Thyroid Weight Research Articles

Valifenalate-induced non-adverse thyroid changes via adaptive induction of uridine 5′-diphospho-glucuronosyltransferase (UGT) in the liver of dogs and rats but not humans

Some rat and dog toxicology studies with the fungicide valifenalate showed minimal, non-adverse thyroid changes, mostly above the maximum tolerated dose, and concomitantly with liver effects. This publication describes their mode of action (MOA), combining in vivo and new approach methodologies (NAMs), in a weight of evidence approach.Data demonstrate a MOA of liver enzyme induction via nuclear receptor CAR/PXR activation, increased thyroxine (T4) metabolism and elevated thyroid stimulating hormone (TSH) level, leading to thyroid follicular cell hypertrophy and increased thyroid weight. Non-human relevance of the MOA was demonstrated in in vitro cross species assays in rat, dog and human hepatocytes. Increased gene expression and activity of cytochrome P450s (CYPs) and uridine 5′-diphospho-glucuronosyltransferases (UGTs) were observed in rat and dog hepatocytes exposed to valifenalate, with increased T4 clearance and/or T4 glucuronidation/T4-UGT activity. Therefore, a causal relationship between increased liver enzyme induction and thyroid effects in dogs and rats is concluded. Rat hepatocytes were most sensitive, while valifenalate did not increase T4-UGT activity above 2-fold of vehicle control or T4 glucuronidation and T4 clearance in human hepatocytes. Consequently, valifenalate exposure in humans is unlikely to lead to decreased T4 levels, and subsequent thyroid and developmental neurotoxicity effects. Alternative human-relevant thyroid MOAs were excluded, i.e. inhibition of deiodinases (DIO), thyroperoxidase (TPO) or the sodium iodide symporter (NIS).Due to known species differences in thyroid homeostasis between humans and laboratory animals and, importantly, based on the presented data, this liver enzyme mediated MOA is considered not relevant for human hazard assessment.

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

12602 The Effect of Three-Month Semaglutide Treatment on Serum TSH and Thyroid Hormones in Individuals with Obesity

Abstract Disclosure: P. Konopka: None. A. Janucik: None. A. Citko: None. A. Paszko: None. A.J. Kretowski: None. L. Szczerbinski: None. Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) play a crucial role in managing obesity and diabetes, significantly influencing glycemic control and weight management. Previous studies showed that GLP-1 RAs therapy affects thyroid-stimulating hormone (TSH) levels; however, they were limited by small sample sizes and did not extensively cover newer agents like semaglutide. Thus, the aim of this study was to assess the impact of a three-month semaglutide treatment on thyroid hormones and TSH levels in individuals with obesity, without diabetes, and examine the relationship of these changes with weight loss. Methods: We analyzed data from 290 patients participating in the GAROS study, excluding those on medications affecting thyroid function or with a known history of thyroid disease. All participants underwent a three-month treatment with oral semaglutide, followed by a three-month discontinuation phase. Measurements of TSH, free triiodothyronine (fT3), free thyroxine (fT4), and body weight were taken at baseline, at the end of the treatment period, and three months post-treatment discontinuation. To compare changes in TSH, fT3, and fT4 levels, as well as weight, across the study timelines we used non-parametric tests due to the non-normal distribution of the data. We also employed multiple linear regression models to evaluate the association between thyroid hormone changes and weight loss, both in the aggregate and stratified by sex. Results: Initial fT3, fT4, and TSH levels were 3.13 pg/ml (SD=0.38), 0.94 ng/dl (SD=0.10), and 1.64 mIU/l (SD=0.82), respectively. Post-treatment, fT3 decreased on average by 0.33 pg/ml (p<0.001), TSH by 0.32 mIU/l (p<0.001), and fT4 increased by 0.06 ng/dl (p<0.001). Upon discontinuation, fT3 and fT4 levels did not fully return to baseline values but showed a significant shift in that direction (p<0.001 for fT3 and p=0.006 for fT4, compared to baseline). Conversely, TSH levels adjusted back to their baseline values (p=0.26). Notably, changes in fT4 levels, unlike fT3 and TSH, were significantly negatively associated with weight changes during (p=0.030) and post-treatment (p=0.008), across sex-stratified analyses. Conclusions: Semaglutide treatment significantly alters thyroid hormones and TSH levels in patients with obesity, with some effects reversible post-discontinuation. Except for fT4, these hormonal changes appear to be independent of the weight loss effects of semaglutide. Although the magnitude of these alterations might not be clinically significant, they do imply that GLP-1 RAs may have additional physiological effects. The exact nature of the interaction between semaglutide and thyroid function, however, remains to be fully elucidated, highlighting the need for further research to clarify these mechanisms. Presentation: 6/2/2024

