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Aims: Thyroid hormones impact lipid metabolism and glucose homoeostasis through both central and peripheral regulation; however, little research has delved into the association between thyroid hormone sensitivity and metabolically obese phenotypes. We aimed to investigate the correlation between indices of central and peripheral sensitivity to thyroid hormones and metabolically obese phenotypes in euthyroid Chinese adults., Methods: This cross-sectional study included 20,084 euthyroid individuals. Central thyroid hormone sensitivity was assessed using the thyroid feedback quantile-based index (TFQI), parametric thyroid feedback quantile-based index (PTFQI), thyroid-stimulating hormone index (TSHI), and thyrotropin thyroxine resistance index (TT4RI), while peripheral thyroid hormone sensitivity was measured by FT3/FT4. Metabolically obesity phenotypes included metabolically healthy non-obesity (MHNO), unhealthy non-obesity (MUNO), metabolically healthy obesity (MHO), and unhealthy obesity (MUO). Multinomial logistic regression and restricted cubic spline analyses were conducted to investigate the association between thyroid hormone sensitivity indices and metabolically obese phenotypes risk. Subgroup analysis was also performed to examine this association stratified by sex and age. Mediation analysis was performed to estimate direct and indirect effects of BMI., Results: Prevalence of MHNO, MUNO, MHO and MUO was 66.1% (n = 13,273), 21.3% (n = 4271), 5.3% (n = 1055), and 7.4% (n = 1485) respectively. After adjustment for potential confounders, the odds ratios (ORs) (95% CI) for MUNO and MUO were increased with all elevated thyroid hormones sensitivity indices (per SD increase) [MUNO: TFQI 1.14(1.09-1.19), PTFQI 1.18(1.23-1.23); TSHI 1.26(1.19-1.33), TT4RI 1.41, (1.31-1.53), FT3/FT4 1.20(1.14-1.25) and [MUO: TFQI 1.20(1.11-1.31), PTFQI 1.26(1.16-1.37), TSHI 1.39 (1.26-1.54), TT4RI 1.70(1.48-1.95), FT3/FT4 1.26 (1.16-1.37)] (p value < 0.001), and only TSHI and TT4RI (per SD increase) significantly increased the risk of MHO (TSHI: OR = 1.12, 95% CI 1.01-1.24; TT4RI: OR = 1.25, 95%CI 1.08-1.4) (p value < 0.05). Non-linear relationships were observed between central thyroid hormones sensitivity indices and MUNO and MUO(p for nonlinearity  < 0.05). Conversely, a linear relationship between FT3/FT4 and metabolically obese phenotypes was noted in all subjects (p for nonlinearity  > 0.05). Besides, subgroup analysis indicated that this association remained consistent among sex and age (p for interaction  > 0.05). The proportions mediated by BMI on the association of TFQI, PTFQI, TSHI, TT4RI, FT3/FT4 and risk of metabolically unhealthy conditions were 13.73%, 25.38%, 22.75%, 17.94% and 62.28%, respectively., Conclusions: In euthyroid adults, central and peripheral sensitivity to thyroid hormones indices are positively associated with metabolically obese phenotypes risk, especially MUNO and MUO phenotypes., (© 2024 John Wiley & Sons Ltd.)

Aim: Thyroid dysfunction is closely associated with periodontitis. We aim to explore the association between sensitivity to thyroid hormones (THs) and periodontitis and to investigate the mediating role of serum 25-hydroxyvitamin D[25(OH)D] in this relationship in Chinese euthyroid populations., Methods: This population-based retrospective study included 2,530 euthyroid participants. Central sensitivity to THs was assessed by the thyroid feedback quantile-based index (TFQI), parametric thyroid feedback quantile-based index (PTFQI), thyrotrophic thyroxine resistance index (TT4RI) and thyroid-stimulating hormone index (TSHI), while FT3/FT4 was evaluated to assess peripheral sensitivity. Multivariable regression analysis and restricted cubic spline were performed to explore the association between sensitivity to THs and periodontitis. Threshold effect and subgroup analysis were also conducted. Mediation analysis was performed to estimate direct and indirect effects through 25(OH)D., Results: Multivariable regression analysis indicated that central sensitivity to THs indices(per SD increase) were positively associated with periodontitis risk [TFQI: OR=1.19,95% CI (1.09, 1.31); PTFQI: OR=1.22, 95% CI(1.12,1.34); TSHI: OR=1.36, 95% CI (1.21,1.52); TT4RI: OR=1.43, 95% CI (1.25,1.63)](all P value <0.001). TT4RI only had a non-linear relationship with periodontitis in euthyroid participants. Subgroup analysis showed that no significant correlations were founded among those aged over 65 years or with hypertension/diabetes. Mediation analysis revealed that the proportions mediated by 25(OH)D on the association of TFQI, PTFQI,TSHI, TT4RI and periodontitis risk were 16.37%, 16.43%, 9.93% and 10.21%, respectively., Conclusions: Impaired central sensitivity to THs is positively associated with periodontitis in euthyroid and serum 25(OH)D might be one of its biological mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Lu, Zhao, He, He and Chen.)

Aims: We evaluated the association of multiple thyroid parameters with the levels interleukin 6 (IL6) and interleukin 8 (IL8) in patients with euthyroid type 2 diabetes (T2D)., Methods: A total of 166 adults with euthyroid T2D were examined. Serum IL6, IL8, triiodothyronine (FT3), free thyroxin (FT4), thyroid-stimulating hormone (TSH), five thyroid sensitivity indexes (FT3/FT4, TSH index [TSHI], thyrotroph T4 resistance index [TT4RI], thyroid feedback quantile-based index by FT3 [TFQI FT3 ], and TFQI FT4 ), and biochemical parameters were determined., Results: The median age was 64 years (IQR: 54.75,70) and the median duration of diabetes was 10 years (IQR: 3,18). Patients with high levels of IL6 (≥2.38 pg/mL) had lower levels of FT3 and TFQI FT3 ( P <0.05). Patients with high levels of IL8 (≥18.1 pg/mL) had lower levels of TSH and higher levels of FT4 ( P <0.05). IL6 was negatively correlated with FT3 (r=-0.359, P <0.001), TFQI FT3 (r=-0.273, P =0.009), and FT3/FT4 (r=-0.22, P =0.037). IL8 was negatively correlated with TSH (r=-0.256, P =0.01), TSHI (r=-0.226, P =0.033), and TT4RI (r=-0.244, P =0.021). Binary logistic regression analysis with multiple adjusted models showed that a high level of IL6 was negatively associated with FT3 (aOR: 0.529; 95%CI: 0.302, 0.926, P =0.026), and that a high level of IL8 was negatively associated with TSH (aOR: 0.343; 95%CI: 0.155, 0.759; P =0.008) and TT4RI (aOR: 0.398;95%CI: 0.191, 0.831; P= 0.014)., Conclusion: Patients with euthyroid T2D who had lower levels of FT3 had significantly higher levels of IL6, and those with lower levels of TSH and TT4RI had significantly higher levels of IL8., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Shi, Chen, Chen, Chen, Fu, Xiao, Duan and Zhang.)

Background: Subclinical hypothyroidism (SCH) in pregnancy is associated with adverse foetomaternal outcomes. The literature is scarce with respect to maternal and perinatal outcomes in women with mild SCH (TSH levels between 2.5-4 mIU/L)., Objectives: The primary objective of the study was to compare the pregnancy outcome between SCH and euthyroid women. The secondary objectives were to find out the proportion of women with SCH having thyroid peroxidase antibodies (TPOAb) and to see the effect of TPOAb positivity on foetomaternal outcomes., Materials and Methods: A total of 178 pregnant women were recruited in the first trimester, and those with TSH between 0.1 and 2.4 mIU/L were considered as euthyroid and 2.5-4mIU/L were labelled as SCH. Women with SCH underwent testing for TPOAb. All women were followed until delivery, and foetomaternal outcomes were assessed., Results: Amongst SCH group, there was a significantly higher proportion of overweight and obese women (76/91 (83.51%) vs 59/87 (68%), p = 0.031). The neonatal intensive care unit (NICU) admission was higher with adjusted odds ratio of 3.24 (1.41-7.43) in women with SCH as compared to euthyroid women. Otherwise, there was no difference in foetomaternal outcomes between the two groups. The proportion of gestational diabetes mellitus, intrauterine growth retardation and still birth were higher in SCH women with TPOAb as compared to euthyroid. Amongst SCH women, the proportion of induced labour was lower (aOR:0.27 (0.08-0.93) whereas the proportion of stillbirth and low APGAR scores were higher in TPOAb-positive women with a statistically significant difference and adjusted odds ratio (aOR:20.18 (1.84-220.83)) and (aOR:4.77 (1.06-21.3)), respectively, when compared to TPOAb-negative women., Conclusion: There appears to be no difference in pregnancy outcomes between women with SCH and euthyroid women except higher NICU admission in SCH group. Future multi-centre large prospective studies are required to understand better about the pregnancy outcomes in these women., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Associative learning deficits are constantly found in subclinical hypothyroidism (SCH). Despite achieving normal thyroid stimulating hormone (TSH) levels, a considerable number of patients undergoing levothyroxine (LT-4) treatment frequently complain about memory retrieval. The Paired Association Learning (PAL) task involves computerised testing on the CANTAB- Cambridge Neuropsychological Test Automated Battery, also considered a screening tool for Alzheimer's disease (AD)., Purpose: This study aimed to investigate the impact of different levels of TSH on visual associative learning in SCH and determine if these impairments were reversed with LT-4., Methods: A total of 134 participants were included in this cross-sectional study. Group 1: 35 healthy controls; patients with SCH (Group 2: 33 newly identified cases; Group 3: 32 patients on LT-4 with elevated TSH; Group 4: 34 euthyroid but on LT-4). A thyroid profile and a neuropsychological clinical assessment were done. The visual PAL task was performed on CANTAB., Results: PAL was significantly impaired (p = <0.05) in all 3 patient groups as compared to Group 1. The PAL total errors (adjusted) scores were significantly higher in Groups 2 and 3, indicating that associative learning is definitely impaired in SCH, reaching levels previously seen in patients with AD., Conclusion: Our findings encourage screening for visual associative learning or memory retrieval in patients with SCH. The study present has established a more reasonable threshold of TSH 2.5mIU/L to encourage examination of associative learning and the initiation of LT-4 in SCH. Poor PAL task performance in patients with SCH may have significant implications in clinical settings for suspecting AD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Thyroid hormone levels are associated with the distribution of body components in humans., Objective: This study aimed to investigate the associations between thyroid hormone (TH) levels, central sensitivity to THs, and body composition in overweight and obese patients with euthyroid type 2 diabetes mellitus (T2DM)., Methods: This cross-sectional study included 1215 euthyroid T2DM patients (721 men and 494 women) aged 20-80 years. The thyroid hormone sensitivity indices included the thyroid feedback quartile-based index (TFQI), thyrotroph T3 resistance index (TT3RI), thyrotroph T4 resistance index (TT4RI), and thyroid-stimulating hormone index (TSHI). The appendicular fat ratio, trunk fat ratio, android fat ratio, gynoid fat ratio, and appendicular skeletal muscle mass (ASM) were measured via dual-energy X-ray absorptiometry., Results: The data revealed a greater proportion of subjects with impaired central sensitivity to THs in the obese group. TFQI FT4 and TFQI FT3 levels were positively correlated with the upper limb fat ratio, lower limb fat ratio, gynoid fat ratio, and total fat ratio. TSHI was positively correlated with body mass index (BMI), upper limb fat ratio, lower limb fat ratio, trunk fat ratio, android fat ratio, gynoid fat ratio, total fat ratio, and appendicular skeletal muscle mass index (ASMI) in women. In men, TSHI was only positively correlated with upper limb fat ratio, lower limb fat ratio, and total fat ratio. Logistic regression analysis indicated that TT3RI and TFQI FT3 were independently and positively associated with central obesity and low muscle mass in overweight and obese men. No significant differences were found among the women., Conclusion: THs central sensitivity is related to the body composition of euthyroid T2DM patients. Specifically, high levels of TT3RI and TFQI FT3 are associated with central obesity and low muscle mass in T2DM men with overweight and obesity., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Chen et al.)

