Free Thyroxine Concentrations Research Articles

Redefining the Cut-Off Ranges for TSH Based on the Clinical Picture, Results of Neuroimaging and Laboratory Tests in Unsupervised Cluster Analysis as Individualized Diagnosis of Early Schizophrenia

Thyroid abnormalities, including mild forms of hypothyroidism and hyperthyroidism, are reported as risk factors for the development of a number of neuropsychiatric disorders, including schizophrenia. The diagnostic process still takes into account the extreme ranges of the accepted reference values for serum TSH since the concentration of free thyroxine in the serum does not change by definition. TSH mU/L cut-off values in psychiatric patients are currently clinically considered in the case of extremely high serum TSH levels (>4.0 mU/L). The results obtained in this study suggest that the clinically significant value has a lower TSH cut-off point with an upper limit of 2–2.5 mU/L. The criteria for the differential diagnosis of patients with schizophrenia, however, mainly take into account statutory reference ranges without a background related to the history of thyroid diseases in the family. The results indicate the need to lower the upper cut-off values for TSH among patients with early psychosis, which is related to the potential clinical significance of the obtained values both in the field of clinical evaluation and neuroimaging and laboratory evaluation parameters. The cut-off points obtained with the prior available knowledge coincided with the values established in the unsupervised clustering method, which further confirms the legitimacy of their use in the individualized diagnosis strategy of schizophrenia.

СРАВНИТЕЛЬНЫЕ ПОКАЗАТЕЛИ ЙОДНОГО СТАТУСА И ФУНКЦИОНАЛЬНОЙ АКТИВНОСТИ ЩИТОВИДНОЙ ЖЕЛЕЗЫ У ШКОЛЬНИКОВ СЕВЕРНОГО РЕГИОНА В ЗАВИСИМОСТИ ОТ МАССЫ ТЕЛЫ

In 112 schoolchildren from the city of Surgut: group I with normal body weight (n = 68), group II – overweight and obese (n = 44), the concentrations of pituitary thyroid stimulating hormone (TTG), free triiodothyronine (T3) and free thyroxine (T4) in blood serum by enzyme immunoassay methods, as well as the content of iodine in hair by AES-ICP and MS-ICP methods. Signifi cantly higher concentrations of TSH (p < 0,001) in combination with lower T3 (p = 0,047) and iodine (p = 0,027) were found in overweight and obese schoolchildren from the northern region.

Clinical utility of urinary levels of catecholamines and their fraction ratios related to heart rate and thyroid function.

Urinary catecholamines (CAs) have been examined for the screening of pheochromocytomas. The decision to perform screening is based on symptoms suggesting secondary hypertension or hyperactivities of the sympathetic nervous system. To elucidate the usefulness of urinary fractions and ratios of CAs, 79 patients in whom 24-h excretions of urinary CAs including adrenaline (AD), noradrenaline (NA) and dopamine (DA) had been examined from 2015 until 2020 were retrospectively analyzed. There were no significant differences in urinary CA levels between two age groups, gender groups and two BMI groups. Patients with histories of preexisting hypertension and diabetes showed significantly higher levels of urinary NA excretion, and the urinary ratio of NA/DA was also increased in the patients with a history of hypertension. Heart rate (HR) was significantly correlated with the urinary ratio of NA/DA. Serum free thyroxine (FT4) concentration and ratio of FT4/thyrotropin (TSH) were correlated with the level of urinary AD. The levels of TSH and FT4/TSH showed negative and positive correlations, respectively, with the urinary NA/DA ratio. Thus, increases of HR are related to the enhanced conversion of DA to NA and increased thyroid hormones are involved in the increase in urinary AD and the conversion of DA to NA. History of lifestyle-related diseases and changes of HR and thyroid functions need to be considered for the evaluation of urinary CAs and their ratios.

Gestational trimester-specific reference ranges for serum thyrotropin and free thyroxine in Japanese.

