antibody (TgAb) status in children and adolescents with PTC.MethodsThis study retrospectively reviewed 179 patients of PTC who underwent a thyroidectomy from January 2000 to June 2021 at Tianjin Medical University Cancer Hospital. We compared preoperative TgAb and TPOAb status with the clinicopathological features and prognosis of children and adolescents with PTC in different age groups.ResultsPatients with positive preoperative TPOAb and TgAb had lower recurrence rate in the younger group (P = 0.006, 0.047, respectively). Patients with positive TPOAb preoperatively had normal level of preoperative Tg and less cervical LNM than patients with negative TPOAb in children and adolescents (P < 0.05). Positive TPOAb preoperatively of PTC patients had a longer median DFS (113.4 months) than negative TPOAb (64.9 months) (P = 0.009, log-rank). Univariate analyses showed age, maximal tumor size, T stage, multifocality, lateral LNM and N staging were predictors for cancer recurrence in children and adolescents (P<0.05). Cox regression analysis found younger age (HR 0.224, P < 0.001), lateral LNM (HR 0.137, P = 0.010), N stage (HR 30.356, P < 0.001) were independent risk factors for recurrence.ConclusionsOur study found that presence of preoperative TPOAb and TgAb could serve as novel prognostic factors for predicting recurrence of PTC in children.

Levothyroxine Therapy for Pregnant Women with Negative Thyroid Peroxidase Antibody and Subclinical Hypothyroidism May Be Associated with Improved Intellectual Development of the Offspring

Levothyroxine Therapy for Pregnant Women with Negative Thyroid Peroxidase Antibody and Subclinical Hypothyroidism May Be Associated with Improved Intellectual Development of the Offspring

Autoimmune Thyroid Disorders in Autoimmune Addison Disease.

ContextAutoimmune thyroid disease is the most common endocrine comorbidity in autoimmune Addison disease (AAD), but detailed investigations of prevalence and clinical course are lacking.ObjectiveThis work aimed to provide comprehensive epidemiological and clinical data on autoimmune thyroid disorders in AAD.MethodsA nationwide registry-based study including 442 patients with AAD and autoimmune thyroid disease were identified through the Norwegian National Registry of Autoimmune Diseases.ResultsOf 912 registered AAD patients, 442 (48%) were diagnosed with autoimmune thyroid disease. A total of 380 (42%) had autoimmune hypothyroidism. Of the 203 with available thyroid function tests at time of diagnosis, 20% had overt hypothyroidism, 73% had subclinical hypothyroidism, and 7% had thyroid levels in the normal range. Negative thyroid peroxidase antibodies was found in 32%. Ninety-eight percent were treated with levothyroxine, 5% with combination therapy with liothyronine or thyroid extracts, and 1% were observed without treatment. Seventy-eight patients (9%) were diagnosed with Graves disease (GD), of whom 16 (21%) were diagnosed with autoimmune hypothyroidism either before onset or after remission of GD. At the end of follow-up, 33% had normal thyroid hormone levels without antithyroid-drugs or levothyroxine treatment. The remaining had either active disease (5%), had undergone ablative treatment (41%), or had developed autoimmune hypothyroidism (21%).ConclusionThe true prevalence of hypothyroidism in AAD is lower than reported in the current literature. Careful consideration of the indication to start thyroxin therapy is warranted. Long-term remission rates in GD patients with AAD are comparable to recent reports on long-term follow-up of patients without AAD.

Seasonal Changes of Thyroid Function Parameters in Women of Reproductive Age Between 2012 and 2018: A Retrospective, Observational, Single-Center Study.