Subclinical hypothyroidism and thyroid autoimmunity in pregnancy are common conditions. They are both associated with adverse maternal and offspring outcomes. Women with thyroid autoimmunity should be monitored with regular thyroid function tests preconception and during gestation to identify women who develop hypothyroidism. The effectiveness of thyroid hormone treatment in reducing adverse outcomes in pregnancy has been studied in a number of randomized controlled trials. Current evidence shows obstetrical benefits of levothyroxine treatment in pregnant women with a thyroid-stimulating hormone level greater than 4 mU/L., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Graves' disease is the most common form of hyperthyroidism in children and adolescents. There are three primary lines of treatment for Graves' disease: antithyroid drugs (ATDs), thyroidectomy, and radioactive iodine. Ideally, patients should be rendered euthyroid before surgery to minimize complications. Here, we report on a 14-year-old girl with severe Graves' disease refractory to conventional treatments despite maximal therapy over 18 months. The patient received two types of ATDs, beta-blockers, and different courses of steroids; however, her thyroid function tests remained high. She was then given an adjunctive four-week course of cholestyramine, to which she responded well and became euthyroid. Subsequently, a thyroidectomy was performed without complications. Cholestyramine is an effective adjunctive treatment for refractory Graves' disease in adolescents., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Alsaidalani et al.)

Background: Teprotumumab, a novel IGF-1R antibody was recently shown to significantly reduce the signs of acute and chronic thyroid eye disease (TED) related to hyperthyroidism. Given the lower incidence of TED associated with hypothyroidism / euthyroidism, there is a paucity of data regarding the efficacy of teprotumumab in this group., Methods: In this multicenter study, consecutive patients who had been diagnosed with TED, presenting with either hypothyroidism or euthyroidism as their baseline thyroid dysfunction and treated with teprotumumab were included. All patients had measurements of proptosis, clinical activity scores (CAS), diplopia scores and four-point strabismus scores before and after therapy., Results: Twenty-six patients met the inclusion criteria. Mean age was 48 ± 14 years old and mean duration of TED prior to treatment was 31 ± 43 months. All patients received 8 infusions. Mean (SD) reduction in proptosis for study orbits was 2.7 mm (1.8) (p < 0.05) and 1.8 mm (2.0) for the fellow orbit (p < 0.05). In the study orbit, mean (SD) CAS was 2.3 (1.3) before therapy and 1.0 (1.0) following therapy (p < 0.05). At baseline, mean (SD) diplopia score was 1.2 (1.1) and 0.9 (1.1) following therapy (p < 0.05)., Conclusion: Teprotumumab reduces proptosis and inflammation in patients presenting with TED associated with hypothyroidism and euthyroidism. The results of this study highlight the potential for teprotumumab therapy in this subgroup and also provide a unique insight into the potential role of the IGF-1R in these patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The effectiveness of newborn screening (NBS) for congenital hypothyroidism (CH) relies on timely screening, confirmation of diagnosis, and initiation and ongoing monitoring of treatment. The objective of this study was to ascertain the extent to which infants with CH have received timely and appropriate management within the first 3 years of life, following diagnosis through NBS in Alberta, Canada. Deidentified laboratory data were extracted between 1 April 2014 and 31 March 2019 from Alberta Health administrative databases for infants born in this time frame. Time to lab collection was anchored from date of birth. Timeliness was assessed as the frequency of monitoring of Thyroid Stimulating Hormone (TSH) and appropriateness as the frequency of children maintaining biochemical euthyroidism. Among 160 term infants, 95% had confirmation of diagnosis by 16 days of age. The cohort had a median of 2 (range 0-5) TSH measurements performed in the time interval from 0 to 1 month, 4 (0-12) from 1 to 6 months, 2 (0-10) from 6 to 12 months, and 7 (0-21) from 12 to 36 months. Approximately half were still biochemically hypothyroid (TSH > 7 mU/L) at 1 month of age. After becoming euthyroid, at least some period of hypo- (60%) or hyperthyroidism (TSH < 0.2 mU/L) (39%) was experienced. More work needs to be performed to discern factors contributing to prolonged periods of hypothyroidism or infrequent lab monitoring.

Background: Subclinical hypothyroidism, defined by elevated thyrotropin (TSH) and normal free thyroxine levels, is associated with adverse pregnancy outcomes, including preterm birth, pre-eclampsia, and small for gestational age. Despite the uncertainty regarding the effectiveness of levothyroxine (LT4) treatment on pregnancy outcomes in subclinical hypothyroidism, LT4 is widely administered with a pre-treatment threshold TSH level of 2.5 mU/L. The aim of this study is to investigate the efficacy of periconceptional LT4 treatment for subclinical hypothyroidism, including TSH levels >2.5 mU/L, and identify the characteristics of subclinical hypothyroidism that can benefit from LT4 treatment. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials from inception to February 2023. We analyzed the pooled effects of LT4 on subclinical hypothyroidism before and during pregnancy. The main outcomes before pregnancy were live birth, pregnancy, and miscarriage. The main outcomes during pregnancy were live birth, miscarriage, and preterm birth. We conducted subgroup analyses to compare the effects of LT4 on subclinical hypothyroidism with TSH levels of 2.5-4.0 and >4.0 mU/L. Results: Of the 888 studies identified, 27 full-text articles were screened for eligibility. Five studies on pre-conception treatment with 768 participants and eight studies on treatment during early pregnancy with 2622 participants were analyzed. One of the two studies on pre-conception treatment in subclinical hypothyroidism with TSH >4.0 mU/L had high risk of bias and the other was composed of 64 participants. Pre-conception LT4 treatment had no significant effect in improving rates of live births and pregnancies, or reducing miscarriages (risk ratio [RR], 95% confidence interval): 1.41 (0.84-2.36), 1.73 (0.88-3.39), and 0.46 (0.11-2.00), respectively. LT4 treatment during pregnancy was not significantly associated with higher rates of live births (RR 1.03, 0.98-1.09) nor decreased miscarriage rates (RR 1.01, 0.66-1.53). The effect of LT4 treatment on preterm birth during pregnancy was significantly different depending on the TSH values ( p  = 0.04); a positive effect was shown in the subclinical hypothyroidism subgroup with TSH >4.0 mU/L (RR 0.47, 0.20-1.10), while no significant effect was observed in the subgroup with TSH 2.5-4.0 mU/L (RR 1.35, 0.79-2.31). Conclusions: Pre-conceptional LT4 treatment for subclinical hypothyroidism does not improve fertility or decrease the incidence of miscarriages. However, further well-designed studies are needed for pre-conceptional treatment, especially in TSH >4.0 mU/L. LT4 treatment during pregnancy had a positive effect on preterm birth; nevertheless, this was only applicable to subclinical hypothyroidism with TSH >4.0 mU/L.

