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The aim of the present study was to assess changes in thyroid function and thyroid autoimmunity (TAI) throughout ovarian stimulation (OS) for intracytoplasmic sperm injection (ICSI) and the association of these changes with ICSI outcome. A flexible gonadotrophin-releasing hormone (GnRH) antagonist protocol was used in 42 women and their thyroid function and TAI were assessed at baseline and five times during OS (Days 3 and 5 of the menstrual cycle, the day of hCG administration, the day of ovum pick-up and the day of the pregnancy test). The primary outcome measure was the change in thyroid function throughout OS. No overall change was recorded in thyrotropin-stimulating hormone (TSH) concentrations throughout OS (P=0.066). In women who became pregnant (n=8), an increase in TSH concentrations was noted on the day of the pregnancy test compared with Day 3 of the menstrual cycle (3.410±1.200 vs 2.014±0.950 µIU mL-1, respectively; P=0.001; mean ± s.d.). TAI was present in 11 of 42 women. Biochemical pregnancy was negatively correlated with changes in TSH (r=-0.7, P=0.004). No such association was noted regarding the live birth rate. The present study provides evidence that TSH concentrations could increase during OS, especially in women who become pregnant. [ABSTRACT FROM AUTHOR]

The incidence of most thyroid diseases: hypothyroidism, nodular goitre, and cancer is highest among postmenopausal and elderly women. The diagnosis of thyroid dysfunction in this group of patients is difficult because the symptoms can be nonspecific or common with menopausal and ageing complaints. In the interpretation of thyroid function tests the physiological changes in secretion and metabolism of thyrotropin (TSH) and thyroid hormones must be considered, as well as the influence of comorbidities. Unrecognised thyroid dysfunction leads to increased: cardiovascular risk, bone fractures, cognitive impairment, depression, and mortality. Therapy of thyroid dysfunction is different in postmenopausal and elderly women than in young people; hypothyroidism should be treated with caution, because high doses of L-thyroxine can lead to cardiac arrhythmias and increased bone turnover, and hyperthyroidism should be preferentially treated with radioiodine. Thyroid status beneficially influencing longevity relates to low thyroid function. Thyroid nodules and cancer often affect women over 50 years old; the diagnostic and therapeutic approach is the same as in the general population, but the surgical risk and cancer prognosis is worse than in young patients. [ABSTRACT FROM AUTHOR]

Background: MST-4 and TRAF-6 are involved in the regulation of inflammatory and immune responses. However, whether they participate in the pathogenesis of Graves' disease (GD) has not yet been reported. Therefore, the purpose of this study was to investigate the expression of MST-4 and TRAF-6 in the peripheral blood of patients with GD to understand their role in the pathogenesis of GD. Methods: Thirty newly diagnosed GD patients, 24 GD patients in remission (eGD) and 30 normal controls (NC) were recruited. Thyroid function and autoantibody levels were determined using a chemiluminescence immunoassay. Peripheral blood mononuclear cells (PBMCs) were extracted, and MST-4 and TRAF-6 mRNA and protein levels were determined using real-time PCR and Western blotting, respectively. Results: 1. Thyroid function in the GD group was significantly different from that in the eGD and NC groups (P < 0.05); however, there was no difference in thyroid function between the eGD group and the NC group (P > 0.05). The autoantibody levels in the NC group were significantly different from those in the GD and eGD groups (P < 0.05); however, the difference in the levels between the GD group and eGD group was not statistically significant (P > 0.05). 2. The MST-4 and TRAF-6 mRNA and protein levels in the GD group were significantly lower than those in the NC group (P < 0.05); however, there were no differences in mRNA and protein levels between the GD group and the eGD group or between the eGD group and the NC group (P > 0.05). 3. The correlation between the MST-4 and TRAF-6 mRNA and protein levels was not significant. However, there was a significant correlation between the TRAF-6 mRNA and TPO Ab levels in the eGD group and between the TRAF-6 mRNA and TR Ab levels in the NC group. Conclusion: The MST-4 and TRAF-6 mRNA and protein levels were lower in the GD group than in the NC group, suggesting that MST-4 and TRAF-6 may be important in the pathogenesis of GD. Whether MST-4 influences the innate immune response through TRAF-6 and thus regulates the imbalance in downstream effector T cells requires further study. Investigating the expression of MST-4 and TRAF-6 in GD can provide a new perspective and targets for further study of the upstream mechanism responsible for effector T cell imbalance. [ABSTRACT FROM AUTHOR]

Humans are exposed to 131I in medical diagnostics and treatment but also from nuclear accidents, and better knowledge of the molecular response in thyroid is needed. The aim of the study was to examine the transcriptional response in thyroid tissue 24 h after 131I administration in rats. The exposure levels were chosen to simulate both the clinical situation and the case of nuclear fallout. Thirty-six male rats were i.v. injected with 0–4700 kBq 131I, and killed at 24 h after injection (Dthyroid = 0.0058–3.0 Gy). Total RNA was extracted from individual thyroid tissue samples and mRNA levels were determined using oligonucleotide microarray technique. Differentially expressed transcripts were determined using Nexus Expression 3.0. Hierarchical clustering was performed in the R statistical computing environment. Pathway analysis was performed using the Ingenuity Pathway Analysis tool and the Gene Ontology database. T4 and TSH plasma concentrations were measured using ELISA. Totally, 429 differentially regulated transcripts were identified. Downregulation of thyroid hormone biosynthesis associated genes (e.g. thyroglobulin, thyroid peroxidase, the sodium-iodine symporter) was identified in some groups, and an impact on thyroid function was supported by the pathway analysis. Recurring downregulation of Dbp and Slc47a2 was found. Dbp exhibited a pattern with monotonous reduction of downregulation with absorbed dose at 0.0058–0.22 Gy. T4 plasma levels were increased and decreased in rats whose thyroids were exposed to 0.057 and 0.22 Gy, respectively. Different amounts of injected 131I gave distinct transcriptional responses in the rat thyroid. Transcriptional response related to thyroid function and changes in T4 plasma levels were found already at very low absorbed doses to thyroid. [ABSTRACT FROM AUTHOR]

Hashimoto thyroiditis (HT) is a common autoimmune disease. Genistein is an isoflavone with immunomodulatory functions in various diseases. In this double-blind, randomized, placebo-controlled clinical study, we investigated the effects of genistein on patients with HT. A total of 218 patients were recruited. Genistein treated patients had a significant increased T 4 , fT 4 levels, as well as reduction in serum TSH, TPOAb and TgAb levels, compared with those receiving placebo. Furthermore, Th1 related cytokine IFN-γ and IL-2 changes after genistein treatment suggest the immune modulating effect of genistein is mediated through regulating the function of Th1 cells. Overall, the genistein administration was effective and well tolerated in HT patients. These results demonstrate an immunological effect of genistein on HT patients. Further studies are warranted to determine the longer-term effects and possible chemopreventive effects on thyroid cancer in HT patients. [ABSTRACT FROM AUTHOR]

Objective: The differentiation program for human thyroid follicular cells (TFCs) relies on the interplay between sequence-specific transcription factors and transcriptional co-regulators. Transcriptional co-activator with PDZ-binding motif (TAZ) is a co-activator that regulates several transcription factors, including PAX8 and NKX2-1, which play a central role in thyroid-specific gene transcription. TAZ and PAX8/NKX2-1 are co-expressed in the nuclei of thyroid cells, and TAZ interacts directly with both PAX8 and NKX2-1, leading to their enhanced transcriptional activity on the thyroglobulin (TG) promoter and additional genes. Methods: The use of a small molecule, ethacridine, recently identified as a TAZ activator, in the differentiation of thyroid cells from human embryonic stem (hES) cells was studied. First, endodermal cells were derived from hES cells using Activin A, followed by induction of differentiation into thyroid cells directed by ethacridine and thyrotropin (TSH). Results: The expression of TAZ was increased in the Activin A-derived endodermal cells by ethacridine in a dose-dependent manner and followed by increases in PAX8 and NKX2-1 when assessed by both quantitative polymerase chain reaction and immunostaining. Following further differentiation with the combination of ethacridine and TSH, the thyroid-specific genes TG, TPO, TSHR, and NIS were all induced in the differentiated hES cells. When these cells were cultured with extracellular matrix-coated dishes, thyroid follicle formation and abundant TG protein expression were observed. Furthermore, such hES cell-derived thyroid follicles showed a marked TSH-induced and dose-dependent increase in radioiodine uptake and protein-bound iodine accumulation. Conclusion: These data show that fully functional human thyroid cells can be derived from hES cells using ethacridine, a TAZ activator, which induces thyroid-specific gene expression and promotes thyroid cell differentiation from the hES cells. These studies again demonstrate the importance of transcriptional regulation in thyroid cell development. This approach also yields functional human thyrocytes, without any gene transfection or complex culture conditions, by directly manipulating the transcriptional machinery without interfering with intermediate signaling events. [ABSTRACT FROM AUTHOR]