Thyroid diseases in pregnant and lactating women may result in adverse outcomes for both mothers and infants. A reference range for thyroid function is required in different areas; however, few studies on the gestational change or reference ranges of thyrotropin (TSH) and free thyroxine (FT4) concentrations for Japanese pregnant women have been reported. To establish the gestational trimester-specific reference ranges of serum TSH and FT4 concentrations, our previously published data on 481 pregnant women with the mean age of 30.8 years who provided serum samples as early as gestational week (GW) 6 was compiled by using their percentile values. The overall median urinary iodine concentration (UIC) during pregnancy was 201 μg/L suggesting adequate iodine intake. The prevalence of positive serum thyroid autoantibody (ThAb), i.e., antithyroid peroxidase antibody (TPOAb) and antithyroglobulin antibody (TgAb), was 11.4%. The reference ranges (2.5-97.5th percentile) of serum TSH and FT4 concentration calculated for samples with negative TgAb and TPOAb were 0.04-6.06 mIU/L in the first trimester (T1), 0.31-3.11 mIU/L in the second trimester (T2) and 0.48-3.93 mIU/L in the third trimester (T3) for TSH, and 1.10-1.87 ng/dL (T1), 0.76-1.56 ng/dL (T2) and 0.76-1.14 ng/dL (T3) for FT4. Compared to published data around the world in the 2017 American Thyroid Association (ATA) guideline, both the upper and lower limits of our TSH and FT4 reference ranges in the first trimester were higher than those in other countries. Further research is necessary in larger samples.

Association Between Low-normal Range Free Thyroxine Concentration and Increase in Carotid Intima–Media Thickness with Age among Euthyroid Japanese Men

Association Between Low-normal Range Free Thyroxine Concentration and Increase in Carotid Intima–Media Thickness with Age among Euthyroid Japanese Men

Effect of Levothyroxine Replacement on Cognitive Function Impairment in a Sample of Egyptian Population with Subclinical Hypothyroidism

Introduction: Subclinical hypothyroidism (SHT) is characterized by a normal range of free thyroxin concentrations together with increased serum TSH levels. SHT is defined as serum thyroid-stimulating hormone (TSH) concentration above the upper limit of the reference range in the face of normal free FT4 and FT3 levels. The effect of SHT on cognitive function has been investigated in several preclinical studies, and a growing body of evidence has suggested a relevant link between thyroid hormones and the central nervous system. Objectives: This study aimed to investigate the effect of levothyroxine replacement on cognitive impairment in a sample of Egyptian patients with SHT. Methods: A prospective cohort study conducted on 30 patients with cognitive impairment and SHT attending an endocrine outpatient clinic at the Ain Shams University Hospital to study the effect of levothyroxine supplementation on cognitive impairment in patients with SHT. The study was conducted on 30 patients. All participants were subjected to a full history taking; thorough clinical examination; laboratory investigations including thyroid profile (FT3, FT4, TSH), anti-thyroid peroxidase antibodies, anti-thyroglobulin antibodies, and lipid profile; imaging tests as neck ultrasound, echocardiography, and carotid duplex; and finally Addenbrooke’s questionnaire used to diagnose mild cognitive impairment. Results: A highly statistically significant difference was found before, 3 months and 6 months after treatment with levothyroxine regarding all clinical data, TSH, LDL, T. cholesterol, FT3, FT4 and HDL, carotid intima-media thickness, and Addenbrooke’s questionnaire. Our study showed a statistically significant inverse correlation between TSH level and mild cognitive impairment before and after treatment with levothyroxine at 3 and 6 months intervals as when TSH increased, results of Addenbrooke’s questionnaire decreased and, so, cognitive impairment increased, while when TSH decreased in response to thyroxine replacement, cognitive impairment improved as detected by an increase in the patient’s score. Conclusion: SHT has a great effect on cognitive impairment, as normalization in TSH level results in improvement in cognitive function. Also, there was a significant reduction in carotid intima-media thickness, which may contribute to improvement of cognitive function in addition to a great improvement in lipid profile, which in turn positively affects cardiac and cognitive function.

The prevalence of autoimmune thyroiditis in adolescent girls with polycystic ovary syndrome.

