Low triiodothyronine syndrome and depression: a cross-sectional study in the elderly based on comprehensive geriatric assessment.

INTRODUCTION: Thyroid diseases such as low triiodothyronine syndrome (LT3S) are more common in the elderly population. Comprehensive geriatric assessment (CGA) has been proposed as a supplementary tool for evaluating medical, functional, psychological, and frailty status and various geriatric syndromes. This study aimed to evaluate the impact of thyroid diseases on overall health status using a novel CGA strategy. MATERIAL AND METHODS: 477 patients were enrolled between January 2019 and December 2022. A structured CGA was conducted by a multidisciplinary team to identify older high-risk patients. Multivariate regression was performed to assess independent factors associated with thyroid status and CGA. RESULTS: The prevalence of abnormal thyroid hormone levels in the elderly was 34.2%. LT3S and anti-thyroglobulin antibody (anti-TgAb)-positivity or anti-thyroid peroxidase antibody (anti-TPOAb)-positivity were the main manifestations of thyroid diseases in elderly patients. The patients with LT3S had a higher prevalence of diabetes (p = 0.023), were older (p = 0.000), more often female (p = 0.014), with higher C-reactive protein (p = 0.001), and with lower body mass index (BMI) (p = 0.002), albumin (Alb) (p = 0.000), and haemoglobin (Hb) (p = 0.000) than patients with normal thyroid function. The CGA results showed higher rates of malnutrition and depression in patients with LT3S. Further multivariate logistic regression analysis showed that Hb [odds ratio (OR): 0.975; 95% confidence interval (CI): 0.959-0.990; p = 0.002] and LT3S (OR: 2.213; 95% CI: 1.048-4.672; p = 0.037) were independently associated with depression. Female (OR: 0.393; 95% CI: 0.160-0.968; p = 0.042), Alb (OR: 0.892; 95% CI: 0.811-0.981; p = 0.018), Hb (OR, 0.964; 95% CI: 0.939-0.989; p = 0.006), and LT3S (OR: 3.749; 95% CI: 1.474-9.536; p = 0.006) were independently associated with malnutrition. CONCLUSIONS: LT3S was closely related to depression and malnutrition. Physicians should be more concerned about elderly patients with LT3S for their physical and mental status. Regular thyroid function checks might help to detect depression earlier.

Radiofrequency ablation for papillary thyroid microcarcinoma close to the thyroid capsule versus far from the thyroid capsule: a retrospective study.

INTRODUCTION: The aim of this study was to evaluate the safety and efficacy of ultrasound-guided radiofrequency ablation (RFA) for the management of papillary thyroid microcarcinoma (PTMC) close to the thyroid capsule. MATERIAL AND METHODS: This was a retrospective study of 202 patients with PTMC who underwent RFA close to the thyroid capsule and 80 patients with PTMC who underwent RFA far from the thyroid capsule between June 2015 and December 2022. The follow-up time after RFA, change in size of tumour, location, thyroid function, the rates of PTMC disappearance, and complications were evaluated. RESULTS: A total of 202 patients with PTMC close to the thyroid capsule and 80 patients with PTMC far from the thyroid capsule successfully treated with RFA were studied. The thyroid function including free triiodothyronine (fT3), free thyroxine (fT4), triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) showed no changes after RFA for one months in both groups. The tumour size was increased at 1, 3, and 6 months after RFA compared with pre-operative RFA in both groups. The tumour size was decreased at 12 and 24 months after RFA compared with pre-operative RFA both in both group. Seventy-nine PTMC close to the thyroid capsule and 30 PTMC far from the thyroid capsule completely disappeared as assessed by ultrasound examination. Eighty-four PTMC patients close to the thyroid capsule and 34 PTMC patients far from the thyroid capsule had minor complications after RFA treatment. The complication rates between the 2 groups were similar. CONCLUSION: Ultrasound-guided RFA seems to be an effective and safe method for patients with PTMC close to the thyroid capsule.

Serum FT3/FT4, but not TSH is associated with handgrip strength in euthyroid U.S. population: evidence from NHANES.

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 (ß=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 (ß=0.163, t=2.121, P=0.035; ß=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.

Investigating the connection among thyroid function, sensitivity to thyroid hormones, and metabolic syndrome in euthyroid children and adolescents affected by type 1 diabetes.