Thyroxine (T 4 ) and triiodothyronine (T 3 ) concentrations in pregnant and nonpregnant bitches were measured. The allantoic and amniotic fluid samples were collected separately in the third week of pregnancy, and fetal blood samples were collected in the fourth week of pregnancy. There was no difference between T 4 results in the pregnant and nonpregnant animals, but the measured serum concentrations exceeded the healthy range for normal adults. Serum T 4 concentrations were lower in the fetus than those in adults ( P < 0.01). Fetal T 4 concentrations continuously increased and reached 13.38 ± 6.19 nmol/L before birth. The fetal serum T 4 concentrations were lower than the T 4 concentrations in allantoic and amniotic fluid until the seventh week, and the fetal serum T 3 concentrations were lower than those in fetal fluids throughout the pregnancy ( P < 0.01). Maximum T 3 concentrations in allantoic and amniotic fluid exceeded the concentrations in the fetal and maternal serum. It is conceivable that the considerable differences between maternal and fetal serum T 4 concentrations in healthy animals are explained by the T 4 impermeability of the placenta. Extremely high maternal T 4 (193.5 nmol/L) in 1 bitch was associated with T 4 concentrations under the detection limit in the fetal fluids and serum suggesting an inhibitory effect. The T 4 concentrations in all the fetal fluids and serum were under the detectable concentration that can be defined by 3.0 nmol/L in that bitch. We have demonstrated that fetal thyroid glands start functioning independently at the same time as thyroid cell formation in the dog, but the overproduction of maternal T 4 may have a suppressive effect on fetal iodothyronine production. [ABSTRACT FROM AUTHOR]

Thyroid hormones are involved in many developmental and physiological processes, including osmoregulation. The regulation of the thyroid system by environmental salinity in the euryhaline gilthead seabream ( Sparus aurata ) is still poorly characterized. To this end seabreams were exposed to four different environmental salinities (5, 15, 40 and 55 ppt) for 14 days, and plasma free thyroid hormones (fT3, fT4), outer ring deiodination and Na + /K + -ATPase activities in gills and kidney, as well as other osmoregulatory and metabolic parameters were measured. Low salinity conditions (5 ppt) elicited a significant increase in fT3 (29%) and fT4 (184%) plasma concentrations compared to control animals (acclimated to 40 ppt, natural salinity conditions in the Bay of Cádiz, Spain), while the amount of pituitary thyroid stimulating hormone subunit β ( tshb ) transcript abundance remained unchanged. In addition, plasma fT4 levels were positively correlated to renal and branchial deiodinase type 2 ( dio2 ) mRNA expression. Gill and kidney T4-outer ring deiodination activities correlated positively with dio2 mRNA expression and the highest values were observed in fish acclimated to low salinities (5 and 15 ppt). The high salinity (55 ppt) exposure caused a significant increase in tshb expression (65%), but deiodinase gene expression ( dio1 and dio2 ) and activity did not change and were similar to controls (40 ppt). In conclusion, acclimation to different salinities led to changes in the peripheral regulation of thyroid hormone metabolism in seabream. Therefore, thyroid hormones are involved in the regulation of ion transport and osmoregulatory physiology in this species. The conclusions derived from this study may also allow aquaculturists to modulate thyroid metabolism in seabream by adjusting culture salinity. [ABSTRACT FROM AUTHOR]

Organization of epithelial cells during follicular lumen formation is crucial for thyroid morphogenesis and function of the thyroid gland; however, the molecular mechanisms underlying this are poorly understood. To investigate this process, we established threedimensional (3D) epithelial culture model systems using Fischer rat thyroid (FRT) cells or murine primary thyrocytes that developed polarized spherical structures with a central lumen, mimicking thyroid follicles. Using microarray-based differential expression analysis of FRT cells grown under 2D or 3D conditions, followed by RNAmediated interference (RNAi) and morphogenetic analysis, we identified a key role for the thyroid transcription factor Pax8 and its target cadherin-16 (Cdh16) in the generation of polarized follicle-like structures. Silencing Pax8 expression inhibited the acquisition of apical-basal membrane polarity and impaired lumen formation. Both laminin and ß1-integrin (Itgb1) expression was reduced, and cell cytoskeleton polarized distribution was altered. Silencing Cdh16 expression also led to the formation of defective structures characterized by very low laminin expression at the follicle-matrix interface, downregulation of Itgb1, and unpolarized distribution of cell cytoskeleton. Our results demonstrate that Pax8 controls apical-basal follicular polarization and follicle formation through Cdh16. [ABSTRACT FROM AUTHOR]

Background Scant data exist on the longitudinal association between thyroid function and lipid concentrations. We investigated associations of TSH and lipid concentrations cross-sectionally and longitudinally in a nationwide population sample. Methods A total of 5205 randomly sampled participants representative of Finns aged ≥30 years were examined in 2000-2001 and included in cross-sectional analyses. A total of 2486 were re-examined 11 years later and included in longitudinal analyses. With linear regression models adjusted for age, gender, smoking and body mass index, we assessed the associations of baseline TSH and TSH categories (low, reference range and high) with total, high-density lipoprotein ( HDL) and low-density lipoprotein ( LDL) cholesterol; apolipoprotein A1 and B; and triglycerides at baseline and follow-up. Results At baseline, higher TSH associated with higher total cholesterol (β = 0·025, standard error [SE] = 0·007, P < 0·001), LDL cholesterol (β = 0·020, SE = 0·007, P = 0·002), apolipoprotein B (β = 0·006, SE = 0·002, P < 0·001) and log triglycerides (β = 0·008, SE = 0·003, P = 0·004), but not with other lipid outcomes. Higher baseline TSH associated with higher total cholesterol (β = 0·056, SE = 0·026, P = 0·033), LDL cholesterol (β = 0·057, SE = 0·023, P = 0·015) and apolipoprotein B (β = 0·012, SE = 0·006, P = 0·028) at follow-up in women, but not with any lipid outcomes in men. Participants with high TSH at baseline had a 0·22 mmol/l (95% confidence interval 0·02-0·41 mmol/l) higher LDL cholesterol at follow-up ( P = 0·028) than participants with TSH in the reference range (0·4-3·4 mU/l). However, exclusion of participants with high-risk baseline lipid values rendered these positive longitudinal associations nonsignificant ( P ≥ 0·098). Conclusions We could confirm a modest association between higher TSH and an adverse lipid profile cross-sectionally but not indisputably longitudinally. [ABSTRACT FROM AUTHOR]

Objective Thyroid disease can be subtle in its presentation, and TSH reference intervals may be artefactually increased by including persons with subclinical thyroid disease. We have therefore used a thyroid disease-free population to determine TSH and fT4 reference intervals. Design Apparently healthy subjects were assessed by health questionnaire, drug history, clinical assessment and measurement of thyroid antibodies. Patients Healthy subjects in a community setting. Measurements TSH, free T4, antithyroglobulin and anti- TPO were measured on the Abbott Architect analyser. Subjects with clinical abnormalities, consumption of thyroid-active medications or with thyroid antibodies above the manufacturer-quoted reference intervals were excluded. TSH and fT4 data were log-transformed, and the central 95% was used to calculate reference intervals. We assessed whether these data were normally distributed. We compared samples spanning the reference intervals for both TSH and fT4 between different assays looking at biases. Results From a population of 1,606 subjects, 140 males (18%) and 284 females (34%) were excluded. The central population 95% for TSH was 0·43-3·28 mU/l and for fT4 10·8-16·8 pmol/l. There were no age- or sex-related differences. For both analytes, the distribution was not significantly different to a Gaussian distribution ( P > 0·05). For 5 commonly used assays for TSH, the maximum difference in the upper limit of the TSH reference interval was 0·48 mU/l and for fT4 the maximum difference for the upper reference limit was 4·1 pmol/l. Conclusions A substantial proportion of apparently healthy persons have subclinical thyroid disease. These subjects must be excluded for any thyroid hormone reference interval studies. [ABSTRACT FROM AUTHOR]

