Circulating Thyroid Hormone Research Articles

Subclinical Hypothyroidism in Danish Lean and Obese Children and Adolescents.

Objective:Thyroid abnormalities are common in obese children. The aim of the present study was to examine the prevalence of subclinical hypothyroidism (SH) and to determine how circulating thyroid hormone concentrations correlate with anthropometrics in Danish lean and obese children and adolescents.Methods:In this cross-sectional study, we included 3006 children and adolescents, aged 6-18 years, from the Registry of the Danish Childhood Obesity Biobank. The overweight/obese group (n=1796) consisted of study participants with a body mass index (BMI) standard deviation score (SDS) ≥1.28. The control group (n=1210) comprised lean children with a BMI SDS <1.28. All participants were characterized by anthropometrics (weight, height, and waist circumference) and fasting serum concentrations of thyroid-stimulating hormone (TSH), free triiodothyronine, and free thyroxine (fT4) at baseline.Results:The prevalence of SH was higher among overweight/obese compared to lean study participants (10.4% vs. 6.4%, p=0.0001). In the overweight/obese group, fasting serum TSH concentrations were associated positively with BMI SDS (p<0.0001) and waist-height ratio (WHtR) (p<0.0001) independent of age, sex, and pubertal developmental stage, whereas fasting serum fT4 concentrations were associated positively only with WHtR. The odds ratio of exhibiting SH was 1.8 when being overweight/obese compared with lean (p=0.0007) and 1.8 when presenting with a WHtR >0.5 (p=0.0003).Conclusion:The prevalence of SH was higher among overweight/obese study participants. The positive correlations of circulating TSH and fT4 with WHtR suggest that central obesity, independent of the overall degree of obesity, augments the risk of concurrent thyroid abnormalities in children and adolescents with obesity.

Free Thyroid Hormones and Mortality in Caucasians Undergoing Angiography: The Ludwigshafen Risk and Cardiovascular Health (Luric) Study

AbstractObjective: Alterations in thyroid hormone functions are associated with mortality and morbidity. Data on euthyroid individuals are very limited and controversial. We therefore investigated the relationship between circulating thyroid hormones and all-cause and cardiovascular (CV) mortality in participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study and their association with morbidity.Methods: LURIC, a prospective, observational study of a hospital-based cohort of Caucasians, was recruited between June 1997 and May 2001 at the Ludwigshafen General Hospital, Ludwigshafen, Germany. Mortality was recorded for a follow-up period of 10 years. The current investigation includes 2,507 patients without overt thyroid disease who all underwent coronary angiography. Blood was drawn before angiography. We evaluated the association between thyroid hormone concentrations and mortality.Results: Low free triiodothyronine (FT3) (hazard ratio [HR], 1.00 versus 0.54; lowest versus highest quartile) and high free thyroxine (FT4) (HR, 1.52 versus 1.00; highest versus lowest quartile) were significant predictors of all-cause and CV mortality, independent of age and sex. Thyroid-stimulating hormone showed no consistent correlation with mortality.Conclusion: High FT4 and low FT3 concentrations are significantly related to all-cause and CV mortality. These findings suggest that free thyroid hormones should be measured and considered in patients at intermediate to high risk of coronary heart disease.Abbreviations: BMI = body mass index CAD = coronary artery disease CCI = Charlson Comorbidity Index CI = confidence interval CV = cardiovascular eGFR = estimated glomerular filtration rate FT3 = free triiodothyronine FT4 = free thyroxine HR = hazard ratio T3 = triiodothyronine T4 = thyroxine TSH = thyroid-stimulating hormone

Retrospective evaluation of circulating thyroid hormones in critically ill dogs with systemic inflammatory response syndrome

Critical illness can be associated with transient alterations in circulating thyroid hormone concentrations, indicating the presence of non-thyroidal illness (NTI). NTI is well described in humans, but there are few reports on its occurrence and prognostic significance in dogs. This retrospective study assessed the occurrence of NTI in a population of dogs with systemic inflammatory response syndrome (SIRS) and investigated its association with disease severity (APPLEfast scores). A total of 41 SIRS dogs were included and were divided by SIRS origin (non-septic SIRS, n = 10; septic SIRS, n = 41) and final outcome (survivors, n = 37; non-survivors, n = 4). Healthy, age-matched dogs (n = 15) were included as controls. Serum thyroid hormone levels including total T3, free T3, total T4, and reverse T3 were measured upon admission. Compared to controls, there were significant changes in serum thyroid hormone concentrations in SIRS dogs, suggesting the presence of NTI. Septic SIRS dogs had higher APPLEfast scores and lower serum thyroid hormones concentrations than those in non-septic SIRS and control dogs. In conclusion, NTI was frequent in dogs with SIRS and may be associated with the presence of sepsis or high illness severity.