OBJECTIVES: A connection between thyroid hormones (THs) and diverse metabolic pathways has been reported. We evaluated thyroid function and tissue sensitivity to THs in children and adolescents with T1D in comparison to euthyroid controls. Additionally, we investigate whether a relationship exists between sensitivity indices and metabolic parameters. METHODS: A retrospective analysis was conducted on 80 pediatric patients diagnosed with T1D. Clinical parameters, TSH, FT3, FT4, and the presence of MS were documented. Additionally, indices of peripheral sensitivity (FT3/FT4 ratio) and central sensitivity (TSH index, TSHI; TSH T4 resistance index, TT4RI; TSH T3 resistance index, TT3RI) were assessed. Thirty healthy subjects were considered as controls. RESULTS: The overall prevalence of MS was 7.27 %, with MS identified in 8 out of 80 (10 %) T1D subjects; none of the controls manifested MS (p<0.01). No significant differences were observed in indexes of tissue sensitivity to THs between subjects with or without MS (all p>0.05). Correlations between THs and indexes of THs tissue sensitivity and metabolic parameters in controls and T1D patients were noted. CONCLUSIONS: This study affirms a heightened prevalence of MS in children with T1D compared to controls and underscores the potential role of THs in maintaining metabolic equilibrium.

Takotsubo syndrome outcomes predicted by thyroid hormone signature: insights from cluster analysis of a multicentre registry.

BACKGROUND: Recently, abnormal thyroid function was shown to be common in patients with Takotsubo syndrome (TTS), being classified into "endocrine-type" and "stress-type" responses. The aim of this study was to investigate the association between thyroid homeostasis and TTS in a larger international registry. METHODS: In total 288 patients with TTS were enrolled through the GEIST multicentre registry from Germany, Italy and Spain. Thyrotropin (TSH), free T4 (FT4) and free T3 (FT3) concentrations were analysed at admission. Data were collected both retrospectively and prospectively from 2017 onwards. Primary endpoints included in-hospital and all-cause fatality, determined by cluster analysis using an unsupervised machine learning algorithm (k-medoids). FINDINGS: Three clusters were identified, classifying TTS with low (TSLT), high (TSHT) and normal (TSNT) thyroid output, based on TSH and FT4 levels in relation to the median thyroid's secretory capacity (SPINA-GT). Although TSH and FT4 concentrations were similar among survivors and non-survivors, these clusters were significantly associated with patient outcomes. In the longitudinal Kaplan-Meier analysis including in- and out-of-hospital survival, the prognosis related to concentrations of TSH, FT4, and FT3 as well as SPINA-GT, deiodinase activity (SPINA-GD) and clusters. Patients in the TSHT cluster and with cardiogenic shock had a lower initial left ventricular ejection fraction (LVEF). INTERPRETATION: This study suggests that thyroid hormones may impact the evolution and prognosis of TTS. The findings indicate that thyroid-derived biomarkers may help identify high-risk patients and pave the way for novel personalized and preventive therapeutic options. FUNDING: This research was not funded by any public, commercial, or not-for-profit agencies.

The crosstalk between benign thyroid disease and breast cancer: A single center study.

This study aims to investigate the relationship between benign thyroid disease and breast cancer. The clinical study includes a total of 600 participants, divided into 2 groups: the control group (N = 300), which consists of individuals from the checkup population during the same periods, and the experimental group (N = 300), which consists of patients with breast cancer. General data of the participants, including age, tumor diameter, tumor staging, pathological classification, lymph node metastasis, and classification of benign thyroid disease, were collected and analyzed. The levels of TT3, TT4, FT3, FT4, TSH, TPOAb, and TgAb in blood samples from the experimental and control groups were determined using a radioimmune method. The levels of TPOAb, TgAb, and TSH in the experimental group were significantly higher than those in the control group, while the levels of TT3, TT4, FT3, and FT4 in the experimental group were significantly lower. The general data of the participants contributed to the appropriate sample size and allocation. Furthermore, benign thyroid disease contributes to the development of breast cancer by regulating the levels of TT3, TT4, FT3, FT4, TSH, TPOAb, and TgAb.

Associations among thyroid hormone levels and mean corpuscular volume in adults in the US: A cross-sectional examination of the NHANES 2007-2012 dataset.

