Thyroid T4 Research Articles

Thy and mighty: the importance of T3 thyroid hormone on dyadic structure and function in cardiac health and disease.

Thy and mighty: the importance of T3 thyroid hormone on dyadic structure and function in cardiac health and disease.

8398 Non-genomic Effects of Thyroid Hormones on the Breast Cancer Microenvironment

Abstract Disclosure: L. Drago: None. S. Shahrivari: None. N. Schwenk: None. P. Nelson: None. H. Hosseini: None. C. Spitzweg: None. Objective: Mesenchymal stem cells (MSCs) are central players in the genesis of the breast cancer tumor microenvironment and play a role in tumor initiation, progression, invasion, metastasis, angiogenesis as well as resistance to treatment. There is increasing evidence for an association between thyroid function and breast cancer risk. Thyroid hormone effects mediated through the αvβ3 integrin, a thyroid hormone receptor, are proposed as a pathophysiologic link to this observation. Methods: To evaluate the migratory behavior of MSCs in the presence or absence of thyroid hormone treatment in response to tumor-derived signals, a 3D migration assay was performed. MSCs pretreated with T3 (1nM) or T4 (1μM) with or without tetrac (100nM) (T4 analog, specific inhibitor of αvβ3 integrin-mediated thyroid hormone action) for 24 h were subjected to a gradient between serum-free medium and serum-free conditioned medium (CM) from five different breast cancer cell lines representative of different breast cancer subtypes including T47D as Luminal B, MCF7 as Luminal A, BT-474 and MDA-MB-453 as HER2, and MDA-MB-231 as Triple negative subtype. Results: MSCs subjected to a gradient between CM derived from each breast cancer cell line and serum-free medium showed directed chemotaxis towards tumor-CM with a significantly increased forward migration index (FMI) and center of mass (CoM). This migratory behavior was significantly enhanced upon treatment with T3 or T4. The cellular migration towards tumor-CM of MDA-MB-453, BT-474, and T47D was more effective upon MSC treatment with T3, but less so with T4. MSCs treated with T4 showed a better migratory performance towards the CM of MCF7 and MDA-MB-231. Except for T47D-CM, additional treatment with tetrac inhibited the enhanced effects of T3 and T4 on MSC migration demonstrating that this effect is mediated through αvβ3 integrin. Conclusion: Our preliminary in vitro data on the effects of thyroid hormones T3 and T4, and the thyroid hormone metabolite tetrac on MSC migration shows a distinct behaviour of MSCs in the presence of either T3 or T4 depending on the breast cancer cell subtype, suggesting a role of non-genomic, integrin αvβ3-mediated thyroid hormone action on MSC biology within the breast tumor microenvironment that warrants further investigation. Presentation: 6/3/2024

8398 Non-genomic Effects Of Thyroid Hormones On The Breast Cancer Microenvironment

Abstract Disclosure: L. Drago: None. S. Shahrivari: None. N. Schwenk: None. P. Nelson: None. H. Hosseini: None. C. Spitzweg: None. Objective: Mesenchymal stem cells (MSCs) are central players in the genesis of the breast cancer tumor microenvironment and play a role in tumor initiation, progression, invasion, metastasis, angiogenesis as well as resistance to treatment. There is increasing evidence for an association between thyroid function and breast cancer risk. Thyroid hormone effects mediated through the αvβ3 integrin, a thyroid hormone receptor, are proposed as a pathophysiologic link to this observation. Methods: To evaluate the migratory behavior of MSCs in the presence or absence of thyroid hormone treatment in response to tumor-derived signals, a 3D migration assay was performed. MSCs pretreated with T3 (1nM) or T4 (1μM) with or without tetrac (100nM) (T4 analog, specific inhibitor of αvβ3 integrin-mediated thyroid hormone action) for 24 h were subjected to a gradient between serum-free medium and serum-free conditioned medium (CM) from five different breast cancer cell lines representative of different breast cancer subtypes including T47D as Luminal B, MCF7 as Luminal A, BT-474 and MDA-MB-453 as HER2, and MDA-MB-231 as Triple negative subtype. Results: MSCs subjected to a gradient between CM derived from each breast cancer cell line and serum-free medium showed directed chemotaxis towards tumor-CM with a significantly increased forward migration index (FMI) and center of mass (CoM). This migratory behavior was significantly enhanced upon treatment with T3 or T4. The cellular migration towards tumor-CM of MDA-MB-453, BT-474, and T47D was more effective upon MSC treatment with T3, but less so with T4. MSCs treated with T4 showed a better migratory performance towards the CM of MCF7 and MDA-MB-231. Except for T47D-CM, additional treatment with tetrac inhibited the enhanced effects of T3 and T4 on MSC migration demonstrating that this effect is mediated through αvβ3 integrin. Conclusion: Our preliminary in vitro data on the effects of thyroid hormones T3 and T4, and the thyroid hormone metabolite tetrac on MSC migration shows a distinct behaviour of MSCs in the presence of either T3 or T4 depending on the breast cancer cell subtype, suggesting a role of non-genomic, integrin αvβ3-mediated thyroid hormone action on MSC biology within the breast tumor microenvironment that warrants further investigation. Presentation: 6/3/2024

