T4 Hormone Research Articles

PTPN22 through the regulation of Th17/Treg balance acts as a potential target for the treatment of Graves' disease

Graves' disease (GD) is an autoimmune disease and the most common cause of hyperthyroidism. While the phosphotyrosine phosphatase non-receptor type 22 (PTPN22) variant is associated with GD susceptibility, its precise role and mechanism in GD remain unclear. To investigate this, we induced GD in mice using Ad-TSHR289 and isolated CD4+ T cells from spleen tissues. We conducted a series of experiments, including hematoxylin-eosin staining, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, flow cytometry, immunofluorescence (IF), reverse transcription quantitative PCR (RT-qPCR), and western blotting. PTPN22 expression was found to be downregulated in GD mice. Overexpression of PTPN22 ameliorated pathological damage and increased serum levels of T4 and thyroid stimulating hormone receptor antibody (TRAb), as well as the ratio of thyroid weight to body weight in GD mice. Furthermore, GD mice exhibited elevated levels of CD4+ and IL-17+ T cells, an increased Th17/Treg ratio, and upregulation of IL-17A mRNA expression. Conversely, there was a decrease in Foxp3+ T cells and transcriptional levels of Foxp3, which were reversed by PTPN22 overexpression. In vitro experiments showed that PTPN22 overexpression in CD4+ T cells from spleen tissues of GD mice enhanced Foxp3 expression while reducing IL-17A expression. Mechanistically, PTPN22 overexpression led to decreased levels of phosphorylated Lck (p-Lck), Lck, phosphorylated Fyn (p-Fyn), Fyn, phosphorylated Zap70 (p-Zap70), and Zap70 in both in vivo and in vitro GD models. In summary, PTPN22 can alleviate thyroid dysfunction in GD by modulating Th17/Treg balance through the downregulation of the Lck/Zap70 signaling axis.

Effects of yeast culture on growth performance, immune function, antioxidant capacity and hormonal profile in Mongolian ram lambs.

As effective growth-promoters and immune-modulators, yeast fermented products have shown positive effects in ruminants. To explore the mechanisms of yeast culture promoting growth and regulating immunity, this study investigated the effects of yeast culture, and β-glucan as one of its main active ingredients, on the growth performance, immune function, antioxidant capacity and hormonal profile in Mongolian ram lambs. One hundred and five Mongolian ram lambs were randomly assigned to 3 groups, with 35 replicates in each group. The dietary treatments were: total mixed ration (TMR) as the control group, TMR supplemented with 50-70 g/kg yeast culture (YC) or 75 mg/kg β-glucan. The test period was 137 days. All the sheep were weighed and 6 serum samples were collected in each group on days 0, 30, 60, 90 and 130, respectively. The results showed that both YC and β-glucan could promote the growth performance with increased average daily gain and decreased feed to weight gain ratio. Moreover, these two feed additives facilitated the immune function by selectively increasing the serum levels of lysozyme, IgG, IgM, INF-γ, TNF-α and some interleukins (IL-1β, IL-2, IL-6 and IL-8); ameliorated the antioxidant capacity with higher total antioxidant capacity and enzyme activities of catalase and glutathione peroxidase; altered the metabolism-associated hormone levels with higher growth hormone and thyroid hormone T3 but lower cortisol and insulin. In conclusion, both YC and β-glucan could improve the growth performance, immune function and antioxidant capacity, and regulate the serum levels of metabolism-associated hormones, thus exerting effects of promoting growth and improving immune function. Therefore, YC could be considered as a suitable potential alternative strategy to antibiotics and be used as an animal feed additive. This article provides a theoretical basis for the clinical application of such yeast fermented preparations in mutton sheep husbandry.