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

PSI-21 Limited impact of hypothyroidism on porcine fetal growth during mid to late gestation

Abstract In the fetal pig, both circulating thyroid hormone and growth rate are known to increase throughout gestation; however, the functional association between these coincident factors has not been established. Thus, the objective of this project was to investigate this cause-and-effect relationship by evaluating the impact of induced fetal hypothyroidism on fetal growth during mid to late gestation. To induce fetal hypothyroidism, n = 12 pregnant gilts were orally treated with the goitrogen methimazole (MMI) at a dose of 5 mg/kg/d for 21 d, with n = 3 gilts starting treatment on gestation d 34, 45, 55 and 65. An equivalent group n = 12 of gilts were sham treated for the same periods to produce gestationally age-matched euthyroid control litters (CON). Upon completion of the treatment period, gilts were humanely euthanized, and the resulting populations of n = 174 MMI and n = 166 CON fetuses deeply phenotyped. No meconium-stained fetuses were observed at any time point, and only 5 mummified fetuses were observed (3 CON, 2 MMI), indicating treatment has no effect on fetal viability. Fetal body weight (BW) and the weights of individual organs including thyroid, liver, heart, lung, kidney, spleen, and brain were collected. In addition, fetuses were imaged in both left and right lateral recumbency for subsequent morphometric assessment using a custom analysis pipeline in ImageJ. Image analysis yielded parameters including crown-rump length, girth, brow length, depth at the snout/skull junction, depth at the snout/nose junction, and area under the skull curvature (AUC). Left and right measurements for all morphometric parameters were found to be highly correlated (r2 > 0.9) indicating a repeatable measure using this approach. Statistical analysis of all phenotypic differences was carried out using a linear mixed effect model including gestational age and treatment as fixed effects and gilt as a random effect. A significant increase in both absolute and relative thyroid weights indicated the development of goiter and thus, successful induction of hypothyroidism within the MMI litters. In addition, a significant treatment by time interaction was observed, with 0.014 g and 0.21 g increase at d 55 and 66, respectively, indicating reduced compensatory action within the fetal hypothalamic-pituitary-thyroid axis during this earliest period. Liver weight as a percentage of BW decreased from 6.06% to 2.56% between d 55 and 86 in the CON group but was significantly increased at all time points in response to MMI induced hypothyroidism (P < 0.01). A corresponding increase in brain to liver weight ratio over time was suppressed in MMI fetuses (P < 0.05). While all other phenotypic parameters were significantly altered by gestational age, there was no significant impact of fetal hypothyroidism. Collectively, the results indicate that fetal growth during mid to late gestation is not driven by fetal thyroid hormone.

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

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

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.

Sufficiency of a Single Negative Thyroglobulin Standard for Judging the Success of Ablation in Low- and Intermediate-risk Differentiated Thyroid Cancer: A Retrospective Study.

We investigated how reduced successful ablation criteria may be used to evaluate radioiodine remnant ablation in patients with low- and intermediate-differentiated thyroid carcinoma (DTC). Overall, 254 low- and intermediate-risk patients with DTC were categorized into three groups (positive, weak, positive, and negative) on the basis of a visual study of thyroid imaging performed before postoperative iodine treatment. Semi-quantitative analysis parameters were incorporated into the positive Tc-99m pertechnetate scanning to further examine the clinical use of thyroid imaging. We investigated the value of successful judgment criteria and the influencing factors of radioiodine ablation. At the same time, the predictive value of thyroglobulin (Tg) for radioiodine treatment and the overall clinical efficacy were assessed. A total of 250 (98.43%) patients were identified as having functional thyroid tissue residue on the Rx-whole-body scan, and 137 (53.94%) patients had positive Tc-99m pertechnetate scans using semi-quantitative analysis. The single Tg standard could not substitute the double standard (χ2c=22.042, p<0.001) for patients with residual thyroid weight by a semiquantitative analysis. However, the semi-quantitative analysis revealed no association between 99mTcO4-thyroid scan and ablation treatment using semi-quantitative analysis; only preablation sTg levels were related with success in the multivariate logistic regression analysis, with a cut-off value of 2.88 ng/mL. The pre-ablation stimulated Tg level was also the primary factor of satisfactory response following follow-up with an optimal cut-off of 6.506 ng/mL. Even in low- and intermediate-risk patients with DTC, a single negative Tg standard also requires receiving some restrictions in the evaluation of ablation success and is inadequate. Conventional 99mTcO4 thyroid imaging combined with a quantitative analysis program can improve the clinical practice of single negative Tg standard.