BackgroundThyroid function can be influenced by external stimuli such as light and temperature. However, it is currently unknown whether there is seasonal variation of thyroid function in women of reproductive age. Adequate thyroid function in reproductive-aged women is necessary for optimal fetal–maternal outcomes. Therefore, this study aims to evaluate the seasonal changes in levels of thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4), and TSH index (TSHI) in women of reproductive age.MethodsA large retrospective study was conducted that included women aged 20–49 years who visited our outpatient or checkup center between 2012 and 2018. Thyroid function was measured using the automated immunochemiluminescent assay kit. Subjects with overt thyroid dysfunction, pregnancy, thyroid disease, cancer, and severe infectious or psychological disease were excluded. Seasonal differences of thyroid function were analyzed using the Kruskal–Wallis test or the analysis of means with transformed ranks. Spearman’s correlation was performed to evaluate the association between thyroid function parameters and age. A subset of 181 subjects was included in the longitudinal analyses. Differences in thyroid function between summer and winter were analyzed using the Wilcoxon signed-rank test.ResultsA total of 48,990 women with a median age of 39 years were included. The prevalence of subclinical hypothyroidism was lower in summer but higher in winter (5.6% vs. 7.0%, p < 0.05). The TSH, FT3, and FT4 levels and TSHI reached a peak in winter, while they declined to trough in summer. The TSH concentrations (r = 0.044, p < 0.001) and TSHI (r = 0.025, p < 0.001) were positively correlated with age, whereas FT3 (r = -0.073, p < 0.001) and FT4 (r = -0.059, p < 0.001) were negatively correlated with age. The associations of thyroid parameters with age were similar between subjects with positive thyroid peroxidase antibody (TPOAb) and those with negative TPOAb. In the matched longitudinal analysis of 181 subjects, no differences were detected in the thyroid parameters between summer and winter.ConclusionsThis retrospective single-center study showed that thyroid hormone levels and central sensitivity to thyroid hormones are influenced by age and seasonal fluctuations among women of reproductive age, while their impact on reproductive health remains to be elucidated in future studies.

Expression of Thyroid Peroxidase Antibody, Thyroglobulin Antibody, and Thyrotropin Receptor Antibody in Breast Cancer and Their Associations with Clinical Characteristics of Breast Cancer

The relationship between chronic lymphocytic thyroiditis (CLT) and breast cancer was still unclear. We investigated the positivity of thyroid peroxidase antibody (TPO-ab), thyroglobulin antibody (TG-ab), and thyrotropin receptor antibody (TSHR-ab) in 362 patients with breast cancer, 360 patients with benign breast diseases, and 386 healthy controls. Further, we analyzed the associations between TPO-ab, TG-ab, TSHR-ab, and clinical characteristics in coastal residents with breast cancer according to molecular subtype. There were no significant differences in the levels of free triiodothyronine (FT3), free tetraiodothyronine (FT4), thyroid-stimulating hormone (TSH), and the positive rates of TG-ab and TSHR-ab among three groups. The positive rate of TPO-ab in patients with breast cancer was higher compared to patients with benign breast diseases and healthy controls (P=0.002). Axillary lymph node metastasis (ALNM) in breast cancer patients with positive TPO-ab was less frequent than breast cancer patients with negative TPO-ab (P=0.022). The percentage of TNM stage I–II patients with positive TPO-ab were higher than that in patients with negative TPO-ab (P= 0.029). TPO-ab was a predictor for low prevalence of ALNM in breast cancer patients with luminal A subtype (P=0.013) and luminal B subtype (P=0.024), but not for breast cancer patients with HER2 over-expression subtype (P=0.381) and basal-like subtype (P=0.282). Thyroid peroxidase antibody was an independent predictor for the low prevalence of axillary lymph node metastasis in breast cancer patients with luminal A subtype and luminal B subtype.

Effects of Maternal Subclinical Hypothyroidism in Early Pregnancy Diagnosed by Different Criteria on Adverse Perinatal Outcomes in Chinese Women With Negative TPOAb.

