A Study of Non-alcoholic Fatty Liver Disease in Patients With Hypothyroidism: A Cross-Sectional Study in a Tertiary Care Hospital.

Background Hypothyroidism occurs when the thyroid gland is underactive and fails to produce sufficient thyroid hormones. It can affect multiple organs including the heart, brain, liver, kidneys, and reproductive system, leading to symptoms such as fatigue, cognitive impairment, elevated cholesterol, fluid retention, fatty liver, and menstrual irregularities. Given the higher prevalence of fatty liver disease in patients with hypothyroidism, it is important to evaluate the need for routine screening for fatty liver in these patients. Materials and methods This observational, cross-sectional study was conducted at Dr. D. Y. Patil Medical Hospital, Pune, Maharashtra, India, from October 2022 to June 2024. The study included 60 patients aged over 12 years who were known or recently diagnosed with hypothyroidism. Patients with type 2 diabetes mellitus, pregnant women, or those with chronic liver disease were excluded. Data collected included physical examination findings and laboratory test results. Fatty liver was diagnosed using magnetic resonance elastography. Statistical analysis was performed using IBM SPSS statistics for Windows, version 20 (IBM Corp., Armonk, New York). The statistical significance of parametric data was evaluated using the Chi-square test. A p-value less than 0.05 and a confidence interval of 95% were considered statistically significant. Result The study population had an average age of about 45 years, with most participants aged between 40 and 49 years. The majority of the participants were female, making up over 83% of the group, while males constituted about 17%. The most commonly reported symptom was weight gain, followed by constipation and fatigue. For individuals with fatty liver, the average thyroid-stimulating hormone (TSH) level was notably higher compared to those without fatty liver. Additionally, low-density lipoprotein (LDL) levels were higher in individuals with non-alcoholic fatty liver disease (NAFLD) compared to those without. Both TSH and LDL levels showed a statistically significant association with the occurrence of NAFLD. Conclusion Hypothyroidism was more prevalent in females and in the age group 40-49 years. There was a statistical significance between TSH and the occurrence of NAFLD. In this study, statistical significance was also found between LDL and the occurrence of NAFLD.

Roxadustat has risks of reversible central hypothyroidism in patients undergoing hemodialysis: a single-center retrospective cohort study.

Roxadustat, a hypoxia-inducible factor-prolyl hydroxylase inhibitor, has proven efficacy in the treatment of renal anemia; however, evidence indicates that it may cause central hypothyroidism. The prevalence and reversibility of roxadustat-induced central hypothyroidism in patients undergoing hemodialysis remain unclear. Here, we retrospectively analyzed thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels in 51 patients (mean age: 72.3 ± 10.7 years; 58.8% male) undergoing hemodialysis before, during, and after halting roxadustat treatment. TSH levels were significantly decreased from a median of 2.46 (interquartile range:1.60-4.51) mU/L before roxadustat treatment to 1.36 (0.72-2.41) mU/L during treatment (p < 0.001), and improved to 2.56 (1.78-4.63) mU/L after halting roxadustat (p < 0.001). Similarly, FT4 levels decreased from 1.11 (0.97-1.24) ng/dL before roxadustat treatment to 0.92 (0.71-1.03) ng/dL during treatment (p < 0.001) and improved to 1.05 (0.93-1.17) ng/dL after halting roxadustat (p < 0.001). FT3 levels were 2.04 (1.78-2.31) pg/mL before starting roxadustat, 1.97 (1.69-2.27) pg/mL during treatment, and 1.90 (1.63-2.18) pg/mL after halting roxadustat, with no significant difference between each group. Moreover, 2.0% of patients exhibited extremely low TSH levels (≤0.1 mU/L) and low TSH levels (>0.1 mU/L to <0.4 mU/L) before starting roxadustat and that percentage increased to 5.9% and 7.8%, respectively, during treatment. After roxadustat cessation, extremely low or low TSH levels recovered in all patients. Taken together, the results indicate that roxadustat can cause reversible central hypothyroidism in patients undergoing hemodialysis.

Impact of Hashimoto's thyroiditis on the tumor microenvironment in papillary thyroid cancer: insights from single-cell analysis.