Assessment of the Selenium Status in Hypothyroid Children from North East of Iran

Both iodine and selenium are essential important micronutrient required for the synthesis of thyroid hormones. The aims of this study are to assess selenium status in hypothyroid children and to determine its association with thyroid hormones metabolism. This cross-sectional study was conducted using a convenient sample of hypothyroid children attending to children endocrinology clinic between July 2015 and March 2016 in Neyshabur, Iran. Selenium, T4 and TSH in serum of 23 hypothyroid children, 1-72 month of age were measured. SPSS, version 11.5 was used to analyze the data. The Student´s t or the Mann-Whitney U and bivariate and partial correlation tests were used in the analyses. The mean age of the participants was 30 month (±25.09). The mean ± SD of plasma Selenium concentration in hypothyroid children was 98.79 ± 13.63 μg/l. Considering the conventional serum Selenium-deficiency cutoff (<90.0 μg/l), 26.08% of children had low serum selenium. Using the arbitrary level of thyroid hormones for normal thyroid metabolism, 17.39% of the children had elevated TSH level and 4.34% of the children had serum T4 < 4.7 nmol/l. Spearman correlation test showed that selenium level was significantly correlated with TSH (r= 0.63, p =0.001), weight (r= 0.53, p=0.008) and age(r=0.44, p=0.03). In study children, selenium level indicated reverse significant correlation with T4 (r=-.58, p=.004). In the present study, we showed that selenium deficiency plays a role in circulating thyroid hormones concentration and also affect the necessary levothyroxine dose required for hypothyroid children. These findings call for an increased attention to serum selenium levels in hypothyroid children. Selenium supplementation may be useful in hypothyroid treatment.

Novel Mutation (T273R) in Thyroid Hormone Receptor β Gene Provides Further Insight into Cryptic Negative Regulation by Thyroid Hormone

Production of thyroid hormone is precisely regulated in a negative feed-back mechanism that depends critically on thyroid hormone receptor β (TRβ). This mechanism decreases production of thyrotropin- releasing hormone (TRH) and thyrotropin (TSH) in the hypothalamus and pituitary gland in response to high levels of circulating thyroid hormones (TH). Despite the wealth of accumulated knowledge, it is still not clear how exactly this negative regulation is executed. The syndrome of resistance to thyroid hormone (RTH), in which the levels of TH are not properly sensed, represents naturally occurring situations in which molecular components of this regulation are displayed and may be uncovered. TRβ, which is central to this regulation, is in the majority of RTH cases mutated in a way that preserves some functions of the receptor. Approximately 150 different mutations in TRβ have been identified to date. Here, we hypothesized that additional pathogenic mutations in TRβ are likely to exist in human population and analysed clinical cases with suspected RTH. In keeping with our prediction, analysis of 17 patients from nine families led to identification of four presumed pathogenic mutations of TRβ, including a previously unknown mutation, T273R. This suggests that threonine 273 is likely to be critical for the normal function of TRβ, possibly due to its role in helix 12 mobility and interaction with coactivators, and thus supports the concept that TRβ-dependent trans-activating function is necessary for the inhibition of TRH and TSH expression in response to elevated levels of TH.