BACKGROUND: Disruption of thyroid homeostasis has been indicated in human studies targeting effects of persistent organic pollutants (POPs). Influence on the maternal thyroid system by POPs is of special interest during pregnancy because such effects could impair infant thyroid homeostasis. OBJECTIVES: We investigated the association between POPs and thyroid-stimulating hormone (TSH) and thyroid hormones (THs) in mother and child pairs from the Northern Norway Mother-and-Child Contaminant Cohort Study (MISA). METHODS: Nineteen POPs and 10 thyroid parameters were analyzed in serum from 391 pregnant women in their second trimester. In addition, TSH concentrations in heel-prick samples from the infants were analyzed by the Norwegian Newborn Screening program. Association studies with a multipollutant approach were performed using multivariate analyses; partial least squares (PLS) regression, hierarchical clustering, and principal component analysis (PCA). RESULTS: Several POPs were significantly associated with TSH and THs: a) PFOS was positively associated with TSH; h) PCBs, HCB, and nonachlors were inversely associated with T3, T4, and FT4; and, c) PFDA and PFUnDA were inversely associated with T3 and FT3. After mutual adjustments for the other contaminants, only PFDA and PFUnDA remained significantly associated with T3 and FT3, respectively. Infants born to mothers within the highest TSH quartile had 10% higher mean concentrations of TSH compared with children born to mothers in the lowest TSH quartile. CONCLUSION: The present results suggest that background exposures to POPs can alter maternal thyroid homeostasis. This research contributes to the understanding of multipollutant exposures using multivariate statistical approaches and highlights the complexity of investigating environmental concentrations and mixtures in regard to maternal and infant thyroid function. CITATION: Berg V, Nost TH, Pettersen RD, Hansen S, Veyhe AS, Jorde R, Odland JØ, Sandanger TM. 2017. Persistent organic pollutants and the association with maternal and infant thyroid homeostasis: a multipollutant assessment. Environ Health Perspect 125:127 -- 133; http:// dx.doi.org/10.1289/EHP152 [ABSTRACT FROM AUTHOR]

Aim: To prospectively investigate, during a 5-year follow-up, whether the prognosis of thyroid function with Hashimoto thyroiditis (HT) is different in euthyroid girls with Turner syndrome (TS) than in euthyroid girls without TS. Design: In 66 TS girls and 132 non-TS girls with euthyroid HT and similar thyroid functional test results at HT diagnosis, we followed up the evolution of thyroid status over time. Results: At the end of follow-up, the TS girls exhibited higher TSH levels, lower fT 4 levels, and lower prevalence rates of both euthyroidism and subclinical hypothyroidism, but higher prevalence rates of both overt hypothyroidism and hyperthyroidism, irrespective of the karyotype. Conclusions: An association with TS is able to impair the long-term prognosis of thyroid function in girls with HT. Such an effect occurs irrespective of thyroid functional test results at HT diagnosis and is not necessarily linked with a specific karyotype. [ABSTRACT FROM AUTHOR]

Etiologic factors for recurrent miscarriage (RM) include autoimmune diseases, the most frequently antiphospholipid syndrome and thyroiditis. Some women who suffer from RM might also have an altered immune system. We aimed to evaluate possible associations between anti-thyroid and anti-phospholipid antibodies in women with RM. In a retrospective case series 1 on 156 women with RM, major outcome parameters were antibodies against cardiolipin, β2-glycoprotein I, thyreoperoxidase (TPO-Ab), and thyroglobulin (TG-Ab). Significant (p<0.05) positive correlations were found between TPO-Ab and TG-Ab (r=0.577), TPO-Ab and IgG anti-cardiolipin antibodies (r=0.284), TPO-Ab and IgG anti- β2-glycoprotein I antibodies (r=0.196), and TG-Ab and IgG anti-cardiolipin antibodies (r=0.193), as well as between all types of anti-phospholipid antibodies. Women with both increased TPO-Ab and TG-Ab levels revealed higher (p<0.001) IgG anti-cardiolipin and IgG anti-β2-glycoprotein I antibodies. Anti-thyroid antibodies were linked to anti-phospholipid antibodies and should be in the focus of future research on RM. [ABSTRACT FROM AUTHOR]

Aims To compare the clinical and metabolic characteristics of patients with Type 1 diabetes and necrobiosis lipoidica with those of patients with Type 1 diabetes who do not have necrobiosis lipoidica. A multicentre analysis was performed. Methods Clinical and laboratory data were obtained from 64 133 patients (aged 0-25 years) with Type 1 diabetes with and without necrobiosis lipoidica who were registered in the German/Austrian Diabetes Prospective Documentation Initiative registry. Data were analysed using multivariable regression modelling. Age, diabetes duration, treatment year and sex were considered as confounding factors. Results Results adjusted for demographic variables are presented. In patients with necrobiosis lipoidica, metabolic control was worse (HbA1c 72 vs. 67 mmol/mol, 8.7% vs. 8.3%; P = 0.0065) and the duration of diabetes was longer [6.24 (3.28-9.97) vs. 5.11 (2.08-8.83) years; P = 0.014; not adjusted]. Patients with necrobiosis lipoidica required higher insulin doses than those without (1.02 vs. 0.92 U/kg/day; P < 0.0001). There was no significant difference in the frequency of microvascular complications (microalbuminuria and retinopathy) between the groups. Furthermore, 24.8% and 17.5% of patients with Type 1 diabetes with and without necrobiosis lipoidica, respectively, had elevated thyroid antibodies ( P = 0.051). Necrobiosis lipoidica was correlated with coeliac disease in patients with Type 1 diabetes (3.4% vs. 1.0%; P = 0.0035). Conclusions Our data indicate a strong correlation between hyperglycaemia and the development of necrobiosis lipoidica. We postulate that the underlying pathogenic processes differ from those leading to microalbuminuria and retinopathy, and additional immunological mechanisms may play a role. [ABSTRACT FROM AUTHOR]

Background: Excessive iodine intake may have adverse effects on the thyroid, particularly in children, but the safe upper iodine intake concentration in children is unclear. Objective: We assessed the adverse effects of high iodine intake from iodine-rich drinking water on thyroid size in children by examining associations between thyroid volume (Tvol), total goiter rate (TGR), and iodine intake. Design: In a multistage cross-sectional survey, we collected two 24-h urine samples on 2 nonconsecutive days and determined 24-h urinary iodine excretion, then calculated habitual daily iodine intake. Ultrasonographic Tvol was measured, and TGR was calculated based on international and Chinese reference ranges for Tvol in children. Results: This study included 2089 children from Shandong province, where the median (IQR) drinking water iodine concentration was 183 mg/L (69-406 mg/L). The median (IQR) 24-h urinary iodine concentrations for the 2 collections were 381 mg/L (203-649 mg/L) and 398 mg/L (202-687 mg/L), respectively. The median (IQR) habitual daily iodine intake of children was 298 mg/d (186-437 mg/d). Tvols were slightly higher in boys than in girls (P = 0.035). The overall TGR was 9.7% and did not differ by sex. The TGR was ~5% for children aged 7-10 and 11-14 y at iodine intakes of 200-249 and 250-299 mg/d, respectively. With the use of logistic regression and 2-step linear regression, a nonlinear association was observed between Tvol, TGR, and iodine intake, with a threshold intake of 150 mg/d. Conclusions: Tvol begins to increase in children when iodine intake is $ 150 mg/d, and the TGR exceeds 5% when daily iodine intake is $250 mg/d for children aged 7-10 y and $300 mg/d for children aged 11-14 y. Our findings suggest that 150-249 and 150-299 mg/d seem to be safe upper iodine intake ranges for children aged 7-10 and 11-14 y, respectively. [ABSTRACT FROM AUTHOR]

Objective: Genome-wide association studies in adults have identified 42 loci associated with thyroid stimulating hormone (TSH) and 21 loci associated with free thyroxine (FT4) concentrations. While biologically plausible, age-dependent effects have not been assessed. We aimed to study the association of previously identified genetic determinants of TSH and FT4 with TSH and FT4 concentrations in newborns and (pre)school children., Methods: We selected participants from three population-based prospective cohorts with data on genetic variants and thyroid function: Generation R (N = 2169 children, mean age 6 years; N = 2388 neonates, the Netherlands), the Avon Longitudinal Study of Parents and Children (ALSPAC; N = 3382, age 7.5 years, United Kingdom), and the Brisbane Longitudinal Twin Study (BLTS; N = 1680, age 12.1 years, Australia). The association of single nucleotide polymorphisms (SNPs) with TSH and FT4 concentrations was studied with multivariable linear regression models. Weighted polygenic risk scores (PRSs) were defined to combine SNP effects., Results: In childhood, 30/60 SNPs were associated with TSH and 11/31 SNPs with FT4 after multiple testing correction. The effect sizes for AADAT, GLIS3, TM4SF4, and VEGFA were notably larger than in adults. The TSH PRS explained 5.3%-8.4% of the variability in TSH concentrations; the FT4 PRS explained 1.5%-4.2% of the variability in FT4 concentrations. Five TSH SNPs and no FT4 SNPs were associated with thyroid function in neonates., Conclusions: The effects of many known thyroid function SNPs are already apparent in childhood and some might be notably larger in children as compared to adults. These findings provide new knowledge about genetic regulation of thyroid function in early life., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology.)