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.

Changes in thyroid hormones predict weight regain in patients with obesity who undergo metabolic surgery.

To investigate the relationship between thyroid function and weight regain in patients with obesity after metabolic surgery. This retrospective study enrolled 162 patients who underwent metabolic surgery. Correlations between decreases in thyroid hormone levels and changes in weight, waist circumference (WC) and the Chinese visceral adiposity index (CVAI) were assessed. Binary logistic regression and receiver operating characteristic (ROC) curves were used to identify predictors and clinically useful cut-off values, respectively. The levels of thyroid-stimulating hormone (TSH) and free triiodothyronine (FT3) decreased markedly at 1 year after surgery, as did weight, body mass index (BMI), triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, WC and CVAI. Decreases in TSH and FT3 after metabolic surgery were associated with changes in weight, BMI and CVAI. Binary logistic regression and ROC curve analyses confirmed that decreases in TSH can predict good weight loss after metabolic surgery to some extent. Finally, binary logistic regression and ROC curve analyses confirmed that changes in TSH can predict weight regain after metabolic surgery. Changes in TSH and FT3 after metabolic surgery were correlated with changes in weight and CVAI. Changes in thyroid hormones can predict weight regain in patients with obesity who underwent metabolic surgery.

The association of back pain with physical inactivity and hypothyroidism in pregnant women.

During pregnancy, structural and functional changes usually occur in the body, which has various consequences, including lower back pain (LBP) and hypothyroidism. One of the risk factors for these problems is physical inactivity. This study aimed to investigate the association of back pain and physical inactivity, weight gain, and hypothyroidism in pregnant women. In this cohort study, 420 pregnant women (26.333 ± 5.820 years old) were included. At first, participants answered this question: "Do you have any plans for pregnancy in the next month?" If the answer was yes, further evaluations were performed. The physical activity and pain intensity were measured by the International Physical Activity Questionnaire Short Form (IPAQ-S) and Visual Analogue Scale. Serum TSH was measured by automated chemiluminescence and commercial kits. Measurements were conducted before, the first, second, and third trimester of pregnancy. Women reporting LBP were less engaged in physical activities and weight gained in the second and third trimesters of pregnancy was significantly higher than pregnant women without LBP (p< 0.05). TSH level and weight gained in pregnant women with low physical activity level was significantly higher than pregnant women with moderate and high physical activity (p< 0.05) (without significant difference in TSH and BMI). The physical inactivity (before: OR: 1.11 95% CI: 0.89 to 1.22; first trimester: OR: 1.09 95% CI: 1.02 to 1.59; second trimester: OR: 0.92 95% CI: 0.87 to 1.31; third trimester: OR: 1.12 95% CI: 1.02 to 1.39), TSH (OR: 0.85 95% CI: 0.57 to 1.29), and weight gain (second trimester: OR: 0.87 95% CI: 0.92 to 1.59; third trimester: OR: 1.44 95% CI: 1.02 to 1.98; p< 0.05) did predict increased pain intensity. Using health-oriented approaches to increase physical activity and normalize thyroid function and weight gain during pregnancy can have beneficial effects on LBP.

