Serum T4 Research Articles

Peripubertal exposure to oxyfluorfen, a diphenyl herbicide, delays pubertal development in the male rat by antagonizing androgen receptor activity.

We recently identified the herbicide oxyfluorfen as an inhibitor of iodide uptake by the sodium iodide symporter (NIS), a key step in thyroid hormone synthesis, using in vitro assays. We also observed a suppression of serum T4 and T3 in juvenile rats exposed orally to oxyfluorfen for 4-8 days. The purpose of the present study was to further evaluate effects of an extended 31-day oral exposure using a male pubertal rat study (15 to 500 mg/kg). Oxyfluorfen delayed puberty at all doses (1.3 -3.5 days) suppressing ventral prostate at 62.5 mg/kg and above and seminal vesicle weights at 31.25 mg/kg and above with no effect on testosterone or luteinizing hormone. Serum T4 and T3 were suppressed by all doses up to 80%, with a linear increase in serum TSH. Based on delayed puberty without changes in testosterone, we hypothesized that oxyfluorfen interferes with androgen receptor (AR) function. Results from our Hershberger study, with oxyfluorfen (62.5 and 125 mg/kg) co-treated with testosterone proprionate (TP , 1 mg/kg) for 10 days showed 3 of 5 of the androgenic tissue weights were suppressed compared to TP alone indicating AR antagonism. We next confirmed this effect in an in vitro AR transcriptional activation reporter assay (0-20 μM) with 125 pM 5αDH-11-ketotestosterone and found concentration-dependent inhibition of AR luminescence activity (EC50 1.75 µM) without cytotoxicity. Here, we confirmed the endocrine disrupting effects of oxyfluorfen using both in vitro and in vivo evaluations of the thyroid hormone and AR pathways. This abstract doesn't necessarily reflect U.S. EPA policy.

Study Of Calcium Magnesium And Phosphorus In Hypothyroidism - A Case Control Study

Background: Thyroid disorders are the most common endocrine abnormality in the world secondary to diabetes mellitus. Thyroid hormones are essential for growth, neuronal development, reproduction and regulation of energy metabolism. It influences the metabolism of all substrates including minerals. Many studies have shown that mineral metabolism is frequently disturbed in thyroid disorders. Materials and Methods: The study was conducted on sixty newly confirmed hypothyroid cases based on the thyroid profile and sixty euthyroid cases were recruited as controls. Blood samples were collected from all the patients for the estimation of serum T3, T4, FT3, FT4, TSH, calcium, phosphorus and magnesium by auto analyzer method. Modified spectrophotometric micro-method was used to measure Serum copper using Bathocuprine Disulphonate Disodium Salt (BCDS) and Guanidine hydrochloride salt. The Statistical software namely SPSS 18.0, and R environment ver.3.2.2 were used for the analysis of the data. Results: It was found that the levels of serum sodium, potassium and calcium were significantly decreased in cases than the controls. Serum magnesium and phosphorus were significantly elevated in cases than controls. Conclusion: Serum calcium, magnesium and phosphorous levels are significantly altered in patients having hypothyroidism. Thyroid diseases have wide spread systemic manifestations including their effects on bone and mineral metabolism. Also thyroid hormone affects the glomerular filtration rate, renal blood flow, tubular reabsorption and excretion of minerals which have direct effect on Calcium, Magnesium and phosphorous level. Thus monitoring of these minerals in hypothyroid patient will be of great benefit in improving clinical manifestation and can be treated appropriately

Towards a treatment for thyroid hormone transporter MCT8 deficiency: achievements and challenges.

Patients with an inactive thyroid hormone (TH) transporter MCT8 (Allan-Herndon-Dudley Syndrome, AHDS) display severe neurological impairments and motor disabilities indicating an indispensable function of MCT8 in facilitating TH access to the human brain. As a consequence, the CNS of AHDS patients appears to be in a TH deficient state which greatly compromises proper neural development and function. As another hallmark of this disease, patients exhibit elevated serum T3 levels leading to a hyperthyroid situation in peripheral tissues. Several treatment strategies have been developed and evaluated in preclinical mouse models as well as in patients. Here, we discuss these different therapeutic approaches to overcome MCT8 deficiency and summarize the current achievements and challenges in improving brain maturation in the absence of MCT8.