A biologically based computational model was developed to describe the hypothalamic-pituitary-thyroid (HPT) axis in developing Xenopus laevis larvae. The goal of this effort was to develop a tool that can be used to better understand mechanisms of thyroid hormone-mediated metamorphosis in X. laevis and predict organismal outcomes when those mechanisms are perturbed by chemical toxicants. In this report, we describe efforts to simulate the normal biology of control organisms. The structure of the model borrows from established models of HPT axis function in mammals. Additional features specific to X. laevis account for the effects of organism growth, growth of the thyroid gland, and developmental changes in regulation of thyroid stimulating hormone (TSH) by circulating thyroid hormones (THs). Calibration was achieved by simulating observed changes in stored and circulating levels of THs during a critical developmental window (Nieuwkoop and Faber stages 54-57) that encompasses widely used in vivo chemical testing protocols. The resulting model predicts that multiple homeostatic processes, operating in concert, can act to preserve circulating levels of THs despite profound impairments in TH synthesis. Represented in the model are several biochemical processes for which there are high-throughput in vitro chemical screening assays. By linking the HPT axis model to a toxicokinetic model of chemical uptake and distribution, it may be possible to use this in vitro effects information to predict chemical effects in X. laevis larvae resulting from defined chemical exposures., Competing Interests: Declaration of competing interest There are no competing interests for the authors to declare., (Published by Elsevier Inc.)

Background: Moderate caffeine intake decreases the risk of metabolic disorders and all-cause mortality, and the mechanism may be related to its ergogenic actions. Thyroid hormones are vital in metabolic homeostasis; however, their association with caffeine intake has rarely been explored., Objective: To investigate the association between caffeine intake and thyroid function., Methods: We collected data on demographic background, medical conditions, dietary intake, and thyroid function from the National Health and Nutrition Examination Survey (NHANES) 2007-2012. Subgroups were classified using two-step cluster analysis, with sex, age, body mass index (BMI), hyperglycemia, hypertension, and cardio-cerebral vascular disease (CVD) being used for clustering. Restrictive cubic spline analysis was employed to investigate potential nonlinear correlations, and multivariable linear regression was used to evaluate the association between caffeine consumption and thyroid function., Results: A total of 2,582 participants were included, and three subgroups with different metabolic features were clustered. In the most metabolically unhealthy group, with the oldest age, highest BMI, and more cases of hypertension, hyperglycemia, and CVD, there was a nonlinear relationship between caffeine intake and serum thyroid stimulating hormone (TSH) level. After adjusting for age, sex, race, drinking, smoking, medical conditions, and micronutrient and macronutrient intake, caffeine intake of less than 9.97 mg/d was positively associated with serum TSH (p = 0.035, standardized β = 0.155); however, moderate caffeine consumption (9.97-264.97 mg/d) indicated a negative association (p = 0.001, standardized β = - 0.152)., Conclusions: Caffeine consumption had a nonlinear relationship with serum TSH in people with metabolic disorders, and moderate caffeine intake (9.97 ~ 264.97 mg/d) was positively associated with serum TSH., (© 2023. The Author(s).)

Background: The higher prevalence of thyroid dysfunction in type 1 diabetes patients has been well established, whereas it is a matter of debate whether that is also observed in type 2 diabetes patients. This study was conducted to reveal whether higher prevalence of thyroid dysfunction is observed in patients with type 2 diabetes., Methods: We examined thyroid functions and thyroid autoantibodies in 200 patients with type 2 diabetes and 225 controls, with 24 months follow up for those with type 2 diabetes., Results: Serum free triiodothyronine (fT3) levels and fT3/free thyroxine (fT4) ratio were significantly lower, while fT4 levels were significantly higher in patients with type 2 diabetes. The number of patients with thyroid dysfunction or patients positive for thyroid autoantibodies were not different between the two groups. The fT3/fT4 ratio was positively and negatively correlated with serum c-peptide and HbA1c levels, respectively, suggesting that the difference can be attributable to insulin resistance and diabetic control. In the follow-up observation, we found no significant correlation between basal thyrotropin (TSH), fT3, fT4 or fT3/fT4 ratio with the amounts of changes of HbA1c levels at 12 or 24 months after the basal measurements. There was a negative relationship between TSH levels and eGFR at baseline measurements, but TSH levels did not seem to predict future decline of eGFR levels. No relationship was observed between urine albumin/ g‧cre levels and thyroid function., Conclusion: Thyroid dysfunction and thyroid autoantibodies were not different in prevalence between patients with type 2 diabetes and controls, although in patients with type 2 diabetes, the fT3/fT4 ratio was decreased. Basal thyroid function did not predict future diabetes control or renal function within 24 months of follow-up., (© 2023. The Author(s).)

Background: Sleeve gastrectomy (SG) continues to be one of the most popular bariatric procedures all over the world. Thyroid-stimulating hormone (TSH) frequently shows a slight elevation in patients with obesity. The effect of SG on thyroid hormones has been rarely investigated., Aim of the Study: This study aimed to assess the short-term effect of SG on thyroid functions in Egyptian patients with morbid obesity and the potential predictors of the postoperative thyroid functions., Patients and Methods: This study included patients undergoing SG at kasr al ainy hospitals. The patients underwent preoperative 3-, 6-, and 12-month postoperative analyses of the thyroid functions and other biochemical markers., Results: The study included 106 patients who showed significant improvement in thyroid functions at the follow-up assessment. Twelve-month TSH positively correlated with the 12-month measures of LDL and HbA1c. TSH change at 12-month follow-up (TSH) was inversely correlated to 12-month BMI and positively correlated to preoperative TSH and 12-month percentage of total weight loss (TWL%). Univariable linear regression analysis demonstrated that preoperative TSH (p < 0.001), 12-month TWL% (p = 0.042), 12-month HbA1c (p = 0.001), and 12-month LDL (p = 0.049) were significant predictors for the 12-month TSH levels. Multivariable analysis showed that only preoperative TSH levels (p < 0.001) and 12-month HbA1c levels (p = 0.021) could affect the 12-month TSH levels., Conclusion: The current study supports the evidence of thyroid function improvement after sleeve gastrectomy. This improvement was affected by the amount of weight loss after surgery., (© 2023. The Author(s).)

Background: Knowledge of the physiological mechanisms of adaptation arising in response to changes in photoperiods is especially important for residents of the European North. In the literature, there is practically no information about photoperiodic dynamics of serum dopamine level, despite its significant role in the regulation of the body's activity. The mutual modulating effect of the dopaminergic and thyroid systems is known., Aim: To show the ratio of dopamine levels and the content of hormones, protines and autoantibodies of the thyroid system, taking into account photoperiod of the year, in practically healthy populations of the European North., Materials and Methods: Healthy male population (20 men) of Arkhangelsk was examined in various photoperiods of the year (80 samples): an increase in the length of daylight hours (March), its maximum duration (June), a decrease (September), and a minimum duration (December). The inhabitants of the settlements and the nomadic aboriginal population (100 men) were examined during 2 photoperiods of the year - March and December. The serum levels of iodothyronines, TSH, TG, antibodies to TPO, antibodies to TG and plasma level of dopamine were determined using ELISA methods., Results: Residents of Arkhangelsk in June compared to December have higher levels of dopamine (0.502 and 0.365 nmol/l, p=0.01), T3 (1.09 and 0.94 nmol/l, p=0.003), T4 (113.45 and 99.03 nmol/l, p=0.0002). In September, compared with June, a decrease in dopamine (0.235 nmol/l, p=0.0003), T3 (0.92 nmol/l, p=0.004) was recorded with an increase in T4/T3 ratio from 106.54 to 117.89 units (p=0.006). The nomadic aboriginal population in March compared with December showed a tendency to a higher content of dopamine (0.00 and 0.394 nmol/l, p=0.07) with the decrease in fT4 (15.20 and  13.90, p=0.015), fT4/fT3 ratio from 3.13 to 2.28 units (p=0.006). In December, 67% of nomadic population had undetectable dopamine values (0 nmol/l) and 22% - excess dopamine values, in March 27% - excess values., Conclusion: Unidirectional changes in dopamine and thyroid activity in men of the European North were shown with their decrease during periods of decrease and minimum daylight hours and an increase during periods of increase and maximum daylight hours.

