Positive Thyroid Peroxidase Antibodies Research Articles

The outcome of thyroid disease induced by interferon plus ribavirin in patients with chronic hepatitis C

Objective To explore the long-term outcome of thyroid disease occurred during and after peg-interferon plus ribavirin therapy (PR therapy) in patients with chronic hepatitis C (CHC). Methods CHC patients admitted to Henan People′s Hospital during January 2009 to December 2012 treated with peg-interferon plus ribavirin were included in this study. The thyroid functions were tested before treatment, at week 12, week 24, week 48, week 72 of treatment, and at week 24, week 48, week 96, week 144 after end of treatment. Thyroid function test frequency was increased according to the patients′ test results and medication was registered. Measurement data was analyzed using t test and count data was compared using chi square test or Fisher exact probability test. Results A total of 358 patients was included with mean age of (43±12) years (range 18 to 65 years), of whom 200 were male and 158 were female. There are 300 cases (83.8%) with HCV genotype-1 infection, 56 cases (15.6%) with genotype-2 infection and 2 cases (0.6%) with genotype 3 infection. Eighty out of 358 patients (22.3%) developed thyroid disease, among whom 71 cases (88.75%) were diagnosed with autoimmune thyroiditis and 9 cases (11.25%) were non-autoimmune thyroiditis. At week 144 after end of treatment, 21 (29.6%) cases with autoimmune thyroiditis completely recovered and 9 cases with non-autoimmune thyroiditis fully restored. The comparison between two groups had statistical significance (F=16.69, P=0.00). Patients were divided into non-thyroid disease and thyroid disease groups. The were no significant differences of baseline viral load, HCV genotype, transaminase levels and age between the two group (all P>0.05). The differences of gender, baseline levels of thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb) and treatment outcome were statistically significant (all P<0.05). Conclusions Interferon-induced autoimmune thyroiditis could not be completely reversed. Some patients develop chronic thyroiditis and require long-term drug therapy. Patients with positive TPOAb and TgAb induced by interferon have high risk of developing Hashimoto′s thyroiditis and Graves′disease during follow-up. Appropriate treatment for thethyroid disease induced by interferon does not affect the antiviral treatment. Clinicians should monitor the thyroid function during and after antiviral therapy in patients with CHC. Key words: Hepatitis C, chronic; Thyroid diseases; Interferon; Thyroid Autoantibodies

Relationship between the thyroid autoimmunity and the risk of preterm birth in pregnant women: a meta-analysis

To evaluate the relationship between thyroid autoimmunity and the risk of preterm birth. Literature search was done among PubMed, Embase, Wanfang Medical Database, China Academic Journal Network Publishing Database and China Biology Medicine disc from Jan. 1(st) 1980 to July 31(st), 2015. (1) Literature were extracted according to inclusion and exclusion standards, and the quality of the extracted literature were evaluated by Newcastle-Ottawa Scale (NOS). (2) Meta-analysis was performed by RevMan 5 software formulated by using the Cochrane library databases. Various heterogeneity of the research was inspected firstly. According to the results of the inspection a certain effect model was selected (including fixed effects model, the random effects model) to be utilized in merger analysis. In this study pregnant women with both thyroid peroxidase antibodies (TPO-Ab) and thyroglobulin (TG-Ab) positive were defined as thyroid antibody positive pregnant women. Pregnant women with only TPO-Ab positive were defined as TPO-Ab positive pregnant women. Then the relationship of antibody positive and the risk of a preterm birth was analyzed respectively. (1) Ten cohort studies were enrolled, of which NOS scale score were 7 or higher. All the studies are of medium quality and above. A total of 1 322 cases of preterm birth occurred among 19 910 pregnant women. (2) Positive thyroid autoantibodies did not increase the risk of preterm birth in euthyroid pregnant women (OR=1.41, 95%CI: 0.83-2.40, P=0.200) or in pregnant women with hypothyroidism (OR=0.68, 95% CI: 0.32-1.44, P=0.310) . Positive TPO-Ab in euthyroid pregnant women increase the risk of preterm birth significantly (OR=2.08, 95%CI: 1.09-3.97, P=0.030), but positive TPO-Ab in pregnant women with hypothyroidism did not increase the risk of preterm birth significantly (OR=1.21, 95%CI: 0.65-2.24, P=0.550). Positive TPO-Ab is an independent risk factor of preterm birth in euthyroid pregnant women.