B-114 Reference interval (RI) estimation for TSH in adults using an indirect method with unsupervised machine learning tool and R programming language

Abstract Background Thyroid-stimulating hormone (TSH) plays a fundamental role in regulating thyroid hormones T3 (triiodothyronine) and T4 (thyroxine). Understanding TSH test results is essential for effective management of thyroid disorders and depends, among other factors, on establishing specific reference intervals (RI) for the population being served. We aimed to estimate the reference intervals for TSH in the adult population served by a large diagnostic network in Brazil. Methods We employed data mining followed by estimation using an indirect method through the LabRI™ algorithm with parametric, non-parametric, and robust statistical treatments for outlier exclusion, a series of algorithms programmed in R Language. Included were TSH values from outpatients, aged 20 to 60 years, both sexes, from two analytical platforms. Used as a comparative RI recommended by the American Thyroid Association (ATA, 2014). Data were extracted from the Data Lake, from January to December 2022, from two laboratories in Brazil. Exclusion criteria: samples from hospital sources and referral laboratories; pregnant; some laboratory tests correlated with de TSH test; samples from patients using thyroid hormone and medications that may interfere with hormonal function and TSH laboratory analysis. Results After exclusion criteria, the sample totaled 26,909 adults of both sexes. After excluding 2.24% outliers, the estimated RI was 0.67-4.26 mIU/L, with the comparative RI chosen for this study being the one recommended by ATA of 0.40-4.00 mIU/L. The RI obtained in our study was similar to the Canadian RI harmonization study for TSH (0.60-4.48 mIU/L). Conclusions We estimated the RI, harmonized between Roche and Siemens platforms, to be 0.67-4.26 mIU/L. The RI obtained by the LabRI™ tool is equivalent to the Adeli study (2023) and is under discussion by the company's endocrinology committee for whether to use the estimated RI from our internal study or the one recommended by ATA (2014) in reports.

A Physiological Study of the Effect of Bee Pollen on Albino Rats Induced Hypothyroidism

The current study aimed to evaluate the therapeutic role of bee pollen (BP) in reducing the harmful effects resulting from hypothyroidism compared to the drug thyroxine on some physiological indicators and improving their levels, which included weight gain (gm), hormone level (T3, T4, TSH), level TPO, cholesterol levels, HDL, LDL, VLDL, and liver enzymes ALT, AST, Hypothyroidism was induced in (24) male rats using the drug carbimazole (CBZ) Which lasted for (15) days at 30 mg/kg of body weight. A random sample was chosen to confirm the occurrence of hypothyroidism, as the results of examining blood samples that were drawn from the animals showed a high concentration of the TSH hormone and Low concentrations of thyroid hormones in the serum compared to the negative control., and this indicates the occurrence of hypothyroidism. Then the animals in which hypothyroidism was induced were separated into 3 experimental collections in addition to the control group and a fifth group. Each group consists of (8) animals. The dosing period lasted thirty days orally. The negative control group, G1, was provided with a diet and water freely. G2 was continued to be dosed with the drug (CBZ) at a concentration of 30 mg/kg of body weight. G3 was continued to be dosed with the drug (CBZ) at a concentration of 30 mg/kg and solution (BP). At a concentration of 200 mg/kg body weight, G4 was dosed with levothyroxine at a concentration of 20 mg/kg body weight, while G5 was dosed with BP solution only at a concentration of 200 mg/kg body weight. At the end of the experiment, the animals were sacrificed and blood samples were obtained. The results were less than 0.05 in group G2 in body weight, the concentration of thyroid hormones T3 and T4, and the concentration of TPO and HDL, and a significant increase (P<0.05) in the concentration of TSH, Cholesterol, LDL, and VLDL, respectively, with an increase in the concentration of liver enzymes. AST and ALT compared to the control group. As for the G3 and G4 groups, the result appeared an original increase a total body weight and the concentration of the hormones T3, T4, and the TPO enzyme, a noticeable improvement in the lipid profile, and a low level of the ALT enzyme and the and thyroid-stimulating hormone compared to the G2 group. As for the group G5 has witnessed an increase in T4 concentration and a decrease in ALT concentration and body weight, and the concentrations of T3, TSH, and TPO are closer to control. We conclude from the current study that BP has a role in reducing the effects of hypothyroidism, increasing weight gain, and improving the lipid profile and the level of ALT liver enzymes. AST and Thyroid peroxidase (TPO) level.