Reproductive and developmental toxicity of α-terpineol in Wistar rats

Alpha-terpineol (α-T) is a type of monoterpenoid alcohol commonly present in essential oils, it contributes to a pleasant floral fragrance similar to that of lilacs. This research aimed to evaluate the impact of α-terpineol on the reproductive functions of both male and female rats, including gonadal activity, mating behavior, conception, conceptus development and parturition. Six male and female Wistar rats per group received α-terpineol through gavage at doses of 0, 75, 150 and 300 mg/kg/day. The study revealed changes in body weight gain inhibition, food consumption, azoospermia, decreased testosterone levels (0.7 ± 1.61 ng/mL, 0.7 ± 2.30 ng/mL) as well as histopathological variations in testis and epididymis among males exposed to doses of 150 and 300 mg/kg/day. Moreover, this exposure led to significantly decreased serum T4 levels in both adult males (21.85 ± 12.68 ng/mL, 16.20 ± 9.15 ng/mL) and dams (11.24 ± 12.37 ng/mL, 9.48 ± 11.74 ng/mL) at the dose range of 150 and 300 mg/kg/day without affecting TSH concentrations. In summary, the present study showed that α-terpineol induced reproductive toxicities in male rats. Therefore, a detailed toxicological assessment is highly recommended.

8500 Fvb/Ant Mice Carrying the Thr92Ala-Dio2 Polymorphism Have a Goiter

Abstract Disclosure: A. Batistuzzo: None. B. Bocco: None. E. McAninch: None. M.O. Ribeiro: None. A.C. Bianco: Consulting Fee; Self; Abbvie. Fvb/Ant Mice Carrying the Thr92Ala-Dio2 Polymorphism Have a Goiter Introduction: The Thr92Ala-DIO2 polymorphism is prevalent worldwide, with about 50% of the population carrying at least one polymorphic allele. Ala-D2 is ectopically located in the Golgi apparatus and causes endoplasmic reticulum (ER) stress. It is also about 40 % less active than Thr92-D2, thus T3 production could be compromised in carriers of the polymorphism. Objective: C57BL/6J (B6) mice carrying the Ala92-DIO2 polymorphism exhibit no significant thyroid phenotype as compared to control Thr92-Dio2 mice. Here we wished to test whether changing the genetic background of mice can influence the thyroidal impact of the Thr92Ala-DIO2 polymorphism. Therefore, we backcrossed B6-Thr92Ala-Dio2 mice to the FVB/Ant background for 8 generations. Methods: Mice were killed by asphyxiation in a CO2 chamber and blood collected from 7-18 weeks old female and male FVB/Ant Ala-Dio2 mice to measure plasma levels of TSH, T4, T3, and rT3. The thyroid gland was dissected, weighed and processed for histological analysis. The weight of the thyroid gland was normalized by femoral length. The QuPath Software was used for measuring follicular area, cell height, and the number of internalized follicular cells. Thr92-Dio2 mice of the same age and sex were used as controls. Data were analyzed using PRISM software and expressed as mean±SE (TH plasma levels and thyroid weight) or mean±SD (thyroid histology). A Student t-test was used to compare 2 groups. Results: Male and female Ala mice had significantly higher levels of TSH (males: 0.36±0.04 vs 1.1±0.21 ng/ml; p<0.01 and females: 0.017±0.006 vs 0.12±0.06 ng/ml; p<0.01), lower levels of plasmatic T4 (males: 2.9±0.2 vs 1.3±0.25 µg/dl; p<0.01 and females: 2.1±0.16 vs 1.15±0.16 µg/dl; p<0.001) and lower levels of rT3 (males: 23.8±2 vs 14.2±1.3 ng/dl; p<0.001 and females: 16.45±1.4 vs 10.4±1.17 ng/dl; p<0.01). Additionally, the thyroid gland of female polymorphic mice was heavier (4.3±0.39 vs 1.8±0.17 mg/cm; p<0.001) and both sexes presented enlarged thyroid follicle area (males: 1464±1464 vs 2055±2443 µm2; p<0.0001 and females: 1519±1364 vs 2597±2624 µm2; p<0.0001) and a higher number of internalized follicular cells (females: 0.06±0.007 vs 0.17±0.008 internalized cells/follicle; p<0.0001). No differences in the follicular cell height were observed. Discussion: In contrast to B6, FVB mice carrying the Thr92Ala-D2 polymorphism exhibit goiter, increased follicular area, slightly reduced serum T4 levels, and elevated serum TSH levels. These findings suggest that the impact of the Thr92Ala polymorphism varies according to the genetic background. They may explain why clinical studies of patients carrying the Thr92Ala-DIO2 polymorphism have yielded inconsistent results when different populations are analyzed. Presentation: 6/3/2024

STAT6 blockade ameliorates thyroid function in Graves' disease via downregulation of the sodium/iodide symporter.