Investigation of some fertility indicators in Iraqi women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a complex, heterogeneous, multigenic disorder in women of childbearing age with multiple consequences. The exact mechanism of PCOS is not yet fully understood; There are several factors have a role such as genetic, environmental, nutritional, metabolic and other interactions Therefore, the existing study designed to estimate the levels of some biochemical tests and the sex hormones that have a role in PCOS progress. 100 Iraqi women were agreed to participate in the current study, divided into two groups included 50 clinically diagnosed with PCOS women that compared with 50 healthy women without PCOS as a control group (CTRL). The results showed different significant differences of the studied parameters between the PCOS and the CTRL. There was a significant increased level of FBG, HbA1c, insulin resistant, TG and LDL in the PCOS group in comparison to the CTRL, while a significant decreased level of HDL was appeared in PCOS group in comparison to the CTRL. Regarding the results of sex hormones, there were significant increased levels of LH, FSH, testosterone, estradiol hormones in the PCOS group in comparison to the CTRL. In addition, the results of thyroid hormones appeared a significant increased level of T3 hormone in the PCOS group in comparison to the CTRL. Also, the results of leptin hormone showed a significant increased level in the PCOS group in comparison to the CTRL. In conclusion, there was a significant relationship between FBG, HbA1c, insulin resistant, TG, LDL, HDL, LH, FSH and T3 parameters with PCOS.

Thyroid hormone T4 mitigates traumatic brain injury in mice by dynamically remodeling cell type specific genes, pathways, and networks in hippocampus and frontal cortex

The complex pathology of mild traumatic brain injury (mTBI) is a main contributor to the difficulties in achieving a successful therapeutic regimen. Thyroxine (T4) administration has been shown to prevent the cognitive impairments induced by mTBI in mice but the mechanism is poorly understood. To understand the underlying mechanism, we carried out a single cell transcriptomic study to investigate the spatiotemporal effects of T4 on individual cell types in the hippocampus and frontal cortex at three post-injury stages in a mouse model of mTBI. We found that T4 treatment altered the proportions and transcriptomes of numerous cell types across tissues and timepoints, particularly oligodendrocytes, astrocytes, and microglia, which are crucial for injury repair. T4 also reversed the expression of mTBI-affected genes such as Ttr, mt-Rnr2, Ggn12, Malat1, Gnaq, and Myo3a, as well as numerous pathways such as cell/energy/iron metabolism, immune response, nervous system, and cytoskeleton-related pathways. Cell-type specific network modeling revealed that T4 mitigated select mTBI-perturbed dynamic shifts in subnetworks related to cell cycle, stress response, and RNA processing in oligodendrocytes. Cross cell-type ligand-receptor networks revealed the roles of App, Hmgb1, Fn1, and Tnf in mTBI, with the latter two ligands having been previously identified as TBI network hubs. mTBI and/or T4 signature genes were enriched for human genome-wide association study (GWAS) candidate genes for cognitive, psychiatric and neurodegenerative disorders related to mTBI. Our systems-level single cell analysis elucidated the temporal and spatial dynamic reprogramming of cell-type specific genes, pathways, and networks, as well as cell-cell communications as the mechanisms through which T4 mitigates cognitive dysfunction induced by mTBI.

Physiological Impacts of Cauliflower in Hyperthyroid Rabbits

This study aimed to investigate the effect of cauliflower extract as a remedy for hyperthyroid in rabbits. Twenty rabbits with mean weight 1700 ±95 g and age of 6-7 months were chosen. The animals were randomly divided into four groups (five in each group). The first group (GI) was the control and received normal diet and given tap water. The second and third groups (GII & GIII) were received 30 μg/Kg BW sodium L-Thyroxin injected subcutaneously to induce hyperthyroidism for three weeks. After that, these groups (GII & GIII) were administrated 20 & 30 mg/kg of body weight cauliflower extract for four weeks. Blood samples were collected from hyperthyroid and treated groups after two and four weeks. Serum was centrifuged at 3000 rpm for 15 minutes. The collected serum was used in the assessment of the levels of thyroxine (T4), triiodothyronine (T3) and thyroid stimulating hormones (TSH) by analytical kits which determined on ELISA method. Further, a molecular study was performed to estimate TSHR gene expression. The results of the present work showed that there was a significant (p<0.05) decrease in T3 and T4 hormone levels means in rabbits treated with cauliflower extract as compared with hyperthyroid. It concluded from the present study that the natural products such as phenolic compounds, carotenoids, flavonoid, and ascorbic acid from cauliflower might be used as a remedy to recover from hyperthyroid states in order to reduce the intake of chemical drugs.