Characterization of a human thyroid microtissue model for testing thyroid disrupting chemicals.

Perturbation of thyroid hormone (T4) synthesis is known to cause numerous developmental, metabolic, and cognitive disorders in humans. Due to species differences in sensitivity to chemical exposures, there is a need for human-based in vitro approaches that recapitulate thyroid cellular architecture and T4 production when screening. To address these limitations, primary human thyrocytes, isolated from healthy adult donor tissues and cryopreserved at passage one (p'1) were characterized for cellular composition, 3D follicular architecture, and thyroglobulin (TG)/T4 expression and inhibition by prototype thyroid disrupting chemicals (TDC). Flow analysis of the post-thaw cell suspension showed >80% EpCAM-positive cells with 10%-50% CD90-positive cells. When seeded onto 96-well Matrigel®-coated plates and treated with bovine thyroid stimulating hormone (TSH), thyrocytes formed 3D microtissues during the initial 4-5 days of culture. The microtissues exhibited a stable morphology and size over a 14-day culture period. TG and T4 production were highest in microtissues when the proportion of CD90-positive cells, seeding density and thyroid stimulating hormone concentrations were between 10%-30%, 6K-12Kcells per well, and 0.03-1 mIU/mL, respectively. At maximal TG and T4 production levels, average microtissue diameters ranged between 50 and 200µm. The T4 IC50 values for two prototype TPO inhibitors, 6-propyl-2-thiouracil and methimazole, were ∼0.7µM and ∼0.5 µM, respectively, in microtissue cultures treated between days 9 and 14. Overall, p'1 cryopreserved primary human thyrocytes in 3D microtissue culture represent a promising new model system to prioritize potential TDC acting directly on the thyroid as part of a weight-of-evidence hazard characterization.

Biochemical Study of Hypothyroidism Subjects and Relationship to Overweight

This article evaluates the relationship between thyroid hormone levels, including TSH, fT4, T4, T3, and lipid profiles, such as total cholesterol, LDL, and HDL, in obese individuals compared to healthy ones. The research included 80 individuals, of which 40 were categorized as obese (20 males and 20 females) and 40 were healthy controls (also 20 males and 20 females). All participants were between the ages of 25 and 45. To perform thyroid gland tests, blood samples of 10 ml were taken from both healthy and subjects participants without EDTA and put into test tubes. The plain tube containing blood was centrifuged to separate the serum for further thyroid function and chemical tests. The ELISA device was used following the manufacturer's instructions. The study found significant differences in the levels of TSH hormone between subjects and healthy participants based on the collected data. Furthermore, subjects had significantly lower levels of fT4 hormone in subjects (4.4±2.0) compared to healthy controls (8.1±2.1). The research findings indicated a significant reduction in T4 hormone levels (4.3±1.3) in subjects, which was consistent in both males and females and corresponded with the increase in TSH hormone levels (9.17±2.0) observed in subjects individuals compared to healthy subjects (2.98±2.1).However, there were no significant alterations in T3 hormone levels among subjects when compared to healthy individuals. Hence, the study concludes that there is a definitive correlation between hypothyroidism and obesity.