Aims: To compare the effects of maternal subclinical hypothyroidism (SCH) diagnosed by the 2011 or 2017 “Guidelines of the American Thyroid Association (ATA) for the diagnosis and management of thyroid disease during pregnancy and the postpartum” during the first trimester on adverse pregnancy outcomes in thyroid peroxidase antibody (TPOAb)–negative pregnant women.Methods: There were 1,556 Chinese singleton pregnant women with negative TPOAb diagnosed with either SCH or euthyroidism who were investigated, and the prevalence and risk of obstetric outcomes were compared between the two groups using 2011 and 2017 ATA standards, respectively. The effects of a mildly elevated thyroid-stimulating hormone (TSH) concentration on adverse pregnancy outcomes were evaluated by binary logistic regression.Results: Maternal SCH identified by the 2011 ATA guidelines correlated with higher rates and risks of pregnancy-induced hypertension (PIH), preeclampsia, and low-birth-weight infants, while maternal SCH diagnosed by the 2017 ATA guidelines was more likely to develop PIH, preeclampsia, cesarean delivery, preterm delivery, placenta previa, and total adverse maternal and neonatal outcomes. Moreover, a mildly elevated TSH level was significantly associated with PIH after adjustment for confounding factors.Conclusions: Compared with the 2011 ATA guidelines, the 2017 ATA guidelines could be more applicable to Chinese pregnant women to screen the effects of SCH on the majority of adverse pregnancy outcomes.

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.

Radioiodine Therapy-Induced Conversion of Toxic Adenoma to Graves’ Disease

We present a 50-year-old female who was evaluated for the symptoms of thyrotoxicosis. She had low thyroid stimulating hormone (TSH) 0.02 with normal free thyroxine (FT4) 1.00 (0.61-1.76 ng/dL) and normal total triiodothyronine (TT3) 1.0 (0.60-2.20 ng/mL) levels. Her thyrotropin receptor antibody (TRAbs) and thyroid peroxidase antibody (TPOAb) titers were negative. Thyroid ultrasound revealed an ill-defined, heterogeneous, 1.8 cm x 0.8 cm x 0.7 cm nodule in the left lower lobe. 123-radioiodine (RAI) thyroid scan revealed 38.5% uptake, which was concentrated in the lower left thyroid lobe, a finding consistent with a solitary toxic adenoma of the thyroid.The patient became clinically and biochemically euthyroid on methimazole (MMI). She then underwent 131-RAI therapy with 12 mCi, which cured her hyperthyroidism with normalization of TSH levels for four months. She then developed overt thyrotoxicosis with low TSH of 0.02, elevated TT3 of 3.2, and normal FT4 of 0.91. Repeat TRAbs and TPOAb were elevated along with diffusely increased uptake on the I-123 RAI thyroid uptake scan, consistent with Graves’ disease (GD). The patient was then placed on MMI again to bridge to definitive treatment with total thyroidectomy. Our case is a rare case where the patient with solitary toxic adenoma with negative TPOAb serology developed GD following I-131 RAI treatment.

Low Serum IL-17A in Pregnancy During Second Trimester Is Associated With an Increased Risk of Subclinical Hypothyroidism

Problem: Interleukin-17A (IL-17A) has a role in sustaining normal pregnancy. IL-17A is also associated with thyroid autoimmunity during pregnancy. This study sought to investigate whether IL-17A is a risk factor for thyroid dysfunction during pregnancy in women negative for thyroid autoantibodies.Methods of Study: The study comprised 216 pregnant women with negative thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) during the second trimester who provided blood samples for serum IL-17A, thyroid autoantibodies and thyroid function tests. To further evaluate the ratio of CD4+IL-17A+ Th17 cells, we collected peripheral blood from 26 women with thyroid-stimulating hormone (TSH) levels ≤ 2.5 mIU/L and 26 pregnancy-week matched women with TSH levels >2.5 mIU/L, along with samples from 20 women with TSH levels ≤ 4 mIU/L and 20 pregnancy-week matched women with TSH levels >4 mIU/L.Results: The serum IL-17A levels and ratios of CD4+IL-17A+ cells were significantly lower in women with TSH > 2.5 mIU/L than in those with TSH ≤ 2.5 mIU/L (both P < 0.01). Similar lower differences were noted in women with TSH > 4 mIU/L than in those with TSH ≤ 4 mIU/L (both P < 0.01). Moreover, serum TSH correlated negatively with IL-17A levels (β = −0.195, P = 0.004), but positively with the week of gestation (β = 0.284, P < 0.001). Logistic regression indicated that a lower serum IL-17A level was a risk factor for TSH > 2.5 mIU/L [OR = 0.453 (0.298–0.689), P = 0.000] and TSH > 4.0 mIU/L [OR = 0.588 (0.385–0.899), P = 0.013].Conclusion: A low serum IL-17A level during the second trimester is associated with an increased risk of TSH > 2.5 mIU/L and subclinical hypothyroidism.