Impact of Some Natural and Artificial Sweeteners Consumption on Different Hormonal Levels and Inflammatory Cytokines in Male Rats: In Vivo and In Silico Studies.

Substituting sugar with noncaloric sweeteners prevents overweight and diabetes development. They come in two types: artificial, like aspartame and sucralose, and natural, such as sorbitol. This research aimed to assess the effects of sucrose and these sweeteners on nutritional parameters, hematological parameters, hormones, and anti- and pro-inflammatory cytokines in male rats. Thirty rats had been separated into five groups. The results showed the highest significant increase in body weight gain, total food intake, and feed efficiency noticed in the aspartame group followed by sucralose, sucrose, and sorbitol, respectively. In contrast to RBCs and platelets, all sweeteners significantly reduced the hemoglobin level, Hct %, and WBC count. The aspartame group showed the highest decline in glycoproteins, steroids, and T3, and T4 hormones and a dramatic elevation in thyroid stimulating hormone, eicosanoid, and amine hormones compared with the control group. A vigorous elevation in anti- and proinflammatory cytokine levels was observed in the aspartame group, followed by sucralose, sucrose, and sorbitol groups. Aspartame has the highest docking scores when studying the interactions of sweeteners and a target protein associated with hormones or cytokines using in silico molecular docking, with the best absorption, distribution, metabolism, elimination, and toxicity properties compared to the remaining sweeteners.

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.

Association of Vitamin D Levels and Handgrip Strength among Patients with Hypothyroidism: A Cross-sectional Study Design

Abstract Introduction: There is a notable association between hypothyroidism and reduced muscle function as well as compromised neuromuscular coordination. In this study, we aimed to investigate the potential link between Vitamin D and handgrip strength (HGS) in patients with hypothyroidism. Methods: The study involved 40 patients diagnosed with hypothyroidism and subclinical hypothyroidism while excluding individuals with hypothyroid medications, cardiovascular, pulmonary, renal, neurological, reproductive disorders, hand anomalies, Parkinson’s disease, and Vitamin D supplementation. They were evaluated for T3, T4, and thyroid-stimulating hormone (TSH) levels, HGS, and serum Vitamin D levels; triceps fold was measured using a Lange caliper, and a correlation between these variables was assessed. Results: The mean age of the study group was 39.95 ± 6.41 years, with the majority falling in the age group of 41–50 years. A female preponderance (70%) was observed among the study group. The mean value for Vitamin D and HGS was 14.69 ± 6.12 ng/ml and 19.65 ± 5.38 kg, respectively. The mean values for T3, T4, and TSH were 47.23 ± 14.56 ng/dl, 5.86 ± 2.12 μg/dl, and 18.28 ± 7.64 mIU/ml, respectively. A robust, significant positive correlation was found between HGS and Vitamin D (r = 0.42, P < 0.01). The correlation between body mass index (BMI) and Vitamin D was moderately positive but was not statistically significant (r = 0.26, P > 0.01). No significant correlation was observed between Vitamin D and T4, TSH, and triceps fold. A moderate negative correlation was observed for TSH and BMI but was insignificant (r = −0.27, P > 0.05). Conclusion: A strong, significant positive correlation was found between HGS and Vitamin D, while BMI showed moderate positive correlations. No significant correlation was found between Vitamin D, T4, TSH, or triceps fold.