Signal transducer and activator of transcription 6 (STAT6) is an important nuclear transcription factor. Previous study demonstrated that blockading STAT6 can ameliorate thyroid function by reducing serum T3 and T4. Sodium/iodide symporter (NIS) is a key protein that mediates active iodine uptake and plays an important role in regulating thyroid function. This study explored the interaction between STAT6 and NIS. Immunohistochemical staining was performed for detecting the expression of NIS in different tissues. Reverse transcription-polymerase chain reaction (RT-PCR) was performed for evaluating the mRNA level of NIS when Nthy-ori 3-1cells were incubated with IL4, TSH (Thyroid stimulating hormone) or monoclonal TSAb (thyroid-specific stimulatory autoantibody) for 24h. Quantitative RT-PCR,Western blot and immunofluorescence analysis were performed for detecting NIS expression after inhibiting STAT6 phosphorylation by AS1517499. Finally, we used Luciferase reporter assays to explore the ability of STAT6 to regulate the promoter activity of the NIS-coding gene. NIS was highly expressed in thyroid epithelial cells of EAGD mice or Graves' disease (GD) patients and TSAb increased the expression of NIS. We show that STAT6 phosphorylation inhibitor can attenuate the effect of TSAb on increasing NIS protein and mRNA levels. Finally, we confirm that transcription factor STAT6 can mediate NIS transcription and co-activator P100 protein can enhance STAT6-dependent transcriptional activation. In Graves' disease, TSAb induces STAT6 signaling to upregulate NIS expression and STAT6 blockade ameliorates thyroid function via downregulation of the sodium/iodide symporter. Our study furthers understanding of the effects of STAT6 on thyroid function and reveals new avenues for GD treatment.

Low T3 Syndrome is Associated with Imbalance of Bone Turnover Biomarker in Patients with Type 2 Diabetes.

To investigate the variation in bone turnover biomarkers among patients with type 2 diabetes (T2D) and low triiodothyronine levels (Low T3 syndrome). This retrospective analytic study included 418 inpatient records from Shanghai Pudong Hospital covering the years 2021 to 2023. Laboratory data related to metabolic and bone turnover biomarkers in patients were analyzed with T2D and the low T3 syndrome. The results indicated that patients with reduced serum T3 levels exhibited statistically significant variations in thyroid function, age, fasting plasma glucose (FPG), glycated hemoglobin A1c (HbA1c), and the proportion of medication history associated with diabetes in comparison to euthyroid patients. In addition to parathyroid hormones, bone turnover biomarkers including N-terminal middle molecular fragment of osteocalcin (NMID), plasma calcium (Ca2+), β C-terminal cross-linking telopeptide of type 1 collagen (β-CTX), and 25-hydroxyvitamin D3 (25 OH VitD3) exhibited significant changes in patients with decreased T3 levels. Evident irregularities were observed in patients with a decreased T3 level, including elevated serum creatinine (SCr), decreased concentrations of albumin and total protein, and a decreased estimated glomerular filtration rate (eGFR), as assessed through hepatic and renal testing, respectively. Significant associations between bone turnover biomarkers and the subsequent variables (gender, adiposity, hepatic, renal, and thyroid function) were revealed through the correlational analysis. Further investigation utilized multivariate linear regression to determine that, in addition to thyroid function, several other factors such as age, gender, bodyweight, pancreatic, hepatic, and renal function, affected the variability in bone turnover biomarkers among patients demonstrating a low serum T3 level. This comparative study demonstrated that despite age, gender, bodyweight, hepatic, renal function, thyroid hormone and pancreatic function were significant factors associated with bone metabolism in patients with T2D and Low T3 syndrome, which may increase the risk of osteoporosis.