Both polycystic ovary syndrome (PCOS) and autoimmune thyroiditis (AT) are reported to be common endocrinopathies. In recent years the number of publications assessing the coexistence of these two disease entities in adult women has been growing. There are many suggestions regarding pathophysiological mechanisms that can cause the relationship between AT and PCOS. However, there is still a lack of research among adolescent girls. The aim of the study was to analyze the occurrence of autoimmune thyroiditis in adolescent girls with PCOS. The study group included 80 girls diagnosed with PCOS (chronological age: 16.54 ± 1.00 years, BMI: 22.80 ± 3.27 kg/m2), and the control group - 64 regularly menstruating girls (chronological age: 16.71 ± 0.63 years, BMI: 24.8 ± 5.2 kg/m2). The thyroid function and morphology were assessed based on the concentration of thyroid stimulating hormone (TSH), free thyroxine (fT4), anti thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-TG) antibodies and ultrasound scan of the thyroid gland. AT was diagnosed in 18 (22.5%) girls from the study group and nine (14.06%) from the control group (p > 0.05). Positive anti-TPO titer was observed more often in the study group [21 patients (26.25%)] than in the control group [9 girls (14.06%)] (p = 0.054). Moreover, an abnormal ultrasound scan of the thyroid gland characteristic for AT was found in 18 girls from the study group (22.50%) and 8 girls from the control group (12.50%) (p > 0.05). The results of the analyzed studies do not confirm a significant relationship between PCOS and AT in adolescent girls. However, in the group of girls with PCOS, autoimmune process exponents were more frequent (anti-TPO), reaching the borderline level of statistical significance.

Functional Characterization of the Novel and Specific Thyroid Hormone Transporter SLC17A4.

Background: A recent genome-wide association study identified the SLC17A4 locus associated with circulating free thyroxine (T4) concentrations. Human SLC17A4, being widely expressed in the gastrointestinal tract, was characterized as a novel triiodothyronine (T3) and T4 transporter. However, apart from the cellular uptake of T3 and T4, transporter characteristics are currently unknown. In this study, we delineated basic transporter characteristics of this novel thyroid hormone (TH) transporter. Methods: We performed a broad range of well-established TH transport studies in COS-1 cells transiently overexpressing SLC17A4. We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. Finally, we determined the effect of tunicamycin, a pharmacological inhibitor of N-linked glycosylation, and targeted mutations in Asn residues on SLC17A4 function. Results: SLC17A4 induced the cellular uptake of T3 and T4 by ∼4 times, and of reverse (r)T3 by 1.5 times over control cells. The uptake of T4 by SLC17A4 was Na+ and Cl- independent, stimulated by low extracellular pH, and reduced by various iodothyronines and metabolites thereof, particularly those that contain at least three iodine moieties irrespective of the presence of modification at the alanine side chain. None of the classical TH transporter inhibitors studied attenuated SLC17A4-mediated TH transport. SLC17A4 also facilitates the efflux of T3 and T4, and to a lesser extent of 3,3'-diiodothyronine (T2). Immunoblot studies on lysates of transfected cells cultured in absence or presence of tunicamycin indicated that SLC17A4 is subject to N-linked glycosylation. Complementary mutational studies identified Asn66, Asn75, and Asn90, which are located in extracellular loop 1, as primary targets. Conclusions: Our studies show that SLC17A4 facilitates the transport of T3 and T4, and less efficiently rT3 and 3,3'-T2. Further studies should reveal the physiological role of SLC17A4 in TH regulation.

Cord Blood Thyroid Hormones and Neurodevelopment in 2-Year-Old Boys and Girls.

Objective: Thyroid hormones are essential for neurodevelopment in early life. However, the impact of mild alterations in neonatal thyroid hormones on infant neurodevelopment and its sex dimorphism is unclear. We aimed to assess whether mild variations in neonatal thyroid hormones of term-born newborns with maternal euthyroid are related to neurodevelopment in 2-year-old boys and girls.Methods: This study used data from 452 singleton term-born infants of mothers with normal thyroid function in Shanghai, China, and their follow-up measure at the age of 2 years. Cord serum concentrations of free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), and thyroid peroxidase antibody (TPOAb) were measured by chemiluminescent microparticle immunoassays and classified into three groups: the low (1st, Q1), middle (2nd−4th, Q2–Q4), and high (5th, Q5) quintiles. Neurodevelopment indices were assessed using the Ages and Stages Questionnaire, third edition (ASQ-3), at 24 months of age.Results: Compared to infants with thyroid hormones in the middle (Q2–Q4), boys with FT4 in the lowest quintile had 5.08 (95% CI: 1.37, 8.78) points lower scores in the communication domain, 3.25 (0.25,6.25) points lower scores in the fine motor domain, and 3.84 (0.04, 7.64) points lower scores in the personal-social domain, respectively. Boys with FT3 in the highest quintile had 4.46 (0.81, 8.11) points increase in the personal-social domain. These associations were not observed in girls. No associations were observed between cord blood serum TSH and ASQ-assessed neurodevelopment in the boys or the girls.Conclusions: Mild alterations in thyroid hormones of newborns were associated adversely with neurodevelopment in boys, suggesting the importance of optimal thyroid hormone status for neurodevelopment in early life.