Impact of Metformin on Blood Levels of Thyroid Function Tests, and Some Biochemical Parameters Levels in Polycystic Ovarian Women

Polycystic ovary syndrome (PCOS) is the most common form of chronic female disease associated with androgen excess; perhaps occurring in 5-10% of the reproductive age group in women. PCOS is viewed as a heterogeneous disorder of multifactorial etiology. It is also associated with increased metabolic and cardiovascular risk factors. Objectives: The purpose of this study is to evaluate the serum level of hormones TSH, T3 and T4 in women with PCOS and to investigate the effect of metformin on hormones TSH, T3, and T4 levels in subjects with PCOS. Patients and methods: The present study was conducted at Kirkuk General Hospital and Azadi General Hospital from March 2023 to January 2024.One hundred forty-one women with PCOS were selected as the PCOS group, while 120 healthy women matched for age with the PCOS patients were selected as the control group. The body mass index is determined before and after therapy. They take metformin 850 mg twice daily for three months and provide fasting blood samples on the second day of menstruation before and after treatment. The data collection done through a designed closed and open-ended questionnaire, by using direct interviewing, and Ultrasound examination, Data were analyzed using SPSS for Windows 7. Results: Treatment resulted in a significant decrease in in body mass index at p-values 0.05. This study reveals that the thyroid hormones TSH, T3 and T4 were highly significantly increased (P < 0.001) in the serum of PCOS patients compared to the control group. Serum levels of TSH in women with PCOS were high significantly elevated compared to healthy control group. However, the study found no significant difference (p > 0.05) in TSH level in treated group with metformin compared with pre-treatment. Conclusion: Metformin can induce changes of TSH levels in patients with polycystic ovary syndrome.

Low TSH and low T3 hormone levels as a prognostic for mortality in COVID-19 intensive care patients.

Coronavirus diasease 2019 (COVID-19) can cause both pulmonary and systemic inflammation, potentially determining multi-organ dysfunction. The thyroid gland is a neuroendocrine organ that plays an important role in regulating immunity and metabolism. Low serum levels of thyroid hormones are common in critical disease situations. The association between low thyroid hormone levels and mortality in COVID-19 intensive care patients has yet to be studied. The aim of this study is to compare thyroid hormone levels between patients in the general intensive care unit (ICU) to patients in the COVID-19 ICU. This was a retrospective comparative study of 210 patients who were hospitalized at Ziv Medical Center in the general ICU and in the COVID-19 ICU. Clinical and demographic data were collected from patient's electronic medical records. Serum thyroid hormone levels of Thyroid Simulating Hormone (TSH), T4, and T3 were significantly lower in COVID-19 intensive care unit patients compared to the patients from the general intensive care unit (p < 0.05). The mortality rate in the COVID-19 ICU (44.4%) was higher compared to that in the general ICU (27.3%) (p < 0.05). No significant statistical difference was observed between the two groups in terms of gender and recorded comorbidities of diabetes mellitus, cerebral vascular accident, kidney disease, and cancer. Low serum thyroid hormone levels-T3, T4, and TSH-in COVID-19 ICU patients are associated with higher mortality and could possibly be used as a prognostic factor for mortality among COVID-19 ICU patients. Thyroid hormone levels should be a part in the routine evaluation of COVID-19 ICU patients.

Pretreatment Thyroid Profile and its Relationship with Response to Treatment with Lithium in Bipolar Mood Disorder: A Longitudinal Study from Northeast India