Comparative Analysis of Oxidative Metabolism in Liver in Different Experimental Models of Hypothyroidism: Low Iodine Diet and Anti-Thyroid drug (Methimazole)

Objectives: On the concept of oxidative stress in hypothyroidism, which still remains ambiguous and controversial, the article emphasizes the issue of the impact of the experimental conditions on the validity of the data obtained in different methods of modeling thyroid dysfunction. Materials and Methods: Experiments were conducted on 112 white nonlinear male rats. Thyroid hormones and biomarkers of oxidative metabolism in the liver tissue were determined in rats kept for 3 months on a low-iodine diet (LID) and in rats with methimazole (MMI)-induced hypothyroidism (2,5 mg/100 g of body weight for 3 weeks). Results: In LID-rats (n=96) total serum T4 amounted 43, total T3 in liver tissue - 73% of the level found in euthyroid animal, p=0.0121 and p=0.0051, respectively), whereas in MMI-rats (n=96) both total and free serum T4 were 67% of control (p=0.0002 for both total and free T4). In LID-rats cytochrome oxidase (CcOX) activity in liver tissue was 68.5, concentration of malondialdehyde (MDA) - 58% of euthyroids (p value - 0.0202 and 0.0127, respectively), while protein carbonyls (PC) level was 116% of the control (p=0.0411). In MMI-rats liver malate dehydrogenase (MDH) activity decreased up to 70.9, but succinate dehydrogenase (SDH) activity and MDA concentration increased up to 163.6 and 154% of the level in euthyroid animals respectively (p˂0.05). Conclusion: LID-model led to the more pronounced inhibition of thyroid function, than that the MMI-hypothyroidism model used. LID-model was accompanied by a decrease in the intensity of oxidative metabolism in liver tissue, whereas MMI-hypothyroidism - by activation of the succinate oxidation pathway and an increase in the concentration of secondary lipid peroxidation products in the liver of experimental animals. The results suggest that the conflicting data obtained from studies of oxidative metabolism in hypothyroidism, among other assumptions, may be due to the different approaches used by researchers to model thyroid dysfunction.

ALLEVIATION OF ARSENIC INDUCED THYROID DYSFUNCTION AND BODY WEIGHT ALTERATIONS BY CURCUMIN

Background: Arsenic is notorious for being used in many homicidal cases. This study was designed to observe the toxic effects of low dose of arsenic on thyroid gland and body weight and its amelioration by curcumin. Method: Thirty healthy female Sprague Dawley rats (body weight ~230 g) were procured from The National Institute of Health Islamabad. After one week of acclimatization, animals were randomly divided into three groups (n=10 each), e.g., Control group (C), Experimental group-1 (E1) and Experimental group-2 (E2). The duration of the experiment was one month. Weight of the animals was checked before and at the end of experiment. All the animals were continued on standard diet and distilled water during experimental period. E1 was given 10 µg/10 mL of arsenic by oral gavage daily. E2 was given 10 µg/10 mL of arsenic along with Curcumin (50 mg/Kg body weight/day). At the end of experiment, the rats were euthanized to draw the blood and removal of thyroid gland. Serum Triiodothyronine, Tetraiodothyronine and Thyroid Stimulating Hormone were measured by ELISA. Histological changes were observed after haematoxylin and eosin staining. Statistical analysis was done on SPSS-22 and p?0.05 was considered significant. Results: The histological findings of thyroid gland, body weight and serum T3, T4 and TSH in E1 exhibited abnormal results. E2 group showed the protecting role of curcumin suggesting protective role of curcumin. Conclusion: Curcumin has protective effects against arsenic induced thyroid disruption and body weight alterations. Pak J Physiol 2024;20(3): DOI: https://doi.org/10.69656/pjp.v20i3.1686

Combined Levothyroxine and Propylthiouracil Treatment in Children with Monocarboxylate Transporter 8 Deficiency: A Multicenter Case Series of 12 Patients.