Association of phthalate exposure with thyroid function during pregnancy.

The extent of thyroid disruptive effects of phthalates during pregnancy remains unclear. To investigate the association of maternal urinary phthalates with markers of the thyroid system during early pregnancy. Urinary concentrations of phthalate metabolites and serum concentrations of thyroid stimulating hormone (TSH), free and total thyroxine (FT4 and TT4) and free and total triiodothyronine (FT3 and TT3) were measured in pregnant women in early pregnancy in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study (2007-ongoing), a population-based prospective cohort. In the 1,996 included women, higher di-ethyl-hexyl phthalate (DEHP) metabolites were associated with a lower FT4 (β [SE] for the molar sum: -0.13 [0.06], P=0.03) and a higher TSH/FT4 ratio (0.003 [0.001], P=0.03). Higher concentrations of di-iso-nonyl phthalate (DINP) metabolites were associated with a lower TT4 (β [SE] for the molar sum: 0.93 [0.44], P=0.03) as well as with lower TT4/FT4 and TT4/TT3 ratios. Higher metabolites of both dibutyl and butyl-benzyl phthalate (DBP and BBzP) were associated with lower T4/T3 ratio (free and total) and higher FT4/TT4 and FT3/TT3 ratios. A higher diisononyl cyclohexane dicarboxylate (DINCH) metabolite concentration was associated with a higher TT3. These results translate results from experimental studies suggesting that exposure to phthalates may interfere with the thyroid system during pregnancy. This is also true for compounds that have been introduced to replace known disruptive phthalates. Further experimental studies should take into account the human evidence to better investigate the potential underlying mechanisms of thyroid disruption by phthalates.

Functional State of Rat Heart Mitochondria in Experimental Hyperthyroidism.

In this work, the effect of thyroxine on energy and oxidative metabolism in the mitochondria of the rat heart was studied. Hyperthyroidism was observed in experimental animals after chronic administration of T4, which was accompanied by an increase in serum concentrations of free triiodothyronine (T3) and thyroxine (T4) by 1.8 and 3.4 times, respectively. The hyperthyroid rats (HR) had hypertrophy of the heart. In HR, there was a change in the oxygen consumption in the mitochondria of the heart, especially when using palmitoylcarnitine. The assay of respiratory chain enzymes revealed that the activities of complexes I, I + III, III, IV increased, whereas the activities of complexes II, II + III decreased in heart mitochondria of the experimental animals. It was shown that the level of respiratory complexes of the electron transport chain in hyperthyroid rats increased, except for complex V, the quantity of which was reduced. The development of oxidative stress in HR was observed: an increase in the hydrogen peroxide production rate, increase in lipid peroxidation and reduced glutathione. The activity of superoxide dismutase in the heart of HR was higher than in the control. At the same time, the activity of glutathione peroxidase decreased. The obtained data indicate that increased concentrations of thyroid hormones lead to changes in energy metabolism and the development of oxidative stress in the heart of rats, which in turn contributes to heart dysfunction.