Objective: Although several studies have examined the relationship between thyroid function and muscle strength, their population primarily derived from Asian areas, and their results were controversial. Thus, this study aimed to explore the association between thyroid function and handgrip strength (HGS) in the U.S. population., Methods: A total of 1,067 participants from NHANES were categorized into three different age groups including young (<45 years), middle (45~64 years), and old (≥65 years) age groups. Thyroid function was measured by the competitive binding immune-enzymatic assays, while HGS was examined by a trained evaluator using a dynamometer. The weighted multiple linear regression models were used to examine the association between thyroid function and handgrip strength. The restricted cubic splines were employed to explore the non-linear relationship between these two variables. All statistical analyses were performed using the SPSS version 20.0 and R software., Results: After adjustment for potential covariates, FT3/FT4, but not TSH was positively associated with HGS in middle age group (β=0.091, t=2.428, P=0.016). The subgroup analysis by sex revealed that the positive association between FT3/FT4 and HGS was observed in the middle age group for both male and female participants (β=0.163, t=2.121, P=0.035; β=0.157, t=2.180, P=0.031). The RCS analysis showed a statistically significant non-linear association between FT3/FT4 and HGS in overall population (P for non-linear=0.026). After adjustment for covariates, men with low HGS had a significant lower FT3/FT4 than those without low HGS in old age group (P=0.013). There was a significant increase in TSH level for female participants with low HGS in old age group compared to those with normal HGS (P=0.048)., Conclusions: This study demonstrated FT3/FT4, but not TSH, was positively associated with HGS in middle age group, and the different association was observed in men in middle age group when participants were stratified by sex. Future longitudinal cohort study should be conducted to reveal the causal relationship between thyroid function and muscle strength., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Wu, Yang, Jiang, Wang and Lin.)

Background: There are inconsistent results about the effect of gastric bypass surgery on thyroid function tests in morbidly obese subjects. The aim of this study was to investigate the changes in thyroid function tests and insulin resistance status in euthyroid morbidly obese subjects before and three months after gastric bypass surgery (GBS)., Methods: Twenty-nine subjects with morbid obesity (BMI≥40) were enrolled in this before-after study. Patients with known thyroid disorders or a history of thyroid ablative therapy, users of drugs that affect thyroid function, or fasting blood sugar and insulin were excluded. TSH, Free T4, total T3, fasting blood sugar and insulin level, and BMI were measured before and 3 months after GBS. Statistical analysis was performed with appropriate tests and p<0.05 was considered significant., Results: Body mass index (BMI), insulin sensitivity index (HOMA-IR), and total T3 significantly decreased after bypass surgery (all with p<0.001) but no significant changes were seen in TSH (P=0.203) and FreeT4 (P=0.33). There was a significant negative correlation between changes in HOMA-IR and changes in FreeT4 (P=0.038, r= -0.38). There was no statistically significant correlation between the percentage of excess BMI loss (%EBMIL) and changes in T3 (P=0.66), Free T4 (P=0.92), TSH (P= 0.27), and HOMA-IR (P=0.17)., Conclusion: Although significant changes can occur in BMI, insulin sensitivity index, fasting blood sugar, and T3 in short-time follow-up after bariatric surgery, significant TSH and FreeT4 changes may need longer follow-ups., Competing Interests: There is no conflict of interest with respect to any aspects of this manuscript., (© The Author(s).)

Objective: Previous research on the correlation between thyroid function and carotid plaque has revealed conflicting results, possibly attributable to the sensitivity of thyroid hormone indices. In this study, we aimed to analyze the association between thyroid hormone sensitivity indices and the risk of carotid plaque development in a Chinese health check-up population., Methods: A total of 19,388 health check-up subjects were included in this study (mean age: 50.78±10.17 years). Central sensitivity to thyroid hormone was evaluated using the thyroid feedback quantile-based index (TFQI), the Chinese-referenced parametric TFQI (PTFQI), the TSH index (TSHI), and the thyrotropin thyroxine resistance index (TT4RI), while peripheral sensitivity to thyroid hormone was assessed by free triiodothyronine/free thyroxine (FT3/FT4) ratio. Multivariable logistic regression analyses were performed to detect the association between thyroid hormone sensitivity indices and carotid plaque risk, and subgroup analysis was also conducted to explore this association stratified by sex, age, obesity, and the status of smoking, drinking, diabetes, hypertension and dyslipidemia., Results: Among the 19,388 participants, 3753 (19.4%) had carotid plaque. In multivariable adjustment models, the risk of carotid plaque was positively associated with TSHI (odds ratio [OR]: 1.23; 95% confidence interval [CI]: 1.18~1.28), TT4RI (OR: 1.28; 95% CI: 1.23~1.33), TFQI (OR: 1.06; 95% CI: 1.02~1.10), and PTFQI (OR: 1.11; 95% CI: 1.07~1.16), respectively. Conversely, the risk of carotid plaque was negatively correlated with FT3/FT4 (OR: 0.94; 95% CI: 0.90~0.98). In stratified analyses, all thyroid hormone sensitivity indices significantly increased the risk of carotid plaque especially in females, subjects<65 years, non-obese individuals, and those without current smoking, drinking, diabetes, hypertension and dyslipidemia., Conclusion: In Chinese health check-up populations, a considerable connection between reduced sensitivity to thyroid hormones and carotid plaque has been observed, especially in females, those younger than 65 years, non-obese individuals, and those without any current smoking, drinking, diabetes, hypertension, or dyslipidemia., Competing Interests: The authors declare no potential competing interests in this work., (© 2024 Wang et al.)

Context: The relationship between vitamin D and thyroid profiles lacks consensus despite extensive investigations. Whether vitamin D levels correlate with thyroid hormone sensitivity remains largely unexplored., Objective: To explore the relationship between vitamin D levels and thyroid hormone sensitivity among euthyroid individuals., Methods: This study involved 6452 euthyroid participants. Clinical parameters, including TSH, free thyroxine, 25-hydroxyvitamin D [25(OH)D], and other relevant indicators were extracted from the National Health and Nutrition Examination Survey 2007-2012. To quantify thyroid hormone sensitivity, we calculated the Thyroid Feedback Quantile-based Index (TFQI), the TSH index (TSHI), and the thyrotropin thyroxine resistance index (TT4RI)., Results: Subjects with impaired thyroid hormone sensitivity have decreased 25(OH)D levels (TFQI, TT4RI: P < 0.05; TSHI: P = .05574) following adjustment of confounding variables. Age-specific analysis found negative correlations between thyroid hormone sensitivity indices and 25(OH)D within the 20 to 60 years subgroup, turning positive in the 60 to 80 years subgroup. In females, thyroid hormone sensitivity indices and vitamin D levels were negatively linked, while in males, vitamin D's relationships with TFQI, TT4RI, and TSHI shifted from negative to positive when 25(OH)D levels exceeded 63.5 nmol/L, 56.7 nmol/L, and 56.7 nmol/L, respectively. Stratification by race revealed U-shaped curvilinear patterns resembling those found in the males. In body mass index (BMI) subanalysis, vitamin D had differing associations with thyroid hormone sensitivity indices: negative in the <25 kg/m2 and ≥30 kg/m2 subgroups and U-shaped in the 25-30 kg/m2 subgroup., Conclusion: Impaired thyroid hormone sensitivity correlates with decreased vitamin D levels among euthyroid subjects, with associations varying by age, sex, race, and BMI., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: This study aims to investigate the relationship between thyroid and type 1 diabetic nephropathy (T1DN) in euthyroid populations, focusing on thyroid hormone sensitivity., Methods: A cross-sectional study was conducted between January 2016 and December 2021, including 357 euthyroid patients with type 1 diabetes mellitus (T1DM). Parameters representing thyroid hormone sensitivity were assessed, including the thyroid feedback quantile-based index (TFQI), parameter thyroid feedback quantile index (PTFQI), thyroid stimulating hormone index (TSHI), thyrotropin thyroxine resistance index (TT4RI), and free triiodothyronine/free thyroxine (FT3/FT4). Logistic regression and restricted cubic spline regression were performed to detect the association between thyroid hormone sensitivity and the risk of T1DN., Results: The study found a negative correlation between the risk of T1DN and FT3/FT4 in euthyroid T1DM patients (OR 0.71, 95% CI 0.51-0.97, P <0.01). PTFQI (P<0.05), TSHI (P<0.05), and TT4RI (P<0.01) showed an M-shaped nonlinear relationship with the risk of T1DN. Elevated risk of T1DN was associated with PTFQI, TSHI, and TT4RI values outside the range of zero, 2.3-3.88, and 27.56-32.19, respectively., Conclusion: This study confirms the relationship between impaired thyroid hormone sensitivity and the risk of T1DN in euthyroid patients. It emphasizes the importance of evaluating thyroid hormone sensitivity in T1DM patients, even when their thyroid function appears normal, to promptly prevent the occurrence of T1DN., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Shi et al.)

Objective: Levothyroxine (LT4) is the standard treatment for hypothyroidism. However, certain patients experience persistent symptoms even after achieving euthyroid status with LT4 therapy. We aimed to determine the frequency of persistent or new symptoms in patients with hypothyroidism after initiating LT4., Methods: This retrospective study included patients with hypothyroidism who started on LT4 between January 2017 and December 2019 at Mayo Clinic in Rochester, Minnesota, USA. Five hundred patient charts were randomly selected for review. Patients with at least 1 documented follow-up encounter after LT4 initiation were evaluated for ≤3 follow-up visits regarding their biochemical status and symptoms., Results: We included 356 patients, a majority of whom were female (66.6%), white (92.3%), and obese (71.9%), with an average age of 59.5 years. At the baseline visit, approximately one-half of the patients (177/356, 47.7%) reported hypothyroid symptoms, with fatigue being the most common symptom. During the follow-up periods, we observed that 17.8% (28/157), 17.9% (19/106), and 19.3% (11/57) of patients had normal thyroid stimulating hormone (TSH) values but persistent symptoms, while 12.3% (19/156), 19.9% (16/107), and 8.9% (5/56) had normal TSH values but new symptoms. Overall, during each respective follow-up period, 26.7% (42/157), 27.3% (29/106), and 28% (16/57) of patients experienced persistent or new symptoms alongside normal TSH values, with fatigue being the most constant symptom., Conclusion: Our findings indicate that approximately 1 in every 4 patients with hypothyroidism receiving LT4 therapy and achieving normal TSH levels experience persistent or new hypothyroid symptoms. The cause of these symptoms remains unclear, emphasizing the need for a better understanding of their underlying causes and the development of effective management strategies., Competing Interests: Disclosure The authors have no multiplicity of interest to disclose., (Copyright © 2023 AACE. Published by Elsevier Inc. All rights reserved.)