Development of an animal model of hypothyroxinemia during pregnancy in Wistar rats

AbstractBackgroundHypothyroxinemia is a subclinical thyroid hormone deficiency in which the mother has inadequate levels of T4 during pregnancy. The fetus relies entirely on the mother's T4 hormone level for early neurodevelopment. Isolated maternal hypothyroxinemia (IMH) in the first trimester of pregnancy can lead to lower intelligence, lower motor scores, and a higher risk of mental illness in descendants. Here, we focus on the autism‐like behavior of IMH offspring.MethodsThe animals were administered 1 ppm of propylthiouracil (PTU) for 9 weeks. Then, the concentrations of T3, T4, and thyroid‐stimulating hormone (TSH) were detected using enzyme‐linked immunosorbent assay (ELISA) to verify the developed animal model of IMH. We performed four behavioral experiments, including the marble burying test, open‐field test, three‐chamber sociability test, and Morris water maze, to explore the autistic‐like behavior of 40‐day‐old offspring rats.ResultsThe ELISA test showed that the serum T3 and TSH concentrations in the model group were normal compared with the negative control group, whereas the T4 concentration decreased. In the behavioral experiments, the number of hidden marbles in the offspring of IMH increased significantly, the frequency of entering the central compartment decreased, and the social ratio decreased significantly.ConclusionThe animal model of IMH was developed by the administration of 1 ppm of PTU for 9 weeks, and there were autistic‐like behavior changes such as anxiety, weakened social ability, and repeated stereotyping in the IMH offspring by 40 days.

Sex-specific transgenerational effects on murine thyroid gland imposed by ancestral exposure to neonicotinoid thiacloprid

Neonicotinoids, a relatively new widely used class of insecticide is used in agriculture to control insect populations. We examined the capacity of ancestral exposure to the neonicotinoid thiacloprid (thia) to induce transgenerational effects on thyroid tissue. Pregnant outbred Swiss female mice were exposed to thia at embryonic days E6.5 to E15.5 using 0, 0.6, and 6 mg/kg/day doses. Thyroid paraffin sections were prepared for morphology analysis. We apply ELISA method to measure T4 and TSH levels, RT-qPCR for gene expression analysis, ChIP-qPCR techniques for sperm histone H3K4me3 analysis, and immunofluorescence microscopy and western blots for protein detection. We observed an alteration in the morphology of thyroids in both males and females in the F3 generation. We observed an increase in T4 hormone in F1 females and a significant T4 level decrease in F3 males. T4 changes in F1 females were associated with a TSH increase. We found that the amount of Iodothyronine Deiodinase 1 (DIO1) (an enzyme converting T4 to T3) was decreased in both F1 and F3 generations in female thyroids. GNAS protein which is important for thyroid function has increased in female thyroids. Gene expression analysis showed that the expression of genes encoding thyroid gland development, chromatin, biosynthesis and transport factors were affected in the thyroid gland in both sexes in F1 and F3. The analysis of sperm histone H3K4me3 showed that H3K4me3 occupancy at the Dio1 locus has decreased while Thyroglobulin (Tg) and Matrix Metallopeptidase 2 (Mmp2) genes have increased H3K4me3 occupancy in the sperm of F3 mice. Besides, DNA methylation analysis of our previously published datasets showed that, in the sperm of F1 and F3 thia-derived mice, several genes related to thyroid function show consistent alterations. Our data suggest that ancestral exposure to thiacloprid affects thyroid function not only in exposed but also in indirectly exposed F3 generation.