Abstract Background: The thyroid hormone’s significant impact on the treatment of depressive and other mood disorders is well documented. Even minor hypothyroidism can modify the progression and treatment results of major depressive disorder. This research aims to explore the correlation between initial thyroid levels and the treatment outcome in bipolar mood disorder using lithium, a well-established treatment method. Methodology: The study involved 45 bipolar mood disorder patients diagnosed according to the Diagnostic and Statistical Manual 5 criteria and admitted to a tertiary care teaching institute in Northeast India. The patients received lithium treatment, with injectable lorazepam used for immediate agitation control when necessary. On the 1st day, a semi-structured questionnaire and Brief Psychiatric Rating Scale (BPRS) 24-item scale were used to evaluate symptoms, and samples were collected for a thyroid profile, including T3, T4, FT3, FT4, and thyroid-stimulating hormone (TSH). The BPRS scale was used again on the 30th day to assess treatment response. Results: The BPRS subscale showed the highest treatment response for grandiosity and the lowest for depression. Factors such as age, illness duration, substance use, and family history of mood disorder were inversely correlated with the BPRS score’s decrease. Initial thyroid levels were identified as a predictor of treatment response, with baseline T4 levels showing a significant positive correlation with treatment response, while baseline TSH levels showed a negative correlation. Conclusion: Lithium proved to be an effective treatment for bipolar mood disorder, particularly for the manic subtype. Initial T4 and TSH levels were found to significantly predict treatment response, with T4 showing a positive correlation and TSH showing a negative correlation.

Combined effects of ammonia-N exposure and salinity changes on hematological and serum biochemical factors and thyroid hormones in Nile tilapia (Oreochromis niloticus)

The aim of this research was to evaluate the interaction effects of ammonia-N levels and salinity on hematological and serum biochemical parameters in Nile tilapia (Oreochromis niloticus). The fish were randomly divided into 12 treatments including the levels of salinity (0, 4, 8 and 12 ppt) and 0, 50% of LC50-96 h of ammonia-N and 30% of LC50-96 h of ammonia-N in a factorial design (4 salinity levels x 3 ammonia levels). Hemoglobin value in all treatments, except for salinity treatments, namely 2, 3, 4, showed a significant decrease than the control (0 ppt and no poisoning). Also, red blood cells in treatment ammonia-N levels were significantly less than the control. Serum protein concentration, in treatments 9 (50% of LC50-96 h of ammonia-N) and 5 and also with increasing salinity (treatments 2, 3 and 4) had a significant decrease compared to the control. There is a significant increase in serum glucose, cortisol, ammonia and urea levels in 50% and 30% of LC50-96 h of ammonia-N treatments compared to the control, meanwhile these parameters were significantly increased with increasing salinity. Serum thyroid stimulating hormone (TSH), T3 and T4 levels in acute and sub-acute ammonia-N treatments were significantly lower than the control. Moreover, with increasing salinity in 50% and 30% of LC50-96 h of ammonia-N treatments, TSH showed a decreasing pattern. According to the results, fluctuations in blood biochemical factors, increase of stress and decrease of thyroid hormones show that the salinity, ammonia, and their interaction caused adverse effects on fish health during the 96 h of testing.

Association between thyroid disorders and extra-thyroidal cancers, a review.

Thyroid hormone has been shown to have both tumor-promoting and tumor-suppressing actions, which has led to significant debate over its involvement in the development of cancer. Proliferation, apoptosis, invasiveness, and angiogenesis are all aspects of cancer that are affected by the thyroid hormones T3 and T4, according to research conducted in animal models and in vitro experiments. The effects of thyroid hormones on cancer cells are mediated by many non-genomic mechanisms, one of which involves the activation of the plasma membrane receptor integrin αvβ3. Typically, abnormal amounts of thyroid hormones are linked to a higher occurrence of cancer. Both benign and malignant thyroid disorders were found to be associated with an increased risk of extra-thyroidal malignancies, specifically colon, breast, prostate, melanoma, and lung cancers. The purpose of this review was to shed light on this link to define which types of cancer are sensitive to thyroid hormones and, as a result, are anticipated to respond favorably to treatment of the thyroid hormone axis.

Chronic Kidney Disease affects Thyroid Hormones

Kidney disease is one of the causes of death in many countries around the world. This study found that chronic kidney disease affects thyroid hormone formation, release, and storage. The results show a decrease in T3 and T4 thyroid hormones and an increase in TSH hormone in both sexes and people of different ages. The research aims to study the effect of chronic kidney disease on the thyroid gland’s activity and its deficiency’s effect on health ailments. Results showed a significant decrease in T3 concentration in patients at the probability level (p ≤ 0.05) (0.8±0.1) compared with the control group (1.0±0.1). Additionally, a significant decrease in T4 concentration at the probability level (p ≤ 0.05), (6.8±1.5) compared with the control group (8.7±0.9) and a significant increase in TSH concentration at the probability level (p ≤ 0.05), (4.8±0.6) compared with the control group (1.2±0.5). The CDK affects thyroid hormones; low T3 and T4 are the most common thyroid dysfunction. High TSH, enlarged thyroid gland, hypothyroidism, thyroid dysfunction. Keywords: CKD, Thyroid Hormones, Thyroid dysfunction.