This study investigates the impact of Hashimoto's thyroiditis (HT), an autoimmune disorder, on the papillary thyroid cancer (PTC) microenvironment using a dataset of 140,456 cells from 11 patients. By comparing PTC cases with and without HT, we identify HT-specific cell populations (HASCs) and their role in creating a TSH-suppressive environment via mTE3, nTE0, and nTE2 thyroid cells. These cells facilitate intricate immune-stromal communication through the MIF-(CD74+CXCR4) axis, emphasizing immune regulation in the TSH context. In the realm of personalized medicine, our HASC-focused analysis within the TCGA-THCA dataset validates the utility of HASC profiling for guiding tailored therapies. Moreover, we introduce a novel, objective method to determine K-means clustering coefficients in copy number variation inference from bulk RNA-seq data, mitigating the arbitrariness in conventional coefficient selection. Collectively, our research presents a detailed single-cell atlas illustrating HT-PTC interactions, deepening our understanding of HT's modulatory effects on PTC microenvironments. It contributes to our understanding of autoimmunity-carcinogenesis dynamics and charts a course for discovering new therapeutic targets in PTC, advancing cancer genomics and immunotherapy research.

Establishing the TSH reference intervals for healthy adults aged over 70 years: the Australian ASPREE cohort study.

OBJECTIVES: As thyroid disorders are common amongst the elderly, this study aims to evaluate the reference interval (RI) for thyroid stimulating hormone (TSH) in healthy adults aged 70 years and over. METHODS: A proposed RI was determined from the Australian participants of the ASPirin in Reducing Events in the Elderly (ASPREE) randomised trial. Participants had no history of cardiovascular disease, thyroid cancer, dementia, or life-threatening illnesses. Participants prescribed with any thyroid-related medication at baseline were excluded. TSH levels were measured using a commercial chemiluminescence microparticle immunoassay. The RI was determined using the middle 95th percentile of the logarithmic transformed data of baseline TSH. Cox proportional hazard regression models were used to validate the RI by assessing disease incidence over time. RESULTS: A total of 10,995 participants had baseline TSH measures. Median (IQR) age was 73.9 (71.8-77.3) years. We propose a RI of 0.34-3.75 mU/L. TSH levels did not differ by age or sex. At baseline, there was no association between symptoms associated with thyroid disease and levels of TSH. Over the follow-up period of up to 11 years, no association was seen between baseline TSH levels and relevant disease outcomes for participants within the RI. CONCLUSIONS: From a group of initially healthy, community-dwelling adults aged >=70 years, we propose a RI of TSH to best represent euthyroidism. This concentration was not associated with an increased risk of thyroid related symptoms or outcomes, confirming its appropriateness for clinical use.

Prevalencia de hipertirotropinemia neonatal comoindicador de deficiencia de yodo en la provincia de La Pampa: un análisis epidemiológico / Prevalence of high neonatal thyroid stimulating hormone levels as an indicator of iodine deficiency in the province of La Pampa: An epidemiological analysis

Introducción. El yodo desempeña un rol fundamental en el metabolismo, el crecimiento y el desarrollo humano. Durante el embarazo y la infancia, la demanda de este micronutriente aumenta considerablemente. La tirotropinemia neonatal (TSHn) aumentada, definida como TSHn ≥5 mUI/l, es un marcador que señala la deficiencia de yodo en una población cuando su prevalencia supera el 3 %. Objetivo. Determinar la prevalencia de TSHn ≥ 5 en La Pampa durante el período 2021-2022, analizar su correlación con diferentes variables y compararla con datos de una cohorte histórica. Población y métodos. Estudio transversal, de diseño descriptivo-analítico, sobre una población de neonatos nacidos en las cinco zonas sanitarias de la provincia de La Pampa durante los años 2021 y 2022. Resultados. De los 5778 neonatos evaluados, el 9,6 % presentó niveles de TSHn ≥5 mUI/l. El 70,4 % de estas mediciones fueron realizadas después del tercer día de vida. No se observaron diferencias significativas en la frecuencia de niveles elevados de TSHn según el año de nacimiento, peso al nacer o días hasta la extracción. Se registró una mayor prevalencia en el sexo masculino (10,6 % versus 8,5 %; p = 0,007) y entre los neonatos nacidos a término (9,8 % versus 6,6 %; p = 0,02). La prevalencia de hipertirotropinemia fue superior a la observada en una cohorte de 2001-2002. Conclusiones. La prevalencia de hipertirotropinemia neonatal en La Pampa durante los años 2021 y 2022 fue del 9,6 %, lo que indica un estado de deficiencia leve de yodo en la provincia, superior al reportado hace dos décadas.