Objective: To evaluate the combined administration of propylthiouracil (PTU) and levothyroxine (LT4) in managing monocarboxylate transporter 8 (MCT8) deficiency and identify optimal therapeutic dosages. Methods: This multicenter case series involved 12 male patients with MCT8 deficiency whose parents/guardians consented to PTU and LT4 treatment. Data were collected from January 2008 to June 24, 2024. The study focused on treatment safety and outcomes, analyzing baseline and last encounter biochemical, metabolic, and anthropometric parameters. Statistical analyses included Wilcoxon signed ranks tests and generalized estimated equations to assess effects on thyroid and metabolic markers, and receiver operating characteristics curves to predict optimal dose. Results: Patients showed a significant reduction in serum total triiodothyronine (TT3) concentration and TT3/TT4 ratio, with increased serum TT4 and free T4 (fT4) concentrations. The use of PTU effectively reduced TT3 concentration by 25% at an average dose of 6.8 mg/kg/day, while LT4 increased fT4 concentration by 40% from baseline at an average dose of 4.3 µg/kg/day. Thyrotropin concentration was undetectable on treatment. No statistical differences were observed in metabolic and physical parameters between baseline and last encounter overall for the group, but six of eight patients for whom these data were available had an increase in weight (z-score). There were no adverse effects on liver function or granulocyte numbers noted throughout the period of observation. Conclusion: Combined treatment with PTU and LT4 normalized serum T3, fT4, and TT4 in patients with MCT8 deficiency. Individualized dose adjustments were crucial for achieving therapeutic goals, indicating the need for personalized treatment plans.

PSI-24 Acute and chronic stress response following weaning and transportation in the average piglet

Abstract The American swine industry relies on a model where facilities for farrowing are often geographically isolated from those used later for wean-finish, which necessitates multiple coincident stressors including weaning, mixing, transportation and feed/water restriction. Previous studies indicate this combined stress reduces subsequent growth performance; however, the specific impact of each stressor on an average, objectively healthy piglet is not well understood, nor is the acute physiological response to this life event. The objective of this study was to determine the effect these stressors on thyroid function, intestinal health, and body weight (BW) in average, healthy pigs. In this study, a total population of 588 piglets were weighed the day prior to weaning and 230 piglets with the lowest Z-scores for BW were selected (5.74 ± 0.70 kg). Piglets (n = 70) were weaned directly into nursery pens and provided with feed and water, 70 were transported for 10 h with no access to feed and water, and 70 were grouped together into 2 large pens with no access to feed and water for an equivalent 8 h period. The remaining 20 piglets were not weaned and served as an unstressed control group. A total of 10 pigs from each group were euthanized at 32 and 56 h post-weaning for tissue sampling. Ileal villi height, crypt depth, and goblet cell numbers were measured, and no treatment effects observed (P > 0.05). Serum triiodothyronine (T3) concentrations were measured pre-treatment (t = 0), 24 h (t = 24), 48 h (t = 48), and immediately following euthanasia (t = 32 or 56 d). There were no significant differences in serum T3 among treatments at t = 0. At all-time points post stress event, control piglets had greater T3 concentrations compared with feed restricted (P < 0.05) and transported (P < 0.05) pigs. Weaned pigs at t = 32, t = 48, and t = 56 had decreased T3 concentrations (P < 0.05) and weaned pigs tended (P = 0.0584) to have decreased t = 24 T3 concentrations compared with pigs remaining with the sow. The remaining pigs (n = 50) per weaning group were weighed weekly throughout the nursery phase and every 3 wk in the grow-finish phase to determine the impact of each stressor on growth. There was no significant effect of weaning treatment on BW at any time point (P > 0.10). Carcass data including carcass weight, loin and backfat depths, and lean percentage were measured at time of slaughter with no significant differences found among groups (P > 0.60). As no effect on growth weight or carcass characteristics were observed between treatment groups in average pigs, this suggests that it may be beneficial to transport average pigs the longest distance, while minimizing transport for pigs on either end of the weaning weight spectrum. Further research is needed to compare effects of weaning and transportation stressors on average and weight extremes of weaned pigs.

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

To provide novel aspects for the preoperative diagnosis and appropriate differentiation strategies for follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA). 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. 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. 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.

Sweet cherries modulate thyroid hormones and hepatic glucose metabolism in F344 rats in a photoperiod-dependent manner

Sweet cherry intake affects oxidative stress and hepatic lipid metabolism, depending on composition, mainly (poly)phenol profile and daylight length. Thyroid hormones (TH) respond to daylight changes and regulate the hepatic glucose metabolism. This study investigated whether cherries with different phenolic hallmarks exhibit seasonal responses to TH and hepatic glucose metabolism. Fischer 344 rats fed a standard diet were chronically exposed to L6 (6 h light), L12 (12 h light), and L18 (18 h light) photoperiods and were supplemented with two sweet cherries (Ch1 and Ch2). Serum TH levels and glucose metabolism-related metabolites were affected by both the cherry composition and photoperiod. Thus, Ch1 and Ch2 reduced serum T3 levels in L6, whereas Ch2 increased it in L18, nullifying the photoperiod effect. Moreover, although photoperiod was the main factor affecting the hepatic expression of gluconeogenesis-related genes, Ch1 exerted effects mainly on L6 photoperiod and Ch2 on L18, tending to cancel out the photoperiod effects.