Mean corpuscular volume (MCV) is an important indicator used to determine the etiology of anemia and is associated with a variety of diseases. However, the link between thyroid function and MCV has yet to be clarified. This study was thus developed to assess relationships between thyroid function and MCV in a population of adults in the US. Results from the National Health and Nutrition Examination Survey study performed from 2007 to 2012 were used to conduct a cross-sectional analysis. Key thyroid-related variables included in this analysis were thyroid-stimulating hormone, total thyroxine (TT4), free triiodothyronine (FT3), total triiodothyronine (TT3), free thyroxine (FT4), antithyroglobulin, thyroglobulin, and antithyroid peroxidase levels. Generalized linear regression models were employed when estimating associations between MCV quartiles and thyroid parameters in 8104 adults 18 + years of age. In these participants, the weighted mean (SD) MCV was 89.36 (0.16) fL, with thyroid-stimulating hormone levels of 1.86 (0.03) mIU/mL, FT3 levels of 3.20 (0.01) pg/mL, FT4 levels of 0.80 (0.01) ng/dL, TT3 levels of 115.09 (0.64) ng/dL, and TT4 levels of 7.81 (0.04) µg/dL. When analyses were not adjusted, higher MCV values were related to reduced serum levels of FT3, TT3, or TT4. Following adjustment for possible confounding variables, this significant negative correlation between MCV and levels of FT3, TT3, and TT4 remained, and subgroup analysis revealed that this negative correlation was present in the male group and in the age group >50 years, but not in the female group and in the age group less than or equal to 50 years. These results suggest a significant negative correlation between MCV and FT3, TT3, and TT4, and this negative correlation originated more from the male population and those older than 50 years of age. The underlying mechanisms warrant additional investigation.

Use of thyroid hormones in hypothyroid and euthyroid patients: A survey of members of the Endocrine Society of Australia.

OBJECTIVE: Hypothyroidism is a common endocrine condition usually managed with levothyroxine (LT4). However, controversy remains around the use of liothyronine (LT3). We aimed to investigate the practices of Australian endocrinologists when managing patients with hypothyroidism, their use of LT3 + LT4 combination therapy and use of thyroid hormones in euthyroid patients. DESIGN AND PARTICIPANTS: Members of the Endocrine Society of Australia (ESA) were invited to participate in an online questionnaire. MEASUREMENTS: We analysed questionnaires that had complete demographic data. RESULTS: Eighty-seven questionnaires fulfilled the criteria. LT4 was used as first line treatment for hypothyroidism by all respondents. Only 45% reported that their patients were dispensed the brand of LT4 that they recommend. LT3 (alone or in combination) was prescribed by 44% in their clinical practice. Although 49% of respondents would consider LT3 + LT4 in patients with normal TSH who had ongoing symptoms of hypothyroidism, the inability of LT4 to restore normal physiology was ranked the least likely explanation for persistent symptoms and only 32% would consider it for themselves if they were diagnosed with hypothyroidism. The majority (55%), in accordance with evidence, would not prescribe thyroid hormone to euthyroid individuals but 39% would consider use in euthyroid female infertility with high levels of thyroid antibodies and 11% in euthyroid patients with a simple goitre growing over time. LT4 use in pregnancy was variable among members. CONCLUSIONS: Australian endocrinologists mostly follow international guidelines when prescribing thyroid hormone therapy and many prescribe combination LT3 and LT4 therapy, particularly for patients who remain symptomatic on LT4 monotherapy. Prescribing practices are largely similar to other countries who have completed similar questionnaires.

Correlation between a low serum free triiodothyronine level and mortality of severe pulmonary tuberculosis patients.

BACKGROUND: This study aimed to assess the relationship between a low serum free triiodothyronine (FT3) level and the mortality of severe pulmonary tuberculosis (TB) patients. METHODS: We performed a retrospective study and reviewed the medical records of patients with severe pulmonary TB between January 2016 and June 2022. The patient demographics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, survival or death at 28 and 90 days after hospital admission, and serum FT3 level were recorded. Bivariate regression analysis was performed to study the relationship between mortality and the FT3 level. The Kaplan-Meier method and the log-rank test were used to compare the survival rates between patients with different serum FT3 levels. RESULTS: Our study included 495 severe pulmonary TB patients, with 383 (77.4%) patients having a low serum FT3 level. The low-serum FT3 group had high 28-day and 90-day mortalities. The patients who had died by 28 or 90 days after hospital admission had a low FT3 level. Survival analysis showed that the patients with a low serum FT3 level had a low probability of survival at 28 days and at 90 days after hospital admission. CONCLUSION: The serum FT3 level was correlated with the 28-day and 90-day mortalities in patients with severe pulmonary TB. The serum FT3 level should be monitored in these patients to help manage their disease.