Exposure to common-use pesticides, manganese, lead, and thyroid function among pregnant women from the Infants' Environmental Health (ISA) study, Costa Rica

BackgroundPesticides and metals may disrupt thyroid function, which is key to fetal brain development. ObjectivesTo evaluate if current-use pesticide exposures, lead and excess manganese alter free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) concentrations in pregnant women from the Infants' Environmental Health Study (ISA). MethodsAt enrollment, we determined women's (n = 400) specific-gravity corrected urinary pesticide (μg/L) metabolite concentrations of mancozeb (ethylene thiourea (ETU)), pyrimethanil, thiabendazole, chlorpyrifos, synthetic pyrethroids, and 2,4-D. We also measured manganese hair (MnH) (μg/g) and blood (MnB) (μg/L), and blood lead (PbB) (μg/L) concentrations. To detect an immediate and late effect on thyroid homeostasis, we determined TSH, FT4 and FT3 in serum obtained at the same visit (n = 400), and about ten weeks afterwards (n = 245). We assessed associations between exposures and outcomes with linear regression and general additive models, Bayesian multivariate linear regression, and Bayesian kernel machine regression. ResultsAbout 80%, 94%, and 100% of the women had TSH, FT4, and FT3 within clinical reference ranges, respectively. Women with higher urinary ETU, and pyrimethanil-metabolites, had lower FT4: β = −0.79 (95%CI = −1.51, −0.08) and β = −0.29 (95%CI = −0.62, −0.03), respectively, for each tenfold increase in exposure. MnB was positively associated with FT4 (β = 0.04 (95%CI = 0.00, 0.07 per 1 μg/L increase), and women with high urinary pyrethroid-metabolite concentrations had decreased TSH (non-linear effects). For the late-effect analysis, metabolites of pyrethroids and chlorpyrifos, as well as MnH, and PbB were associated decreased TSH, or increased FT4 and/or FT3. DiscussionMancozeb (ETU) and pyrimethanil may inhibit FT4 secretion (hypothyroidism-like effect), while chlorpyrifos, pyrethroids, MnB, MnH, PbB and Mn showed hyperthyroidism-like effects. Some effects on thyroid homeostasis seemed to be immediate (mancozeb (ETU), pyrimethanil, MnB), others delayed (chlorpyrifos, MnH, PbB), or both (pyrethroids), possibly reflecting different mechanisms of action.

Iron Deficiency Is a Risk Factor for Thyroid Dysfunction During Pregnancy: A Population-Based Study in Belgium.

Background: Iron deficiency affects thyroid hormone synthesis by impairing the activity of the heme-dependent thyroid peroxidase. The prevalence of iron deficiency is elevated particularly in pregnant women. This study aimed to investigate the effects of iron status on thyroid function in a nationally representative sample of mildly iodine-deficient pregnant women. Methods: The study population comprised a sample of pregnant women in Belgium during the first and third trimesters of pregnancy (n = 1241). Women were selected according to a multistage proportional-to-size stratified and clustered sampling design. Urine and blood samples were collected, and a questionnaire was completed face to face with the study nurse. Concentrations of free thyroxine (fT4), total thyroxine (T4), free triiodothyronine, thyrotropin (TSH), thyroglobulin (Tg), thyroid peroxidase antibodies, Tg antibodies, hemoglobin, serum ferritin (SF), soluble transferrin receptor, urinary iodine concentrations (UICs) were measured and body iron stores (BIS) were calculated. Results: Median UICs were 117 and 132 μg/L in the first and third trimesters of pregnancy, respectively (p < 0.05). The frequency of SF <15 μg/L was 6.2% in the first trimester and 39.6% in the third trimester of pregnancy (p < 0.05). UIC was a significant predictor of serum Tg concentrations (p < 0.01) but not of thyroid hormone or TSH concentrations. The frequency of fT4<percentile 10th in the third trimester of pregnancy was 24% and 14% in pregnant women with negative BIS and positive BIS, respectively (p < 0.05). SF and BIS were significant predictors of fT4 and T4 in the first trimester of pregnancy (p < 0.05). Hemoglobin was a significant predictor of fT4 in both trimesters (p < 0.01) and for T4 in the third trimester (p = 0.015). Conclusion: Iron deficiency, but not mild iodine deficiency, is a determinant of serum fT4 and T4 in pregnant women. Correcting iron deficiency may help to maintain optimal thyroid function, in addition to preventing anemia during pregnancy.