Thyrogrit, supplemented with a sub-optimal dose of levothyroxine, restores thyroid function in rat model of propylthiouracil-induced hypothyroidism

BackgroundHypothyroidism is a common endocrine ailment, whose current standard of care is hormonal replacement therapy with levothyroxine (LT4). There is a medical need for alternative and safer therapies as LT4 is associated with special treatment considerations and adverse effects. Thyrogrit (THY) is a polyherbal formulation indicated for the treatment of hypothyroidism. The present study, describes the characterization of the phytocompounds present in THY and its in-vivo efficacy in rat model of hypothyroidism, in combination with a sub-optimal dose of LT4.MethodsUltra High Performance Liquid chromatography was employed for the identification of the phytocompounds present in THY. For the evaluation of its in-vivo efficacy, female Wistar rats were administered THY orally, 15-days prior to disease induction, and continued throughout the experiment. Subsequently, hypothyroidism was induced by oral administration of propylthiouracil (PTU). From day 45 onwards, animals were administered orally with a sub-optimal dose of LT4 (2 μg/kg) till the end of the study. On day 79, animals were euthanized, blood was collected for measurement of thyroid hormones and other clinical chemistry parameters. Weights of liver, kidney and thyroid were recorded. Finally, the thyroid was subjected to histopathological evaluation through hematoxylin and eosin (H&E staining), immunohistochemistry as well as immunofluorescence.ResultsThe principal phyto-components detected in THY by Ultra High Performance Liquid Chromatography included gallic acid, protocatechuic acid, corilagin, ellagic acid, piperine, guggulsterone E and Z, which are documented to exerted beneficial effects on thyroid function. In the in-vivo study, THY when supplemented with a low dose of levothyroxine restored the PTU-induced reduction in the serum levels of T3 and T4 and improved PTU-induced renal impairment. THY treatment ameliorated the hallmark histopathological changes associated with hypothyroidism and C-cell hyperplasia. Further, co-administration of THY and LT4 did not show any major non-clinical safety concerns even after the administration for more than twelve weeks.ConclusionThis study has demonstrated that co-administration of THY and LT4 improves the PTU-evoked alterations in the thyroid ultrastructure and function, abrogates hypothyroidism-associated renal impairment and exhibits an acceptable basic safety profile.Graphical abstract

Evolution in the management of thyroid surgery over a period of 15 years in a Belgian center

BackgroundGuidelines for thyroid surgery have evolved to reflect advances in medical knowledge and decrease the overdiagnosis of low-risk thyroid cancer. Our goal was to analyze the change made in operative thyroid management and the impact on thyroid cancer diagnosis.BackgroundGuidelines for thyroid surgery have evolved to reflect advances in medical knowledge and decrease overdiagnosis of low risk thyroid cancer. Our goal was to study the evolution, over a long period, of pre- and postoperative management and the influence on histological cancer diagnosis and, more particularly, microcancer.MethodsIn this retrospective cohort study, we included 891 consecutive patients who underwent thyroid surgery between 2007 and 2020.ResultsRespectively 305, 290 and 266 patients underwent surgery over the 3 periods of 2007–2010, 2011–2015 and 2016–2020. In all three periods, women represented approximately 70% of the population, and the mean age was 54 years old (range: 67). Most surgeries (90%) involved total thyroidectomies. Over the study period, the proportion of preoperative fine needle aspiration (FNA) increased from 13 to 55%, p < 0,01. Cancer was found in a total of 116 patients: 35 (11%) patients between 2007 and 2010, 50 (17%) between 2011 and 2015 and 32 (12%) between 2016 and 2020 (p = 0.08). For all 3 periods, papillary thyroid cancer (PTC) was the most prevalent, at approximately 80%. The proportion of thyroid cancer > T1a increased significantly from 37% (2011–2015 period) to 81% (2016–2020 period), p = 0.001. Patients treated with radioiodine remained relatively stable (approximately 60%) but were more frequently treated with a low dose of radioiodine (p < 0.01) and recombinant human TSH (p < 0.01). Operative thyroid weight decreased over time in all but the low-risk T1a PTC cases.ConclusionsOver a period of 15 years and according to the evolution of recommendations, the care of patients who underwent thyroid surgery changed with the increased use of preoperative FNA. This change came with a decrease in low-risk T1a PTC.