The analysis of the changes of maternal thyroid autoantibodies during early pregnancy

Objective To investigate the changes and related factors of maternal thyroid autoantibodies during early pregnancy. Methods Urinary iodine concentration(UIC), serum thyroid stimulating hormone(TSH), free thyroxine(FT4), thyroid-peroxidase antibody(TPOAb), thyroglobulin antibody(TgAb)concentrations were determined in 7 190 women during early pregnancy in an iodine-sufficient region of China. Results The prevalence of TPOAb positivity and TgAb positivity were 8.7% and 12.0% respectively. The prevalence of overt hypothyroidism and subclinical hypothyroidism increased significantly in group of thyroid antibody positivity. The prevalence of TPOAb positivity and TgAb positivity presented a U-shaped curve, ranging from mild iodine deficiency to iodine excess, especially increased significantly in the group with UIC<100 μg/L. Conclusion Prevalence of thyroid antibodies positivity became higher during early pregnancy. The positive thyroid autoantibodies during pregnancy were significantly associated with maternal hypothyroidism. Both iodine excess and iodine deficiency are risk factors of positive thyroid antibodies. (Chin J Endocrinol Metab, 2016, 32: 376-379) Key words: Thyroid; Pregnancy; Thyroid antibody; Iodine

Thyroid Function in Patients with Cystic Fibrosis: No Longer a Concern?

Development of goiter and hypothyroidism has been reported in patients with cystic fibrosis (CF) since the 1970s, especially when treated with iodine-based expectorants. With iodine-containing expectorants no longer in routine use, the prevalence of thyroid dysfunction in CF patients is unknown. This cross-sectional study assessed thyroid function status in a large cohort of CF patients. Sera from ambulatory subjects were obtained from an Institutional Review Board (IRB)-approved biorepository of patients seen at the Emory CF Center between January 1, 2011, and December 31, 2014. Sera from hospitalized subjects were obtained from banked specimens from an IRB-approved inpatient clinical trial. Demographics, forced expiratory volume in one second (FEV1), and medication use were assessed from medical records. Thyroid function tests were measured from the stored sera. Multivariate regression models assessed associations between covariates and thyrotropin (TSH), free thyroxine (fT4), and thyroid dysfunction risk. A total of 89 subjects (54% male, 91% white, Mage = 24.4 years, median FEV1 63%) were included in the analyses. One subject was on thyroid hormone replacement, 93% were on pancreatic enzyme replacement, and 68% received antibiotics within six months. None had computed tomography scans with intravenous contrast within six months. One patient had positive thyroid peroxidase (TPO) antibodies. Of the 87 subjects with measured TSH values, seven (8%) had abnormal levels (range 0.2-7.6 μIU/mL; one overt, four subclinical hypothyroidism, and two subclinical hyperthyroidism). Of the 56 subjects with measured fT4 values, 19 (34%) had slightly low levels (range 0.49-0.79 ng/dL; 17 isolated mild hypothyroxinemia). A positive correlation between age and body mass index (BMI; p < 0.001) and a negative correlation between age and FEV1 (p = 0.041) were seen. Age, sex, race/ethnicity, BMI, FEV1, hospitalization status, use of pancreatic enzyme or thyroid hormone replacement, recent antibiotic use, and TPO antibody positivity were not predictive of TSH, fT4, or thyroid dysfunction risk. Stratified analyses by hospitalization did not predict TSH or fT4. Although 24 (27%) of the patients had abnormal serum thyroid function tests, overt thyroid dysfunction was rare in this cohort of 89 patients with CF. The degree of hypothyroxinemia was marginal, likely due to nonthyroidal illness. There were no significant predictors of thyroid dysfunction.