The synthesis of thyroid hormones in the hypothalamic-pituitary-thyroid (HPT) axis was studied. For this purpose, a reaction model for HPT axis with stoichiometric relations between the main reaction species was postulated. Using the law of mass action, this model has been transformed into a set of nonlinear ordinary differential equations. This new model has been examined by stoichiometric network analysis (SNA) with the aim to see if it possesses the ability to reproduce oscillatory ultradian dynamics founded on the internal feedback mechanism. In particular, a feedback regulation of TSH production based on the interplay between TRH, TSH, somatostatin and thyroid hormones was proposed. Besides, the ten times larger amount of produced T 4 with respect to T 3 in the thyroid gland was successfully simulated. The properties of SNA in combination with experimental results, were used to determine the unknown parameters (19 rate constants of particular reaction steps) necessary for numerical investigations. The steady-state concentrations of 15 reactive species were tuned to be consistent with the experimental data. The predictive potential of the proposed model was illustrated on numerical simulations of somatostatin influence on TSH dynamics investigated experimentally by Weeke et al. in 1975. In addition, all programs for SNA analysis were adapted for this kind of a large model. The procedure of calculating rate constants from steady-state reaction rates and very limited available experimental data was developed. For this purpose, a unique numerical method was developed to fine-tune model parameters while preserving the fixed rate ratios and using the magnitude of the experimentally known oscillation period as the only target value. The postulated model was numerically validated by perturbation simulations with somatostatin infusion and the results were compared with experiments available in literature. Finally, as far as we know, this reaction model with 15 variables is the most dimensional one that have been analysed mathematically to obtain instability region and oscillatory dynamic states. Among the existing models of thyroid homeostasis this theory represents a new class that may improve our understanding of basic physiological processes and helps to develop new therapeutic approaches. Additionally, it may pave the way to improved diagnostic methods for pituitary and thyroid disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Iodide has direct effects on thyroid function. Several iodinated lipids are biosynthesized by the thyroid and they were postulated as intermediaries in the action of iodide. Among them, 2-iodohexadecanal (2-IHDA) has been identified and proposed to play a role in thyroid autoregulation. The aim of this study was to compare the effect of iodide and 2-IHDA on thyroid cell physiology. For this purpose, FRTL-5 thyroid cells were incubated with the two compounds during 24 or 48 h and several thyroid parameters were evaluated such as: iodide uptake, intracellular calcium and H 2 O 2 levels. To further explore the molecular mechanism involved in 2-IHDA action, transcript and protein levels of genes involved in thyroid hormone biosynthesis, as well as the transcriptional expression of these genes were evaluated in the presence of iodide and 2-IHDA. The results obtained indicate that 2-IHDA reproduces the action of excess iodide on the “Wolff-Chaikoff” effect as well as on thyroid specific genes transcription supporting its role in thyroid autoregulation. [ABSTRACT FROM AUTHOR]

Objective: Autonomously functioning thyroid areas may be associated with subclinical or overt hyperthyroidism, but may exist even in the presence of normal TSH. This study was aimed at comparing the rate of autonomously functioning areas and their cardiac sequelae in patients with nodular goitre studied with the usual and a novel approach. Design and methods: In total 490 adult outpatients with thyroid nodular goitre, living in a mild iodine-deficient area, were selected in our referral centre for thyroid diseases from 2009 to 2014 on the basis of a suspicion of thyroid functional autonomy. They were divided in three groups according to a non-conventional approach (excessive response to thyroxine treatment: group 1) or conventional approach (low/normal TSH with clinical suspicion or low TSH: groups 2 and 3). All patients of the study with the suspicion of thyroid functional autonomy underwent thyroid scan with radioactive iodine (I131) uptake (RAIU). Results: The percentage of confirmed thyroid functional autonomy was 319/490, being significantly higher in group 3 than in groups 1 and 2 (81.5 vs 64.7 vs 52.6%; chi-square P < 0.0001). However, the diagnosis with non-conventional approach was made at a significant earlier age (P < 0.0001). Cardiac arrhythmias as well as atrial fibrillation were similarly detected by conventional and non-conventional approaches (chi-square test: P = 0.2537; P = 0.8425). Conclusions: The hyper-responsiveness to thyroxine treatment should induce the suspicion of thyroid functional autonomy at an early stage, allowing to detect autonomous functioning areas in apparently euthyroid patients [ABSTRACT FROM AUTHOR]

Objective: Lactating women and their infants are susceptible to iodine deficiency and iodine excess. In South Africa, no data exist on the iodine status and thyroid function of these vulnerable groups. Methods: In a cross-sectional study, urinary iodine concentrations (UIC), thyroid function, and breast-milk iodine concentrations (BMIC) were assessed in 100 lactating women from a South African township and their 2-4-month-old breastfed infants. Potential predictors of UIC, thyroid function, and BMIC, including household salt iodine concentrations (SIC) and maternal sodium excretion, were also investigated. Results: The median (25th-75th percentile) UIC was 373 (202-627) μg/L in infants and 118 (67-179) μg/L in mothers. Median household SIC was 44 (27-63) ppm. Household SIC and maternal urinary sodium excretion predicted UIC of lactating mothers. Median BMIC was 179 (126-269) μg/L. Age of infants, SIC, and maternal UIC predicted BMIC. In turn, infant age and BMIC predicted UIC of infants. Forty-two percent of SIC values were within the South African recommended salt iodine fortification level at production of 35-65 ppm, whilst 21% of SIC were >65 ppm. Thyroid-stimulating hormone, total thyroxine, and thyroglobulin concentrations in the dried whole blood spot specimens from the infants were 1.3 (0.8-1.9) mU/L, 128±33 mmol/L, and 77.1 (56.3-105.7) μg/L, respectively, and did not correlate with infant UIC or BMIC. Conclusion: Our results suggest that the salt fortification program in South Africa provides adequate iodine to lactating women and indirectly to their infants via breast milk. However, monitoring of salt iodine content of the mandatory salt iodization program in South Africa is important to avoid over-iodization of salt. [ABSTRACT FROM AUTHOR]

This case report presents the utility of the thyroid-releasing hormone (TRH) stimulation test for assessing endocrine disease in athletes. On two occasions, 4 years apart (1992 and 1996), a TRH stimulation test was performed to corroborate clinical symptoms and observation. On the first occasion, the patient's symptoms were not attributed to thyroid disease. He was treated for a sinus infection with amoxicillin/clavulanate 500 mg three times per day for 1 wk. On the second occasion, thyroid disease was confirmed and treatment with 100-μg L-thyroxine was initiated. Baseline screening and TRH stimulation testing were used at both assessment time points. Baseline screen for TSH was 2.2 and 1.2 uUI·mL and stimulated TSH was at 15.2 uUI·mL at 30 min and 30.6 uUI·mL at 45 min for the first (1992) and second (1996) assessment, respectively. Patient was positive on the second visit for antithyroglobulin antibodies at 70 IU·mL (normal, 0-59 IU·mL). Three months postdiagnosis, TSH was 0.66 uIU·mL and the patient was asymptomatic. At the most recent visit, 20 years and 4 months later, no symptomology was reported and TSH was 0.55 uIU·mL A greater understanding of the interaction between stress and end organ function is warranted in occupations undergoing unique stressors. [ABSTRACT FROM AUTHOR]

The article presents the discussion on advising health care professionals evaluating thyroid function in pediatric patients. Topics include increasing risk of hypothyroidism or a temporary decrease in thyroid hormone levels after receiving iodine-containing contrast media containing neonates; and hearing and cognitive development requiring levothyroxine (T4) replacement therapy.

The 'cold' property herbs are commonly applied in heat syndrome. Unfortunately, the underlying mechanisms of the 'cold' property herbs on heat syndrome has not been investigated. The study aimed to probe the activities of the four typical 'cold' property herbs on hyperthyroidism. Firstly, the four typical 'heat' property herbs were set as contrasting experiment. Then. the physical sign, thyroid function and metabolism profile (multivariate statistical analysis) were assessing the difference between the four typical 'cod' property herbs and the four typical 'heat' property herbs. H&E staining were used to confirmed the influence of the typical 'cold' property herbs on hyperthyroidism. A metabolomics approach combine with network pharmacology were explored the effected mechanism of the typical 'cold' property herbs on hyperthyroidism. the gene expression of UCP-1 was detected by RT-PCR. The metabolites pathway and target-associated metabolites were verified Na+/K+-ATP enzyme and GSH, as well IL6, IL17, MAPK and PPAR-γ, which detected by commercial kits and Western blot. It is proved that the four typical 'cold' property herbs effectively ameliorate the physical sign, thyroid function and metabolism profile in hyperthyroidism rats, but the four typical 'heat' property herbs showed no benefit. Moreover, the four typical 'cold' property herbs regulated energy metabolism, glutathione metabolism, taurine hypotaurine metabolism, thyroid hormone synthesis, arachidonic acid metabolism and linoleic acid metabolism and the inflammation mediated by inflammatory factor (IL6, IL17), Ca2+ and MAPK signaling pathway. And the levels of UCP-1, Na+/K+-ATP enzyme, GSH, and the targets protein of IL6, IL17, MAPK and PPAR-γ were ameliorated by the four typical 'cold' property herbs. The four typical 'cold' property herbs could alleviate hyperthyroidism by ameliorate thyroid hormone synthesis, restraining inflammation and oxidative stress via regulating energy metabolism, glutathione metabolism, taurine hypotaurine metabolism, arachidonic acid metabolism and linoleic acid metabolism and Ca 2+/MAPK signaling pathway, which might be a useful strategy for treating hyperthyroidism. "Treating cold syndrome with hot herbs & treating heat syndrome with cold herbs" is a fundamental medication principle of Chinese medicine. However, the medication principle still needed scientific explanation. [Display omitted] • "Treating heat syndrome with cold herbs" is a fundamental medication principle. • Multidisciplinary integration could reveal the essence of the medication principle. • The 'cold' property herbs could alleviate heat syndrome, while hot herbs cannot. • TH synthesis, anti-inflammatory and anti-oxidative are the main alleviate mechanism. [ABSTRACT FROM AUTHOR]