SAT-481 Pembrolizumab-Induced Thyroiditis with Negative Thyroid Peroxidase Antibody

Introduction: Immune checkpoint inhibitors (ICI) have reformed oncology treatment through its immunomodulatory effect on T-lymphocytes to target metastatic and locally advanced cancers but have been known to produce immune-related adverse events (irAEs). Thyroiditis is a well-documented endocrinopathy occurring in patients receiving ICI; however, a Thyroid Peroxidase Antibody (TPO Ab) negative case of ICI induced thyroiditis suggests that its pathogenesis is independent of antibody mediated thyroid destruction and more associated with an alternative immunoregulatory mechanism. Case Description: A 60-year-old Caucasian, male with a 37-year smoking history and lung adenocarcinoma with metastasis to the brain was referred to Endocrinology clinic for evaluation of suppressed thyroid stimulating hormone (TSH) level. Patient was treated with a four-month course of IV Pembrolizumab every three weeks. TSH was <0.015 (NL 0.465-4.680 IU/mL) four weeks before being seen at the office. TSH level was normal 2.359 before starting immunotherapy. Patient reported occasional anxiety and heat intolerance, but did not experience other hyperthyroid symptoms. Physical examination in office demonstrated no significant thyromegaly, nodules, or tenderness. Vital signs were normal. Thyroid function tests obtained during the office visit were consistent with subclinical hypothyroidism. TSH was mildly elevated 7.545 with normal Free T4 of 0.94 (NL 0.78 - 2.19 ng/dL) and normal Free T3 level of 3.61 (NL 2.77 - 5.27 pg/mL). TPO antibodies were negative. Four weeks later, patient developed overt hypothyroidism; TSH level was higher 12.437 with low Free T4 of 0.71. Patient was then complaining of fatigue and cold intolerance. A diagnosis of drug-induced thyroiditis from Pembrolizumab was made. The patient was prescribed levothyroxine 75 mcg daily and followed closely. Discussion: While literature exists documenting the rare side effect profile of ICI endocrinopathies, few studies illustrate the implications and correlations of TPO Ab negative findings in ICI induced thyroiditis. The role of thyroid autoantibodies in the presumed antibody mediated pathogenesis of thyroid abnormalities is unclear and warrants further longitudinal studies to determine its function in these patients. This case report hopes to both identify the deficit of pathophysiological knowledge contextualizing irAEs while encouraging current healthcare practitioners to continue close monitoring of patients receiving ICI.

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

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

Improved Thyroid Hypoechogenicity Following Bariatric-Induced Weight Loss in Euthyroid Adults With Severe Obesity-a Pilot Study.