The role of miRNA-624-5p in congenital hypothyroidism and its molecular mechanism by targeting SIRT1

Accumulating reports evidenced that congenital hypothyroidism (CH) is a kind of endocrine diseases caused by thyroid hormone imperfection. MicroRNAs (miRNAs) were confirmed to exhibit protective functions in CH progression. However, the functions and latent mechanism of microRNA-624-5p (miR-624-5p) in CH remains unknown. This report was designed to illustrate the potential molecular mechanisms of miR-624-5p on CH. Rats were induced by 50mg/day propylthiouracil to conduct CH models. Free thyroxine (fT4) and thyroid-Stimulating hormone (TSH) concentrations were measured to confirm CH model conduction. The direct target of miR-624-5p was predicted and verified by Starbase and dual luciferase reporter assay. Besides, the levels of miR-624-5p and sirtuin1 (SIRT1) in hippocampus or hippocampal neuronal cells were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot assays. Then CH rat behaviors were evaluated using open field test (OFT) and forced swim test (FST). Furthermore, neuronal cells viability and apoptosis were checked using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and flow cytometry. qRT-PCR assay suggested that miR-624-5p was up-regulated and SIRT1 was low-expressed in hippocampus tissues of CH rats. SIRT1 was a direct target of miR-624-5p. MiR-624-5p inhibitor signally enhanced fT4 levels and reduced TSH levels in the plasma of CH rats, and improved CH rat depressive behaviors by targeting SIRT1. Moreover, our data also revealed that miR-624-5p inhibitor increased cell viability and reduced apoptotic neuronal cells, which was reversed by silencing of SIRT1. Taken together, this research demonstrated that miR-624-5p serves as a promising target for CH treatment.

Gestational Hormone Concentrations Are Associated With Timing of Delivery in a Fetal Sex-Dependent Manner.

BackgroundEarly delivery remains a significant public health problem that has long-lasting impacts on mother and child. Understanding biological mechanisms underlying timing of labor, including endocrine disruption, can inform prevention efforts.MethodsGestational hormones were measured among 976 women in PROTECT, a longitudinal birth cohort in Puerto Rico. We evaluated associations between hormone concentrations at 18 and 26 weeks gestation and gestational age at birth, while assessing effect modification by fetal sex. Exploratory analyses assessed binary outcomes of overall preterm birth (PTB, <37 weeks gestation) and the spontaneous PTB subtype, defined as preterm premature rupture of membranes, spontaneous preterm labor, or both. Multivariable logistic and linear regressions were fit using visit-specific hormone concentrations, and fetal sex-specific effects were estimated using interaction terms. Main outcome models were adjusted for maternal age, education, marital status, alcohol consumption, environmental tobacco smoke exposure, and pre-pregnancy body mass index (BMI). Exploratory models adjusted for maternal age and education.ResultsWe observed reduced gestational age at birth with higher circulating CRH (β: -2.73 days, 95% CI: -4.97, -0.42), progesterone (β: -4.90 days, 95% CI: -7.07, -2.73), and fT4 concentrations (β: -2.73 days, 95% CI: -4.76, -0.70) at 18 weeks specifically among male fetuses. Greater odds of overall and spontaneous PTB were observed among males with higher CRH, estriol, progesterone, total triiodothyronine (T3), and free thyroxine (fT4) concentrations. Greater odds of PTB among females was observed with higher testosterone concentrations.ConclusionsVarious associations between hormones and timing of delivery were modified by fetal sex and timing of hormone measurement. Future studies are needed to understand differential mechanisms involved with timing of labor between fetal sexes.

Associations between the thyroid panel and serum protein concentrations across pregnancy