Biotechnological methods for improving reproduction on sheep breeding program using laparoscopic artificial inseminations in Debrecen, Hungary

The aim of this study was to evaluate the results of the LAI method in different types of breeds and seasonal variations. Analysing n=536 LAI in 7 years, there were no significant differences observed in the breed in lambing rates. Although the lambing rate of Prolific Merino (F+) was better than any other breed (45.3%). We found significant differences between breeds of Tzigaia, its pregnancy rate was 19.2%. In the case of prolificacy there were significant differences between breeds: Prolific Merino’s (FF) was the highest (2.38) and, Indigenous Tzigaia’s was the lowest (1.4) from all of them. The obtained results showed that summer inseminations were the most effective in concern of pregnancy rate (49.5%). The results are based on use of the types of semen, showed that using frozen semen was most effective than fresh semen in both parameters, however there were no significant differences. Summarising all tested conditions in our study breeds, seasons and type of semen using LAI the total results of pregnancy rate was 40.3% and the prolificacy was 1.78, respectively. Follow up the out-of-season ovarian, progesterone level of n=36 Prolific Merino were examined and insulin, IGF-1, leptin, T3, and T4 hormones as well, to evaluate the energetic status of the flock. Progesterone analysis showed 43% of examined ewes had a cyclical ovarian function in April and a cyclical ones had good reaction for estrus-induction hormonal treatment. Our results showed that valuable information can be obtained about energy supply from the determination of some metabolic hormones as IGF-1, insulin, leptin.

The potential impact of oil pollution on Thyroid and Parathyroid Hormones in directly exposed workers in Al-Shaiba oil refinery

Thyroid hormones are essential for growth, neuronal development, reproduction and regulation of energy metabolism. Hypothyroidism and hyperthyroidism are common conditions with potentially devastating health consequences that affect all populations worldwide. This study aimed to evaluate the effects of exposure to petroleum gases, vapors and pollutant materials on oil refinery workers in Al-Shaiba / Basra-Iraq. However, samples were collected from male workers Ages from (22 – 55) years and divided into four groups according to their years of experience in the same refinery and compared with healthy control. We highlight It also showed that T4, TSH, and PTH hormone more effected by the heavy metals than T3 hormone in comparison to the healthy control group. It showed that worker with direct exposure of pollution sources for more than 5 years of exposure is more affected with oil refinery pollutant than workers who only exposed for 1-5 years.

THE ROLE OF THYROID & PARATHYROID HORMONES IN PROSTHODONTIC TREATMENT- A NARRATIVE REVIEW

Thyroid and parathyroid hormones play an important role in maintaining bone metabolism, which can have a direct effect on the health and stability of residual ridges, especially in edentulous patients. Preservation of residual ridges is critical to the success of dental prostheses such as dentures. Thyroid Hormones Thyroid is the major regulation of metabolism and effects all the bodily functions. Pituitary gland stimulated the thyroid to produce the hormones T4 – Thyroxine ; T3 – Tri iodothyrone and calcitonin. Thyroxine (T4) and Triiodothyronine (T3) hormones are important regulators of metabolism and influence the turnover of bone tissue by affecting the activity of osteoblasts and osteoclasts. a). Activation of osteoblasts: In particular, T3 increases the activity of osteoblasts, the cells responsible for bone formation. This can lead to an increase in bone density and strength, which is necessary to maintain the structure of the residual ridges. (b). Bone Resorption: Excessive levels of thyroid hormones (hyperthyroidism) can increase osteoclast activity, leading to accelerated bone resorption and possible bone loss, which can negatively affect residual ridges.[1]