138 Growth performance and physiological response of nursery pigs fed a high canola meal diet with acidifiers

Abstract This study investigated the impact of feed additives aimed at reducing gut pH on the growth performance and physiological responses of nursery pigs when fed a high canola meal (CM) diet. A total of 315 nursery pigs, 6.0 ± 1.2 kg body weight (BW), were allotted to one of five dietary treatments with 9 replicates (7 pigs/pen) in a randomized complete block design. Dietary treatments were PC: corn-soybean meal-based diet with 20% CM, NC: corn-soybean meal-based diet with 40% CM; NC+A: NC diet with acidifier at 1,500 ppm, NC+B: NC diet with encapsulated butyrate at 500 ppm, and NC+A+B: NC diet with acidifier and encapsulated butyrate. All diets were formulated to meet or exceed the nutrient requirements of NRC (2012). All pigs received a common Phase 1 nursery diet during week 1 following weaning. Experimental diets were provided in Phase 2 (wk 2 and 3) and Phase 3 (wk 4 to 6). Individual pig BW and pen feed consumption were measured for each phase to calculate growth performance. At the conclusion of each phase, blood samples were collected from one pig per pen for analysis of serum triiodothyronine (T3) and thyroxine (T4) concentrations. The selected pig was euthanized within 24 h, and its organ weights and pH of digesta were measured. The results were analyzed using MIXED procedure in SAS with the pen as an experimental unit. There was no difference in BW and average daily gain throughout the overall period. However, PC treatment exhibited greater (P &amp;lt; 0.05) average daily feed intake in phase 3 by 18.2% and overall period by 13.4% compared with NC treatment and no difference with NC+A+B treatment. The NC+A and NC+A+B treatments tended to improve (P ≤ 0.10) gain to feed ratio in phase 3 by 17.9% and overall period by 16.1% compared with PC treatment, respectively. At the end of phase 3, the PC treatment tended (P &amp;lt; 0.10) to have greater serum T4 concentrations compared with NC and NC+A treatments (3.2 vs 2.5 and 2.4 ug/dL, respectively), whereas there was no difference between PC and NC+A+B treatments. In phase 3, the thyroid gland weight for PC treatment was less (P &amp;lt; 0.05) than for NC treatment (0.156 vs 0.202 g/kg), whereas there was no difference among PC, NC+B, and NC+A+B treatments. In phase 3, dietary encapsulated butyrate decreased (P &amp;lt; 0.05) the pH of jejunal digesta compared with PC treatment (6.28 vs 7.01), and dietary encapsulated butyrate treatments (NC+B and NC+A+B) tended to decrease (P &amp;lt; 0.10) the pH of hind-colonic digesta compared with the pH of PC treatment by 6.2% and 7.2%. In conclusion, dietary encapsulated butyrate in combination with acidifier may alleviate thyroid dysfunction that is anti-nutritional effect of high canola meal diets.

Outcomes of Metabolic Surgeries with Special Reference to Weight Loss, Diabetes Mellitus, Hypertension, and Thyroid Profile

Abstract Background: Metabolic surgery, which results in significant weight loss and the improvement, prevention, or remission of multiple related conditions including type 2 diabetes, heart disease, hypertension, sleep apnea, and various malignancies, is the most effective and long-lasting therapy for excessive obesity. Aims and Objectives: To examine the results of metabolic operations with an emphasis on thyroid function, weight reduction, diabetes mellitus, and hypertension. Material and Methods: From June 2021 to June 2022, thirty-two (15 men and 17 women) patients were selected from the outpatient division of state-run Government Medical College. It is a case series analysis on patients who underwent bariatric surgeries which were conducted after clinical history and clinical examination with appropriate investigations on those patients who were admitted. The study only covered those who had no significant organ involvement and those who met the inclusion criteria were invited to take part in the study. Results: About 32 individuals underwent metabolic surgeries in the General Surgery department, at SVBP Hospital affiliated with LLRM Medical College Meerut. The difference between various parameters, such as pre-op and post-op, is compared using the various statistical analysis between the single group that differs from a known mean value. Conclusion: Metabolic surgery is presently the most effective treatment for attaining long-term weight loss and has been demonstrated to benefit T2DM thyroid and Hypertensive patients. Our study supports the statistical significance of variables including hemoglobin, BMI, HbA1c, serum creatinine, total cholesterol, LDL, SBP, and TSH.

Flavouring group evaluation 419 (FGE.419): 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one.