A CLINICAL CASE STUDY OF HYPERTHYROIDISM AND ITS AYURVEDIC MANAGEMENT

Hyperthyroidism or thyrotoxicosis is a disorder of the thyroid gland resulting in hypersecretion of thyroid hormones, namely T3 and T4, that, in turn, result in the diminished secretion of thyroid-stimulating hormone. All these events lead to hyperactivation of metabolism and sympathetic nervous system, resulting in symptoms of increased body secretions, diarrhoea, palpitation, raised blood pressure, fatigue and intolerance to heat. Also, there are symptoms of increased appetite and weight loss and menstrual and erectile dysfunction. In Ayurveda, there is no concept of hormones. On an Ayurveda basis, body and disease are dosa, dhatu and mala, so after reviewing Ayurveda text, Hyperthyroidism seems to be aggravated Pitta-Vata disorder leading to teekshana agni (increased digestive fire) and ati- mala pravritti (frequent stools), ati sweda (excessive sweating), vishrata (smell of raw meat), alpa sukra (oligospermia), alpa putra (less progeny) etc. A 25-year-old female, already diagnosed with Hyperthyroidism, came to OPD of Kayachikitsa CBPACS. On evaluation, it seems that the patient has symptoms of aggregated Pitta Vata; with Ayurvedic medicine, the patient is completely cured and values of TSH raised from 0.030 µIU/ml to TSH- 4.01 µIU/ml within normal limits.

A Retrospective Study to Evaluate the Quality Assurance of Thyroid Profile In A Tertiary Care Clinical Biochemistry Laboratory

Background: The Six Sigma methodology has become a standard in quality assessment and management, widely adopted in various industries since the mid-1980s. This methodology is applicable wherever the outcome of a process needs measurement. One area where Sigma metrics find utility is in laboratory services, particularly in evaluating the quality assurance of biochemical parameters. Aims: This study aimed to measure and analyze the sigma metrics of thyroid hormones T3, T4, and TSH within the framework of NABL accreditation (National Accreditation Board for Testing and Calibration Laboratories). Materials &amp; Methods: The study was designed as a retrospective observational study, utilizing quality control data from the Clinical Biochemistry section spanning from January 2021 to December 2021 retrieved from laboratory records. The data considered included Bio-Rad Lyphochek Immunoassay Internal Quality Control (IQC) Control and Bio-Rad External Quality Assurance Scheme (EQAS) Immunoassay monthly program data. Calculations for Coefficient of variation (CV %), Bias %, and Total Error allowable (TEa) were made to derive the sigma metric. The formula used for sigma calculation was Sigma Σ(σ) = (TEa% - Bias%) / CV%, while the Quality Goal Index (QGI) ratio was determined using the formula QGI = Bias / 1.5CV. Results: The results categorized the assay performance based on sigma levels: &gt;6 denoted world-class performance, 5-6 indicated excellence, 4-5 represented good performance, 3-4 was deemed acceptable, and 2-3 signified poor performance. All analytes demonstrated sigma levels below 6 (2.61-5.85) varying from poor to excellent and the QGI was below 0.8, indicating a need to enhance the precision of assays. Conclusion: The Six Sigma metric analysis serves as a benchmark tool that can aid laboratories in enhancing assay performance, formulating protocols for Internal Quality Control (IQC), and evaluating existing laboratory procedures. Keywords Six sigma, Quality Goal Index, Internal Quality Control

The hypothalamic-pituitary-thyroid axis is intact in male insulin receptor substrate 4 knockout mice.