Alteration of thyroid hormone concentrations in juvenile Chinook salmon (Oncorhynchus tshawytscha) exposed to polybrominated diphenyl ethers, BDE-47 and BDE-99

Polybrominated diphenyl ethers (PBDEs) have been used as flame-retardants in consumer products and are currently detected in salmon globally. The two most predominant PBDE congeners found in salmon are BDE-47 (2,2′,4,4’-tetrabromodiphenyl ether) and BDE-99 (2,2′,4,4′,5-pentabromodiphenyl ether). In the present study, groups of juvenile Pacific Chinook salmon were fed five environmentally relevant concentrations of either BDE-47 (0.3–552 ng total PBDEs/g food), BDE-99 (0.3–580 ng total PBDEs/g food), or nearly equal mixtures of both congeners (0.7–690 ng total PBDEs/g food) for 39–40 days. The concentrations of circulating total thyroid hormones, thyroxine (T4) and 3,5,3’-triiodothyronine (T3), were measured using a hormone-specific time-resolved fluoroimmunoassay to determine if PBDE exposure disrupts the hypothalamic-pituitary-thyroid endocrine axis. The concentrations of both circulating T4 and T3 were altered in juvenile salmon by dietary uptake of BDE-99. Exposure to BDE-47 did not alter either T3 or T4 circulating hormone concentrations. However, exposure to a mixture of BDE-47 and BDE-99 reduced T3 in fish with lower concentrations of total whole body PBDEs than with either congener alone at equivalent PBDE whole body concentrations. Accordingly, the disruption of PBDEs on circulating thyroid hormone concentrations has the potential to impact a number of critical functions in juvenile salmon including growth, parr-smolt transformation, and immunological processes.

Thyroid hormones and cardiovascular disease.

Myocardial and vascular endothelial tissues have receptors for thyroid hormones and are sensitive to changes in the concentrations of circulating thyroid hormones. The importance of thyroid hormones in maintaining cardiovascular homeostasis can be deduced from clinical and experimental data showing that even subtle changes in thyroid hormone concentrations - such as those observed in subclinical hypothyroidism or hyperthyroidism, and low triiodothyronine syndrome - adversely influence the cardiovascular system. Some potential mechanisms linking the two conditions are dyslipidaemia, endothelial dysfunction, blood pressure changes, and direct effects of thyroid hormones on the myocardium. Several interventional trials showed that treatment of subclinical thyroid diseases improves cardiovascular risk factors, which implies potential benefits for reducing cardiovascular events. Over the past 2 decades, accumulating evidence supports the association between abnormal thyroid function at the time of an acute myocardial infarction (MI) and subsequent adverse cardiovascular outcomes. Furthermore, experimental studies showed that thyroid hormones can have an important therapeutic role in reducing infarct size and improving myocardial function after acute MI. In this Review, we summarize the literature on thyroid function in cardiovascular diseases, both as a risk factor as well as in the setting of cardiovascular diseases such as heart failure or acute MI, and outline the effect of thyroid hormone replacement therapy for reducing the risk of cardiovascular disease.

An assessment of exposure and effects of persistent organic pollutants in an urban Cooper's hawk (Accipiter cooperii) population.

Among the stressors confronting urban wildlife, chemical contaminants pose a particular problem for high trophic feeding species. Previous data from fortuitous carcass collections revealed surprisingly high levels of persistent organic pollutants in raptor species, including the Cooper's hawk (Accipiter cooperii), from urbanized areas of southwestern British Columbia, Canada. Thus, in 2012 and 2013, we followed up on that finding by measuring POPs in blood samples from 21 adult and 15 nestling Cooper's hawks in Vancouver, a large urban area in southwestern Canada. Reproductive success and circulating thyroid hormones were measured to assess possible toxicological effects. Model comparisons showed concentrations of polychlorinated biphenyls (ΣPCBs) were positively influenced by the level of urbanization. Total thyroxin (TT4) was negatively associated with increases in ΣPCBs. Total triiodothyronine (TT3) was negatively associated with ΣPCBs and polybrominated diphenyl ethers (ΣPBDEs). The legacy insecticide, dieldrin, appeared to have some negative influence on reproductive success. There is some evidence of biochemical perturbation by PBDEs and lingering impact of legacy POPs which have not been used for at least 40 years, but overall Cooper's hawks have successfully populated this urban environment.