The Effect of Subclinical Maternal Thyroid Dysfunction and Autoimmunity on Intrauterine Growth Restriction: A Systematic Review and Meta-Analysis.

The objective of this study was to evaluate the association between maternal subclinical thyroid dysfunction and autoimmunity with the risk for intrauterine growth restriction (IUGR).Design is a systematic review and meta-analysis.A literature search was conducted using PubMed, Embase, and Cochrane database. A combination of 2 key words was used to search for the eligible studies: one indexed thyroid dysfunction or antithyroid antibodies; and the other one indexed the adverse neonatal outcomes of pregnancy, such as IUGR, small for gestational age, fetal growth restriction, or low birth weight.Two reviewers selected the studies, and eligible studies met the following criteria: prospective cohort studies or case control studies, studies of maternal thyroid dysfunction and positive antithyroid antibodies as the exposure of interest, and studies of IUGR or small for gestational age as the outcome of interest.Data were recorded, including data from maternal thyroid disorders and IUGR, and compared with a reference group.There were 22 individual data from the 13 cohort articles. Among these, 7 were focused on subclinical hypothyroidism (SCH), 4 on subclinical hyperthyroidism, 7 on positivity for thyroid peroxidase antibody (TPOAb), and 4 on isolated hypothyroxinemia. Meta-analysis showed that there was no effect of subclinical hyperthyroidism (odds ratio (OR) = 0.98; 95% confidence interval (CI), 0.40–2.41), TPOAb positivity (OR = 1.57; 95% CI, 0.77–3.18), or isolated hypothyroxinemia (OR = 1.05, 95% CI: 0.37–2.92) on IUGR. However, SCH is associated with IUGR (OR = 1.54; 95% CI, 1.06–2.25).SCH is associated with IUGR; however, subclinical hyperthyroidism, TPOAb positivity, or isolated hypothyroxinemia do not affect the risk of IUGR.

Unusual Presentation of Tuberculous Thyroid Abscess in a Background of Hashimoto’s Thyroiditis in a Chronic Hepatitis B Carrier

Tuberculosis of thyroid gland is a very rare disease. It has variable presentations and may be sometimes associated with autoimmune thyroiditis. We report a case of 45-year-old male, with left sided painless neck swelling, with a purulent discharging sinus over it associated with night sweats and loss of appetite. Thyroid imaging disclosed heterogeneous enhancement of left lobe of thyroid gland with internal vascularity and coarse calcifications. Core needle biopsy revealed caseous necrosis and AFB positivity. Patient had thyroid peroxidase antibody and thyroglobulin antibody positivity and the rest of thyroid function tests were normal. Patient had positive Mantoux test, hepatitis B surface Ag, and low viral DNA. The patient was diagnosed as being a case of tuberculous abscess of thyroid gland and was put on antitubercular therapy for 2 months. Patient subsequently underwent left hemithyroidectomy when there was no response. Histopathological examination revealed tuberculosis of thyroid gland. A final diagnosis of tuberculous abscess of thyroid gland in a background of Hashimoto's thyroiditis in a chronic HBV carrier was made. Therefore, although rare tuberculosis of thyroid should be kept in mind as a differential diagnosis of thyroid swelling.

Circulating Betatrophin Is Increased in Patients with Overt and Subclinical Hypothyroidism.

Thyroid hormone (TH) affects many metabolic processes such as promoting oxidation of sugar, fat, and protein in many tissues. Thyroid dysfunction is associated with metabolic disorders. The newly discovered adipocyte- and hepatocyte-derived cytokine, betatrophin, has been reported to be involved in metabolic diseases, but its influence on thyroid dysfunction is uncertain. Therefore, the present study aims to evaluate circulating betatrophin levels in subjects with different thyroid function status and to predict the factors associated with betatrophin levels, especially whether thyroid stimulating hormone (TSH), TH, or thyroid autoantibodies are associated with betatrophin levels. In the study, serum betatrophin was measured in the subjects grouped as overt hypothyroidism (OH), subclinical hypothyroidism (SCH), euthyroid with isolated thyroid peroxidase antibody positivity (isolated Ab), and healthy control (HC), according to their thyroid functions. From our results, we found that betatrophin may be associated with thyroid insufficiency but not thyroid autoimmunity. Thus, when interpreting the results of betatrophin, thyroid functions should also be taken into consideration.