Women of subfertile couples with thyroid autoimmunity (TAI) have an increased risk of miscarriage when pregnant after an assisted reproductive technology (ART) treatment. This might amongst others be due to the presence of thyrotropin receptor antibodies (TSH-R-Ab) that can impede the development of the corpus luteum. TSH-R-Ab can be present in women with TAI and/or be induced by the ovarian stimulation procedure (OS) that is performed to initiate the ART. In this prospective pilot study, we determined the presence of both binding and functional TSH-R-Ab (stimulating or blocking) with five different assays before and after OS in ten women (eleven cycles) with TAI of subfertile couples and in one woman without TAI. Mean (SD) age was 38.8 (±3.2) years, median (range) cumulative OS dose 1413 (613-2925) IU/L. Median baseline serum levels of thyrotropin, free thyroxine, and thyro-peroxidase antibodies were 2.33 (2.23-2.61) mIU/L, 16.8 (14.4-18.5) pmol/L and 152 (86-326) kIU/L, respectively. Oestradiol levels increased during OS from 40 (26-56) ng/L to 963 (383-5095) ng/L; P < .01. TSH-R-Ab measurements in all subject samples were below the cut-off of the corresponding immunoassay and four bioassays before or after OS., Competing Interests: Conflicts of interest: K.G.P. received lecture fees from the IBSA Institut Biochimique SA, the Berlin-Chemie AG, and the Merck Company between 2016 and 2022. G.J.K. consults for and the JGU Medical Centre receives research-associated funding from Quidelortho, United States., (© The Author(s) 2023. Published by Oxford University Press on behalf of (ESE) European Society of Endocrinology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We studied changes in the secretion of thyroid hormones and pituitary thyroid-stimulating hormone (TSH) in young mature male Wistar rats during gradual decrease in deuterium body content. The rats received deuterium-depleted water ([D]=10 ppm) instead of tap water for 21 days. As soon as after 1 day, an increase in the secretion of thyroid hormones was recorded. On day 14, secondary hypothyroidism due to a sharp decrease in TSH secretion by the pituitary gland was found. By day 21, secretion of the thyroid hormones increased, and the reciprocal dependence between the concentrations of thyroid hormones and TSH was restored. Thus, the thyroid gland showed a higher sensitivity to a decrease in the deuterium content in the body than the hypothalamic-pituitary complex. The second difference was in type of response: activation of the secretory processes in the thyroid gland and a transient decrease in the secretory activity of pituitary gland thyrotropes to a decrease in deuterium content., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

Context: Manganese (Mn) exposure is prevalent, as it is found naturally as ionized trace elements and released into the environment as a byproduct of manufacturing and waste disposal. Animal and human studies have suggested variable effects on thyroid function, but the association of Mn exposure with thyroid function has not been evaluated in a national sample., Objective: To investigate the associations between serum and urinary Mn levels and serum thyroid hormone concentrations in a nationally representative sample., Design, Setting, Participants, and Intervention: This was a cross-sectional analysis of data from the 2011-2012 National Health and Nutrition Examination Survey among 1360 participants., Main Outcome Measures: Serum thyroid stimulating hormone (TSH), total triiodothyronine (T3), total thyroxine (T4), free T3, and free T4., Results: Serum Mn levels were positively associated with increasing total T4, free T3, and total T3 in the whole cohort (p < 0.01). Urinary Mn levels were not associated with thyroid hormone levels. When subgroup analyses were performed by gender, only males had total T4 associated with serum Mn [β = 0.01, p < 0.01, confidence interval (CI): 0.004-0.018]. In individuals under 22 years old, serum Mn was significantly associated with total T4 (β = 0.02, p = 0.002, CI: 0.008-0.029). Serum Mn was positively associated with Free T3 in both genders (β = 0.07, p < 0.001)., Conclusion: While our findings do not suggest clinical thyroid dysfunction, there is an association between serum Mn and subclinical changes in thyroid function that warrant further studies. Regulatory action should be considered as Mn-based organometallic compounds are being considered as replacements for lead in gasoline and may pose future risks to human health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Background: Maternal thyroid function plays an important role in foetal brain development; however, little consensus exists regarding the relationship between normal variability in thyroid hormones and common neurodevelopmental disorders, such as attention-deficit hyperactivity disorder (ADHD)., Objective: We sought to examine the association between mid-pregnancy maternal thyroid function and risk of clinically diagnosed ADHD in offspring., Methods: We conducted a nested case-control study in the Norwegian Mother, Father and Child Cohort Study. Among children born 2003 or later, we randomly sampled singleton ADHD cases obtained through linkage with the Norwegian Patient Registry (n = 298) and 554 controls. Concentrations of maternal triiodothyronine (T3), thyroxine (T4), T3-Uptake, thyroid-stimulating hormone (TSH) and thyroid peroxidase antibody (TPO-Ab) were measured in maternal plasma, collected at approximately 17 weeks' gestation. Indices of free T4 (FT4i) and free T3 (FT3i) were calculated. We used multivariable adjusted logistic regression to calculate odds ratios and accounted for missing covariate data using multiple imputation. We used restricted cubic splines to assess non-linear trends and provide flexible representations. We examined effect measure modification by dietary iodine and selenium intake. In sensitivity analyses, we excluded women with clinically significant thyroid disorders (n = 73)., Results: High maternal T3 was associated with increased risk of ADHD (5th vs 1st quintile odds ratio  2.27, 95% confidence interval 1.21, 4.26). For FT4i, both the lowest and highest quintiles were associated with an approximate 1.6-fold increase in risk of ADHD, with similar trends found for T4. The FT4i association was modified by dietary iodine intake such that the highest risk strata were confined to the low intake group., Conclusions: Both high and low concentrations of maternal thyroid hormones, although within population reference ranges, increase the risk of ADHD in offspring. Increased susceptibility may be found among women with low dietary intake of iodine and selenium., (© 2022 John Wiley & Sons Ltd.)

This study aimed to investigate the single-session complete ablation rate of ultrasound-guided percutaneous laser ablation (LA) for benign thyroid nodules. LA was performed in 90 patients with 118 benign thyroid nodules. Contrast-enhanced ultrasound (CEUS) was used to evaluate complete nodule ablation one day after ablation. Thyroid nodule volumes, thyroid functions, clinical symptoms and complications were evaluated 1, 3, 6, 12, and 18 months after ablation. Results showed that all benign thyroid nodules successfully underwent LA. The single-session complete ablation rates for nodules with maximum diameters ≤2 cm, 2-3 cm and ≥3 cm were 93.4%, 70.3% and 61.1%, respectively. All nodule volumes significantly decreased than that one day after ablation (P<0.05); at the final evaluation, the volume decreased from 6.16±5.21 mL to 0.05±0.01 mL. Thyroid functions did not show significant differences at one month after ablation compared with that before (P>0.05). Three patients had obvious pain during ablation; one (1.1%) had recurrent laryngeal nerve injury, but the voice returned to normal within 6 months after treatment. Thus, ultrasound-guided LA can effectively inactivate benign thyroid nodules. LA is a potentially viable minimally invasive treatment that offers good cosmetic effects. [ABSTRACT FROM AUTHOR]

Background: Hashimoto's thyroiditis is an autoimmune disorder and the most common cause of hypothyroidism. The use of Nigella sativa, a potent herbal medicine, continues to increase worldwide as an alternative treatment of several chronic diseases including hyperlipidemia, hypertension and type 2 diabetes mellitus (T2DM). The aim of the current study was to evaluate the effects of Nigella sativa on thyroid function, serum Vascular Endothelial Growth Factor (VEGF) -- 1, Nesfatin-1 and anthropometric features in patients with Hashimoto's thyroiditis. Methods: Forty patients with Hashimoto's thyroiditis, aged between 22 and 50 years old, participated in the trial and were randomly allocated into two groups of intervention and control receiving powdered Nigella sativa or placebo daily for 8 weeks. Changes in anthropometric variables, dietary intakes, thyroid status, serum VEGF and Nesfatin-1 concentrations after 8 weeks were measured. Results: Treatment with Nigella sativa significantly reduced body weight and body mass index (BMI). Serum concentrations of thyroid stimulating hormone (TSH) and anti-thyroid peroxidase (anti-TPO) antibodies decreased while serum T3 concentrations increased in Nigella sativa-treated group after 8 weeks. There was a significant reduction in serum VEGF concentrations in intervention group. None of these changes had been observed in placebo treated group. In stepwise multiple regression model, changes in waist to hip ratio (WHR) and thyroid hormones were significant predictors of changes in serum VEGF and Nesgfatin-1 values in Nigella sativa treated group (P < 0.05). Conclusions: Our data showed a potent beneficial effect of powdered Nigella sativa in improving thyroid status and anthropometric variables in patients with Hashimoto's thyroiditis. Moreover, Nigella sativa significantly reduced serum VEGF concentrations in these patients. Considering observed health- promoting effect of this medicinal plant in ameliorating the disease severity, it can be regarded as a useful therapeutic approach in management of Hashimoto's thyroiditis. Trial registration: Iranian registry of clinical trials (registration number IRCT2015021719082N4- Registered March-15-2015). [ABSTRACT FROM AUTHOR]