Establishing any characteristic associations between the serum parameters of thyroid function and serum proteins in pregnancy may aid in elucidating the role of the thyroid gland in the regulation of pregnancy-specific metabolic processes and in selecting candidate biomarkers for use in their clinical assessment. Concentrations of thyroid stimulating hormone (TSH), free tri-iodothyronine (fT3) and free thyroxine (fT4), six electrophoretically separated protein fractions (albumin, alpha-1-, alpha2-, beta-1-, beta-2- and gamma-globulins), representative proteins—albumin (ALB), transferrin (TRF), alpha-2-macroglobulin (AMG) and ceruloplasmin (CER) were measured in 136 serum samples from 65 women in their consecutive trimesters of pregnancy. The concentrations of TSH, fT4 and fT3 were significantly correlated (p < 0.05) with the concentrations of the albumin, alpha-2- and beta-1 globulin fractions. Significant correlations (p < 0.05) which were positive between fT4 and ALB and negative between fT4 and TRF were established throughout pregnancy. Significant negative correlations (p < 0.05) were demonstrated for fT3 with alpha-2-globulin, AMG and CER. Changes in the serum concentrations of thyroid hormones seen between the trimesters were found to correlate with the concentrations of high-abundance serum proteins. Opposite directions of correlations between fT4 and ALB and fT4 and TRF observed throughout pregnancy may indicate the shared biological role of these parameters in maintaining maternal homeostasis and they suggest their potential use in the clinic as a simple biomarker panel. A negative correlation of fT3 with CER in the second trimester possibly reflects their involvement in the active regulation of metabolic processes.

Whether a Gluten-Free Diet Should Be Recommended in Chronic Autoimmune Thyroiditis or Not?-A 12-Month Follow-Up.

Elimination diets have recently become extremely popular among people with autoimmune diseases. A gluten-free diet is indicated in celiac disease (CD), but some studies show its effectiveness in cases of autoimmunity. The aim of this study was to assess whether the use of a gluten-free diet is also effective in patients with chronic autoimmune thyroid disease (cAITD), which is the most common thyroid autoimmune pathology associated with chronic inflammation, over-reactivity of the immune system, auto-destruction of thyrocytes and hypothyroidism. The final analysis of the study included 62 Caucasian women randomized into a control group (CG: n = 31) and an experimental group on a gluten-free diet (GFDG: n = 31), were subject to a 12-month follow-up, during which the concentrations of thyrotropin (TSH), free triiodothyronine (fT3), free thyroxine (fT4), anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) antibodies were assessed at baseline and after 3, 6 and 12 months. During the 12-month follow-up between the CG and the GFDG, no differences were found in anti-TPO and anti-TG antibodies, fT3 or fT4 levels, except a significant reduction in TSH levels in the GFDG. Additionally, performed analysis between individual appointments presented no significant differences in changes in the median concentrations of anti-TPO, anti-TG or fT3, but confirmed a significant decrease in TSH and showed accessory an increase in fT4 after 12 months in GFDG. Statistical analyses performed separately for both groups indicated a constant reduction of anti-TG concentrations in the GFDG. In conclusion, a GFD may be administered in cAITD after ruling out celiac disease, but it is necessary to perform more studies to assess if cAITD patients achieve the benefits of following a GFD. Patients with cAITD should be offered proper nutrition education combined with a healthy lifestyle promotion.

Serial measurement of thyroid hormones in hospitalised dogs with canine parvoviral enteritis: Incidence of non-thyroidal illness syndrome and its association with outcome and systemic inflammatory response syndrome

The aim of this study was to serially evaluate the serum concentrations of total thyroxine (tT4), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) in dogs with canine parvoviral enteritis (CPVE) during a 5-day hospitalisation period and assess the association of these hormone concentrations with the outcome and the development of systemic inflammatory response syndrome (SIRS). Dogs with confirmed CPVE that were hospitalised for at least 5 days were included. The thyroid hormones concentrations were measured on days 1, 3 and 5 of hospitalisation.Twenty-eight dogs were included. All (28/28, 100%), 19/28 (69.7%) and 23/28 (82.1%) dogs had a low serum tT4, fT4 and TSH concentration, respectively, on at least 1 day during the hospitalisation period. Overall, 11/28 (39.3%) dogs were diagnosed with SIRS on at least 1 day. In survivors, serum tT4 concentration was significantly higher on day 5 (median, range: 11.8 nmol/L, <6.4–32.2 nmol/L) compared to those on days 1 (<6.4 nmol/L, <6.4–20.1 nmol/L; P = 0.010) or 3 (7.6 nmol/L, <6.4−25.2 nmol/L; P = 0.019). Survivors had a significantly higher tT4 concentration (median, range: 11.8 nmol/L, <6.4–32.2 nmol/L) on day 5 compared to non-survivors (<6.4 nmol/L, <6.4–7.2 nmol/L; P = 0.002). Regardless of the day of hospitalisation, dogs with SIRS had significantly lower tT4 (<6.4 nmol/L, <6.4–16.3 nmol/L) compared to dogs without SIRS (8.6 nmol/L, <6.4–32.2 nmol/L; P = 0.006). A significant difference was also found in fT4 between dogs with SIRS (<3.9 pmol/L, <3.9–16.2 pmol/L) and dogs without SIRS (15.1 pmol/L, <3.9−59.2; pmol/L; P < 0.001). Non-thyroidal illness syndrome was frequently observed in dogs with CPVE, and a negative association between tT4 and fT4 concentrations and SIRS was noted. Serial measurements of tT4 concentrations appeared to have prognostic value.