Anemia among adult patients with diabetes attending King Abdulaziz University Hospital: A retrospective study.

The prevalence of anemia in adults with diabetes is of growing importance due to its impact on overall health and the management of diabetes-related complications. This study aimed to determine the prevalence of anemia among adult patients with diabetes at King Abdulaziz University Hospital in Jeddah, Saudi Arabia. A retrospective study was done on 1208 patients with diabetes >18 years who attended the study setting from 2010 to 2022. Data about patients' demographics, body mass index, glycated hemoglobin (HbA1c; %), hemoglobin (Hb), serum ferritin, iron, mean corpuscular Hb, mean corpuscular volume, free thyroxine and triiodothyronine (T3), and serum thyroid-stimulating hormone (TSH) were collected. Of patients, 86.6% had anemia with a prevalence of 30.2%, 47.6%, and 22.2% for mild, moderate, and severe anemias, respectively. The prevalence of anemia was significantly higher among females, those with high serum ferritin, normal serum iron or normal serum T3, lower mean HbA1c level (%), lower serum iron or T3, and higher serum ferritin or TSH. A significant positive correlation was found between Hb level and HbA1c level (%), serum iron, free T3, and body mass index. A significant negative correlation was found between Hb level and mean corpuscular volume, serum ferritin, and serum TSH. Being female, having high serum ferritin, lower mean free T3, and a high TSH were risk factors for anemia. The prevalence of severe anemia was significantly higher among patients with uncontrolled diabetes mellitus. A high prevalence of anemia was found among studied diabetics. Anemia screening should be included in the routine assessment of patients with diabetes. A multidisciplinary approach involving endocrinologists, hematologists, and dietitians is recommended to ensure holistic care and address all aspects of the patient's health. In addition, further research should be supported to better understand the mechanisms linking diabetes and anemia and to establish evidence-based guidelines for managing anemia in diabetics.

Features of the functioning of the hypothalamic-pituitary-thyroid axis in mice with Lewis carcinoma on the background of induced hyperthyroidism

Thyroid hormones (TH) influence the processes of cell proliferation and differentiation, but their role in the processes of carcinogenesis is contradictory. The purpose of the study. To study the effect of induced hyperthyroidism in mice of both sexes with intertwined Lewis carcinoma (LLC) on the activity of the hypothalamic-pituitary-thyroid axis (GGT). Materials and methods. The experimental model was mixed-sex mice of the C57BL/6 line with subcutaneously transplanted LLC on the background of induced hyperthyroidism (main group). Two control groups were used: control group I – mice with sodium liothyronine- induced hyperthyroidism and control group II – mice with subcutaneously transplanted LLC. On the 25th day after tumor transplantation, the level of thyrotropin- releasing hormone (TRH), thyroid- stimulating hormone (TSH), triiodothyronine (T3), total and free thyroxine (T4, FT4) was determined in the homogenates of GGT organs and in blood serum. Results. In female mice, hyperthyroidism caused an increase in the level of TRH in the hypothalamus and a decrease in TSH in the pituitary gland; in males, a decrease in TRH only in the hypothalamus. In control group II, euthyroid disorder syndrome developed: In mice of both sexes, serum levels of T4 and FT4 were found to decrease against the background of unchanged T3 levels and an increase in TSH content only in females. In the females of the main group, an increase in the level of TSH in the thyroid gland caused a decrease in T3 content in 73 % of animals against the background of normal T4 and elevated FT4 levels, in 27 % of females the T3 level increased. In males, in 73 % of the observations, the T3 level was increased against the background of high T4 and FT4 values and unchanged TSH levels. In the skin and LLC samples of the mice of the main group, an increase in T3 levels was noted. Conclusion. The growth of LLC against the background of hyperthyroidism is a process with multifactorial effects. High levels of T3 in blood serum and skin stimulated the proliferation of tumor cells, which led to the formation of subcutaneous tumors of a larger volume in the mice of the main group. Sex differences in the GGT response indicate different mechanisms that implement pathological processes.