Sudden spontaneous swelling in the neck is an emergency condition required to be addressed immediately. It poses a diagnostic dilemma. It is extremely rare for a thyroid malignancy to present as a sudden onset neck swelling in a euthyroid young male with no obvious trauma to the neck. This is a rare case report of a follicular variant of papillary carcinoma thyroid presenting as sudden neck swelling to the extent of shifting trachea to other side in a young euthyroid male., Competing Interests: Conflicts of interestThe authors have no relevant financial or non-financial interests to disclose., (© Association of Otolaryngologists of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objective: This study aims to investigate the relationship between thyroid computed tomography (CT) density and serum thyroid stimulating hormone (TSH) levels in patients with hypothyroidism., Methods: The research involved 60 hypothyroid patients aged 18 years and older, with TSH levels exceeding 5 mIU/mL or those already receiving thyroid supplementation therapy. These individuals had undergone non-contrast CT chest scans due to concurrent respiratory concerns. The thyroid CT densities, as evaluated through non-contrast chest CT, were compared to those of euthyroid patients with normal TSH levels. Correlation analysis was conducted to assess the relationship between serum TSH levels and thyroid CT densities., Results: Hypothyroid patients exhibited significantly reduced thyroid CT densities (P<0.0001). The correlation analysis revealed an inverse correlation between TSH levels and thyroid CT densities in hypothyroid patients (r=-0.365, p=0.020) and a positive correlation (r=0.270, p=0.036) in euthyroid patients., Conclusion: This study demonstrates a substantial correlation between thyroid CT density and serum TSH levels. As TSH levels increase in hypothyroid patients, thyroid CT density tends to decrease., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Chaudhary et al.)

Introduction A wide range of haematological abnormalities have been observed in patients with goitre. The aim of the study was to evaluate the abnormalities in haematological parameters among patients with goitre in a tertiary care hospital in south India. Methods This was a cross-sectional study carried out in the pathology department of Chengalpattu Medical College from April 1 to June 30, 2019. The lab reports, including the complete blood count (CBC) and serum thyroid profile that included thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) of all the patients with goitre, were retrieved from the laboratory records. Results were tabulated and analysed. Results Out of a total of 200 patients with thyroid dysfunction, 12 (6%) were males and 188 (94%) were females, with the majority (51.5%) of them in the age group of 30-60 years. Serum TSH levels showed a statistically significant association with red cell distribution width (RCDW) (P-value = 0.000), mean corpuscular volume (MCV) (P-value = 0.020), and total white blood cell (WBC) count (P-value = 0.003) among the patients with goiter. There was no significant association between TSH and other parameters like haemoglobin, packed cell volume (PCV), red blood cell (RBC) count, and platelet (PLT) count. Conclusions Red cell distribution width and mean corpuscular volume are useful haematological parameters that will help clinicians in the early diagnosis and proper treatment of haematological abnormalities seen in patients with goitre., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Manoharan et al.)

Purpose: To explore the association between thyroid parameters and subclinical atherosclerosis (AS) in hospitalised euthyroid patients with type 2 diabetes mellitus (T2DM)., Patients and Methods: A retrospective analysis was conducted involving 1245 inpatients with T2DM. Free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) levels were measured, and carotid artery ultrasonography was performed. Thyroid hormone (TH) sensitivity was evaluated using thyroid feedback quantile-based index (TFQI), TSH index (TSHI), thyrotropin thyroxine resistance index (TT4RI), and free triiodothyronine/free thyroxine ratio (FT3/FT4)., Results: In inpatients with T2DM having normal thyroid function, the incidence of subclinical AS declined with increasing levels of FT3, FT4, and FT3/FT4 ( P trend < 0.05). Logistic regression analysis revealed that FT4 (OR, 0.914; 95% CI, 0.845-0.989), FT3 (OR, 0.374; 95% CI, 0.277-0.504), and FT3/FT4 (OR, 0.036; 95% CI, 0.013-0.061) were independently associated with subclinical AS ( P < 0.05). However, TSH, TFQI, TSHI, and TT4RI levels were not associated with subclinical AS ( P > 0.05). FT3/FT4 demonstrated superior predictive accuracy for subclinical AS than that of FT3 or FT4 alone ( P < 0.001), with a cutoff point of 0.25., Conclusion: In euthyroid inpatients with T2DM, subclinical AS exhibited negative correlation with FT3, FT4, and FT3/FT4 levels, independent of other risk factors for AS. Additionally, FT3/FT4 ratio had a good predictive value for subclinical AS., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Du et al.)

Background: There is growing evidence that thyroid function affects bone metabolism and even fractures risk. However, little is known about the relationship between thyroid sensitivity and osteoporosis and fractures. Therefore, we explored the relationship between thyroid sensitivity-related indices and bone mineral density (BMD) and fractures in euthyroid US adults., Methods: In this cross-sectional study, 20,686 subjects from National Health and Nutrition Examination Survey (NHANES) data were extracted and analyzed during 2007 to 2010. A total of 3403 men and postmenopausal women aged 50 years or older with available data on diagnosis of osteoporosis and/or fragility fractures, bone mineral density (BMD) and thyroid function, were eligible. TSH index (TSHI), thyrotrophin T4/T3 resistance index (TT4RI/TT3RI), Thyroid feedback quantile-based index (TFQI), Parametric TFQI (PTFQI), free triiodothyronine to free thyroxine ratio (FT3/FT4), the secretory capacity of the thyroid gland (SPINA-GT) and the sum activity of peripheral deiodinases (SPINA-GD) were calculated., Results: FT3/FT4, SPINA-GD, FT4, TSHI, TT4RI, TFQI and PTFQI FT4 were significantly correlated with BMD (P < 0.001). Multiple linear regression analysis showed that FT3/FT4 and SPINA-GD was significantly positively associated with BMD, while FT4, TSHI, TT4RI, TFQI and PTFQI FT4 were negatively associated with BMD (P < 0.05 or P < 0.001). In logistic regression analysis, the odds ratio (OR) for osteoporosis of TSHI, TFQI and PTFQI FT4 were 1.314(1.076, 1.605), 1.743(1.327, 2.288) and 1.827(1.359, 2.455) respectively, and were 0.746(0.620, 0.898) for FT3/FT4 (P < 0.05)., Conclusions: In elderly euthyroid individuals, impaired sensitivity to thyroid hormones correlates to osteoporosis and fractures, independent of other conventional risk factors., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Objective: Thyroid hormone plays a key role in maintaining cardiovascular system homeostasis. However, there is limited evidence regarding the correlation between normal range thyroid hormone levels and all-cause mortality or cardiovascular mortality among individuals with diabetes., Method: This retrospective study analyzed data from 1,208 individuals with diabetes who participated in the National Health and Nutrition Survey (NHANES) conducted in the United States between 2007 and 2012. Weighted Kaplan-Meier (KM) analysis and Cox proportional hazards models were used to explore the association between thyroid hormone indices and mortality., Results: The Weighted Kaplan-Meier (KM) analysis revealed statistically significant differences in survival probabilities across free triiodothyronine (FT3), free thyroxine (FT4), FT3/FT4 ratio and thyroid-stimulating hormone (TSH) groups (p < 0.05 or < 0.001). In the multivariate adjusted Cox proportional hazards models, higher levels of FT3 were founded to be associated with decreased all-cause mortality (HR (95% CI), 0.715 (0.567, 0.900)), cardio-cerebrovascular mortality (0.576 (0.408, 0.814)) and cardiovascular mortality (0.629 (0.438, 0.904)). Notably, this correlation was more significant among individuals over the age of 60, as indicated by the results of the nonlinear regression analysis., Conclusion: FT3 is an independent predictor of all-cause death, cardio-cerebrovascular and cardiovascular death in euthyroid subjects with diabetes., 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 B.V. All rights reserved.)

This study was established to explore the association of thyroid parameters including thyroid hormone and thyroid sensitivity indices with chronic kidney disease (CKD) in euthyroid patients with type 2 diabetes (T2D). CKD markers were defined by estimated glomerular filtration rate (eGFR) based on serum creatinine (Scr) (eGFRcr), eGFR based on cystatin C (cys C) (eGFRcys), and urinary albumin-to-creatinine ratio (UACR). Thyroid parameters, including triiodothyronine (FT3), free thyroxin (FT4), thyroid-stimulating hormone (TSH), FT3/FT4 ratio, TSH index (TSHI), and thyrotroph T4 resistance index (TT4RI), were measured. The prevalence rates of CKD defined by eGFRcys, eGFRcr, and UACR was 19.9%, 14.1%, and 50.6%, respectively. The eGFRcys and eGFRcr levels increased with increasing FT3 and FT3/FT4 tertiles, while the UACR levels increased with decreasing FT3 tertiles. Spearman's analysis demonstrated that FT3 and FT3/FT4 were positively associated with eGFRcys and eGFRcr, and negatively associated with UACR. In logistic regression analyses, compared with the lowest FT3 tertile (≤4.12 pmol/L), the adjusted ORs for CKD (eGFRcys <60 mL/min/1.73 m 2 ) in the middle FT3 tertile (4.12-4.74 pmol/L) and higher FT3 tertile (>4.74 pmol/L) were 0.248 and 0.153, respectively, but prominent associations of thyroid parameters with eGRFcr <60 mL/min/1.73 m 2 and UACR were not observed after adjustment. Linear regression analysis demonstrated that eGFRcys was more strongly associated with FT3 than eGFRcr or UACR in the adjusted model. Among euthyroid patients with T2D, FT3 in the normal range was the independent factor most strongly related to CKD. Additionally, eGFRcys rather than eGFRcr or UACR was the CKD marker most associated with FT3.