Differentiation and Treatment of Hypothyroidism, Functional Hypothyroidism, and Functional Metabolism.

Less than optimal thyroid effects can occur for many reasons, including lack of production, excessive binding, reduced conversion to the active form of thyroid, poor intracellular transport, poor receptor response, or autoimmune and toxicity issues. Differentiation of where the problem or problems causing the symptoms of hypothyroidism to occur is a key to the return to optimal thyroid response and successful treatment outcome. The concept of hypothyroidism, functional hypothyroidism, and functional hypometabolism as an alternative method to describe classical subclinical hypothyroidism symptoms according to the source of the malfunction are discussed in this article. The author also presents a unique method of using standard thyroid measurements to determine the areas of dysfunction and discusses the possible reasons for low production, excessive binding, poor conversion, and suboptimal receptor response. Appropriate treatment options for each area are discussed, including nutritional requirements. Thyroid replacement therapy options are presented and individualization of therapy based on need established with use of the thyroid gradient levels is discussed. Individualization of thyroid therapy will often require the use of compounded T3 or T4/T3 combination therapy. Compounding thyroid replacement allows for avoiding fillers that can interfere with absorption, unwanted diluents, unknown or nonstandardized ingredients from animal sources, providing more sustained action with less side effects, and individualizing the ratio of T4 and T3 initially, and as improvements are made in the patient's ability to convert T4 to T3.

Association between per- and polyfluoroalkyl substances exposure and thyroid function biomarkers among females attending a fertility clinic.

Per- and polyfluoroalkyl substances (PFAS) exposure was associated with changes in thyroid function in pregnant mothers and the general population. Limited such evidence exists in other susceptible populations such as females with fertility problems. This cross-sectional study included 287 females seeking medically assisted reproduction at a fertility clinic in Massachusetts, United States, between 2005 and 2019. Six long-alkyl chain PFAS, thyroid hormones, and autoimmune antibodies were quantified in baseline serum samples. We used generalized linear models and quantile g-computation to evaluate associations of individual PFAS and their total mixture with thyroid biomarkers. Most females were White individuals (82.7%), had graduate degrees (57.8%), and nearly half had unexplained subfertility (45.9%). Serum concentrations of all examined PFAS and their mixture were significantly associated with 2.6%-5.6% lower total triiodothyronine (TT3) concentrations. Serum concentrations of perfluorononanoate (PFNA), perfluorodecanoate (PFDA), and perfluoroundecanoate (PFUnDA), and of the total mixture were associated with higher ratios of free thyroxine (FT4) to free triiodothyronine (FT3). No associations were found for PFAS and TSH or autoimmune antibodies. Our findings support the thyroid-disrupting effect of long alkyl-chain PFAS among a vulnerable population of subfertile females.

The association between per-/polyfluoroalkyl substances in serum and thyroid function parameters: A cross-sectional study on teenagers living near a Chinese fluorochemical industrial plant.