Seasonal variation in body mass index, cardinal physiological variables and serum thyroid hormones profiles in relation to susceptibility to thermal stress in goat kids

The influence of seasonal changes and susceptibility to thermal stress on body mass index (BMI), cardinal physiological variables (respiratory rate; RR, pulse rate; PR and rectal temperature; RT) and circulating thyroid hormone profiles (T3 and T4) was studied in Red Sokoto (n=60) and Sahel (n=60) goats during the cold-dry (CDS), hot-dry (HDS) and rainy (RAS) seasons. Using the RR, goats were grouped into cold stress susceptible (CSS) and cold stress tolerant (CST) phenotypes in the season with lower temperature humidity index (CDS) or heat stress susceptible (HSS) and heat stress tolerant (HST) phenotypes in the seasons with higher THI (HDS and RAS). Results revealed that the PR and RT were lower (P<0.05), while circulating thyroid hormones and BMI were higher (P<0.05) in Red Sokoto compared with Sahel goats. The RR, PR, RT and T3:T4 were significantly lower, while circulating T3 was higher during the CDS as compared with the HDS. Higher population of the goats were susceptible to cold and heat stress. Discriminant analysis showed higher misclassification of goats into HSS and HST phenotypes as compared with classification into CSS and CST phenotypes. The CSS phenotypes had significantly lower RT, but higher PR than the CST phenotypes. The HSS phenotypes had lower (P<0.05)T3 than the HST phenotypes. Total variation in susceptibility to thermal stress was mainly explained by the RT, T3 and PR. In conclusion, unlike RT, PR and T3, BMI seems to have less influence on the susceptibility of kids to thermal stress. In addition, this study demonstrates the role of the thermogenic effect of T3 in the susceptibility and tolerance of kids to thermal stress.

Thyrotoxicosis due to functioning metastatic follicular thyroid cancer

Thyrotoxicosis is a common condition associated with excess circulating thyroid hormones. Rarely, thyrotoxicosis can be developing due to functioning metastatic thyroid carcinoma. Most of patients with functional thyroid cancer metastases have had normal thyroxine (T4) concentrations but high serum triiodothyronine (T3-thyrotoxicosis). Inappropriately supressed TSH levels with normal T4 levels may be helpful to suspect T3 thyrotoxicosis. In this case report we present a case of thyrotoxicosis due to metastatic follicular thyroid cancer with a huge metastatic lesion.

Transfer of hexabromocyclododecane flame retardant isomers from captive American kestrel eggs to feathers and their association with thyroid hormones and growth

Feathers are useful for monitoring contaminants in wild birds and are increasingly used to determine persistent organic pollutants. However, few studies have been conducted on birds with known exposure levels. We aimed to determine how well nestling feather concentrations reflect in ovo exposure to hexabromocyclododecane (α-, β- and γ-HBCDD), and to determine if feather concentrations are related to physiological biomarkers. Captive kestrels (n = 11) were exposed in ovo to maternally transferred HBCDD-isomers at concentrations of 127, 12 and 2 ng/g wet weight of α-, β- and γ-HBCDD (measured in sibling eggs), respectively, and compared to controls (n = 6). Nestling growth was monitored at 5 d intervals and circulating thyroid hormone concentrations assessed at d 20. Tail feathers were collected prior to the first molt and analyzed for HBCDD isomers. The mean ΣHBCDD concentration in feathers was 2405 pg/g dry weight (in exposed birds) and α-, β- and γ-HBCDD made up 32%, 13%, and 55%, respectively of the ΣHBCDD concentrations. This isomer distribution deviated from the typical dominance of α-HBCDD reported in vertebrate samples. Exposed chicks had significantly higher feather concentrations of β- and γ-HBCDD compared with controls (p = 0.007 and p = 0.001 respectively), while α-HBCDD concentrations did not differ between the two groups. Feather concentrations of α-HBCDD were best explained by egg concentrations of β- or γ-HBCDD concentrations (wi = 0.50, 0.30 respectively), while feather concentrations of β- and γ-HBCDD were influenced by growth parameters (rectrix length: wi = 0.61; tibiotarsus length: wi = 0.28). These results suggest that feather α-HBCDD concentrations may reflect internal body burdens, whereas β- and γ-HBCDD may be subject to selective uptake. The α-HBCDD concentrations in the feathers were negatively associated with the ratio of plasma free triiodothyronine to free thyroxine (T3:T4; p = 0.020), demonstrating for the first time that feather concentrations may be used to model the effect of body burdens on physiological endpoints.

Cardiac connexin-43 and PKC signaling in rats with altered thyroid status without and with omega-3 fatty acids intake.