Background: Obesity may affect both biochemical thyroid function tests; and thyroid morphology, as assessed using ultrasound scans (US). The aim of the present pilot study was to explore whether weight loss achieved by bariatric surgery alters thyroid US morphology including gray-scale measurements; and/or function in euthyroid adults with severe obesity.Methods: Euthyroid adults (>18 years) with body mass index (BMI) ≥40 kg/m2 and negative thyroid peroxidase antibodies were assessed at baseline (pre-surgery) and after achieving at least 5% weight loss of their baseline body weight following bariatric surgery. Anthropometric assessments, biochemical/hormonal measurements (TSH, free-T4, free-T3, reverse-T3, and leptin) and thyroid US with gray-scale histogram analysis were performed at the baseline and post-surgery follow-up.Results: Ten Caucasian, euthyroid patients (women/men: 8/2; age: 48.6 ± 3.1 years; BMI: 51.4 ± 1.8 kg/m2) successfully completed this study with significantly decreased body weight (>5% weight loss), waist circumference and serum leptin levels post-surgery (mean post-surgery follow-up duration: 16.5 ± 2.5 months). In parallel to the observed bariatric-induced weight loss, thyroid US echogenicity increased by 25% (p = 0.03), without significant changes in thyroid volume. No significant changes in thyroid function tests were detected. No significant correlations were observed between the increase in thyroid echogenicity and the decreases in anthropometric parameters and circulating leptin.Conclusion: Our results indicate that in euthyroid adults with severe obesity, marked weight loss achieved by bariatric surgery is associated with a parallel significant increase in the thyroid US echogenicity, suggesting that morphological changes of the thyroid in obesity are reversible with weight loss.Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03048708

An exploration on the influence of positive simple thyroid peroxidase antibody on female infertility.

The aim of the present study was to explore the influence of positive simple thyroid peroxidase antibody (TPO-Ab) on female infertility. Venous blood was collected on an empty stomach from infertile female patients (all of whom were in line with the World Health Organization's diagnostic criteria for infertility) receiving treatments at The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University from 2014 to 2017 to detect thyroid function and thyroid antibodies [thyroglobulin antibody (TG-Ab), TPO-Ab and thyroid microsome antibody (TM-Ab)]. A total of 529 patients with normal thyroid function, TG-Ab and TM-Ab were included in the present study; they were divided into the positive group (121 cases with positive TPO-Ab) and the negative group (408 cases with negative TPO-Ab). Comparisons of age, body mass index (BMI), basal hormone levels, irregular menstruation, tubal obstruction, premature ovarian failure (POF), endometriosis (EMT) and polycystic ovary syndrome (PCOS) between the two groups of patients were conducted in order to determine whether the differences were statistically significant. The incidence rate of EMT was 39.6% in the positive group and 17.1% in the negative group (P<0.05). The incidence rate of PCOS in the observation group was 43.9%, which was significantly higher than that of the control group (21.3%; P<0.01). The results revealed that the differences in age, BMI, basal hormone levels, irregular menstruation and POF between the two groups were not statistically significant (P>0.05). Finally, the factors that had statistical significance (EMT and PCOS) were stratified by different age groups to compare the incidence rate of positive results among the different age groups, thus concluding which age group was influenced to a greater extent by TPO-Ab. The results indicated that positive TPO-Ab may be associated with PCOS and EMT, though particularly with PCOS. Infertile PCOS patients aged 28–35 years old were influenced more by TPO-Ab than those in other age groups. Thus, it is recommended that thyroid autoantibodies are detected in infertile PCOS females aged 28–35 years old, and treatment should be administered as soon thereafter.

The TSH levels and risk of hypothyroidism: Results from a population based prospective cohort study in an Iranian adult's population