Thyroid hormones (THs) play an important role in a wide range of crucial biological functions related to growth and development, and thyroid antibodies (TAs) can influence the biosynthesis of THs. Epidemiological studies have indicated that per- and polyfluoroalkyl substances (PFAS) could induce thyroid disruption, but studies on teenagers living in areas with high PFAS exposure are limited. This cross-sectional study focused on 836 teenagers (11- 15 years) living near a Chinese fluorochemical industrial plant. Decreased levels of free thyroxine (FT4, ﹤9.6 pmol/L, abnormal rate = 19.0 %) and elevated levels of free triiodothyronine (FT3, ï¹¥6.15 pmol/L, abnormal rate = 29.8 %) were observed. Correlations of serum PFAS concentrations and TAs/THs were analyzed. Increased PFOA was identified as a risk factor of decreased FT4 by using unadjusted (OR: 11.346; 95 % CI: 6.029, 21.352, p < 0.001) and adjusted (OR: 12.566; 95 % CI: 6.549, 24.115, p < 0.001) logistic regression models. In addition, significantly negative correlations were found between log10 transformed PFOA and FT4 levels using linear (unadjusted: ß = -1.543, 95 % CI: -1.937, -1.148, p < 0.001; adjusted: ß = -1.534, 95 % CI: -1.930, -1.137, p < 0.001) and BKMR models. For abnormal FT3, a significantly positive association between PFHxS and FT3 levels was observed in a regression model (unadjusted: ß = -0.903, 95 % CI: -1.212, -0.595, p < 0.001; adjusted: ß = -0.894, 95 % CI: -1.204, -0.583, p < 0.001), and PFHxS was identified as a risk factor (unadjusted: OR: 4.387; 95 % CI: 2.619, 7.346, p < 0.001; adjusted: OR: 4.527; 95 % CI: 2.665, 7.688, p < 0.001). Sensitivity analyses confirmed the robustness of the above results. This study reported the elevated PFAS exposure and thyroid function of teenagers living near a fluorochemical industrial plant from China.

Effect of DIO2 Gene Polymorphism on Thyroid Hormone Levels and Its Correlation with the Severity of Schizophrenia in a Pakistani Population.

Low levels of triiodothyronine (T3) in the brain lead to increased dopamine receptor sensitivity, potentially resulting in schizophrenia. Iodothyronine deiodinase 2 (DIO2) is the only enzyme which converts tetraiodothyronine (T4) to T3 in the brain. DIO2 polymorphism of rs225014 results in the expression of non-functioning DIO2. Therefore, this study aimed to investigate the association of rs255014 with schizophrenia and its impact on thyroid hormone levels. This study included 150 schizophrenia cases and 150 controls. DNA was extracted from blood and subjected to PCR and amplicon sequencing. Serum thyroid profiles were determined using chemiluminescent magnetic microparticle immunoassay. Statistical analyses involved independent sample t-tests, Chi-square, and Pearson's correlation tests. The results revealed a higher frequency of the reference genotype (TT) in controls compared to cases (p < 0.05). However, rs225014 did not influence serum thyroid levels or the severity of schizophrenia (p > 0.05). Interestingly, control subjects exhibited significantly higher T3 levels (p < 0.001) than cases. Regardless of the genotype (TT or CC), the control group had higher mean T3 levels than the corresponding case group (p < 0.05). In conclusion, rs225014 is associated with schizophrenia and has no effect on serum thyroid hormone levels.

Total weight loss induces the alteration in thyroid function after bariatric surgery.

Background: Bariatric surgery is an effective approach to weight loss, which may also affect thyroid function. However, alteration in thyroid-stimulating hormone (ΔTSH) and thyroid hormones after bariatric surgery and the relationship between thyroid function and postoperative weight loss still remains controversial. Methods: Data were collected from euthyroid patients with obesity who underwent sleeve gastrectomy and Roux-en-Y gastric bypass from 2017 to 2022. The alterations of free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), total triiodothyronine (TT3), and TSH were calculated 1 year after surgery. Pearson correlation analysis was used to assess the correlation between the percentage of total weight loss (%TWL) and ΔTSH. Multivariable linear regression was utilized to determine the association between %TWL and ΔTSH. Results: A total of 256 patients were included in our study. The mean %TWL was 28.29% after 1 year. TSH decreased from 2.33 (1.67, 3.04) uIU/mL to 1.82 (1.21, 2.50) uIU/mL (P < 0.001), FT3 decreased from 3.23 ± 0.42 pg/mL to 2.89 ± 0.41 pg/mL (P < 0.001), FT4 decreased from 1.11 ± 0.25 ng/dL to 1.02 ± 0.25 ng/dL (P < 0.001), TT3 decreased from 1.13 (1.00, 1.25) ng/mL to 0.89 (0.78, 1.00) ng/mL (P < 0.001), and TT4 decreased from 8.28 ± 1.69 ug/mL to 7.82 ± 1.68 ug/mL 1 year postoperatively (P < 0.001). %TWL was found to be significantly correlated to ΔTSH by Pearson correlation analysis (Pearson correlation coefficient = 0.184, P = 0.003), indicating that the more weight loss, the more TSH declined. After adjusting for covariates in multivariable linear regression, %TWL was found to be independently associated with ΔTSH (ß = 0.180 [95% confidence interval (CI), 0.048 - 0.312], P = 0.008). Moreover, %TWL was divided into 3 categorical groups (%TWL ≤ 25%, 25% < %TWL ≤ 35%, and %TWL > 35%) for further exploration, and was also found to be an independent predictor for ΔTSH after adjusting for covariates in multivariable linear regression (ß = 0.153 [95% CI, 0.019 - 0.287], P = 0.025). Conclusion: TSH, FT4, FT3, TT4, and TT3 decrease significantly 1 year after bariatric surgery. The decline in TSH is independently mediated by postoperative weight loss; the more the weight loss, the more the TSH decrease.