Objective: To compare the demographic and clinical phenotypes of thyroid-associated ophthalmopathy (TAO) with euthyroidism (Eu-TAO), hyperthyroidism (Hr-TAO), and hypothyroidism (Ho-TAO)., Methods: We enrolled 2158 TAO patients in this retrospective study and assessed their demographics, clinical manifestations, activity, and severity., Results: Among the enrolled patients, 526 (24.37%) had Eu-TAO, 1544 (71.55%) had Hr-TAO, and 88 (4.08%) had Ho-TAO. Compared to Hr-TAO (2.02) and Ho-TAO (2.52) patients, Eu-TAO (1.57) patients had the lowest female-to-male ratio (p = 0.026). The mean ages of Eu-TAO, Hr-TAO, and Ho-TAO patients were 43.11 ± 12.05, 42.23 ± 13.63, and 47.39 ± 13.28 years, respectively (p = 0.001). Patients with Eu-TAO had more unilateral involvement (50% vs. 14.38% vs. 21.59%, p < 0.001) than Hr-TAO or Ho-TAO patients. Clinically active TAO patients presented 8.56% in euthyroid vs. 13.86% in hyperthyroid vs. 11.36% in hypothyroid (p = 0.006). Regarding the severity of the European Group on Graves' Orbitopathy (EUGOGO) classification among euthyroid, hyperthyroid, and hypothyroid patients, mild TAO was present in 67.68, 54.27, and 72.72% of participants, moderate-to-severe TAO in 31.18, 42.49, and 26.14%, and sight-threatening TAO in 1.14, 3.24, and 1.14%, respectively. Eu-TAO was positively correlated with unilateral involvement (OR = 5.671, p < 0.001) and age (OR = 1.013, p = 0.003) and negatively correlated with the female-to-male ratio (OR = 0.656, p < 0.001) and TAO severity (OR = 0.742, p < 0.01)., Conclusions: Eu-TAO patients are older and less likely to be female, and show more unilateral and milder clinical phenotypes than hyper/hypothyroid TAO patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The aim of this study was to elaborate the link of thyroid hormones (THs) and metabolic syndrome (MetS) in a Chinese euthyroid employee population with MetS component(s)., Methods: An annual health checkup was performed on employees in 2019. Anthropometric parameters, metabolic parameters, and thyroid function were measured. A questionnaire was used in conjunction with Zhenhai Lianhua Hospital database to receive employees' medication records and thyroid surgical history records., Results: A total of 5486 eligible employees were included; the prevalence of MetS was generally higher in males than in females (38.9 vs. 30.4%, P < 0.001). Among employees with central obesity, hypertriglyceridemia, hyperglycemia, hypertension, and low high-density lipoprotein cholesterol (HDL-C), the prevalence of MetS was 68.8, 63.6, 68.2, 48.8, and 60.0% in males and 72.6, 63.3, 61.3, 42.3, and 42.3% in females, respectively. Logistic regression analysis showed that thyroid-stimulating hormone and free thyroxine (FT4) quartiles had no significant impact on MetS. Free triiodothyronine/free thyroxine (FT3/FT4) and free triiodothyronine (FT3)) quartiles were positively associated with the increased odds ratio (OR) for MetS and dyslipidemia (hypertriglyceridemia and low HDL-C), regardless of gender. In males, FT3 and FT3/FT4 quartiles were positively associated with the OR for central obesity, whereas FT4 quartiles were negatively associated; both FT3 and FT4 quartiles were positively associated with increased OR of hyperglycemia, while similar results were not observed in females. Interaction analysis indicated no significant effect of gender and TH interactions on risk of MetS., Conclusion: High FT3 and FT3/FT4 were strongly linked with MetS and dyslipidemia in our study, even in the euthyroid individuals. Tighter control of thyroid function was necessary for those with preexisting MetS component(s).

Objective: Impaired sensitivity to thyroid hormones has been reported as a common metabolic disorder, and it remains poorly understood whether it interplays with uric acid (UA) metabolism as an established risk factor for cardiovascular diseases (CVDs). We aimed to investigate the relationship between thyroid hormone sensitivity and elevated UA in a Chinese euthyroid population., Methods: A total of 15,955 euthyroid subjects were included in this study. Thyroid hormone sensitivity indices were calculated, including the thyroid feedback quantile-based index (TFQI), the Chinese-referenced parametric TFQI (PTFQI), the TSH index (TSHI), and the thyrotropin thyroxine resistance index (TT4RI), and the FT3/FT4 ratio. Linear and logistic regression analyses were performed to detect the association between thyroid hormone sensitivity and elevated UA., Results: Subjects with reduced sensitivity to thyroid hormones had increased UA levels in both genders ( p for trend < 0.001). Logistic and linear regression analyses showed that higher TFQI, PTFQI, TSHI, and TT4RI were positively associated with elevated UA levels, but negatively associated with the FT3/FT4 ratio. The odds ratio (OR) of the highest versus the first quartile of TFQI was 1.20 (1.05, 1.38) in men and 1.80 (1.46, 2.23) in women ( p < 0.001). PTHQI, TSHI, and TT4RI obtained similar results in both genders. Conversely, the highest quartile of the FT3/FT4 ratio was negatively correlated with elevated UA levels [men: OR 0.78 (0.68,0.89), women: OR 0.66 (0.53,0.81)]., Conclusion: Impaired sensitivity to thyroid hormones was associated with elevated UA levels in euthyroid subjects. Our findings shed light on the role of thyroid hormone sensitivity in UA metabolism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lu, Wang, An, Liu, Wang, Wang and Leng.)

Introduction: There is evidence that subclinical hypothyroidism is associated with infertility, miscarriage and obstetric complications. However, there is controversy regarding the optimal TSH value in women seeking pregnancy. Current guidelines recommend that hypothyroid women with levothyroxine replacement who are planning pregnancy should optimise the dose of levothyroxine to achieve thyrotrophin (TSH) levels <2.5 mU/l, since these requirements increase in pregnancy, thus reducing the risk of TSH elevation during the first trimester. In women with infertility, who undergo highly complex treatments and have positive thyroid autoimmunity, values of TSH <2.5 mU/l prior to fertility treatment are suggested. Although this is a different population, these «optimal» TSH levels were also extended to euthyroid women without evidence of infertility, who are seeking pregnancy., Objectives: Determine whether preconception TSH levels between 2.5 and 4.64 mIU/l are associated with adverse obstetric outcomes in euthyroid women., Materials and Methods: Retrospective cohort study. We evaluated 3265 medical records of pregnant women aged 18-40 years, euthyroid (TSH 0.5-4.64 mU/ml), with TSH measurement at least one year before gestation. 1779 met inclusion criteria. The population was divided according to categories: TSH 0.5-2.4 mU/l (optimal) and TSH 2.5-4.6 mU/l (suboptimal). Information on maternal and fetal obstetric outcomes was collected from each group., Results: We found no statistical difference in the occurrence of adverse obstetric events between the two groups. There was also no difference when adjusting for thyroid autoimmunity, age, body mass index, previous diabetes and previous arterial hypertension., Conclusion: Our results suggest that the reference range of TSH used in the general population could be used in women seeking pregnancy, even in the presence of thyroid autoimmunity. Treatment with levothyroxine should be considered only in patients with special situations., (Copyright © 2023 SEEN and SED. Published by Elsevier España, S.L.U. All rights reserved.)

Thyroid disorders were reported to be associated with various diseases, particularly dyslipidemia. This study aimed to assess the prevalence of thyroid disorders in a group of apparently healthy Syrians and investigate the relationship between subclinical hypothyroidism and metabolic syndrome (MetS)., Methods: A retrospective, cross-sectional study was performed at Al-Assad University Hospital. Participants were healthy individuals aged 18 years and older. Data about their biochemical tests, weight, height, BMI, and blood pressure were collected and analyzed. Participants were categorized according to their thyroid tests into euthyroid, subclinical hypothyroid, subclinical hyperthyroid, and according to their BMI into normal, overweight, and obese, and according to the International Diabetes Foundation into normal and having MetS., Results: A total of 1111 participants were involved in this study. Subclinical hypothyroidism and subclinical hyperthyroidism were found in 4.4 and 1.2% of participants, respectively. The incidence of subclinical hypothyroidism was significantly increased in females and in the presence of positive antithyroid peroxidase. Subclinical hypothyroidism was significantly associated with MetS, a higher waist circumference, central obesity, and triglycerides; however, there was no correlation with high-density lipoprotein., Conclusion: The prevalence of thyroid disorders among Syrians was consistent with the results of other studies. These disorders were significantly more common in females compared to males. Add to that, subclinical hypothyroidism was significantly associated with MetS. Since MetS is a known factor for morbidity and mortality, this may raise the attention needed to perform future prospective trials to evaluate the possible benefits of subclinical hypothyroidism treatment with a low dose of thyroxin., Competing Interests: The author declares that they have no conflicts of interest regarding this study. The author declares that it has not been published elsewhere and that it has not been simultaneously submitted for publication elsewhere.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Women with thyroid autoimmunity (TAI), predominately characterized by increased levels of thyroid peroxidase antibody (TPOAb), are at risk for developing pregnancy related complications. In this review, we discuss the importance of TAI during natal and perinatal stages. Before pregnancy, TAI is associated with higher mean serum TSH levels and certain causes of subfertility. During pregnancy, TAI increases the risk of an insufficient response of the thyroid to an increasing strain induced by pregnancy, and consequently (subclinical) hypothyroidism might develop. Euthyroid women with TAI have a higher rate of maternal and foetal complications, but it seems that causality cannot be pinned down to thyroid dysfunction alone. Almost half of the women known with TAI prior to pregnancy will also develop post-partum thyroiditis (PPT). However, any relation between PPT and post-partum depression remains uncertain. More research is required to explain possible associations between TAI and pregnancy morbidities, and studies should focus on a better understanding of TAI as such. Given the many unanswered questions, at present, it is not recommended to screen all (potentially) pregnant women for the presence of TAI., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This study aimed to investigate the effects of a marine exercise retreat program on thyroid-related hormone levels. A total of 62 middle-aged euthyroid women participated in a 6-day marine exercise retreat program. Using thyroid-stimulating hormone (TSH) and free thyroxine (fT4) hormone levels, the participants were divided into high and low-hormone-level groups. Despite decreased TSH and fT4 levels after the program, the factors influencing changes in each group were different. TSH levels were influenced by changes in the normalized low frequency (nLF) of heart rate variability and carbon monoxide (CO) from all the participants, and changes in body fat percentage, nLF, and nitrogen dioxide (NO 2 ) exposure level in the high TSH group. fT4 levels were influenced by changes in body mass index (BMI), NO 2 exposure, and particulate matter diameter of 10 µm or less (PM 10 ) exposure in all participants. Changes in BMI and CO exposure influenced the low fT4 group. Lastly, changes in the exercise stress test affected the high fT4 group. Thus, the marine exercise retreat program affected euthyroid thyroid-related hormone levels, and influencing factors differ depending on the initial value of the hormone.