Although numerous pesticides may interfere with thyroid function, however, epidemiological evidence supporting this relationship is limited, particularly regarding modern non-persistent pesticides. We sought to evaluate the association of agricultural work practices, use of contemporary-use pesticides, and OC pesticides residue levels in serum with circulating thyroid hormone levels in an agricultural population. A cross-sectional study was conducted with a random sample of 275 male and female farm residents in Farroupilha, South of Brazil. Information on sociodemographics, lifestyle and agricultural work was obtained through questionnaire. Blood samples were collected on all participants and analyzed for cholinesterase activity, serum residues of OC pesticides, and levels of free T4 (FT4), total T3 (TT3) and TSH. Non-persistent pesticides exposure assessment was based on questionnaire information on current use of pesticides, and frequency and duration of use, among others. Associations were explored using multivariate linear regression models. Total lifetime years of use of fungicides, herbicides and dithiocarbamates in men was associated with increased TSH accompanied by decrease in FT4, with evidence of a linear trend. In addition, there was an association between being sampled in the high pesticide-use season and increased TSH levels. Conversely, farm work and lifetime use of all pesticides were related with slight decrease in TSH and increased TT3 and FT4, respectively. In general, pesticide use was not associated with thyroid hormones in women. Subjects with detected serum concentrations of β-hexachlorocyclohexane, endrin, dieldrin, heptachlor epoxide B, γ-chlordane, transnonachlor, heptachlor, p , p ′-dichlorodiphenylethane and endosulfan II experienced slight changes in TT3; however, associations were weak and inconsistent. These findings suggest that both cumulative and recent occupational exposure to agricultural pesticides may affect the thyroid function causing hypothyroid-like effects, particularly in men. [ABSTRACT FROM AUTHOR]

Overt thyroid dysfunction is recognized as a risk factor for neuropsychological deficits in aging populations, yet evidence for how changes in levels of circulatory thyroid hormones impact specific neuropsychological domains is limited. Here we report cross-sectional associations between serum thyroid hormone concentrations and several neuropsychological function domains among men and women aged 55–74 years. We administered neuropsychological tests to assess memory, learning, executive function, measures of attention, visuospatial function, affective state, and motor function. Multivariable linear regression analyses were performed adjusting for age, sex, education, and cigarette smoking. Effects were reported as differences in test scores per one interquartile range (IQR) increase in hormone concentration. Higher total thyroxine (T4) and free thyroxine (fT4) were associated with improved visuospatial function, as measured by Block Design Subtest total scores; associated increments per IQR differences in T4 and fT4 were 15% and 19%, respectively (false discovery rate q-values < 0.05). We also detected statistical interactions between age and fT4 for effects in tasks of memory and learning. Concurrent increases in age and fT4 were associated with deficits in memory and learning as measured by California Verbal Learning Test subtests (10% and 16% deficits in t -score and short delay free recall score, respectively). Our findings suggest that changes in thyroid hormones may have important implications for neuropsychological function in aging populations. Further large-scale studies with comprehensive thyroid function and neuropsychological outcome assessments are warranted to confirm these results. [ABSTRACT FROM AUTHOR]

Objective: Over 300 million people rely on desalinated seawater and the numbers are growing. Desalination removes iodine from water and could increase the risk of iodine-deficiency disorders (IDD). The present study assessed the relationship between iodine intake and thyroid function in an area reliant on desalination.Design: A case-control study was performed between March 2012 and March 2014. Thyroid function was rigorously assessed by clinical examination, ultrasound and blood tests, including serum thyroglobulin (Tg) and autoimmune antibodies. Iodine intake and the contribution made by unfiltered tap water were estimated by FFQ. The contribution of drinking-water to iodine intake was modelled using three iodine concentrations: likely, worst-case and best-case scenario.Setting: The setting for the study was a hospital located on the southern Israeli Mediterranean coast.Subjects: Adult volunteers (n 102), 21-80 years old, prospectively recruited.Results: After screening, seventy-four participants met the inclusion criteria. Thirty-seven were euthyroid controls. Among those with thyroid dysfunction, twenty-nine were classified with non-autoimmune thyroid disease (NATD) after excluding eight cases with autoimmunity. Seventy per cent of all participants had iodine intake below the Estimated Average Requirement (EAR) of 95 µg/d. Participants with NATD were significantly more likely to have probable IDD with intake below the EAR (OR=5·2; 95 % CI 1·8, 15·2) and abnormal serum Tg>40 ng/ml (OR=5·8; 95 % CI 1·6, 20·8).Conclusions: Evidence of prevalent probable IDD in a population reliant on desalinated seawater supports the urgent need to probe the impact of desalinated water on thyroid health in Israel and elsewhere. [ABSTRACT FROM AUTHOR]

Background: The objective of the study was to analyze a potential association between cognitive functions and thyroid status in postmenopausal women with different polymorphisms of the apolipoprotein E gene (APOE) . Methods: The examined population included 402 postmenopausal women from south-eastern Poland. The evaluation of cognitive functions was made with the use of the diagnostic Central Nervous System-Vital Signs equipment (Polish version). Multiplex polymerase chain reactions were performed to assess APOE polymorphisms. The thyroid hormone tests were assessed by an accredited laboratory. Results and Conclusion: Lower results of cognitive functions were associated with the presence of the ε4 APOE allele in postmenopausal women. The ε4 APOE polymorphism was associated with a higher concentration of thyroid-stimulating hormone and lower concentrations of free triiodothyronine and total triiodothyronine. [ABSTRACT FROM AUTHOR]

The potencies of resorcinol, 6-propylthiouracil (PTU) and methimazole (MMI) for inducing developmental toxicity and neurotoxicity were compared in pregnant rats, regarded as valid model for human thyroid toxicity. Profound differences on maternal thyroid hormone levels (THs), maternal toxicity as well as developmental and neurotoxicity sequelae occurred. Resorcinol affected none of those end points. PTU and MMI caused significant effects. Therapy with either PTU or MMI during the first trimester of human pregnancy can cause reductions of maternal THs, accompanied by disruptions of prenatal development. Clinical MMI studies show sporadic evidence of teratogenic effects, with equivocal relation to thyroid peroxidase (TPO) inhibition. In recent decades no MMI associated prenatal toxicity has been reported, an outcome possibly related to carefully managed therapy. Orally administered resorcinol was rapidly absorbed, metabolized and excreted and was undetectable in the thyroid. In contrast, PTU or MMI accumulated. Resorcinol’s potency to inhibit TPO was profoundly lower than that of PTU or MMI. Quantum chemical calculations may explain low resorcinol reactivity with TPO. Thus, distinctions in the target organ and the TPO inhibitory potency between these chemicals are likely contributing to different reductions of maternal THs levels and affecting the potency to cause developmental toxicity and neurotoxicity. [ABSTRACT FROM AUTHOR]

Background: The association between thyroid function and cardiovascular disease is well established, but no study to date has assessed whether it is a risk factor for sudden cardiac death (SCD). Therefore, we studied the association of thyroid function with SCD in a prospective population-based cohort.Methods: Participants from the Rotterdam Study ≥45 years with thyroid-stimulating hormone or free thyroxine (FT4) measurements and clinical follow-up were eligible. We assessed the association of thyroid-stimulating hormone and FT4 with the risk of SCD by using an age- and sex-adjusted Cox proportional-hazards model, in all participants and also after restricting the analysis to euthyroid participants (defined by thyroid-stimulating hormone 0.4-4.0 mIU/L). Additional adjustment included cardiovascular risk factors, notably hypertension, serum cholesterol, and smoking. We stratified by age and sex and performed sensitivity analyses by excluding participants with abnormal FT4 values (reference range of 0.85-1.95 ng/dL) and including only witnessed SCDs as outcome. Absolute risks were calculated in a competing risk model by taking death by other causes into account.Results: We included 10 318 participants with 261 incident SCDs (median follow-up, 9.1 years). Higher levels of FT4 were associated with an increased SCD risk, even in the normal range of thyroid function (hazard ratio, 2.28 per 1 ng/dL FT4; 95% confidence interval, 1.31-3.97). Stratification by age or sex and sensitivity analyses did not change the risk estimates substantially. The absolute 10-year risk of SCD increased in euthyroid participants from 1% to 4% with increasing FT4 levels.Conclusions: Higher FT4 levels are associated with an increased risk of SCD, even in euthyroid participants. [ABSTRACT FROM AUTHOR]