The Differential Effect of a Shortage of Thyroid Hormone Compared with Knockout of Thyroid Hormone Transporters Mct8 and Mct10 on Murine Macrophage Polarization.

Innate immune cells, including macrophages, are functionally affected by thyroid hormone (TH). Macrophages can undergo phenotypical alterations, shifting between proinflammatory (M1) and immunomodulatory (M2) profiles. Cellular TH concentrations are, among others, determined by TH transporters. To study the effect of TH and TH transporters on macrophage polarization, specific proinflammatory and immunomodulatory markers were analyzed in bone marrow-derived macrophages (BMDMs) depleted of triiodothyronine (T3) and BMDMs with a knockout (KO) of Mct8 and Mct10 and a double KO (dKO) of Mct10/Mct8. Our findings show that T3 is important for M1 polarization, while a lack of T3 stimulates M2 polarization. Mct8 KO BMDMs are unaffected in their T3 responsiveness, but exhibit slight alterations in M2 polarization, while Mct10 KO BMDMs show reduced T3 responsiveness, but unaltered polarization markers. KO of both the Mct8 and Mct10 transporters decreased T3 availability and, contrary to the T3-depleted BMDMs, showed partially increased M1 markers and unaltered M2 markers. These data suggest a role for TH transporters besides transport of TH in BMDMs. This study highlights the complex role of TH transporters in macrophages and provides a new angle on the interaction between the endocrine and immune systems.

Intestinal remodeling during Xenopus metamorphosis as a model for studying thyroid hormone signaling and adult organogenesis.

Intestinal development takes places in two phases, the initial formation of neonatal (mammals)/larval (anurans) intestine and its subsequent maturation into the adult form. This maturation occurs during postembryonic development when plasma thyroid hormone (T3) level peaks. In anurans such as the highly related Xenopus laevis and Xenopus tropicalis, the larval/tadpole intestine is drastically remodeled from a simple tubular structure to a complex, multi-folded adult organ during T3-dependent metamorphosis. This involved complete degeneration of larval epithelium via programmed cell death and de novo formation of adult epithelium, with concurrent maturation of the muscles and connective tissue. Here, we will summarize our current understanding of the underlying molecular mechanisms, with a focus on more recent genetic and genome-wide studies.

Patients' Persistent Symptoms, Clinician Demographics, and Geo-Economic Factors Are Associated with Choice of Therapy for Hypothyroidism by European Thyroid Specialists: The "THESIS" Collaboration.

Background: Hypothyroidism is common, however, aspects of its treatment remain controversial. Our survey aimed at documenting treatment choices of European thyroid specialists and exploring how patients' persistent symptoms, clinician demographics, and geo-economic factors relate to treatment choices. Methods: Seventeen thousand two hundred forty-seven thyroid specialists from 28 countries were invited to participate in an online questionnaire survey. The survey included respondent demographic data and treatment choices for hypothyroid patients with persistent symptoms. Geo-economic data for each country were included in the analyses. Results: The response rate was 32.9% (6058 respondents out of 17,247 invitees). Levothyroxine (LT4) was the initial treatment preferred by the majority (98.3%). Persistent symptoms despite normal serum thyrotropin (TSH) while receiving LT4 treatment were reported to affect up to 10.0% of patients by 75.4% of respondents, while 28.4% reported an increasing such trend in the past 5 years. The principal explanations offered for patients' persistent symptoms were psychosocial factors (77.1%), comorbidities (69.2%), and unrealistic patient expectations (61.0%). Combination treatment with LT4+liothyronine (LT3) was chosen by 40.0% of respondents for patients who complained of persistent symptoms despite a normal TSH. This option was selected more frequently by female thyroid specialists, with high-volume practice, working in countries with high gross national income per capita. Conclusions: The perception of patients' dissatisfaction reported by physicians seems lower than that described by hypothyroid patients in previous surveys. LT4+LT3 treatment is used frequently by thyroid specialists in Europe for persistent hypothyroid-like symptoms even if they generally attribute such symptoms to nonendocrine causes and despite the evidence of nonsuperiority of the combined over the LT4 therapy. Pressure by dissatisfied patients on their physicians for LT3-containing treatments is a likely explanation. The association of the therapeutic choices with the clinician demographic characteristics and geo-economic factors in Europe is a novel information and requires further investigation.