Introduction. Iodine plays a key role in human metabolism, growth, and development. During pregnancy and childhood, the demand for this micronutrient increases notably. Increased neonatal thyroid stimulating hormone (nTSH) levels, defined as nTSH ≥ 5 mIUL, are a marker of iodine deficiency in a population if its prevalence is higher than 3%.Objective. To establish the prevalence of nTSH ≥ 5 in La Pampa in the 2021­2022 period, analyze its correlation with different variables, and compare it with data from a historical cohort.Population and methods. Cross-sectional, descriptive-analytical study in a population of newborn infants born in the 5 health regions of the province of La Pampa in 2021 and 2022. Results. Of  the  5778  assessed  newborn  infants,  9.6%  had  nTSH  levels  ≥  5  mIU/L. It was reported that 70.4% of these measurements were done after the third day of life. No significant differences were observed in the frequency of high nTSH levels by year of birth, birth weight, or days until samplecollection.A higher prevalence was observed among male infants (10.6% versus 8.5%; p = 0.007) and term infants (9.8% versus 6.6%; p = 0.02). The prevalence of high TSH levels was superior to that observed in the 2001­2002 cohort. Conclusions. The  prevalence of high nTSH levels in La Pampa during 2021 and 2022 was 9.6%, suggesting the presence of mild iodine deficiency in the population of this province, higher that what  had been reported 2 decades ago.

Association between Subclinical Hypothyroidism and Adverse Pregnancy Outcomes in Assisted Reproduction Technology Singleton Pregnancies: A Retrospective Study.

Background/Objectives: Women with subclinical hypothyroidism (SCH) were reported to be at an increased perinatal risk. We aimed to investigate the relationship between SCH and perinatal outcomes in singleton pregnancies resulting from assisted reproduction technology (ART). Methods: We retrospectively examined the perinatal outcomes of ART singleton pregnancies in women who underwent thyroid function screening before conception and delivered at our hospital from January 2020 to July 2023. We defined SCH as thyroid-stimulating hormone (TSH) levels > 2.5 mU/L and normal free T4 levels. The patients were categorized into three groups: normal thyroid function (group A), SCH without levothyroxine therapy (group B), and SCH with levothyroxine therapy (group C). The risks of preterm birth, preeclampsia, fetal growth restriction, manual placental removal, and blood loss at delivery were compared among the three groups. Results: Out of the 650 ART singleton deliveries, 581 were assigned to group A, 34 to group B, and 35 to group C. The preterm birth rate at <34 weeks was significantly higher in group B and significantly lower in group C than in group A. The rate of preterm delivery at <34 weeks increased in correlation with TSH levels. Levothyroxine therapy was the significant preventive factor for preterm birth at <34 weeks. Conclusions: The preterm birth rate before 34 weeks was significantly higher in the SCH group. Levothyroxine therapy is a significant protective factor against preterm birth before 34 weeks. Universal screening for thyroid function and appropriate hormone therapy in pregnant women may help reduce perinatal risks, including preterm birth.

When the Expected Becomes Unexpected: An Acute Presentation of Hypothyroidism.

Myxedema coma is an uncommon and life-threatening manifestation of severe hypothyroidism. Its occurrence in the pediatric population is exceptionally rare and can result from long-standing untreated hypothyroidism or nonadherence to treatment. Identifying this condition can be challenging because it requires a high level of clinical suspicion along with thyroid function testing. We present a 17-year-old female with a history of anxiety who had widespread nonspecific symptoms, including persistent bradycardia, which were found to be caused by hypothyroidism. Our goal is to raise awareness of the varied clinical manifestations of pediatric myxedema to promote early recognition and prompt medical interventions that can lead to better outcomes.

Distinct transcriptional profiles in rat thyroid glands after developmental exposure to three in vitro thyroperoxidase inhibiting chemicals.