The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one [FL-no: 16.134] as a new flavouring substance, in accordance with Regulation (EC) No 1331/2008. The substance has not been reported to occur naturally and is chemically synthesised. In food, it is intended to be used as a flavouring substance only in chewing gum. The chronic dietary exposure to [FL-no: 16.134] was estimated to be 45 μg/person per day for a 60-kg adult and 28.4 μg/person per day for a 15-kg 3-year-old child. [FL-no: 16.134] did not show genotoxicity in a bacterial reverse mutation test and an invitro mammalian cell micronucleus assay. Based on the submitted toxicokinetic and metabolism data, it can be predicted that the flavouring substance is metabolised to innocuous products only. The Panel derived a lower confidence limit of the benchmark dose (BMDL) of 0.71 mg/kg bw per day for a 20% increase in the relative thyroid (including parathyroid) weight observed in a 90-day toxicity study in rats. Based on this BMDL, adequate margins of exposure of 887 and 374 could be calculated for adults and children, respectively. The Panel concluded that there is no safety concern for [FL-no: 16.134], when used as a flavouring substance at the estimated level of dietary exposure, based on the intended use and use levels as specified in Appendix B. The Panel further concluded that the combined exposure to [FL-no: 16.134] from its use as a food flavouring substance and from its presence in toothpaste and mouthwash is also not of safety concern.

Factors affecting timing of hypothyroidism following radioactive iodine therapy (RAIT) for patients with Graves' disease: A 12-month observational study.

This retrospective study analyzed factors influencing hypothyroidism development after radioactive iodine therapy for Graves' disease. Three hundred and three patients with Graves' disease treated with radioactive iodine (RAI) from 2013 to 2022 at two Egyptian hospitals were included. Data collected included demographics, lab values, thyroid imaging, RAI doses, and outcomes. Patients were followed for ≥1 year to assess hypothyroidism onset. At the end of 1 year, around 79.5% of the individuals developed hypothyroidism while 12.5% continued to experience hyperthyroidism. The onset of hypothyroidism occurred earlier in those with thyroid volume (≤75.5 cm 3 ), lower thyroid weight (≤84.7 g), thyroid uptake (≤18.8%), and higher RAI dose/volume (≥0.1022 mCi/ml) ( P < 0.001). Additionally, there was a correlation between anti-thyroid peroxidase (anti-TPO) antibodies and faster development of hypothyroidism compared to those who were negative for antibodies (2.9 vs 8.9 months, P = 0.001). When considering factors in analysis it was found that anti-TPO antibodies were the only independent predictor, for developing hypothyroidism (hazard risk 30.47, P < 0.001). Additionally, thyroid volume and uptake independently predicted successful treatment outcomes ( P < 0.05). Positive anti-TPO antibodies strongly predict hypothyroidism risk after RAI therapy for Graves' disease. Smaller thyroid size, lower uptake, and higher RAI dose/volume correlate with earlier hypothyroidism onset but are less significant predictors than anti-TPO status. Findings can guide RAI therapy personalization to optimize outcomes.

High-dose exposure to butylparaben impairs thyroid ultrastructure and function in rats

Parabens (PBs) are a class of preservatives commonly used in cosmetics and pharmaceuticals. Studies have shown that these compounds may act as endocrine disruptors, affecting thyroxine levels in humans. PBs with longer chain substituents, such as butylparaben (BuP), are less prone to complete biotransformation and are therefore more likely to accumulate in the body. In this study, the effect of high-dose exposure to BuP on thyroid microstructure, ultrastructure, and function was investigated in rats. 50 mg/kg bw per day of BuP was injected subcutaneously into the neck of rats for 4 weeks. Rat thyroid weight, microstructure, and ultrastructure were determined, and the levels of thyroid sodium/iodide symporter (NIS), serum thyroid hormones, and thyroid autoantibodies were measured. The human thyroid cell line was used to study the mechanism of BuP on thyroid epithelial cells. The weight of the thyroid gland of BuP-exposed rats was increased, the structure of the thyroid follicles was irregular and damaged, the mitochondria and rough endoplasmic reticulum were swollen and damaged, and the microvilli at the tip of the epithelium were reduced and disappeared. Serum total T3, total T4, free T3, and free T4 were decreased in BuP-exposed rats, and TSH, peroxidase antibody, and thyroglobulin antibody were increased. In vitro, BuP decreased the level of NIS in thyroid epithelial cells, inhibited proliferation and viability, and induced apoptosis in a dose-dependent manner. This study demonstrated that high-dose exposure to BuP induced structural, ultrastructural, and functional impairment to the thyroid gland of rats, which may be one of the factors leading to hypothyroidism.