Engineered PDGFA-ligand-modified exosomes delivery T3 for demyelinating disease targeted therapy.

Demyelination is a proper syndrome in plenty of central nervous system (CNS) diseases, which is the main obstacle to recovery and still lacks an effective treatment. To overcome the limitations of the brain-blood barrier on drug permeability, we modified an exosome secreted by neural stem cells (NSCs), which had transfected with lentivirus armed with platelet-derived growth factors A (PDGFA)-ligand. Through the in vivo and in vitro exosomes targeting test, the migration ability to the lesion areas and OPCs significantly improved after ligand modification. Furthermore, the targeted exosomes loaded with 3,5, 30-L-triiodothyronine (T3) have a critical myelination ability in CNS development, administrated to the cuprizone animal model treatment. The data shows that the novel drug vector loaded with T3 significantly promotes remyelination compared with T3 alone. At the same time, it improved the CNS microenvironment by reducing astrogliosis, inhibiting pro-inflammatory microglia, and alleviating axon damage. This investigation provides a straightforward strategy to produce a targeting exosome and indicates a possible therapeutic manner for demyelinating disease.

Quemeiteng granule relieves goiter by suppressing thyroid microvascular endothelial cell proliferation and angiogenesis via miR-217-5p-mediated targeting of FGF2-induced regulation of the ERK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Goiters are enlargements of the thyroid gland and are a global public issue. Quemeiteng granule (QMTG) is a traditional Chinese medicine (TCM) formula used to treat goiter in Yunnan Province. However, the effectiveness and underlying mechanism of these treatments have not been fully elucidated. AIM OF THE STUDY: This study aimed to investigate the therapeutic effects of QMTG on goiter and the downstream regulatory mechanisms. MATERIALS AND METHODS: In this study, we first evaluated the antigoiter efficacy of QMTG through biochemical indices [body weight, thyroid coefficient, triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH)] and hematoxylin-eosin (HE) staining in a Propylthiouracil (PTU)-induced model. Based on microRNA sequencing (miRNA-seq) and bioinformatics analysis, key miRNA was screened out. A dual-luciferase reporter assay was performed to confirm the transcriptional regulation of the target gene by the miRNA. The viability of rat thyroid microvascular endothelial cells (RTMECs) and human thyroid microvascular endothelial cells (HTMECs) was assessed using the CCK-8 assays. The migration and angiogenesis of RTMECs and HTMECs were visualized through tube formation and wound scratch assays. Proteins involved in angiogenesis and the ERK pathway were assessed via Western blotting. RESULTS: QMTG significantly increased body weight, decreased the thyroid coefficient, increased the levels of T3, T4, FT3 and FT4 and reduced TSH levels in rats with goiter. QMTG also promoted the morphological recovery of thyroid follicles. MiR-217-5p was identified as a key miRNA. Our studies revealed that miR-217-5p directly targets FGF2 and that QMTG promotes the recovery of thyroid hormone (TH) levels and morphological changes in the thyroid, suppresses thyroid microvascular endothelial cell vitality, tube formation and migration, and reduces the expression of VEGF, Ang-1 and VCAM-1 triggered by miR-217-5p, thereby inhibiting the Ras/MEK/ERK cascade through FGF2. CONCLUSIONS: Our experiments demonstrated that the QMTG had therapeutic effects on goiter. These effects were attributed to the inhibition of ERK pathway-induced proliferation and angiogenesis through the targeting of FGF2 by miR-217-5p.