ObjectiveThe aim of current study was to assess the relationship between serum TSH levels and hypothyroidism risk in the euthyroid population. MethodsIn a population-based cohort study, a total of 615 individuals with a normal baseline TSH, from of total population (n=2254) in 2006, were followed up for 6years. TSH, total T4, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) were measured. The relative risk (RR) and 95% confidence interval (95%CI) were calculated based on logistic regression. The Receiver Operating Characteristic (ROC) analysis along with area under the curve (AUC) was used to prediction of future hypothyroidism. ResultsTSH level in 2006 was a significant predictor for overt hypothyroidism, in the total population (RR=3.5) and female (RR=1.37) (all, P value<0.05). A cutoff value of TSH at 2.05mIU/L [AUC: (CI95 %), 0.68 (0.44–0.92; P=0.05)] was obtained for differentiating the patients with overt hypothyroidism from euthyroid. However, this cut off was not observed when we included only negative TPO and TgAbs people in 2006. The RR of hypothyroidism increased gradually when TSH level increased from 2.06–3.6mIU/L to >3.6mIU/L in the total population and both sexes. In women, the risk of overt hypothyroidism was significantly higher in subjects with TSH above 3.6 than those subject with THS levels≤2.05 [RR: (CI95 %), 20.57(2.−207.04), P value<0.05]. ConclusionA cutoff value of TSH at 2.05mIU/L could predict the development of overt hypothyroidism in future. However, it was not applicable for people with negative TPOAb and negative TgAb.

Obstetric Outcomes of an Afro-Caribbean Cohort Following Universal Screening and Treatment of Subclinical Hypothyroidism.

Restoration of euthyroidism with l-thyroxine reportedly reduces obstetric complications associated with subclinical hypothyroidism (SCH). The objective was to determine if obstetric outcomes of treated subjects were equivalent to euthyroid subjects. This was a prospective cohort study. Subjects were considered euthyroid if serum thyroidstimulating hormone (TSH) was 0.4-3 mIU/L and free thyroxine (FT4) 10.29-17.05 pmol/L with negative thyroid peroxidase antibodies (TPOAb). Subclinical hypothyroidism was diagnosed if FT4 was 10.29-24.45 pmol/L and TSH 2.5-3 mU/L with positive TPOAb, or TSH > 3.0 mU/L regardless of antibody status. Subclinical hypothyroidism subjects were treated with l-thyroxine until TSH < 2.5 mIU/L. Data were analysed with Stata (StataCorp, USA). Seven hundred and sixty-nine singleton pregnancies were screened; 96% at 14 weeks gestation. Five hundred and eleven (66%) were euthyroid by study definition. Prevalence of SCH was 1.9% (15/769); 26% (4/15) were TPOAb positive. Eighty-one per cent were treated according to protocol; compliance was 54%. Mean gestational age (GA) at first endocrinologist visit was 22.7 ± 2.7 weeks. Normal TSH was documented in 36% at GA 33 ± 2.94 weeks. Subjects with SCH had significantly greater pre-existing history of preterm premature rupture of membranes (PPROM) and preterm labour, Caesarean sections for non-reassuring fetal heart rate and neonatal necrotizing enterocolitis. L-thyroxine appeared to reduce obstetric complications. However, prevalence of SCH was low and compliance was < 50%.

Gestational hypothyroidism: development of mild hypothyroidism in early pregnancy in previously euthyroid women

To determine the proportion of euthyroid women attending a fertility practice who develop hypothyroidism in very early pregnancy (gestational hypothyroidism [GHT]), and to examine the association of GHT with exogenous gonadotropin treatment. Retrospective cohort study. A private reproductive medicine practice. All healthy women (N = 94) with infertility or recurrent pregnancy loss, TSH level <2.5 mIU/L, negative thyroid peroxidase antibodies at initial evaluation, and not taking thyroid medication, who conceived during an 18-month period. Usual fertility care; 30 women who had received exogenous gonadotropins. Serum TSH level at the time of pregnancy detection. Gestational hypothyroidism (TSH ≥ 2.5 mIU/L) developed in 23 of 94 women (24%). The mean increase in serum TSH level from initial evaluation to early pregnancy was 0.45 ± 0.08 [SE] mIU/L. There was a trend toward the association of GHT with use of exogenous gonadotropins. Gestational hypothyroidism was positively associated with initial prepregnancy TSH level. Euthyroid women may develop mild hypothyroidism in early pregnancy, especially after exogenous gonadotropin treatment. Appropriate vigilance will allow for timely levothyroxine treatment.