Loss of function mutations in the insulin receptor substrate 4 (IRS4) gene cause a rare form of X-linked congenital central hypothyroidism in boys and men. Affected individuals show decreased thyroid-stimulation hormone (TSH) secretion. Members of the IRS family canonically act as scaffold proteins between tyrosine kinase receptors and downstream effectors. How loss of IRS4 affects TSH synthesis or secretion is unresolved. We therefore assessed IRS4's role in the hypothalamic-pituitary-thyroid axis of Irs4 knockout mice. We generated two global Irs4 knockout mouse lines harboring either two or four base-pair deletions that result in frameshifts and loss of most of the IRS4 protein. Under normal laboratory conditions, Irs4 knockout males did not exhibit impairments in pituitary expression of TSH subunit genes (Tshb or Cga) or in the thyrotropin-releasing hormone (TRH) receptor. Additionally, their serum thyroid hormone, T3 (triiodothyronine) and T4 (thyroxine), and hypothalamic Trh expression levels were normal. When Irs4 knockouts were rendered hypothyroid with a low-iodine diet supplemented with propylthiouracil (PTU) for 3 weeks, their serum TSH increased similarly to wild-type males. Overall, Irs4 knockout mice do not exhibit central hypothyroidism or otherwise appear to phenocopy IRS4 deficient patients. Compensation by another IRS protein may explain euthyroidism in these animals.

Correlation of Thyroid Stimulating Hormone (TSH), T3, and T4 Hormones with Histopathological Characteristics of Thyroid Cancer at Cipto Mangunkusumo General Hospital

Introduction. In a study spanning 2008 to 2012 at Cipto Mangunkusumo General Hospital (CMGH) Jakarta, 668 cases of thyroid cancer were identified among 18,216 cancer cases. Globally, the papillary subtype is prevalent, and prior research indicates a link between thyroid hormone changes and thyroid carcinoma risk. To improve surgical care, this study aims to find the association between thyroid hormone levels and histological subtypes in thyroid carcinoma patients. Method. This cross-sectional study focused on thyroid cancer patients managed from 2013 to 2017. Despite subjects' characteristics, thyroid hormone levels and histopathological findings were the variables of interest. The findings were analyzed using ANOVA, Kruskal-Wallis, unpaired T-tests, Mann-Whitney tests, and Pearson or Spearman tests to find correlations with age, gender, clinical presentation, and body mass index. Results. The mean age was 48.7 years, with subjects having an average body weight of 64.5 kg, height of 154.4 cm, and BMI of 24.8 kg/m2. Hormonal analysis revealed mean T3 levels at 2.02 ng/mL, T4 levels were slightly lower at 1.92 ng/mL, and TSH levels were the lowest at 1.22 ng/mL. A very weak correlation existed between the T3 hormone and age (r = 0.05, p = 0.77). In the correlation between T4 thyroid hormone levels and age, a weak correlation was found between T4 thyroid hormone levels and age (r = 0.31, p = 0.08). In the correlation between thyroid cancer histopathology and gender, clinical presentation, and BMI, there was no significant association with gender, 𝑟s = 0,01; 95% 𝐵𝐶𝑎 [-3,37; 3.34]; p=0,94 Conclusion. This study indicates that the TSH, T3, and T4 hormone levels were not associated with the histopathological characteristics of thyroid cancer at CMGH. The T3, T4, and TSH hormone levels were unaffected by gender, nodule involvement, and age.

Role of Unani Medicine in Hyperthyroidism - A Case Report

Background: Hyperthyroidism is a clinical and biochemical state caused by elevated thyroid hormones T3 and T4 level in the blood. It is caused due to collection of various pathological state like Toxic Adenoma, Toxic multinodular goitre, and Graves’ disease (Diffuse toxic goitre) etc., To elaborate from the perspective of Unani system of Medicine, clinical presentation of hyperthyroidism resembles abnormal temperament of bile (Su i mizaj safrawi) or abnormal hot substantial temperament (Su i mizaj har māddi). Case presentation: The subject of the study was 37 years old male. He was diagnosed as a case of hyperthyroidism. Keeping the concept of Unani system of medicine, treatment was planned which included pharmacotherapy (Khamira Sandal sāda and Anushdaru Sada). Evaluation of the patient was done before and after treatment using a thyroid profile as a tool. There was significant improvement during entire period of treatment with the respect of his symptoms and thyroid profile. Conclusion: The effect of the drugs in bringing back the temperament and humours to its normal state in function. Khamira Sandal sāda and Anushdaru Sada is effective in bringing the thyroid profile to its normal state. This case report has also illustrated the importance of understanding how drugs bring about change in the body and discovering the benefits of medicine in treating contemporary labelled disorders. Keywords: Hyperthyroidism, Sue Mizaj, Unani system of medicine, case study