Psychometric properties of the thyroid-specific quality of life questionnaire ThyPRO in Singaporean patients\xa0with Graves\u2019 disease

BackgroundGraves’ disease is the most common cause of hyperthyroidism. It results in accelerated tissue metabolism with multi-organ involvement ranging from cardiovascular to neuropsychological function. This results in a negative impact on the quality of life (QOL) of the individual patient. We aim to evaluate the psychometric properties of ThyPRO, a Thyroid-related Patient Reported Outcome questionnaire, and validate its use in our multi-ethnic Asian patients with Graves’ hyperthyroidism.MethodsForty-seven consecutive Graves’ hyperthyroidism patients answered the ThyPRO questionnaire at baseline and at 4 months after treatment initiation. Data were recorded for thyroid related symptoms and signs, thyroid function tests and thyroid volume. We analyzed the internal consistency using Cronbach’s alpha, construct validity by evaluating relationship between clinical variables and ThyPRO scales, ceiling and floor effects, and responsiveness of ThyPRO to treatment based on Cohen’s effect size.ResultsCorrelations between individual scale scores and free thyroxine concentrations were moderate and statistically significant: 0.21–0.64 (p < 0.05). There was high internal consistency between the items in this instrument, Cronbach’s alpha > 0.7 for all scales. ThyPRO was responsive to the changes in QOL after treatment (Effect Size: 0.20–0.77) in 9 of the 14 scales including the hyperthyroid symptoms and psychosocial scales (Tiredness, Cognitive complaints, Anxiety, Emotional susceptibility, Impact on Social, Daily and Sex life).ConclusionThis study provides evidence that ThyPRO has satisfactory measurement properties in hyperthyroid Graves’ disease patients in Singapore population with the potential to complement clinical care.

Polymorphism in INSR Locus Modifies Risk of Atrial Fibrillation in Patients on Thyroid Hormone Replacement Therapy.

AimsAtrial fibrillation (AF) is a risk for patients receiving thyroid hormone replacement therapy. No published work has focused on pharmacogenetics relevant to thyroid dysfunction and AF risk. We aimed to assess the effect of L-thyroxine on AF risk stratified by a variation in a candidate gene.Methods and ResultsA retrospective follow-up study was done among European Caucasian patients from the Genetics of Diabetes Audit and Research in Tayside Scotland cohort (Scotland, United Kingdom). Linked data on biochemistry, prescribing, hospital admissions, demographics, and genetic biobank were used to ascertain patients on L-thyroxine and diagnosis of AF. A GWAS-identified insulin receptor-INSR locus (rs4804416) was the candidate gene. Cox survival models and sensitivity analyses by taking competing risk of death into account were used. Replication was performed in additional sample (The Genetics of Scottish Health Research register, GoSHARE), and meta-analyses across the results of the study and replication cohorts were done. We analyzed 962 exposed to L-thyroxine and 5,840 unexposed patients who were rs4804416 genotyped. The rarer G/G genotype was present in 18% of the study population. The total follow-up was up to 20 years, and there was a significant increased AF risk for patients homozygous carriers of the G allele exposed to L-thyroxine (RHR = 2.35, P = 1.6e–02). The adjusted increased risk was highest within the first 3 years of exposure (RHR = 9.10, P = 8.5e–04). Sensitivity analysis yielded similar results. Effects were replicated in GoSHARE (n = 3,190).ConclusionHomozygous G/G genotype at the INSR locus (rs4804416) is associated with an increased risk of AF in patients on L-thyroxine, independent of serum of free thyroxine and thyroid-stimulating hormone serum concentrations.