Thyroperoxidase (TPO) is central in thyroid hormone (TH) synthesis and inhibition can lead to TH deficiency. Many chemicals can inhibit TPO activity in vitro, but how this may manifest in the developing thyroid gland at the molecular level is unclear. Here, we characterized the thyroid gland transcriptome of male rats developmentally exposed to the in vitro TPO-inhibitors amitrole, 2-mercaptobenzimidazole (MBI), or cyanamide by use of Bulk-RNA-Barcoding (BRB) and sequencing. Amitrole exposure caused TH deficiency and 149 differentially expressed genes in the thyroid gland. The effects indicated an activated and growing thyroid gland. MBI caused intermittent changes to serum TH concentrations in a previous study and this was accompanied by 60 differentially expressed genes in the present study. More than half of these were also affected by amitrole, indicating that they could be early effect biomarkers of developmental TH system disruption due to TPO inhibition. Further work to validate the signature is needed, including assessment of substance independency and applicability domain.

Regulatory Effects of 5-Day Oral and Intraperitoneal Administration of a Thienopyrimidine Derivative on the Thyroid Status in Rats.

In experiments on rats, we studied the effect of 5-day intraperitoneal (15 mg/kg/day) and oral (40 mg/kg/day) administration of compound TPY3m, a stimulator of the production of thyroid hormones by the thyroid gland developed by us, on the blood levels of thyroxine, triiodothyronine, and thyroid-stimulating hormone and on morphology of the thyroid gland. With both routes of administration, TPY3m caused a sustained moderate elevation of thyroid hormones, mainly thyroxine, with little effect on the level of thyroid-stimulating hormone. TPY3m did not reduce the stimulating effect of thyroliberin on the levels of thyroid hormones and had no damaging effect on the thyroid gland. During long-term administration, compound TPY3m stimulates the production of thyroid hormones without weakening the activity of the thyroid axis. Thus, TPY3m is a prototype of drugs for correcting thyroid hormone deficiency.

A predictive model for L-T4 dose in postoperative DTC after RAI therapy and its clinical validation in two institutions.

Purpose: To develop a predictive model using machine learning for levothyroxine (L-T4) dose selection in patients with differentiated thyroid cancer (DTC) after resection and radioactive iodine (RAI) therapy and to prospectively validate the accuracy of the model in two institutions. Methods: A total of 266 DTC patients who received RAI therapy after thyroidectomy and achieved target thyroid stimulating hormone (TSH) level were included in this retrospective study. Sixteen clinical and biochemical characteristics that could potentially influence the L-T4 dose were collected; Significant features correlated with L-T4 dose were selected using machine learning random forest method, and a total of eight regression models were established to assess their performance in prediction of L-T4 dose after RAI therapy; The optimal model was validated through a two-center prospective study (n=263). Results: Six significant clinical and biochemical features were selected, including body surface area (BSA), weight, hemoglobin (HB), height, body mass index (BMI), and age. Cross-validation showed that the support vector regression (SVR) model was with the highest accuracy (53.4%) for prediction of L-T4 dose among the established eight models. In the two-center prospective validation study, a total of 263 patients were included. The TSH targeting rate based on constructed SVR model were dramatically higher than that based on empirical administration (Rate 1 (first rate): 52.09% (137/263) vs 10.53% (28/266); Rate 2 (cumulative rate): 85.55% (225/263) vs 53.38% (142/266)). Furthermore, the model significantly shortens the time (days) to achieve target TSH level (62.61 ± 58.78 vs 115.50 ± 71.40). Conclusions: The constructed SVR model can effectively predict the L-T4 dose for postoperative DTC after RAI therapy, thus shortening the time to achieve TSH target level and improving the quality of life for DTC patients.

The alternative value of thyroid stimulating hormone instead of thyroglobulin in differentiation of follicular thyroid neoplasm in Hashimoto's thyroiditis.