Anti-oxidant effects of herbal residue from Shengxuebao mixture on heat-stressed New Zealand rabbits

Heat stress can lead to hormonal imbalances, weakened immune system, increased metabolic pressure on the liver, and ultimately higher animal mortality rates. This not only seriously impairs the welfare status of animals, but also causes significant economic losses to the livestock industry. Due to its rich residual bioactive components and good safety characteristics, traditional Chinese medicine (TCM) residue is expected to become a high-quality feed additive with anti-oxidative stress alleviating function. This study focuses on the potential of Shengxuebao mixture herbal residue (SXBR) as an anti-heat stress feed additive. Through the UPLC (ultra performance liquid chromatography) technology, the average residue rate of main active ingredients from SXBR were found to be 25.39%. SXBR were then added into the basal diet of heat stressed New Zealand rabbits at the rates of 5% (SXBRl), 10% (SXBRm) and 20% (SXBRh). Heat stress significantly decreased the weight gain, as well as increased neck and ear temperature, drip loss in meat, inflammation and oxidative stress. Also, the hormone levels were disrupted, with a significant increase in serum levels of CA, COR and INS. After the consumption of SXBR in the basal diet for 3 weeks, the weight of New Zealand rabbits increased significantly, and the SXBRh group restored the redness value of the meat to a similar level as the control group. Furthermore, the serum levels T3 thyroid hormone in the SXBRh group and T4 thyroid hormone in the SXBRm group increased significantly, the SXBRh group showed a significant restoration in inflammation markers (IL-1β, IL-6, and TNF-α) and oxidative stress markers (total antioxidant capacity, HSP-70, MDA, and ROS) levels. Moreover, the real-time fluorescence quantitative PCR analysis found that, the expression levels of antioxidant genes such as Nrf2, HO-1, NQO1, and GPX1 were significantly upregulated in the SXBRh group, and the expression level of the Keap1 gene was significantly downregulated. Additionally, the SXBRm group showed significant upregulation in the expression levels of HO-1 and NQO1 genes. Western blot experiments further confirmed the up-regulation of Nrf2, Ho-1 and NQO1 proteins. This study provides a strategy for the utilization of SXBR and is of great significance for the green recycling of the TCM residues, improving the development of animal husbandry and animal welfare.

Dose Response, Dosimetric, and Metabolic Evaluations of Replacement PFAS Perfluoro-(2,5,8-trimethyl-3,6,9-trioxadodecanoic) Acid (HFPO-TeA).

Few studies are available on the environmental and toxicological effects of perfluoroalkyl ether carboxylic acids (PFECAs), such as GenX, which are replacing legacy PFAS in manufacturing processes. To collect initial data on the toxicity and toxicokinetics of a longer-chain PFECA, male and female Sprague Dawley rats were exposed to perfluoro-(2,5,8-trimethyl-3,6,9-trioxadodecanoic) acid (HFPO-TeA) by oral gavage for five days over multiple dose levels (0.3-335.2 mg/kg/day). Clinically, we observed mortality at doses >17 mg/kg/day and body weight changes at doses ≤17 mg/kg/day. For the 17 mg/kg/day dose level, T3 and T4 thyroid hormone concentrations were significantly decreased (p < 0.05) from controls and HFPO-TeA plasma concentrations were significantly different between sexes. Non-targeted analysis of plasma and in vitro hepatocyte assay extractions revealed the presence of another GenX oligomer, perfluoro-(2,5-dimethyl-3,6-dioxanonanoic) acid (HFPO-TA). In vitro to in vivo extrapolation (IVIVE) parameterized with in vitro toxicokinetic data predicted steady-state blood concentrations that were within seven-fold of those observed in the in vivo study, demonstrating reasonable predictivity. The evidence of thyroid hormone dysregulation, sex-based differences in clinical results and dosimetry, and IVIVE predictions presented here suggest that the replacement PFECA HFPO-TeA induces a complex and toxic exposure response in rodents.