Background: Isotretinoin is widely used in the treatment of acne.Aims: We investigated the effects of isotretinoin on thyroid function tests and thyroid volume in acne patients.Methods: In this prospective study, a total of 104 acne patients were included. Sixty-six patients were treated with isotretinoin for at least 4 months. Thirty eight patients were included in the control group. The levels of thyroid stimulating hormone, free triiodothyronine, free thyroxine, antithyroglobulin and antithyroid peroxidase antibodies were measured and a thyroid ultrasound was performed in all the subjects before treatment and 4 months after treatment. A "p" value of < 0.05 was considered significant.Results: In the isotretinoin-treated group, thyroid stimulating hormone levels increased significantly during isotretinoin treatment (P = 0.018). Free triiodothyronine, free thyroxine, anti-thyroid peroxidase levels and thyroid volume decreased significantly during treatment (P = 0.016, P= 0.012, P= 0.006, P = 0.020 respectively).Limitations: The major limitation of this study is the lack of follow-up data after the cessation of isotretinoin therapy in acne patients.Conclusion: Patients treated with isotretinoin should be monitored with thyroid function tests. [ABSTRACT FROM AUTHOR]

Nitric oxide participates in the regulation of thyroid function. Aims: The purpose of this study was to determine whether there is an association between serum nitric oxide metabolites (NOx) and free thyroxine (free T4), anti-thyroid peroxidase (anti-TPO), and thyroid-stimulating hormone (TSH) levels. Methods: Study subjects were adults, aged ≥20 years, who participated in the Tehran Thyroid Study (TTS). In a cross-sectional study, in the third phase of TTS, serum NOxconcentrations were measured in 1974 adult participants; pregnant women and subjects who had chronic diarrhea, cancer, weight loss, and hospitalization within the past 3 months were excluded, as were those taking medicines that affect thyroid function; the remaining 1771 subjects were grouped according to tertiles of free T4, anti-TPO, and TSH. Spearman’s correlation coefficients and multivariable linear regression analysis were used to determine the relationship between serum NOxlevels and free T4, anti-TPO, and TSH. Results: Serum NOxlevels were negatively correlated with free T4in men (r= −0.083;p= 0.029). An inverse association between the third tertile of free T4and NOxlevels was found in both non-adjusted (β= −0.095,p= 0.031) and multivariable-adjusted (β= −0.094,p= 0.039) analyses, only in men. After multivariable adjustment, the third tertile of anti-TPO was significantly associated with NOxlevels in women (β= −0.067,p= 0.050). Conclusions: Based on the result, serum NOxconcentration was found to be associated with free T4 in men and anti-TPO in women. [ABSTRACT FROM AUTHOR]

Rab7 regulates the biogenesis of late endosomes, lysosomes, and autophagosomes. It has been proposed that a functional and physical interaction exists between Rab7 and Rac1 GTPases in CDH1 endocytosis and ruffled border formation. In FRT cells over-expressing Rab7, increased expression and activity of Rac1 was observed, whereas a reduction of Rab7 expression by RNAi resulted in reduced Rac1 activity, as measured by PAK1 phosphorylation. We found that CDH1 endocytosis was extremely reduced only in Rab7 over-expressing cells but was unchanged in Rab7 silenced cells. In Rab7 under or over-expressing cells, Rab7 and LC3B-II co-localized and co-localization in large circular structures occurred only in Rab7 over-expressing cells. These large circular structures occurred in about 10% of the cell population; some of them (61%) showed co-localization of Rab7 with cortactin and f-actin and were identified as circular dorsal ruffles (CDRs), the others as mature autophagosomes. We propose that the over-expression of Rab7 is sufficient to induce CDRs. Furthermore, in FRT cells, we found that the expression of the insoluble/active form of Rab7, rather than Rab5, or Rab8, was inducible by cAMP and that cAMP-stimulated FRT cells showed increased PAK1 phosphorylation and were no longer able to endocytose CDH1. Finally, we demonstrated that Rab7 over-expressing cells are able to endocytose exogenous thyroglobulin via pinocytosis/CDRs more efficiently than control cells. We propose that the major thyroglobulin endocytosis described in thyroid autonomous adenomas due to Rab7 increased expression, occurs via CDRs. J. Cell. Physiol. 231: 1695-1708, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the association between thyroid function and exposure to selected polycyclic aromatic hydrocarbons (PAH) among those aged ≥ 20 years. Thyroid variables considered for evaluation were thyroid-stimulating hormone, free and total serum thyroxine (FT4, TT4), free and total triiodothyronine (FT3, TT3), and thyroglobulin. PAH metabolites in urine for which data were analyzed were 1-hydroxynaphthalene, 2-hydroxynaphthalene, 2-hydroxyfluorene, 3-hydroxyfluorene, 9-hydroxyfluorene, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, and 1-hydroxypyrene. Using data from 2007 to 2008 National Health and Nutrition Examination Survey, regression models with logs of thyroid variables as dependent variables and PAH exposure, age, race/ethnicity, iodine sufficiency, smoking status, and others as independent variables were fitted. For females, increased levels of 2-hydroxynapthalene, 2-hydroxyphenanthrene, and 1-hydroxypyrene were associated with elevated levels of TT3. For males, increased levels of 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, and 9-hydroxypyrene were associated with decreased levels of FT4. [ABSTRACT FROM AUTHOR]

Intakes of radionuclides can be estimated through in vivo measurements, and the uncertainties associated to the measured activities should be clearly stated in monitoring program reports. This study aims to evaluate the uncertainties of in vivo monitoring of iodine 131 in the thyroid. The reference values for high-energy photons are based on the IDEAS Guide. Measurements were performed at the In Vivo Monitoring Laboratory of the Institute of Radiation Protection and Dosimetry (IRD) and at the Internal Dosimetry Laboratory of the Regional Center of Nuclear Sciences (CRCN-NE). In both institutions, the experiment was performed using a NaI(Tl) 3′′3″ scintillation detector and a neck-thyroid phantom. Scattering factors were calculated and compared in different counting geometries. The results show that the technique produces reproducibility equivalent to the values suggested in the IDEAS Guide and measurement uncertainties is comparable to international quality standards for this type of in vivo monitoring. [ABSTRACT FROM AUTHOR]

The thyroid gland is an important endocrine organ modulating development, growth, and metabolism, mainly by controlling the synthesis and secretion of thyroid hormones (THs). However, little is known about the pig thyroid transcriptome. Long non-coding RNAs (lncRNAs) regulate gene expression and play critical roles in many cellular processes. Yorkshire pigs have a higher growth rate but lower fat deposition than that of Jinhua pigs, and thus, these species are ideal models for studying growth and lipid metabolism. This study revealed higher levels of THs in the serum of Yorkshire pigs than in the serum of Jinhua pigs. By using Ribo-zero RNA sequencing--which can capture both polyA and non-polyA transcripts--the thyroid transcriptome of both breeds were analyzed and 22,435 known mRNAs were found to be expressed in the pig thyroid. In addition, 1189 novel mRNAs and 1018 candidate lncRNA transcripts were detected. Multiple TH-synthesis-related genes were identified among the 455 differentially-expressed known mRNAs, 37 novel mRNAs, and 52 lncRNA transcripts. Bioinformatics analysis revealed that differentially-expressed genes were enriched in the microtubule-based process, which contributes to THs secretion. Moreover, integrating analysis predicted 13 potential lncRNA-mRNA gene pairs. These data expanded the repertoire of porcine lncRNAs and mRNAs and contribute to understanding the possible molecular mechanisms involved in animal growth and lipid metabolism. [ABSTRACT FROM AUTHOR]

Objective: In obese subjects, slight increases have been observed in thyrotropin [thyroid-stimulating hormone (TSH)] levels, but data in children are scarce. The aim of this study was to evaluate whether thyroid function and autoimmunity vary with weight status in a healthy population of children and adolescents and to determine whether hyperthyrotropinemia is associated with any cardiovascular risk factor. Methods: This cross-sectional epidemiological study was conducted in Almería (Spain) on a representative sample of 1317 healthy subjects aged 2-16 years. Thyroid function, thyroid autoimmunity and cardiovascular risk factors were measured. Chisquare test, analysis of variance and multiple linear regression were used in the statistical analyses. Results: The obese children and adolescents had thyrotropin levels (mean ± standard deviation) of 3.12±2.44 mU/L. These levels were higher than those of overweight subjects (2.79±1.51 mU/L) and of normal weight subjects (2.73±1.30 mU/L) (p=0.02). Levels of free thyroxine and urinary iodine did not differ significantly between the groups. The prevalence (95% confidence interval) of thyroid autoimmunity was lower in the individuals with normal weight (2.9%; 2.0-4.2) than in the overweight (6.3%; 3.9-9.9) and obese subjects (5.6%, 2.5-11.3) (p=0.02). TSH levels were associated with obesity (β=0.36; p<0.001) and thyroid autoimmunity (β=1.10; p<0.001). They were not associated with any cardiovascular risk factor. Conclusion: Obese children and adolescents had higher levels of thyrotropin than those who were overweight and of normal weight. The differences among the groups were of very little clinical significance and could possibly be linked to the higher prevalence of thyroid autoimmunity in obese subjects. The hyperthyrotropinemia in these subjects was not associated with any cardiovascular risk factor. [ABSTRACT FROM AUTHOR]