Purposes: To provide novel aspects for the preoperative diagnosis and appropriate differentiation strategies for follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA). Methods: Among 25,765 cases, a total of 326 patients with follicular thyroid neoplasms between 2013 and 2019 were enrolled. Patient demographics, perioperative parameters, surgical profiles and oncologic outcomes were collected and analyzed. Results: There were no significant differences in preoperative ultrasound findings between FTA and FTC patients. The true positive rate (sensitivity) and true negative rate (specificity) of fine needle aspiration (FNA) for FTA patients were 0.6956 and 0.5000, respectively, and those for FTC patients were 0.0714 and 0.9348, respectively. Patients with FTC presented significantly higher serum thyroglobulin (TG) levels than patients with FTA. Preoperative TG level was positively related to tumor invasiveness and recurrence or distant metastases in FTC patients. There were 55 patients with Hashimoto's thyroiditis (HT), accounting for 16.87% of enrolled patients. HT patients had significantly lower serum TG concentrations than antibody-negative patients. Among HT patients, no significant differences were observed in TG levels between the FTA and FTC groups. Instead, FTA patients had significantly higher serum thyroid stimulating hormone (TSH) levels and lower serum T3 (Triiodothyronine) levels compared to FTC patients. Serum TSH level >1.736U/L was associated with benign follicular neoplasms in HT patients according to the receiver operating characteristic (ROC) curve. Conclusion: Distinguishing FTC from FTA remains a challenge for ultrasonography and FNA. Serum TG should be measured as a risk factor of FTC. However, in HT patients, serum TSH levels can serve as a more reliable indicator for differentiating FTC from FTA preoperatively.

Effect of Presence of Uni- or Bilateral Thyroid Adenoma on Recovery of Pituitary-Thyroid Axis and Creatinine Concentration in Radioiodine-Treated Cats.

Radioiodine therapy (RAIT) is the gold standard for treatment of hyperthyroidism in cats. The aim of this study was to evaluate the effect of the presence of uni- or bilateral thyroid adenoma on changes in total thyroxine (TT4), thyroid-stimulating hormone (TSH), and creatinine concentration over a period of 6 to 12 months following RAIT. Fifty-one hyperthyroid cats presented for RAIT between April 2021 and April 2022 were prospectively enrolled. Cats with an increased creatinine concentration (creatinine ≥ 140 µmol/L), renal morphology abnormalities, and suspected thyroid carcinoma were excluded. TT4, TSH, and creatinine were determined before and one week and one, three, six, and twelve months following RAIT. The effects of the re-examination timepoint following RAIT and the presence of uni- or bilateral thyroid adenoma based on technetium-99m scintigraphy on TT4, TSH, and creatinine were analysed by mixed effects modelling. Cats with bilateral adenoma had significantly higher TSH concentrations after RAIT compared to those with unilateral adenoma. TT4 concentration significantly decreased one week (p < 0.001) and again one month following RAIT (p < 0.001). TSH and creatinine concentration significantly increased one month post RAIT (both p < 0.001). As indicated by an increase in TSH concentration, the pituitary-thyroid axis needs a minimum of one month post RAIT to recover from hyperthyroidism-induced suppression, but hypothyroidism necessitating levothyroxine supplementation might not be diagnosed before 6 or even 12 months post RAIT. Although creatinine did not increase significantly after one month post RAIT in this cohort, an increased creatinine concentration was detected at later timepoints in individual cats.

Age-Specific Reference Intervals for Thyroid-Stimulating Hormones and Free Thyroxine to Optimize Diagnosis of Thyroid Disease.

Background: Thyroid-stimulating hormone (TSH) and subsequent free thyroxine (FT4) concentrations outside the reference interval (RI) are used to diagnose thyroid diseases. Most laboratories do not provide age-specific RIs for TSH and FT4 beyond childhood, although TSH concentrations vary with age. Therefore, we aimed to establish TSH and FT4 age-specific RIs throughout life and aimed to determine whether using these RIs would result in reclassification of thyroid disease diagnoses in adults. Methods: This multicenter retrospective cross-sectional study used big data to determine indirect RIs for TSH and FT4. These RIs were determined by TMC and refineR-analysis, respectively, using four different immunoassay platforms (Roche, Abbott, Siemens, and Beckman Coulter). Retrospective data (2008-2022) from 13 Dutch laboratories for general practitioners and local hospitals were used. RIs were evaluated per manufacturer. Age groups were established from 2 to 20 years by 2-year categories and decade categories between 20 and 100 years. Results: We included totally 7.6 million TSH and 2.2 million FT4 requests. TSH upper reference limits (URLs) and FT4 lower reference limits were higher in early childhood and decreased toward adulthood. In adulthood, TSH URLs increased from 60 years in men, and from 50 years in women, while FT4 URLs increased from 70 years onward. Using adult age-specific RIs resulted in a decrease in diagnoses of subclinical and overt hypothyroidism in women above 50 and men above 60 years in our Roche dataset. Conclusion: This study stressed the known importance of using age-specific RIs for TSH and FT4 in children. This study also showed the clinical relevance of using age-specific RIs for TSH in adulthood to reduce diagnoses of subclinical hypothyroidism in older persons. Therefore, implementation of adult TSH age-specific RIs should be strongly considered. Data are less uniform regarding FT4 age-specific RIs and more research should be performed before implementing these in clinical practice.