Purpose: The objective of this study was to evaluate the association between thyroid hormone and bone mineral density (BMD) among euthyroid adults., Methods: This cross-sectional study researched the information from the National Health and Nutrition Examination Survey 2007-2010. We included 3,759 euthyroid participants finally. We used multivariate linear regression models to evaluate the linear relationship between the thyroid hormone profile and BMD. Subgroup analyses stratified by gender and age were further performed. Moreover, the nonlinear relationship was characterized by fitted smoothing curves and generalized additive models, and logistic regression models were used to determine the association of thyroid-stimulating hormone (TSH) and thyroxine (T4) with previous fractures., Results: The weighted multivariable linear regression models showed no association between TSH and BMD. Free thyroxine (FT4), T4, free triiodothyronine (FT3), and total triiodothyronine (T3) were negatively associated with the total femur BMD and the total spine BMD after adjusting for all covariates. Subgroup analyses demonstrated that all groups had a negative association between T4 and BMD, even in patients with osteopenia/osteoporosis. The nonlinear relationship characterized by smooth curve fittings and generalized additive models suggested that an obvious U-shaped, an inverted U -shaped, and an L - shaped curve was exhibited between thyroid hormone and BMD in the different subgroups. In addition, normal high-level T4 was associated with an increased prevalence of previous fractures than normal low-level T4., Conclusions: In this sample of euthyroid adults, T4 exhibits a negative correlation with BMD, regardless of age and gender, in subjects with either normal or lowered BMD. Moreover, high-normal FT4 was associated with an increased prevalence of previous fractures. TSH was not associated with variations of BMD and the fracture risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sheng, Xing, Wang, Duan and Xiang.)

Background The time to hypothyroidism post hemithyroidectomy is variable. There are multiple risk factors for developing hypothyroidism. The aim of this study was to identify the time of hypothyroidism and other predictors of hypothyroidism in euthyroid patients following hemithyroidectomy. Methods This was a retrospective study. Of 170 euthyroid patients who underwent hemithyroidectomy for benign disease between 2006 - 2014, age, gender, pre-operative thyroid function tests, body mass index (BMI), and other co-morbidities were examined to determine predictors of early (<3 months) or late (>3 months) hypothyroidism. A high normal preoperative thyroid stimulating hormone (HN-TSH) was defined as ≥2.01 uIU/ml, and a low normal TSH (LN-TSH) was defined as <2.01 uIU/ml. Results A total of 63 of the 170 patients (37%) became hypothyroid. At 3 months, 21.5% of patients were hypothyroid. At 6 months after operation, an additional 5% had become hypothyroid, and after 1 year, 8% more were hypothyroid. The only independent predictor of hypothyroidism was preoperative HN-TSH (≥2.01) (p<0.001) on multivariate analysis. Conclusion In addition to known predictors of hypothyroidism following hemithyroidectomy for benign disease, such as the size of the thyroid remnant, a history of neck irradiation, and coexisting thyroid autoimmune disease, a BMI ≥35 kg/m 2 , age ≥45, and preoperative HN-TSH are risk factors for postoperative hypothyroidism within 3 months of operation. Such patients should be closely monitored., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Abraham et al.)

Background: Graves' disease (GD) is the most common cause of childhood hyperthyroidism. Surgery is often chosen as a treatment modality given the high relapse rates and side effects of antithyroid drugs and has shown to be safe and efficacious. The goal of our study was to evaluate whether hyperthyroidism at time of thyroidectomy is associated with higher intra and postoperative complication rates., Methods: A retrospective cohort study of children who underwent thyroidectomy for GD by high-volume pediatric otolaryngologists between 2014 and 2021., Results: 64 patients met inclusion criteria. Patients with hyperthyroidism (defined as free T4≥1.63 ng/dL) were more likely to be treated with beta-blocker preoperatively compared to the euthyroid group (20/24 patients (83%) vs 23/40 patients (58%) respectively, p = 0.035). Twenty (83%) patients with hyperthyroidism and 39 euthyroid patients (98%) were treated with methimazole prior to surgery. Intraoperative tachycardia was noted in 5% of euthyroid patients and 20.8% of patients with hyperthyroidism. The mean peak heart rate intra-operatively and the number of patients with heart rate ≥120bmp were significantly higher for patients with hyperthyroidism (96.5 ± 16.2 vs 87.6 ± 22.1bpm, p = 0.02). Two patients required administration of esmolol during surgery for heart rate control, both with hyperthyroidism. Intra-operative peak systolic blood pressure, operative time, estimated blood loss, persistent hypocalcemia, length of admission and recurrent laryngeal nerve paralysis rates were similar among groups., Conclusions: Hyperthyroidism at surgery is associated with increased heart rate intraoperatively, with no increased risk for other complications. While optimizing thyroid hormone levels before surgery should be pursued in all children, our data suggest that hyperthyroidism should not delay the surgery., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: In the euthyroid state, the risk of developing diabetes according to changes in thyroid-stimulating hormone (TSH) levels remains controversial. Additionally, the correlation of various body indices affecting blood glucose levels according to changes in TSH levels over a certain period is not well known., Methods: Patients who underwent health check-ups twice at a 2 year interval at a tertiary university hospital between 2009 and 2018 were included. By dividing baseline TSH levels into quartiles (TSH&#95;Q1, Q2, Q3, and Q4), various variables were compared, and their changes after 2 years (∆TSH&#95;Q1, Q2, Q3, and Q4) were confirmed., Results: Among 15 557 patients, the incidence of diabetes mellitus after 2 years was 2.4% (377/15 557 patients). There was no statistically significant difference in the incidence of diabetes according to TSH&#95;Q (p = 0.243) or ∆TSH&#95;Q (p = 0.131). However, as TSH levels increased, skeletal muscle mass decreased (p < 0.001), and body fat mass and percent body fat significantly increased (p < 0.001). As ∆TSH increased, ∆fasting blood glucose and ∆body mass index also significantly increased (all p < 0.001). The incidence of diabetes decreased significantly as skeletal muscle mass increased (odds ratio 0.734, p < 0.001)., Conclusions: Owing to the short study period, it was not possible to prove a statistical relationship between the incidence of diabetes mellitus and TSH levels in the euthyroid state. Significant decreases in skeletal muscle mass and increases in body mass index and body fat mass according to baseline TSH levels were demonstrated. Therefore, a focus on improving physical functions, such as increasing muscle mass and decreasing fat, is required in this case., (© 2022 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Objectives: Many studies have shown that socio-economic status (SES) contributes to health inequalities, with nutrition as one of the major risk factors. Iodine intake entirely depends on external sources, and deficiencies are known to be more prevalent in lower social groups, especially in countries with limited access to iodized salt. This study aimed to determine the influence of SES on iodine status and iodine availability from household salt in North Macedonia., Methods: Using cluster sampling, 1,200 children were recruited, and 1,191 children participated (response rate: 99.2%). Iodine status was assessed through urinary iodine concentration (UIC), and iodine availability through iodine content in household salt requested from participants. SES was assessed using standardized Family Affluence Score (FAS)., Results: No statistically significant correlation was found between FAS and iodine in salt. Median regression revealed no significant associations of middle vs. low FAS (β=0.00; 95%-confidence interval (CI)=[-0.61, 0.62]; p=0.999) or high vs. low affluence (β=0.48; 95% CI=[-1.37, 0.41]; p=0.291) with iodine content in household salt. UIC levels were significantly lower in middle FAS children compared to low FAS children (β=-16.4; 95% CI=[-32.3, -0.5]; p=0.043). No statistically significant differences in UIC were found between children with high and low affluence (β=-12.5; 95% CI=[-35.5, 10.5]; p=0.287), possibly due to lowered statistical power for this comparison., Conclusions: Universal salt iodization (USI) proves to be a cost-effective measure for appropriate iodine intake in healthy children and adults, irrespective of their social status. It can thus be concluded that USI contributes to reducing health inequalities related to iodine status among population of different social strata., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Context: Homocysteine (Hcy), a known risk factor for cardiovascular disease, has been reported to be linked with thyroid dysfunction. However, the association of thyroid hormones sensitivity with Hcy levels remains unknown., Objective: We aimed to investigate the relationship between thyroid hormone sensitivity and elevated Hcy levels in the euthyroid population., Methods: A total of 8957 euthyroid adults were included in this study. Free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), Hcy levels, and other clinical parameters were measured. Hyperhomocysteinemia (HHcy) was defined as serum Hcy level > 15 μmol/L. Thyroid hormone sensitivity indices were calculated by thyroid feedback quantile-based index (TFQI), Chinese-referenced parametric TFQI (PTFQI), TSH index (TSHI) and thyrotropin thyroxine resistance index (TT4RI)., Results: Subjects with decreased sensitivity to thyroid hormones had higher Hcy levels (P for trend < 0.001). Logistic regression analysis revealed the higher quartiles of TFQI, PTFQI, TSHI, and TT4RI were significantly associated with elevated Hcy levels, and these associations remained significant even after adjustment for multiple risk factors. After adjusting for age, sex, body mass index, dyslipidemia, fatty liver, diabetes, and hypertension, the odds ratio (95% CI) for having HHcy of the TFQI in the highest quartile was 1.393 (1.210, 1.603), the PTFQI in the highest quartile was 1.409 (1.225, 1.621), the TSHI in the highest quartile was 1.372 (1.190, 1.583), and the TT4RI in the highest quartile was 1.315 (1.141, 1.515) (all P < 0.001)., Conclusion: In euthyroid subjects, impaired sensitivity to thyroid hormones was associated with elevated Hcy levels., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Thyroid dysfunction is associated with classic cardiometabolic risk factors in humans. However, this relationship remains unclear in young euthyroid adults. The present work examines the associations of circulating thyroid hormones (THs) and thyroid-stimulating hormone (TSH) concentrations with body composition and cardiometabolic risk factors in young euthyroid adults. A total of 106 sedentary, euthyroid adults (72 women; 22 ± 2 years old) participated in this cross-sectional study. THs and TSH serum concentrations were determined in fasting conditions (6 h). Body composition (fat mass (FM), lean mass (LM), and visceral adipose tissue (VAT)) was determined by dual-energy X-ray absorptiometry, anthropometric parameters (weight, height, and waist circumference) were measured, and neck adipose tissue mass was quantified through computed tomography (CT) scanning. Cardiometabolic risk factors including fasting glucose and lipid metabolism markers, hepatic phosphatase and transaminases, and blood pressure were also assessed. Free triiodothyronine (FT3) concentration was positively associated with body mass index, LM, VAT, and waist circumference (all P ≤ 0.038). FT3 was also associated with glucose, insulin, HOMA-IR, fatty liver index, and blood pressure (all P < 0.024). All the associations were attenuated when adjusting for sex. In contrast, we found no associations of TSH or free thyroxine with any body composition parameter or cardiometabolic risk factors. In conclusion, FT3 is associated with central adiposity and cardiometabolic risk factors including insulin resistance, fatty liver index, and mean, systolic and diastolic blood pressure in young euthyroid adults. ClinicalTrials.gov identifier: NCT02365129., (© 2022. The Author(s).)