A preliminary study on the pregnancy outcomes of pregnant women with positive thyroid peroxidase antibody

Objective To explore the correlation between simple thyroid peroxidase antibody(TPOAb)positive(higher than the normal reference value )and the adverse pregnancy outcomes; and to discuss the necessity of clinical intervention on TPOAb positive and the characteristic of gestational thyroid peroxidase antibody changes. To study wether clinical intervention affects its direction. Methods Subjects were selected from TPOAb positive pregnant women during June 2012 to February 2015. They were registered regularly for thyroid function during pregnancy and 6 weeks postpartum, and timely treated for abnormal thyroid function. They were grouped according to the thyroid function: Group 1(n=122), simple TPOAb positive group; Group 2(n=67), patients with elevated TSH and positive TPOAb who accept the levothyroxine(L-T4)intervention; Group 3(n=120), TPOAb negative healthy pregnant women. They were regularly tested for thyroid function during pregnancy, and with follow-up until 6 weeks postpartum. Results When Group 1 compared with Group 3: the risk of premature rupture of membranes, abnormal amniotic fluid, and fetal distress rate increased, the relative risk(RR)were 3.066, 4.782, 2.605, all P 0.05). When Group 2 compared with Group 3, the risk of premature rupture of membranes, abnormal amniotic fluid, and fetal distress increased(RR were 3.830, 5.537, 3.600 respectively, all P 0.05). Compared with Group 2, Group 1 had no statistical difference between the above observational parameters. The levels of TPOAb from stage T1(the first trimester)to T3(the third trimester)showed a overall downward trend in Group 1 and Group 2, rise again six weeks after child birth. Comparison of the two groups(Group 1 and Group 2), the median value during this period did not reveal any significantly statistical differences(P>0.05). Conclusion In simple TPOAb positive pregnant women, premature rupture of membranes, abnormality in amniotic fluid, and fetal distress were significantly higher than those in healthy pregnant women; even with thyroid function correction the TPOAb positive pregnant women still cannot reduce the adverse pregnancy outcomes. Levels of TPOAb from T1 to T3 presented the overall downward trend and to rise again six weeks after pregnancy. L-T4 intervention for TPOAb positive pregnancy did not show any significant effect.(Chin J Endocrinol Metab, 2015, 31: 1041-1045) Key words: Pregnancy; Thyroid peroxidase antibody; Pregnancy outcomes

Positive thyroid peroxidase antibodies at diagnosis of type 1 diabetes mellitus is associated with earlier onset of thyroid disorders

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Can levothyroxine treatment reduce urinary albumin excretion rate in patients with early type 2 diabetic nephropathy and subclinical hypothyroidism? A randomized double-blind and placebo-controlled study

Objective:To investigate the effect of levothyroxine (LT4) therapy on urinary albumin excretion rate (UAER) in early type 2 diabetic nephropathy (DN) and subclinical hypothyroidism (SCH) patients with mildly increased thyroid stimulating hormone (TSH) levels and serum thyroid peroxidase antibody (TPO-Ab) positivity.Methods:Application of randomized double-blind and placebo-controlled methods. A total of 136 normotensive patients with early type 2 DN and SCH (TSH 4.0–7.0 mIU/L and TPO-Ab positive) were selected, and were randomly divided into two groups for LT4 or placebo treatments, respectively. Changes in UAER, serum creatinine, glomerular filtration rate (GFR), blood pressure, serum uric acid and lipids in patients before and after 48 weeks of treatment were examined and compared between groups.Results:There were no statistically significant differences in the baseline characteristics of study participants between two treatment groups (p > 0.05 for all). After 48 weeks of treatment, compared to the placebo treatment, the LT4 treatment was more effective in reducing total cholesterol (p < 0.05). Further comparison of therapy-related differences between groups showed that the LT4 treatment was better in reducing UAER, low-density lipoprotein cholesterol and uric acid than the placebo group (p < 0.01 for all).Conclusion:The LT4 treatment may decrease UAER and exert kidney protection effects in early type 2 DN and SCH patients with mildly increased TSH levels and serum TPO-Ab positivity. However, due to the short duration of follow-up and small number of cases, the results of this study need future trials with larger numbers of patients and longer follow-up periods to verify whether such a strategy can provide durable benefits.

Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphology in childhood: a population-based prospective cohort study

Thyroid hormone is involved in the regulation of early brain development. Since the fetal thyroid gland is not fully functional until week 18-20 of pregnancy, neuronal migration and other crucial early stages of intrauterine brain development largely depend on the supply of maternal thyroid hormone. Current clinical practice mostly focuses on preventing the negative consequences of low thyroid hormone concentrations, but data from animal studies have shown that both low and high concentrations of thyroid hormone have negative effects on offspring brain development. We aimed to investigate the association of maternal thyroid function with child intelligence quotient (IQ) and brain morphology. In this population-based prospective cohort study, embedded within the Generation R Study (Rotterdam, Netherlands), we investigated the association of maternal thyroid function with child IQ (assessed by non-verbal intelligence tests) and brain morphology (assessed on brain MRI scans). Eligible women were those living in the study area at their delivery date, which had to be between April 1, 2002, and Jan 1, 2006. For this study, women with available serum samples who presented in early pregnancy (<18 weeks) were included. Data for maternal thyroid-stimulating hormone, free thyroxine, thyroid peroxidase antibodies (at weeks 9-18 of pregnancy), and child IQ (assessed at a median of 6·0 years of age [95% range 5·6-7·9 years]) or brain MRI scans (done at a median of 8·0 years of age [6·2-10·0]) were obtained. Analyses were adjusted for potential confounders including concentrations of human chorionic gonadotropin and child thyroid-stimulating hormone and free thyroxine. Data for child IQ were available for 3839 mother-child pairs, and MRI scans were available from 646 children. Maternal free thyroxine concentrations showed an inverted U-shaped association with child IQ (p=0·0044), child grey matter volume (p=0·0062), and cortex volume (p=0·0011). For both low and high maternal free thyroxine concentrations, this association corresponded to a 1·4-3·8 points reduction in mean child IQ. Maternal thyroid-stimulating hormone was not associated with child IQ or brain morphology. All associations remained similar after the exclusion of women with overt hypothyroidism and overt hyperthyroidism, and after adjustment for concentrations of human chorionic gonadotropin, child thyroid-stimulating hormone and free thyroxine or thyroid peroxidase antibodies (continuous or positivity). Both low and high maternal free thyroxine concentrations during pregnancy were associated with lower child IQ and lower grey matter and cortex volume. The association between high maternal free thyroxine and low child IQ suggests that levothyroxine therapy during pregnancy, which is often initiated in women with subclinical hypothyroidism during pregnancy, might carry the potential risk of adverse child neurodevelopment outcomes when the aim of treatment is to achieve high-normal thyroid function test results. The Netherlands Organisation for Health Research and Development (ZonMw) and the European Community's Seventh Framework Programme.

Positivity rates of antithyroid antibody, antinuclear antibody and thyroid peroxidase antibody in different types of vitiligo.