A Critical Investigation of Sick Euthyroid Syndrome in Chronic Heart Failure Patients: Addressing the Need for Accurate Thyroid Assessment.

Background The body undergoes numerous metabolic changes during severe illness or physiological stress to protect itself by lowering metabolism and reducing overall demands. This evolutionary adaptation dates back to early human development, long before the advent of ICU facilities and advanced treatments. One such protective mechanism is Sick Euthyroid Syndrome (SES), also known as Non-thyroidal Illness Syndrome (NTIS). SES commonly occurs in critically ill patients and is frequently observed in conditions such as heart failure, chronic kidney disease, and severe sepsis. This syndrome is characterized by abnormal thyroid function tests in patients with acute or chronic systemic illnesses who do not have intrinsic thyroid disease. Typically, these patients exhibit low serum levels of triiodothyronine (T3), normal or low levels of thyroxine (T4), and normal or low thyroid-stimulating hormone (TSH) levels. SES is believed to be an adaptive response to illness, aimed at reducing the body's metabolic rate and conserving energy during severe physiological stress. This original article delves into SES's prevalence and clinical impact in these settings. Materials and methods The study aims to determine the prevalence of SES in patients with long-standing heart failure, elucidate the relationship between thyroid function and heart failure severity, and assess its impact on various hematological and clinical parameters. This observational, cross-sectional study was conducted at Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, India, a 2011-bed hospital, over one and a half years. This study included 70 patients with chronic heart failure, aged 18 years and above, defined by a left ventricular ejection fraction of 40% or less and a Boston criteria score of 8 or more. Patients were excluded if they had a history of thyroid dysfunction, clinical sepsis, or were taking thyroid-affecting drugs.  Results The study provides important insights into the prevalence and impact of SES in long-standing heart failure patients. It found that a significant 44.29% of these patients exhibited low T3 levels, highlighting the substantial occurrence of SES in this population. Additionally, the study revealed a negative correlation between N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels, Boston score, and total T3, suggesting that as indicators of heart failure severity worsen, total T3 levels may decrease further. Another key finding is the high prevalence of anemia among heart failure patients, with a notable gender disparity: 92.11% of male patients were affected compared to 50% of female patients.  Conclusion The study concluded that SES is significantly prevalent among long-standing heart failure patients, further indicating that thyroid suppression increases with the severity of heart failure. Recognizing SES can guide tailored treatments, prompting intensive monitoring and optimized heart failure management. Additionally, the study found a high prevalence of anemia, particularly among male patients, highlighting the need for gender-specific considerations in managing heart failure. These findings underscore the importance of routine thyroid function assessments and regular monitoring of anemia in heart failure patients. Future research should focus on improving clinical outcomes through comprehensive management of both thyroid function and anemia in these patients.

Correlation between ultrasonographic and cytologic features of thyroid nodules: a single-center cross-sectional study.