Background: Appropriate iodine intake for adults is essential to reduce the prevalence of thyroid diseases, but there is little research data on iodine requirement of Chinese population. This study aimed to explore the iodine requirement of young adults to maintain a healthy status based on 'overflow theory'., Methods: Iodine-balance experiment has been performed in this project. We conducted an 18-day study consisted of a 6-day acclimation period and 3 consecutive experimental stages in 37 Chinese healthy young adults (23 female and 14 male). Each stage was consumed for 4 days. Strictly-controlled low-iodine intake diets were provided for adults in the first period, an egg or 125mL milk was added in the second and third period, respectively. The dietary samples, 24-h urine specimens and faeces of volunteers were collected daily for assessment of iodine intake and excretion in volunteers., Results: Mean values of iodine intake (22.7±3.6, 35.1±3.7, and 52.2±3.8μg/d), excretion (64.7±13.9, 62.3±12.6, and 94.3±14.5μg/d) and iodine balance (-35.2±19.5, -21.0±19.8, and -33.5±26.9μg/d) were significantly different among three periods for male (P<0.001 for all); mean values of iodine intake (16.6±3.1, 29.7±2.7, and 48.0±2.7μg/d), and excretion (47.0±9.9, 55.5±8.1, and 75.7±12.4μg/d) were significantly different among three periods for female (P < 0.001 for all). No significant difference was observed among the 3 periods for female in the iodine balance (-30.5±9.3, -25.9±7.3, and -27.6±12.1μg/d). The linear regression equation of iodine excretion on iodine intake was Y=0.979X+37.04 (male) and Y=0.895X+31.48 (female). Compared with stage 2, iodine excretion increments in stage 3 had exceeded the iodine intake increment for men. The ratio of increment was 1.675 for male when the average iodine intake was 52.2μg/d in stage 3. When the iodine excretion increment equaled to the iodine intake increment, the daily iodine intake of men was 47.0μg., Conclusion: We have evaluated the iodine requirement of young adults in southern China based on overflow theory. Our results indicate the lower limit of iodine requirement for Chinese young men is 47.0μg/d. The trial was registered at www.chictr.org.cn as ChiCTR1800014877., (© 2022. The Author(s).)

Background and objective Among the common endocrinological disorders of pregnancy, thyroid disorders rank second after diabetes. Thyroid autoimmunity is linked to sub-fertility, miscarriages, preterm birth, gestational diabetes, and adverse neurodevelopmental sequelae in children. Peroxidase and thyroglobulin autoantibodies may be associated with enhanced global autoimmune state, which may have adverse effects on the fetal or placental development. It is the main cause of hypothyroidism in reproductive-age women and is associated with poor obstetric outcomes. In Gulf countries, a higher prevalence of thyroid antibodies during pregnancy was reported. However, there is paucity of data in the literature in the Gulf countries in this regard. Our study was conducted to assess the effects of thyroid antibodies on adverse maternal and neonatal outcomes in pregnancy in a multiethnic population of Qatar. The study aimed to assess the prevalence of thyroid antibodies in pregnant hypothyroid women and their impact on adverse fetal outcomes in pregnancy. Design A Retrospective study of patients' notes (retrospective chart review) was conducted at a secondary hospital in Qatar. Records of the women who delivered from January 2017 to June 2018 were evaluated. A total of 384 women were included after applying exclusion criteria. Neonatal outcomes were compared in hypothyroid women with (group A1) and without thyroid antibodies (group A2) and were compared with euthyroid women (group B). Statistical analysis was performed using SPSS Statistics version 27.0 (Armonk, NY: IBM Corp). Results A total of 7978 women delivered during the study period and the prevalence of hypothyroidism in our sample was 3.47%; 33.33% had thyroid antibodies. Women with more than one miscarriage were 30% (odds ratio {OR}: 2.06, 95% confidence interval {CI}: 1.112-3.811, p<0.05), 21.24% (OR: 1.20, 95% CI: 0.676-2.115, p>0.05), and 17% in group A1, A2, and B, respectively. The incidence of preterm births was 10% (OR: 2.22, 95% CI: 0.760-6.495, p>0.05), 4.23% (OR: 0.94, 95% CI: 0.308-2.876, p>0.05), and 4.5% in groups A1, A2, and B, respectively. Small for gestational age infants were 10% (OR: 3.33, 95% CI: 1.036-10.71, p<0.05), 5.93% (OR: 1.97, 95% CI: 0.640-6.023, p>0.05), and 3% in groups A1, A2, and B, respectively. The study revealed an association between thyroid antibodies and adverse maternal and neonatal outcomes in pregnancy. Conclusion Thyroid autoimmunity is associated with poor fetal outcomes. In Gulf countries with higher prevalence of endocrinological disorders (obesity and diabetes), thyroid disorders need attention. As fewer studies were reported from these areas with limited results in literature, this study gives an insight into the prevalence of thyroid disorders, thyroid antibodies, and their association with pregnancy outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Athar et al.)

Objective: To investigate the relationship between thyroid functions and asymmetric dimethylarginine (ADMA), ischemia-modified albumin (IMA), and other metabolic laboratory markers in euthyroid adults and whether narrower thyroidal targets are required for lower metabolic risk., Materials and Methods: Thyroid functions, antithyroid autoantibodies, and metabolic parameters were measured for 115 patients. Forty-seven had autoimmune thyroiditis (AIT). Analyses were performed according to cutoff values of 1, 2, 2.5, and 3 mIU/L for thyrotropin, 0.84 ng/dL for free thyroxine (fT4), and 3.59 ng/dL for free tri-iodothyronine (fT3)., Results: There was no relationship between thyrotropin and fT3 cutoff values and metabolic parameters. Only C-reactive protein was lower in the group with thyrotropin ≤2.5 μIU/L. A weak positive correlation was found between fT4 with IMA and IMA corrected for albumin (r = 0.187, P = .05; r = 0.204, P = .034, respectively). There was no difference between AIT and the metabolic laboratory parameters examined in the study., Conclusion: This study is the first to evaluate ADMA in AIT. Narrower thyroid function targets are not required for better metabolic control in euthyroid adults., (© American Society for Clinical Pathology, 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Thyroid goiter is a benign chronic enlargement of the thyroid gland, which presents as a painless anterior neck mass with occasional extension to the mediastinum. Retropharyngeal goiter is a rare presentation and hardly reported in the literature., Presentation of Case: A 70-year-old male presented with a multinodular goiter with a large retropharyngeal component., Clinical Findings and Investigations: Physical examination of the head and neck revealed a massive anterior neck mass. Laryngeal endoscopy with a 70-degree rigid endoscope demonstrated a large retropharyngeal mass completely obstructing the view of the larynx. Computed tomography (CT) scan revealed a large multinodular goiter with suprahyoid and retrosternal extension, resulting in displacement of the trachea., Interventions and Outcome: The mass was excised completely under general anesthesia and intubation was done under fiberoptic bronchoscopy guidance. The mass was sent for histological analysis, which confirmed the diagnosis of Hashimoto thyroiditis., Conclusion: Eventually, upon follow-up at three months post excision, no evidence of recurrence was detected., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Pregnant women with autoimmune (subclinical) hypothyroidism have an increased risk of developing gestational diabetes mellitus (GDM). However, this association remains controversial in euthyroid women with thyroid autoimmunity (TAI). Therefore, the aim of the study was to determine the association between TAI and GDM in euthyroid women in a logistic regression analysis with adjustments for baseline/demographic parameters., Methods: Cross-sectional study in 1447 euthyroid women who performed their entire clinical/biological workup and oral glucose tolerance test (OGTT) in our center. At median 13 (11-17) weeks of gestation, thyroid-stimulating hormone, free T4, and thyroid peroxidase antibodies (TPOAb) were measured, baseline characteristics were recorded, and an OGTT was performed between 24 and 28 weeks of pregnancy. Exclusion criteria were pre-pregnancy diabetes, assisted pregnancies, and women with (treated) thyroid dysfunction before or after screening. The diagnosis of GDM was based on 2013 World Health Organization criteria, and TAI was defined as TPOAb levels ≥60 kIU/L., Results: Two hundred eighty women were diagnosed with GDM (19.4%), 26.1% in women with TAI, and 18.9% in women without TAI (P = 0.096). In the logistic regression analysis, TAI was associated with GDM in women older than 30 years (adjusted odds ratio 1.68 (95% CI, 1.01-2.78); P = 0.048). Maternal age >30 years, pre-pregnancy BMI ≥30 kg/m2, and other than Caucasian background were also associated with GDM; aOR 1.93 (95% CI, 1.46-2.56); P < 0.001, 2.03 (95% CI, 1.46-2.81); P < 0.001 and 1.46 (95% CI, 1.03-2.06); P = 0.034, respectively., Conclusions: In older pregnant women, the presence of TAI in euthyroid women was associated with GDM. In line with the literature data, (higher) age and BMI were strongly associated with GDM. Future investigations should focus on treatments that might prevent the development of GDM in euthyroid women with TAI.