Vitiligo is associated with various autoimmune disorders, and organ-specific autoantibodies are frequently found in patients with this disorder. Vitiligo is classically divided into segmental vitiligo (SV) and nonsegmental vitiligo (NSV), and it is believed that the pathogenesis differs between these two types. As the NSV type is related to an autoimmune mechanism, autoantibody detection rates are likely to be higher in the NSV type than in the segmental type; however, no comparative studies have been performed. To analyse the rates of autoantibody positivity according to the clinical features in patients with vitiligo. Rates of antithyroid antibody (Tg Ab), antinuclear antibody (ANA) and thyroid peroxidase antibody (TPO Ab) positivity were analysed and compared according to the sex, clinical type and age of onset of 807 patients with vitiligo. There were 106 patients with SV (13.1%) and 701 patients with NSV (86.9%). Tg Ab and ANA positivity did not differ between the SV and NSV types. A positive TPO Ab result was obtained in 16 patients with SV (15.1%) and 173 patients with NSV (24.7%). The TPO Ab positivity rate was significantly higher in NSV (χ² = 4.14, P < 0.05). The positivity rates of the three autoantibodies differed significantly according to age of onset (P = 0.001, P = 0.02 and P < 0.001 for Tg Ab, ANA and TPO Ab positivity, respectively). The TPO Ab positivity rate also showed a sex difference (P < 0.001). The positivity rates for the three autoantibodies showed differences according to age of onset and sex. The rates of Tg Ab and ANA positivity showed no significant differences according to clinical type, but the TPO Ab positivity rate was significantly different between SV and NSV. It appears likely that an autoimmune mechanism contributes to the pathogenesis of SV.

Autoimmune thyroid disease in a cohort of Malaysian SLE patients: frequency, clinical and immunological associations.

Autoimmune thyroid disease (ATD) has been associated with other systemic autoimmune diseases. To date, there is limited data on thyroid disorders and autoimmune thyroid disease in Malaysia. The frequency of ATD among 189 systemic lupus erythematosus (SLE) patients was 6.3%, with 2.6% in the hyperthyroid group and 3.7% in the hypothyroid group. Hypothyroidism developed at a much younger mean age (24.3 years), suggesting that SLE might be a predisposing factor for the development of Hashimoto's thyroiditis. There was a higher rate of thyroid peroxidase antibody (TPO) positivity compared with anti-thyroglobulin antibody (Tg) in the hyperthyroid subgroup. This study also demonstrated a greater proportion of ATD patients who demonstrated high titres (≥ 1:6400) of TPO compared with high titres of Tg. Although there was an association between ATD and the presence of anti-Ro/SSA and/or anti-La/SSB antibodies, the absence of sicca symptoms and negative Schirmer's tests suggest a lack of association with secondary Sjogren's syndrome. A novel association between ATD and antiphospholipid syndrome (APS) was detected in our cohort. Hence we propose that patients affected by APS be routinely screened for ATD.

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%.

Thyroid function and age-related macular degeneration: a prospective population-based cohort study--the Rotterdam Study.

BackgroundIn animal models, lack of thyroid hormone is associated with cone photoreceptor preservation, while administration of high doses of active thyroid hormone leads to deterioration. The association between thyroid function and age-related macular degeneration (AMD) has not been investigated in the general population.MethodsParticipants of age ≥55 years from the Rotterdam Study with thyroid-stimulating hormone (TSH) and/or free thyroxine (FT4) measurements and AMD assessment were included. We conducted age- and sex-adjusted Cox proportional hazards models to explore the association of TSH or FT4 with AMD, in the full range and in those with TSH (0.4-4.0 mIU/L) and/or FT4 in normal range (11–25 pmol/L). Cox proportional hazards models were performed for the association of TSH or FT4 with retinal pigment alterations (RPA), as an early marker of retinal changes. Multivariable models additionally included cardiovascular risk factors and thyroid peroxidase antibodies positivity. We also performed stratification by age and sex. A bidirectional look-up in genome-wide association study (GWAS) data for thyroid parameters and AMD was performed. Single nucleotide polymorphisms (SNPs) that are significantly associated with both phenotypes were identified.ResultsWe included 5,573 participants with a median follow-up of 6.9 years (interquartile range 4.4-10.8 years). During follow-up 805 people developed AMD. TSH levels were not associated with increased risk of AMD. Within normal range of FT4, participants in the highest FT4 quintile had a 1.34-fold increased risk of developing AMD, compared to individuals in the middle group (95% confidence interval [CI] 1.07-1.66). Higher FT4 values in the full range were associated with a higher risk of AMD (hazard ratio 1.04, CI, 1.01-1.06 per 1 pmol/L increase). Higher FT4 levels were similarly associated with a higher risk of RPA. Restricting analyses to euthyroid individuals, additional multivariable models, and stratification did not change estimates. We found a SNP (rs943080) in the VEGF-A gene, associated with AMD, to be significant in the TSH GWAS (P = 1.2 x 10−4). Adding this SNP to multivariable models did not change estimates.ConclusionsHigher FT4 values are associated with increased risk of AMD - even in euthyroid individuals - and increased risk of RPA. Our data suggest an important role of thyroid hormone in pathways leading to AMD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0329-0) contains supplementary material, which is available to authorized users.