A thyroid nodule is managed according to the clinical context, ultrasound (US) findings, and fine needle aspiration (FNA) results. Most thyroid nodules are benign; however, nodule classification is crucial to avoid unnecessary thyroid surgery. We conducted this study to compare the findings of fine-needle aspiration cytology (FNAC) expressed using the Bethesda system with the features of thyroid US classified using the EU-TIRADS classification to assess the risk of malignancy. A descriptive and analytical study involving 99 patients with thyroid nodules followed up in the Department of Endocrinology-Diabetology and Nutrition. Data were collected from medical records and analyzed using SPSS software V21. FNA was performed on 121 nodules using the BETHESDA system. These nodules were classified as malignant, suspicious for follicular neoplasm, and suspicious for malignancy in 5.8%, 5%, and 1.7% of cases, respectively. As for the EU-TIRADS 2017 classification, 59.5% of benign nodules were classified as EU-TIRADS III, whereas 66.7% of malignant nodules were classified as EU-TIRADS V and significantly related to malignant prediction (P = 0.000). The size of nodules was significantly correlated to the risk of malignancy (P = 0.013). Seventy-five percent of nodules with central vascularity were malignant (P = 0.012). Irregularity of nodule contours was significantly associated with the risk of malignancy, as 30% of nodules with irregular contours were Bethesda VI (P = 0.003). Hypoechogenicity was found in 77.8% of malignant nodules (P = 0.004). Additionally, only 9.2% of the nodules were taller than wide, of which 37.5% were malignant (P = 0.012). For a safe management strategy, US-guided FNAC should be performed on each suspicious thyroid nodule, given the correlation between EU-TIRADS classification features and the risk of malignancy.

Protective effect of Korean red ginseng water extract on levothyroxine-induced hyperthyroidism and propylthiouracil-induced hypothyroidism in rats.

Background: Korean red ginseng extract (KRGE) (Family: Araliaceae) is one of the most widely used traditional herbs in Asia. Multiple studies have shown that KRGE has anti-inflammation, anti-fatigue, anti-obesity, anti-oxidant, and anti-cancer effects. Methods: Sprague-Dawley rats were divided into five groups for PTU-induced hypothyroidism and six groups for LT4-induced hyperthyroidism. At the experiment's conclusion, rats were sacrificed, and blood, thyroid gland, and liver samples were collected. Body weight was recorded weekly, and serum hormone levels were assessed using enzyme-linked immunoassay. Thyroid gland and liver tissues were stained with hematoxylin and eosin. KRGE was prepared in 0.5% CMC and stored at 4 °C before administration. Results: In the LT4-induced hyperthyroidism model, KRGE prevented decreases in body weight, thyroid gland weight, liver weight, serum glucose, and thyroid hormone levels compared to the PTU group. It also reduced increases in T3, T4, and serum aspartate aminotransferase levels after LT4 treatment. Additionally, KRGE improved thyroid gland and liver histopathology, effects not observed in the PTU-induced hypothyroidism model. Conclusion: All things considered, our research points to KRGE's potential protective role in rat hyperthyroidism caused by LT4 by lowering thyroid hormone production.

Thyroid Disease in Rabbits and Rodents.

While thyroid disease is generally uncommon in rabbits and rodents, it is most frequently diagnosed in guinea pigs. Particularly, hyperthyroidism and thyroid neoplasms are diagnosed regularly in this species, while thyroid neoplasia is the most common thyroid disorder found in other rodents. Thyroid disease appears to be rare in rabbits, though modalities to reliably diagnose different disorders like hypothyroidism are currently lacking.

Local TSH/TSHR signaling promotes CD8+ T cell exhaustion and immune evasion in colorectal carcinoma.