Thyroid hormones are powerful modulators of heart function and susceptibility to arrhythmias via both genomic and non-genomic actions. We aimed to explore expression of electrical coupling protein connexin-43 (Cx43) in the heart of rats with altered thyroid status and impact of omega-3 polyunsaturated fatty acids (omega-3) supplementation. Adult male Lewis rats were divided into following six groups: euthyroid controls, hyperthyroid (treated with T(3)) and hypothyroid (treated with methimazol) with or without six-weeks lasting supplementation with omega-3 (20 mg/100 g/day). Left and right ventricles, septum and atria were used for immunoblotting of Cx43 and protein kinase C (PKC). Total expression of Cx43 and its phosphorylated forms were significantly increased in all heart regions of hypothyroid rats compared to euthyroid controls. In contrast, the total levels of Cx43 and its functional phosphorylated forms were decreased in atria and left ventricle of hyperthyroid rats. In parallel, the expression of PKC epsilon that phosphorylates Cx43, at serine 368, was increased in hypothyroid but decreased in hyperthyroid rat hearts. Omega-3 intake did not significantly affect either Cx43 or PKC epsilon alterations. In conclusion, there is an inverse relationship between expression of cardiac Cx43 and the levels of circulating thyroid hormones. It appears that increased propensity of hyperthyroid while decreased of hypothyroid individuals to malignant arrhythmias may be in part attributed to the changes in myocardial Cx43.

Thyroid Emergencies.

Myxedema coma and thyroid storm are thyroid emergencies associated with increased mortality. Prompt recognition of these states-which represent the severe, life-threatening conditions of extremely reduced or elevated circulating thyroid hormone concentrations, respectively-is necessary to initiate treatment. Management of myxedema coma and thyroid storm requires both medical and supportive therapies and should be treated in an intensive care unit setting.

Thyroidal response following iodine excess for cardiac catheterisation and intervention in early infancy

BackgroundCardiac catheterisation requiring the use of contrast medium is increasingly utilised in infants with congenital heart disease. Thyroid function in infants is potentially vulnerable to relatively high doses of iodine. MethodsSingle-centre prospective study of 21 patients (10 neonates, 11 infants) exposed to iodine during cardiac catheterisation. Median age was 30days (1–180), median body weight 3.3kg (1.6–7.0). Serum-levels of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3) and free thyroxine (fT4) were measured at baseline before, and at three different times points after intervention. ResultsBaseline thyroidal levels were within normal range in all patients. After applying contrast media of median 6.8ml/kg (range 4.5–14.9), we observed a wide range of TSH values: median 5.01μg/l (range 0.59–37.73; reference 0.72–11.0) three to five days after catheterisation. Five of the 10 neonates demonstrated transient TSH elevation consistent with latent hypothyroidism, and a sixth a transient drop in all hormone levels typical of non-thyroidal illness syndrome. However, circulating thyroid hormones remained within normal range, except for two borderline-low fT4 values within the first week after catheterisation that normalised without any medical intervention. ConclusionSystemic iodine exposure during cardiac catherterisation seems to be clinically well tolerated in early infancy. However, exposure to iodine has demonstrable but apparently reversible effects on thyroid hormones during a potentially important developmental period. The implications of this are unclear, but warrant further investigation in larger cohorts.

Pesticide exposure and thyroid function in an agricultural population in Brazil

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.

Original Research: Metabolic alterations from early life thyroxine replacement therapy in male Ames dwarf mice are transient.

Ames dwarf mice are exceptionally long-lived due to a Prop1 loss of function mutation resulting in deficiency of growth hormone, thyroid-stimulating hormone and prolactin. Deficiency in thyroid-stimulating hormone and growth hormone leads to greatly reduced levels of circulating thyroid hormones and insulin-like growth factor 1, as well as a reduction in insulin secretion. Early life growth hormone replacement therapy in Ames dwarf mice significantly shortens their longevity, while early life thyroxine (T4) replacement therapy does not. Possible mechanisms by which early life growth hormone replacement therapy shortens longevity include deleterious effects on glucose homeostasis and energy metabolism, which are long lasting. A mechanism explaining why early life T4 replacement therapy does not shorten longevity remains elusive. Here, we look for a possible explanation as to why early life T4 replacement therapy does not impact longevity of Ames dwarf mice. We found that early life T4 replacement therapy increased body weight and advanced the age of sexual maturation. We also find that early life T4 replacement therapy does not impact glucose tolerance or insulin sensitivity, and any deleterious effects on oxygen consumption, respiratory quotient and heat production are transient. Lastly, we find that early life T4 replacement therapy has long-lasting effects on bone mineral density and bone mineral content. We suggest that the transient effects on energy metabolism and lack of effects on glucose homeostasis are the reasons why there is no shortening of longevity after early life T4 replacement therapy in Ames dwarf mice.