Resorcinol as “endocrine disrupting chemical": Are thyroid-related adverse effects adequately documented in reptiles? In vivo experimentation in lizard Podarcis siculus

The endocrine system and particularly thyroid hormones regulate almost all physiological processes in a timely manner in all vertebrates, from fish to reptiles to mammals, so risk assessment of endocrine disrupting chemicals (EDCs) is extremely important given their persistent presence in all environmental matrices. Resorcinol, as well as nonylphenol, octylphenol, and bisphenol A, F, S, are non-Halogenated Phenolic (non-HPCs) Chemicals known as EDCs. Resorcinol is a particular example in that most studies are based exclusively on humans while animal studies are few and often inadequate. The aim of this study was to assess the effects of exposure to different doses of resorcinol on the thyroid gland of the lizard Podarcis siculus during different periods of the thyroid gland activity cycle. Our results showed histopathologic changes in thyroid (follicular cell height increase and colloid area decrease), a thyroid weight increase in combination with serum T4 and T3 decrease, serum TSH, TRH increase in male lizards treated with 0.8,3.9,13.1, and 36.9 mg/kg/d of resorcinol. Besides, we also investigated the impacts of resorcinol treatments on hepatic 5′ORD (type II) deiodinase and hepatic content of T3 and T4. Our findings showed that they are in agreement with in vivo in humans and in rodents data and therefore, resorcinol in reptiles may meet the WHO definition of ECDs.

Comparative assessment of climate resilient potential in four poultry genotypes reared in hot-humid tropical environment: a preliminary evaluation.

The general objective of this study is to comparatively assess the climate-resilient potential of four different poultry genotypes-Giriraja (n = 8), Country chicken (n = 8), Naked neck (n = 8), and Kadaknath (n = 8)-reared in a hot-humid tropical environment. Birds from all genotypes had ad libitum access to feed and water and were exposed to identical environmental temperatures in the experimental shed. Diurnal meteorological data were recorded inside and outside the shed daily. Blood biochemical, hormonal, and endocrine variables were monitored monthly until the birds reached 12 weeks of age. Significant variations (P < 0.01) were observed at different intervals in variables, including total protein, albumin, globulin, triglycerides, and cholesterol. Genotype-specific differences were noted in triglycerides (P < 0.01), albumin (P < 0.01), total protein (P < 0.05), and cholesterol (P < 0.05). Inter-genotype variations (P < 0.05) were also observed in serum cortisol, T3, and T4 levels. Distinct variations (P < 0.05) were also observed during specific intervals, particularly in cortisol and T3 levels. The study of hepatic mRNA expression of HSPs and HSF-1 revealed a significant breed difference (P < 0.05) in the expression pattern of HSP60, HSP70, HSP90, and HSP110, while no difference was observed between genotypes for HSP40 and HSF-1. The study highlights the Naked Neck breed as an exemplar of resilience, showcasing its distinctive ability to maintain homeostasis under heat stress compared to other genotypes. The genetic and physiological insights gained from this investigation offer prospective pathways for aligning sustainable poultry farming with environmental exigencies.

Thyroid hormone levels in children with Prader-Willi syndrome: a randomized controlled growth hormone trial and 10-year growth hormone study.

Several endocrine abnormalities were reported in children with Prader-Willi syndrome (PWS), including hypothyroidism. Growth hormone (GH) treatment may impact the thyroid hormone axis by direct inhibition of T4 or TSH secretion or by increased peripheral conversion of free T4 (FT4) to T3. The objective of this study is to evaluate thyroid function during GH treatment in a large group of children with PWS. Serum FT4, T3, and TSH are measured in a 2-year randomized controlled GH trial (RCT) and 10-year longitudinal GH study (GH treatment with 1.0 mg/m²/day [∼0.035 mg/kg/day]). Forty-nine children with PWS were included in the 2-year RCT (median [interquartile range, IQR] age: GH group 7.44 [5.47-11.80] years, control group 6.04 [4.56-7.39] years). During the first 6 months, median (IQR) FT4 standard deviation score (SDS) decreased in the GH group from -0.84 (-1.07 to -0.62) to -1.32 (-1.57 to -1.08) (P < .001) and T3 SDS increased from 0.31 (-0.01-0.63) to 0.56 (0.32-0.79) (P = .08), while in the control group, FT4 and T3 SDS remained unchanged. In our 10-year GH study, 240 children with PWS (median [IQR] age: 1.27 (0.54-4.17) years] were included. Between 2 and 10 years, median (IQR) FT4 SDS remained unchanged, being -0.87 (-0.98 to -0.77) after 2 years and -0.88 (-1.03 to -0.74) after 10 years (P = .13). TSH SDS decreased from -0.35 (-0.50 to -0.21) after 2 years to -0.68 (-0.84 to -0.53) after 10 years (P < .001). Our findings suggest that GH treatment decreases FT4 levels, due to increased peripheral conversion of FT4 to T3 in the first months of treatment, but thereafter, FT4 and T3 normalize and remain stable during long-term GH treatment in almost all children and adolescents with PWS.