Thyroid disorders are common in first-degree relatives of individuals with type 1 diabetes mellitus

Thyroid diseases are common in individuals with type 1 diabetes mellitus (T1DM) and should be investigated annually in these individuals. The aim of this study was to evaluate the frequency of thyroid diseases in first degree relatives (FDR) of patients with T1DM. Eighty individuals (40 patients with T1DM and 40 FDR) were interviewed and blood was sampled for thyroid-stimulating hormone (TSH), free thyroxine (FT4) and thyroid peroxidase (TPO) antibodies measurement. Autoantibodies against glutamic acid decarboxylase 65 (GAD65), islet antigen-2 (IA2) and autoantibodies against insulin (AAI) were measured in FDR. We found a similar prevalence of thyroid dysfunction in patients with T1DM and their FDR (22.5% vs. 27.5%; p = 0,79). There were no differences in serum TSH levels (p = 0.29), FT4 (p = 0,45), frequency of abnormal TSH (p = 0.28), positive TPO antibodies (p = 0.13), titers of TPO antibodies (in positive cases) between patients with T1DM and their FDR (p = 0.94). Thyroid abnormalities seem to be common not only in patients with T1DM but also in their FDR, which suggests that screening strategies for thyroid diseases might also be useful to these individuals.

Sonographic appearance of thyroid cancer in patients with Hashimoto thyroiditis.

To determine whether the sonographic appearance of thyroid cancer differs in patients with and without Hashimoto thyroiditis. Patients with histologically proven thyroid cancer who had thyroid peroxidase (TPO) antibodies measured and sonography performed preoperatively were included. We evaluated each nodule for size, echogenicity, composition, margins, halo, and vascularity and evaluated the background heterogeneity of the gland. There were 162 thyroid cancers in 145 patients. Forty-two patients (29.0%) had Hashimoto thyroiditis with positive TPO antibodies, and 103 patients (71.0%) had negative TPO antibodies. The background echogenicity was more often heterogeneous in TPO antibody-positive patients compared to those who had negative TPO antibodies (57.1% versus 26.2%; P= .0005). Comparing cancers in TPO antibody-positive to TPO antibody-negative patients, there was no significant difference in the size, echogenicity, composition, margins, halo presence, calcification presence and type, or vascularity of the cancerous nodule (P > .05). Among TPO antibody-positive patients, comparing thyroid cancerous nodules in patients with heterogeneous glands to those with homogeneous glands, there was no significant difference in any sonographic characteristic except the margin of the nodule, which was more often irregular or poorly defined in heterogeneous glands and more often smooth in homogeneous glands (P< .05). Sonographic features of thyroid cancer are similar in patients with and without Hashimoto thyroiditis. Among patients with Hashimoto thyroiditis and thyroid cancer, the sonographic appearance of the cancerous nodule is similar, except that cancerous nodule margins are more likely to be irregular or poorly defined when the gland is heterogeneous.

Thyroid hormonal status among children with obesity.