Thyroid status in patients with early stages of cancer of various localization

Purpose of the study. To determine the thyroid status of primary cancer patients in the early stages of uterine body cancer, kidney cancer, breast cancer, skin melanoma and lung cancer without a history of endocrine pathology.Patients and methods. The content levels of thyroid-stimulating hormone (TSH), thyroid hormones (THs) T4 and T3 of total and free forms were determined in the blood serum by RIA method in 132 patients with breast cancer, uterine body cancer, lung cancer, kidney cancer and skin melanoma (average age 55 years). The comparison group consisted of practically healthy donors.Results. Only in skin melanoma, serum TSH levels were reduced by 1.5 times (p < 0.05). The T4 content was reduced by 1.4–1.7 times (p < 0.05) in uterine body cancer and kidney cancer, increased in lung cancer patients and 16 % of breast cancer patients by 1.4–1.7 times though (p < 0.05). A 1.3–1.5‑fold low (p < 0.05) T3 level was found in breast cancer, kidney cancer, and skin melanoma, while an 1.6‑fold increase (p < 0.05) was found in uterine body cancer. The revealed changes in THs by the type of clinical hyperthyroidism are an increase of 1.8 times (p < 0.05) FT3 on the background of low TSH in the blood in patients with skin melanoma, and by the type of hyperthyroxinemia in patients with lung cancer and breast cancer, consisting in increased concentrations of T4 and FT3, and with free and total T3 levels in patients uterine body cancer, as well as FT4, without changes in TSH in the blood serum of patients, may be associated with the features of malignant pathology, since it is known that THs are proliferation stimulants and can build up in tumors.Conclusion. The development of a malignant tumor even in the early stages of the disease is perceived by the body as a threat for homeostasis and the response to the occurrence of neoplasm is the reaction of the hypothalamicpituitary-thyroid regulatory axis. As an outcome, patients develop euthyroid disorder syndrome.

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.

A practical gestational age-based algorithm for timely detection of hypothyroidism in premature infants.

To assess utility and accuracy of a gestational age-based screening targeting premature infants to detect congenital hypothyroidism. A prospective cohort study was conducted in infants <35 weeks' gestational age with clinical outcomes at 2-3 years of age. Patients received newborn screenings at 24 hours and 10-14 days of life. Free T4 (FT4) and thyroid-stimulating hormone (TSH) levels were measured at one month of life and repeated based on algorithm by corrected gestational age. Among infants <35 weeks gestation (n = 938), the incidence of hypothyroidism requiring treatment was 1:58. TSH levels at one month of age was predictive of treatment (AUC 0.96, 95% CI 0.88-1). The optimal TSH threshold of 8 mIU/L (8 µU/ml) increased the specificity to 0.97 and sensitivity to 0.88. Following initiation of treatment forhypothyroidism during NICU hospitalization,43.8% (n = 7) were diagnosed with permanent congenital hypothyroidism. Our study supports a gestational age-based screening algorithm for early detection of hypothyroidism in premature infants.

Phase II Clinical Trial of Intravenous Levothyroxine to Mitigate Pharyngocutaneous Fistula in Euthyroid Patients Undergoing Salvage Laryngectomy.

Patients undergoing head and neck cancer surgery after prior radiation or chemoradiation are at high risk for wound complications. Hypothyroidism is a known risk factor for wound complications, especially fistulae after salvage total laryngectomy. The purpose of this phase II clinical trial is to investigate the effect of perioperative intravenous levothyroxine supplementation on wound complications in patients undergoing salvage total laryngectomy. Euthyroid patients previously treated with radiation/chemoradiation undergoing total laryngectomy were prospectively recruited (n = 72). Postoperatively, intravenous levothyroxine was administered at a weight-based dose (1.3 mcg/kg/d) and transitioned to enteral dosing on day 7. Free T3, T4, and thyroid-stimulating hormones were collected, and dosing was adjusted accordingly. The primary endpoints were rates of fistula formation and fistula requiring reoperation, compared with matched historic controls. All patients were monitored for adverse effects. The rate of postoperative hypothyroidism was 21% compared with 49% in a matched historic cohort. The rate of fistula formation was 18.1%, whereas the rate of fistula requiring reoperation was 4.2%, significantly lower than rates in our historic cohort (34.6% and 14.8%, respectively; P = 0.02 and 0.01). Postoperative hypothyroidism and recurrent clinical stage predicted fistula requiring reoperation in multivariate analysis; other acute phase reactants were not predictive. There were no observed adverse events related to levothyroxine supplementation. Postoperative intravenous levothyroxine supplementation reduced rates of acute hypothyroidism, fistula formation, and fistula requiring reoperation in patients undergoing salvage total laryngectomy without adverse effects. Intravenous levothyroxine is a viable strategy to reduce wound complications in this high-risk patient population.