Sex-specific changes in thyroid gland function and circulating thyroid hormones in nestling American kestrels (Falco sparverius) following embryonic exposure to polybrominated diphenyl ethers by maternal transfer.

High concentrations of polybrominated diphenyl ethers (PBDEs) accumulate in predatory birds. Several PBDE congeners are considered thyroid disruptors; however, avian studies are limited. The authors examined circulating thyroid hormones and thyroid gland function of nestling American kestrels (Falco sparverius) at 17 d to 20 d of age, following embryonic exposure by maternal transfer only to environmentally relevant levels of PBDEs (DE-71 technical mixture). Nestlings were exposed to in ovo sum (Σ) PBDE concentrations of 11 301 ± 95 ng/g wet weight (high exposure), 289 ± 33 ng/g wet weight (low exposure), or 3.0 ± 0.5 ng/g wet weight (controls, background exposure). Statistical comparisons are made to controls of the respective sexes and account for the relatedness of siblings within broods. Circulating concentrations of plasma total thyroxine (TT4 ) and total triiodothyronine (TT3 ) in female nestlings were significantly influenced overall by the exposure to DE-71. Following intramuscular administration of thyroid-stimulating hormone, the temporal response of the thyroid gland in producing and/or releasing TT4 was also significantly affected by the females' exposure to DE-71. The altered availability of T4 for conversion to T3 outside of the gland and/or changes in thyroid-related enzymatic activity may explain the lower TT3 concentrations (baseline, overall) and moderately altered temporal TT3 patterns (p = 0.06) of the treatment females. Controlling for the significant effect on TT3 levels of the delayed hatching of treatment females, baseline TT3 levels were significantly and positively correlated with body mass (10 d, 15 d, 20 d), with PBDE-exposed females generally being smaller and having lower TT3 concentrations. Given that exposure concentrations were environmentally relevant, similar thyroidal changes and associated thyroid-mediated processes relating to growth may also occur in wild female nestlings. Environ Toxicol Chem 2016;35:2084-2091. © 2016 SETAC.

The Hypercoagulable state in Hyperthyroidism is mediated via the Thyroid Hormone β Receptor pathway.

Hyperthyroidism is associated with a hypercoagulable state, but the underlying mechanism is unknown. Patients with resistance to thyroid hormone (RTH) due to defective thyroid hormone receptor β (TRβ) exhibit elevated circulating thyroid hormones (TH) with refractoriness to TH action in TRβ-expressing tissues. We tested the hypothesis that the hypercoagulable state in hyperthyroidism is mediated via the TRβ. We conducted a cross-sectional study from November 2013 to January 2015 in 3 hospitals in the Netherlands and the United Kingdom. Patients with RTH due to defective TRβ (n=18), patients with hyperthyroidism (n=16) and euthyroid subjects (n=18) were included. TH concentrations and markers of coagulation and fibrinolysis were measured. Data are expressed as median [interquartile range]. Free thyroxine (FT4) levels were slightly higher in hyperthyroid patients than in RTH patients (53.9 [30.5-70.0] and 34.9 [28.4-42.2]pmol/l, respectively, P=0.042). Both groups had raised FT4 levels compared to euthyroid subjects (14.0 [13.0-15.8] pmol/l, P≤0.001). Levels of von Willebrand factor (VWF), factor (F) VIII, fibrinogen, and D-dimer were significantly higher in hyperthyroid patients than in RTH patients (VWF 231 [195-296] vs. 111 [82-140]%, FVIII 215 [192-228] vs. 145 [97-158]%, fibrinogen 3.6 [3.0-4.4] vs. 2.8 [2.5-3.2]g/L, D-dimer 0.41 [0.31-0.88] vs. 0.20 [0.17-0.26]mg/L, respectively, P≤0.001), while there were no differences between RTH patients and euthyroid controls. Parameters of coagulation and fibrinolysis were elevated in hyperthyroid patients compared to patients with RTH due to defective TRβ, whereas these parameters were not different between euthyroid controls and RTH patients, despite elevated FT4 concentrations in RTH patients. This indicates that the procoagulant effects observed in hyperthyroidism are mediated via the TRβ.