It is presumed that free T4 and thyroid-stimulating hormone (TSH) levels are related to obesity, but the findings are inconsistent. In this study we evaluated T4 and TSH concentrations between normal children and those with obesity and possible correlations between body mass index (BMI) and these markers. In this prospective study, 190 children who were overweight and obese and 133 children without obesity of the same age and sex were evaluated. Thyroid function tests (TSH, total T4, free T4 and free T3) were measured in all subjects in both groups. Thyroid antibodies (thyroid peroxidase and thyroglobulin) were determined among those with elevated TSH levels. Levels of TSH and total T4 were significantly higher in children with obesity compared with the control group. Subclinical hypothyroidism was significantly higher in children with obesity (14.7%) compared with normal subjects (6.8%, p = 0.02). Among children with obesity and increased TSH levels, 10.7% had positive thyroid peroxidase and thyroglobulin antibodies. There was significantly positive correlation between BMI z score and TSH level (r = 0.198, p < 0.001) and T4 level (r = 0.18, p = 0.001). TSH and total T4 levels are increased in children who are overweight or obese and are a common finding in these children, but the incidence of thyroid antibodies is low in these patients and so could not be accounted for by thyroid autoimmunity. Due to these findings it is possible that increased TSH and total T4 levels are a consequence of obesity and could be reduced by decreasing BMI.

Optimal and safe upper limits of iodine intake for early pregnancy in iodine-sufficient regions: a cross-sectional study of 7190 pregnant women in China.

The WHO Technical Consultation recommends urinary iodine concentrations (UIC) from 250 to 499 μg/L as more-than-adequate iodine intake and UIC ≥ 500 μg/L as excessive iodine for pregnant and lactating women, but scientific evidence for this is weak. We investigated optimal and safe ranges of iodine intake during early pregnancy in an iodine-sufficient region of China. Seven thousand one hundred ninety pregnant women at 4-8 weeks gestation were investigated and their UIC, serum thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroid-peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), and thyroglobulin (Tg) were measured. The prevalence of overt hypothyroidism was lowest in the group with UIC 150-249 μg/L, which corresponded to the lowest serum Tg concentration (10.18 μg/L). Prevalences of subclinical hypothyroidism (2.4%) and isolated hypothyroxinemia (1.7%) were lower in the group with UIC 150-249 μg/L. Multivariate logistic regression indicated that more-than-adequate iodine intake (UIC 250-499 μg/L) and excessive iodine intake (UIC ≥ 500 μg/L) were associated with a 1.72-fold and a 2.17-fold increased risk of subclinical hypothyroidism, respectively. Meanwhile, excessive iodine intake was associated with a 2.85-fold increased risk of isolated hypothyroxinemia. Moreover, the prevalence of TPOAb positivity and TgAb positivity presented a U-shaped curve, ranging from mild iodine deficiency to iodine excess. The upper limit of iodine intake during early pregnancy in an iodine-sufficient region should not exceed UIC 250 μg/L, because this is associated with a significantly high risk of subclinical hypothyroidism, and a UIC of 500 μg/L should not be exceeded, as it is associated with a significantly high risk of isolated hypothyroxinemia.

High Body Mass Index Is an Indicator of Maternal Hypothyroidism, Hypothyroxinemia, and Thyroid-Peroxidase Antibody Positivity during Early Pregnancy.

Background. Maternal thyroid dysfunction in early pregnancy may increase the risk of adverse pregnancy complications and neurocognitive deficiencies in the developing fetus. Currently, some researchers demonstrated that body mass index (BMI) is associated with thyroid function in nonpregnant population. Hence, the American Thyroid Association recommended screening thyroid function in obese pregnant women; however, the evidence for this is weak. For this purpose, our study investigated the relationship between high BMI and thyroid functions during early pregnancy in Liaoning province, an iodine-sufficient region of China. Methods. Serum thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroid-peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb) concentration, urinary iodine concentration (UIC), and BMI were determined in 6303 pregnant women. Results. BMI ≥ 25 kg/m2 may act as an indicator of hypothyroxinemia and TPOAb positivity and BMI ≥ 30 kg/m2 was associated with increases in the odds of hypothyroidism, hypothyroxinemia, and TPOAb positivity. The prevalence of isolated hypothyroxinemia increased among pregnant women with BMI > 24 kg/m2. Conclusions. High BMI during early pregnancy may be an indicator of maternal thyroid dysfunction; for Asian women whose BMI > 24 kg/m2 and who are within 8 weeks of pregnancy, thyroid functions should be assessed especially.