Routine Use of Neck Drains Following Thyroid Operations to Prevent Complications Is No Longer Advisable.

The use of cervical drains to prevent cervical hematoma or seroma after thyroidectomy remains a controversial issue. Identify clinical and surgical risk factors for hematoma or seroma and evaluate the usefulness of routine use of drains following thyroid surgery. The authors conducted a retrospective multicentric study related to consecutive patients submitted to thyroid surgery in seven Portuguese hospitals between January 2018 and December 2020 (n=945). The data collected included the following parameters: age and gender of the patients, anticoagulation or anti-aggregating therapy, histological diagnoses, type of surgery, the presence or absence of postoperative drains, thyroid weight, length of hospital stay, postoperative complications, and reinterventions. In this study, surgical complications evaluated were limited to the presence of hematoma or seroma. A total of 945 patients who underwent thyroid surgery were included in the study. Twenty-seven patients (2.9%, n=27) experienced complications classified as hematomas or seromas. In the series, significant differences were observed between the two groups according to hypocoagulation or anti-aggregation status (OR=3.62; 95% CI 1.14-11.4) (p=0.001) and the nature of histological diagnosis (toxic vs. non-toxic benign disease) (OR=6.59; 95% CI 1.83-23.7). Hypocoagulation or anti-aggregation status were independently associated with a higher risk of complications. The presence of drains was associated with longer hospitalization periods (p<0.001) and not a decreased need for reintervention. Cervical hematoma or seroma are rare complications associated with both hypocoagulation and anti-aggregation therapy and with the presence of benign toxic pathology. The use of drains does not decrease the need for reintervention and is even associated with a longer length of hospital stay; therefore, their routine use should not be advised.

Predictive Factors for the Efficacy of Radioactive Iodine Treatment of Graves’ Disease

Objective: The utilization of radioactive iodine‐131I (RAI) has long been established as a cost‐effective and conventional treatment for managing Graves’ disease (GD). However, the accurate prediction of the clinical response to RAI treatment remains difficult. The successful resolution of GD through RAI therapy is typically characterized by the induction of hypothyroidism or euthyroidism. Thus, the principal aim of this study was to identify plausible predictors of RAI efficacy in the treatment of GD.Methods: The clinical data of 613 GD patients, who underwent RAI treatment for the first time, were retrospectively analyzed, including age, gender, duration of hyperthyroidism, presence or absence of ocular signs, thyroid volume, thyroid weight, thyroid function (FT3, FT4, and TSH), radioactive iodine uptake (RAIU) at 2 h/6 h/24 h (2‐h/6‐h/24‐h RAIU) prior to RAI treatment, the highest RAIU (RAIUmax), and administered activity of 131I and 131I activity per gram of thyroid tissue. Success of RAI treatment was defined as achieving hypothyroidism or euthyroidism for more than 1 year after the initial treatment. Univariate and multivariate logistics regression analyses were conducted to identify factors that influence the efficacy of RAI treatment for GD. And at last, based on the results of the multivariate logistic regression analysis, a nomogram model was established.Results: In this study, the success rate of RAI treatment for GD was 91.2% (559/613). Univariate analysis demonstrated that several factors, including age (p = 0.005), thyroid volume (p = 0.001), thyroid‐stimulating hormone (TSH, p = 0.042), ratio of RAIU at 6 h to 24 h (6‐h/24‐h RAIU, p = 0.048), total 131I activity (p = 0.026), and 131I activity per gram of thyroid tissue (p = 0.001), were significantly associated with treatment outcome. Multivariate logistic regression analysis indicated thyroid volume and 131I activity per gram of thyroid tissue as significant independent predictors of radioactive iodine therapy (RIT) efficacy. The area under the ROC curve of the established nomogram model was 0.769 (95% confidence interval [CI]: 0.692–0.846), indicating that the model has good discriminatory ability.Conclusion: Calculated‐dose RAI is effective in the treatment of GD. The smaller thyroid volume and the higher 131I activity per gram of thyroid tissue are predictors of RAI efficacy in the treatment of GD.