A low TSH profile predicts olanzapine-induced weight gain and relief by adjunctive topiramate in healthy male volunteers

Second generation antipsychotics, like olanzapine (OLZ), have become the first line drug treatment for patients with schizophrenia. However, OLZ treatment is often associated with body weight (BW) gain and metabolic derangements. Therefore, the search for prospective markers for OLZ's negative side effects as well as adjunctive treatments to inhibit these has been of major interest.The aim of this study was to investigate in healthy male volunteers (age: 36±11years; BW: 84±12kg; BMI=25.5±2.5) whether adjunctive topiramate (TPM) administration opposes OLZ-induced weight gain over the course of 14 days treatment. In addition, we investigated behavioral, endocrine and metabolic characteristics as underlying and potentially predictive factors for weight regulation and/or metabolic derangements associated with OLZ and TPM treatment.While adjunctive TPM indeed reduced OLZ-induced weight gain (P<0.05, Mann–Whitney U), behavioral/metabolic/endocrine characteristics of OLZ treatment were not affected by TPM. Using multiple regression analysis, BW gain was the key factor explaining metabolic disturbances (e.g., plasma insulin— LDL interaction: P<0.01, R2=.320), and cumulative food intake during treatment was the best denominator of BW gain (P<0.01, R2=.534). Neither TPM treatment, nor its circulating levels, contributed to variation observed in ΔBW. In a second multiple regression analysis, we observed that a low baseline thyrotropin profile (TSHAUC) before the start of drug treatment was associated with an increase in ΔBW over the course of drug treatment (P<0.05, R2=.195). Adding TSHAUC as covariate revealed that adjunctive TPM treatment did attenuate OLZ induced BW gain (P<0.05, ANCOVA). Further exploration of the circulating thyroid hormones revealed that individuals with a low plasma TSH profile were also those that were most sensitive to adjunctive TPM treatment blocking OLZ-induced ΔBW gain. Others have shown that OLZ-induced BW gain is associated with improvement in brief psychiatric rating scores (BPRS); adjunctive TPM treatment may be a solution specifically for those subjects susceptible to OLZ-induced rapid weight gain who—on a therapeutic level—benefit most of OLZ treatment.

Hypothyroidism in Pregnancy: A Hospital based cross sectional study

Introduction: Uncontrolled hypothyroidism is associated with serious maternal, fetal, and neonatal morbidity, and mortality. Overt hypothyroidism is defined as a clinical syndrome of hypothyroidism associated with elevated TSH and decreased serum levels of T4 or T3. Subclinical hypothyroidism is defined as a condition without typical symptoms of hypothyroidism, elevated TSH (>5 µU/mL), and normal circulating thyroid hormone. Material & Methods: The present hospital based cross sectional study was conducted in the Department of Obstetrics and Gynaecology, Dr. B. R. Ambedkar Medical College & Hospital, Bangalore. From the outpatient clinics, a total of 200 pregnant women of 1st trimester were selected in the study. Informed consent was taken from the study participants. Complete thyroid profile was done. Results: Mean age was found to be 23.6±2.5 and mean gestational age 8.2±2.6. Among the total study participants (n=200), the overall prevalence of hypothyroidism was 16.5% (n=33). Elevated TSH levels (>5mIU/ml) was found in 16.5% (33) of the study population. With regards to thyroid hormone levels, decreased levels of T3 & T4 were observed in 24.3% (08) and 75.7% (25) had normal levels of T3 & T4. Majority had subclinical hypothyroidism 75.7% (n=25) and 24.3% (n=8) had overt hypothyroidism. Keywords: Pregnancy, Hypothyroidism, Prevalence, Thyroid profile, Subclinical