BACKGROUND: Dysfunction of CD8+ T cells in the tumor microenvironment (TME) contributes to tumor immune escape and immunotherapy tolerance. The effects of hormones such as leptin, steroid hormones, and glucocorticoids on T cell function have been reported previously. However, the mechanism underlying thyroid-stimulating hormone (TSH)/thyroid-stimulating hormone receptor (TSHR) signaling in CD8+ T cell exhaustion and tumor immune evasion remain poorly understood. This study was aimed at investigating the effects of TSH/TSHR signaling on the function of CD8+ T cells and immune evasion in colorectal cancer (CRC). METHODS: TSHR expression levels in CD8+ T cells were assessed with immunofluorescence and flow cytometry. Functional investigations involved manipulation of TSHR expression in cellular and mouse models to study its role in CD8+ T cells. Mechanistic insights were mainly gained through RNA-sequencing, Western blotting, chromatin immunoprecipitation and luciferase activity assay. Immunofluorescence, flow cytometry and Western blotting were used to investigate the source of TSH and TSHR in CRC tissues. RESULTS: TSHR was highly expressed in cancer cells and CD8+ T cells in CRC tissues. TSH/TSHR signaling was identified as the intrinsic pathway promoting CD8+ T cell exhaustion. Conditional deletion of TSHR in CD8+ tumor-infiltrating lymphocytes (TILs) improved effector differentiation and suppressed the expression of immune checkpoint receptors such as programmed cell death 1 (PD-1) and hepatitis A virus cellular receptor 2 (HAVCR2 or TIM3) through the protein kinase A (PKA)/cAMP-response element binding protein (CREB) signaling pathway. CRC cells secreted TSHR via exosomes to increase the TSHR level in CD8+ T cells, resulting in immunosuppression in the TME. Myeloid-derived suppressor cells (MDSCs) was the main source of TSH within the TME. Low expression of TSHR in CRC was a predictor of immunotherapy response. CONCLUSIONS: The present findings highlighted the role of endogenous TSH/TSHR signaling in CD8+ T cell exhaustion and immune evasion in CRC. TSHR may be suitable as a predictive and therapeutic biomarker in CRC immunotherapy.

Effect of traditional Chinese medicine on Graves' disease: a network meta-analysis.

Introduction: Graves' disease (GD) is the most common cause of hyperthyroidism and can affect multiple systems of the body. Currently, commonly-used treatment methods for GD have a series of shortcomings. In contrast, traditional Chinese medicine has been proven to be effective in inhibiting the progression of GD and is expected to become a key direction for the development of new drugs in the future. Therefore, a network meta-analysis was performed to compare the impacts of different traditional Chinese medicines on the curative effect, thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroglobulin antibody (TGAb), thyroid peroxidase antibody (TPOAb) and thyrotropin receptor antibody (TRAb) in patients with GD. Methods: PubMed, Embase, Cochrane Library, Web of Science, WanFang, Weipu, and CNKI were searched for the randomized controlled trials of traditional Chinese medicine on GD patients up to 19 December 2023. The quality of the included studies was evaluated regarding the risk of bias, and the data were analyzed by R software. Results: Thirty-five articles were included in the analysis, involving 2828 GD patients and traditional Chinese medicines including Bailing Capsule, Jinshuibao Capsule, Astragalus injection, Jiakangling Tablet, Jiakangling Capsule, Tripterygium Wilfordii, Sanjie Xiaoying Decoction, Prunella vulgaris (L.) Oral Liquid, P. vulgaris (L.) Granules, Xiehuo Xiaoying Recipe, Xiehuo Yangyin Powder, Yikang Pill and Yinjia Pellet. The results of network meta-analysis suggested that for GD patients, Bailing Capsule, Jiakangling Capsule, Tripterygium wilfordii, P. vulgaris (L.) Oral Liquid and Yinjia Pellet had better curative effect compared with Western medicine. Prunella vulgaris (L.) Granules and Yikang Pill could improve the TSH level. Prunella vulgaris (L.) Granules, P. vulgaris (L.) Oral Liquid and Yikang Pill could reduce FT3 level. Jiakangling Capsule, P. vulgaris (L.) Granules, P. vulgaris (L.) Oral Liquid and Yikang Pill could reduce the FT4 level. Prunella vulgaris (L.) Oral Liquid can reduce the level of TPOAb and TRAb. Besides, Yinjia Pellet was the most helpful in improving the curative effect. Yikang Pill could best improve TSH. Prunella vulgaris (L.) Granules had the best effect on reducing FT3. Prunella vulgaris (L.) Granules performed best in reducing FT4. Prunella vulgaris (L.) Oral Liquid had the most favorable effect on reducing TPOAb and TRAb. Conclusion: Based on the current research, it is safe to conclude that Chinese medicine can improve the curative effect and TSH level of patients with GD, and reduce the levels of FT3, FT4, TPOAb and TRAb. Besides, Yinjia Pellet is the most helpful in improving the curative effect. Yikang Pill can best improve TSH. Prunella vulgaris (L.) Granules have the best effect on reducing FT3. Prunella vulgaris (L.) Granules perform best in reducing FT4. Prunella vulgaris (L.) Oral Liquid has the most favorable effect on reducing TPOAb and TRAb. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42024521912.