A Prospective Randomized Controlled Clinical Study to Investigate the Efficacy and Safety of Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitors in Non-Dialysis Patients with Chronic Heart Failure and Renal Anemia Switched from Continuous Erythropoietin Receptor Activator Treatment.

Background/Objectives: Chronic kidney disease (CKD) and anemia are independent prognostic factors for heart failure. In recent years, hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitors have become available for the treatment of renal anemia. This prospective randomized controlled study aimed to investigate the effects of switching from a continuous erythropoietin receptor activator (CERA) to one of four HIF-PH inhibitors in patients with chronic heart failure and renal anemia. Methods: Forty patients were randomized by the envelop method to receive treatment with roxadustat, daprodustat, vadadustat, or molidustat. The primary endpoint was the change in the hemoglobin (Hb) level. Secondary endpoints included changes in erythropoietin, changes in free T3, free T4, and thyroid-stimulating hormone (TSH), adverse effects, and drug dose increases and decreases. This study was preregistered in the University Hospital Medical Information Network Clinical Trials Registry (study ID: UMIN000041651). Results: We found no statistically significant difference between Hb levels with HIF-PH inhibitors and CERA, but at month 6, the Hb level was significantly higher with roxadustat than with vadadustat and daprodustat. Erythropoietin decreased significantly after switching to HIF-PH inhibitors. HIF-PH inhibitors had various significant effects on free T3, free T4, and TSH. No adverse events occurred. The doses of some drugs had to be increased or decreased. Conclusions: In patients with heart failure and renal anemia receiving CERA, Hb, NT-ProBNP, and renal function were similar after switching from CERA to HIF-PH inhibitors. The individual HIF-PH inhibitors appear to have different effects on anemia and thyroid function. However, because this was a single-center study with a limited sample size, the efficacy and potential limitations of HIF-PH inhibitors need to be further clarified.

Impact of the thyroid hormone T3 and its nuclear receptor TRα1 on colon cancer stem cell phenotypes and response to chemotherapies

Colorectal cancers (CRCs) are highly heterogeneous and show a hierarchical organization, with cancer stem cells (CSCs) responsible for tumor development, maintenance, and drug resistance. Our previous studies showed the importance of thyroid hormone-dependent signaling on intestinal tumor development and progression through action on stem cells. These results have a translational value, given that the thyroid hormone nuclear receptor TRα1 is upregulated in human CRCs, including in the molecular subtypes associated with CSC features. We used an established spheroid model generated from the human colon adenocarcinoma cell line Caco2 to study the effects of T3 and TRα1 on spheroid formation, growth, and response to conventional chemotherapies. Our results show that T3 treatment and/or increased TRα1 expression in spheroids impaired the response to FOLFIRI and conferred a survival advantage. This was achieved by stimulating drug detoxification pathways and increasing ALDH1A1-expressing cells, including CSCs, within spheroids. These results suggest that clinical evaluation of the thyroid axis and assessing TRα1 levels in CRCs could help to select optimal therapeutic regimens for patients with CRC.Proposed mechanism of action of T3/TRα1 in colon cancer spheroids. In the control condition, TRα1 participates in maintaining homeostatic cell conditions. The presence of T3 in the culture medium activates TRα1 action on target genes, including the drug efflux pumps ABCG2 and ABCB1. In the case of chemotherapy FOLFIRI, the increased expression of ABC transcripts and proteins induced by T3 treatment is responsible for the augmented efflux of 5-FU and Irinotecan from the cancer cells. Taken together, these mechanisms contribute to the decreased efficacy of the chemotherapy and allow cells to escape the treatment. Created with BioRender.com.

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.