The ratio of free triiodothyronine (FT3) to free thyroxine (FT4) (FT3/FT4), a maker of peripheral thyroxin deiodination, could indicate activity of thyroid hormone. Since positive association between subclinical hypothyroidism (SCH) and chronic kidney disease (CKD) was reported, clarifying the association among FT3/FT4, SCH, and CKD could be an efficient tool to make a strategy for preventing CKD. A cross-sectional study with 1724 Japanese with normal thyroid hormone was conducted. Significant positive association between SCH and CKD was observed; the adjusted odds ratio (OR) and 95% confidence interval (95% CI) was 2.23 (1.38, 3.59). Even though, FT3/FT4 was found to be inversely associated with CKD whereas positively associated with SCH; the adjusted ORs and 95% CIs for 1 standard deviation (SD) increment of FT3/FT4 were 0.51 (0.35, 0.74) for CKD and 2.40 (1.34, 4.29) for SCH, respectively. FT3/FT4 was also found to be positively associated with SCH without CKD but not those with CKD; 1 SD increment of FT3/FT4 were 3.44 (1.72, 6.91) for SCH without CKD and 1.11 (0.40, 3.06) for SCH with CKD, respectively. Although further investigation is necessary, present study indicates that higher activity of peripheral thyroxin deiodination might have beneficial association on absence of CKD even among SCH which is positively associated with CKD.

Background: Non-alcoholic fatty liver disease (NAFLD) has become a major public health problem concern in recent decades. The specific mechanism of NAFLD is still not clear. Previous studies had shown the correlation between NAFLD and thyroid dysfunction. The correlation between thyroid hormones within the euthyroid range and NAFLD has not yet been clarified. This study sought to investigate the association between NAFLD and thyroid hormones in euthyroid patients., Methods: A retrospective cross-sectional study was conducted at Beijing Tiantan Hospital from January 1, 2019, to October 1, 2021. Eighty-one NAFLD patients with normal thyroid function and 34 healthy individuals were enrolled. Participants' demographic information, biochemical parameters, and thyroid hormone levels were collected. The severity of NAFLD was assessed by abdominal computed tomography (CT). The association between NAFLD and thyroid hormones was analyzed., Results: Patients in the NAFLD group were older and more likely to be female than those in the healthy control group (P<0.05). Compared to the healthy control group, the serum levels of fasting plasma glucose (FPG), alanine transaminase (ALT), plasma aspartate transaminase (AST), triglyceride, gamma-glutamyl transferase (γ-GT), and uric acid (UA) were higher, but the levels of high-density lipoprotein cholesterol (HDL-C), and free thyroxine (FT4) were lower in the NAFLD group (P<0.05). NAFLD is more severe in females than males (P<0.05). ALT, AST, low-density lipoprotein cholesterol (LDL-C), γ-GT, tetraiodothyronine, and free triiodothyronine (FT3) levels increased significantly as the severity of NAFLD increased (P<0.05). The results of the Spearman correlation analysis indicated that the severity of NAFLD was positively correlated with ALT (r=0.376, P=0.001), AST (r=0.275, P=0.015), and LDL (r=0.313, P=0.007). The multiple logistic regression analysis showed that age [odds ratio (OR) =1.071; 95% confidence interval (CI): 1.010-1.136, P=0.021], ALT (OR =1.091; 95% CI: 1.034-1.150, P=0.001), HDL-C (OR =0.085; 95% CI: 0.010-0.690, P=0.021), and FT4 (OR =0.738; 95% CI: 0.545-1.001, P=0.046) were independently related to the risk of NAFLD in patients with normal thyroid function., Conclusions: FT4 within the normal range was lower in the NAFLD group compared to the healthy control group. The serum level of FT4 is an independent risk factor of NAFLD in euthyroid people.

Among euthyroid individuals, having an anti-thyroid peroxidase antibody (TPO-Ab) titer in the normal range (negative) is positively associated with atherosclerosis as evaluated based on carotid intima-media thickness (CIMT). Atherosclerosis is an established risk factor for cardiovascular disease, but no significant association between yearly progression in CIMT and cardiovascular disease has been reported. Therefore, clarifying the association between having a TPO-Ab titer in the normal range and yearly progression in CIMT (i.e., active arterial wall thickening) among euthyroid individuals could help inform strategies for preventing cardiovascular disease. We conducted a prospective study of 1069 Japanese subjects with free triiodothyronine and free thyroxine levels within the normal range. Having a TPO-Ab titer in the normal range was significantly positively associated with baseline atherosclerosis and significantly inversely associated with active arterial wall thickening. After adjusting for known confounding factors, the adjusted odds ratio (OR) and 95% confidence interval (CI) of log (TPO-Ab titer) for baseline atherosclerosis and active arterial wall thickening was 2.16 (1.07, 4.35) and 0.59 (0.37, 0.93), respectively. Since progression in CIMT is a process of aggressive endothelial repair, deficient endothelial repair inhibits active arterial wall thickening. Therefore, high-normal TPO-Ab titers might induce a deficiency in endothelial repair.

Introduction Subclinical hypothyroidism (SCH) and gestational diabetes mellitus (GDM) are common endocrinological abnormalities associated with pregnancy. The presence of a raised anti-thyroperoxidase (anti-TPO) antibody titer increases the risk of progression of subclinical hypothyroidism to overt hypothyroidism. Subclinical hypothyroidism and GDM are known to affect maternal and fetal outcomes adversely. A few studies have shown an increased risk of GDM with autoimmune hypothyroidism. However, data regarding this association between GDM, SCH, and anti-TPO Ab are scarce. This study aimed to find the prevalence of autoimmune subclinical hypothyroidism and its association with GDM in pregnancy. Materials and methods In a cross-sectional study, 382 pregnant women at their first antenatal checkup (ANC) were enrolled in the study. Serum thyroid-stimulating hormone (TSH), free T4 (FT4), anti-TPO Ab, and the 75 g oral glucose tolerance test (OGTT) were evaluated. The results obtained were analyzed in Systat Version 13.2 (SPSS Inc., Chicago, IL). Observations Results showed an SCH prevalence of 37.69% with a raised anti-TPO Ab titer in 49.31% of the diagnosed SCH cases, pointing towards an autoimmune etiology. Our study revealed a GDM prevalence of 12.04%. Out of the 46 GDM cases, 16 were found to have SCH and 3 cases had raised anti-TPO Ab titers. In our study, 27.73% of euthyroid pregnant women had a raised anti-TPO Ab titer. Our study revealed no significant association between GDM, SCH, and raised anti-TPO Ab titer. Conclusion Anti-TPO antibody subsequently leads to hypothyroxinemia, for which it is necessary that cases with high titer of anti-TPO antibody though euthyroid should be meticulously followed up and screened for to detect development of hypothyroidism or SCH, particularly in future pregnancies. However, GDM prevalence was at par with the national figure, but with no significant association of SCH and a high anti-TPO ab titer was found with GDM in our study. Further studies with a larger cohort may establish a causal association between the two most common endocrinological disorders observed in pregnancy., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Dash et al.)

Thyroid disease is known to affect brain metabolism and cognitive function, although the recovery of thyroid-induced brain functional changes after treatment remains unclear. We aimed to investigate the alteration in brain functional connectivity and its correlation with neuropsychological variables in hyperthyroid patients before and after anti-thyroid treatment using a resting-state functional magnetic resonance imaging (rsfMRI) technique. This is a follow-up rsfMRI study of previous work that showed impaired brain functional connectivity in hyperthyroid patients compared to healthy controls. We included rsfMRI and neuropsychological data from 21 hyperthyroid patients out of an original cohort of 28 patients, before and after anti-thyroid treatment for 30 weeks. Functional connectivity analysis and neuropsychological scores were compared using paired t tests in patients at baseline and at follow-up. Patients showed an improvement in some of the memory (p < .05) and executive, visuospatial and motor (p < .001) functions after treatment, and also showed increased functional connectivity in the regions of the right fronto-parietal network, left fronto-parietal network, and default mode network (DMN) (p < .05). At follow-up, the functional connectivity of the right fronto-parietal network showed a significantly positive correlation with the recognition of objects memory score. The overall findings suggest that anti-thyroid treatment with carbimazole improves the functional connectivity within some of the resting state networks in the hyperthyroid patients, whereas the remaining networks still show impairment., (© 2021 British Society for Neuroendocrinology.)