The Relationship between Thyroid Hormones and Insulin Resistance in Polycystic Ovary Syndrome Women.

This study aimed to investigate the changes in thyroid hormones in the serum of patients with polycystic ovary syndrome (PCOS) and their correlation with insulin resistance. This is a retrospective study. 84 patients having insulin resistance and 76 patients without insulin resistance were included. 90 women without history of PCOS were selected as a healthy control group. This study was conducted at Shijiazhuang Fourth Hospital. Blood samples were collected from each group on days 3-5 of their menstrual cycle, and their triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) levels were analyzed and compared between groups. We investigated the changes of serum thyroid hormones in patients with PCOS and their correlation with insulin resistance. We found that serum levels of T3 and T4 were significantly decreased, while TSH levels were significantly increased in PCOS patients compared with HCs. Moreover, we found that patients with insulin resistance had significantly lower levels of serum T3 and T4 and higher levels of TSH compared to those PCOS participants without insulin resistance. This study was a retrospective and single-center study, which had selection bias, information bias, and confounding variables may affect the accuracy and reliability of the conclusion. Insulin resistance negative correlates with their serum T3, T4, and positive correlates with their TSH levels. Our results develop a combined test model with the serum T3, T4, and TSH levels for the clinical diagnosis of insulin resistance in PCOS women.

Inhibitors of LAMP used to detect Tenacibaculum sp. strain Pbs-1 associated with black-spot shell disease in Akoya pearl oysters, and additives to reduce the effect of the inhibitors

Black-spot shell disease is an unresolved disease that decreases pearl quality and threatens pearl oyster survival. In previous studies, the bacterium Tenacibaculum sp. strain Pbs-1 was isolated from diseased Akoya pearl oysters Pinctada fucata, and a rapid, specific, and sensitive loop-mediated isothermal amplification (LAMP) assay for detecting this pathogen was established. This technology has considerable potential for routine diagnosis of strain Pbs-1 in oyster hatcheries and/or pearl farms; therefore, it is vital to identify substances in environmental samples that might inhibit LAMP and to find additives that can reduce the inhibition. In this study, we investigated the effects of six chemicals or proteins, otherwise known as conventional PCR inhibitors, on LAMP, using the DNA of strain Pbs-1 as template: humic acid, urea, iron (III) chloride hexahydrate, melanin, myoglobin, and Ethylenediamine-N,N,N′,N′-tetraacetic acid, disodium salt, dihydrate (EDTA; pH 6.5). Next, to reduce the effects of identified inhibitors, we tested the addition of bovine serum albumin (BSA) or T4 gene 32 protein (gp32) to the LAMP assay. When 50 ng of DNA template was used, 4 ng/μL of humic acid, 0.05% melanin, and 10 mM of EDTA (pH 6.5) inhibited the LAMP reaction, whereas myoglobin, urea, and FeCl3 had no effect. When 50 pg of DNA template was used, 4 ng/μL of humic acid, 0.05% melanin, 4 μg/μL of myoglobin, 10 μg/μL of urea, and 10 mM of EDTA inhibited the LAMP reaction. Thus, it was shown that the gene-amplification inhibitory effect of melanin, humic acid, and urea could be reduced by adding BSA or gp32 to the LAMP reaction mixture. This technique could be applied as part of a protocol to prevent mass mortalities of pearl oysters; moreover, the results enhance our knowledge about substances that inhibit LAMP and methods to reduce the inhibition, which have rarely been reported.