Increased TSH Levels Research Articles

Hypothyroidism Induced by a TSH Receptor Peptide-Implications for Thyroid Autoimmunity.

Background: The "neutral" thyrotropin receptor autoantibodies (N-TSHR-Ab) directed at the TSHR ectodomain's hinge region have been shown to induce thyroid cell damage in vitro. During these earlier studies, we developed a mouse monoclonal antibody (MC1) specific for a peptide (amino acid 322-340) in the region (MC1-Mab) which was able to induce thyroid cell stress and apoptosis when administered invivo. Methods: In order to examine the effect of invivo generated N-TSHR-Abs, rather than an acutely administered monoclonal antibody, we immunized Balb/c mice with the hinge region peptide over 18 weeks. Serum TSHR antibodies, specific TSHR hinge region antibodies, serum thyroglobulin (TG) and anti-TG as well as thyroxine and thyrotropin (TSH) levels were examined to evaluate the response to the immunization. Histological examination of the thyroid glands and flow cytometry of spleen T cells, B cells and macrophages were also performed to explore the underlying mechanisms. Results: We found that TSHR-peptide immunized mice developed N-TSHR-Abs against the peptide which resulted in thyroid damage shown by thyroid follicular destruction with follicular cell apoptosis, M1 macrophage infiltration, thyroglobulin release, and induction of thyroglobulin antibodies. This resulted in hypothyroidism with increased TSH levels. Conclusion: This study demonstrated that endogenous neutral antibodies to the TSHR could induce thyroid cell damage from apoptosis and M1 macrophage infiltration and resulted in hypothyroidism.

6430 SAT-534 Evaluating the Effectiveness of Combined T4 and T3 Therapy or Desiccated Thyroid Versus T4 Monotherapy in Hypothyroidism: A Systematic Review and Meta-Analysis

Abstract Disclosure: M. Nassar: None. A. Hassan: None. M.T. Desouki: None. S. Ramadan: None. M.A. Hassan: None. A. Chaudhuri: None. Background: Many patients with hypothyroidism experience persistent symptoms despite normalized TSH levels, which highlights the need for alternative treatment strategies. This study aims to evaluate the effectiveness of combined T4 and T3 therapy or desiccated thyroid (DTE) compared to T4 monotherapy, with a focus on thyroid profile, lipid profile, and quality of life metrics, including the 36-point thyroid symptom questionnaire (TSQ-36), Beck Depression Inventory (BDI) scores, and General Health Questionnaire (GHQ)-28 scores. Methods: A systematic literature search was conducted using a Boolean strategy on the following databases: Embase, Medline/PubMed, and Web of Science. The search included results from the inception of each database until 11/23/2023. We used the following keywords: "Armour Thyroid," OR "Thyroid Extract," OR "Natural Desiccated Thyroid," OR "Nature-Throid," "Desiccated Thyroid," OR "NP Thyroid," OR "Synthroid," OR "Levothyroxine," OR "Liothyronine," "Cytomel," OR "Thyroid USP," OR "Unithroid." AND "hypothyroidism. " We only included RCTs. We excluded non-English articles. Results: Initially, 6,394 records were identified. After removing 477 duplicate records, 5,917 records underwent title and abstract screening, excluding 5,874 records. The full texts of the remaining 43 articles were examined for eligibility, excluding 27 articles. Ultimately, 16 studies met the inclusion criteria and were incorporated into our analysis. We included two studies on desiccated thyroid and 15 studies on combined therapy. In this meta-analysis, combination therapy with T4+T3 revealed a significant reduction in free T4 levels (mean difference (MD): -0.34; 95% CI: -0.47, -0.20), total T4 levels (mean difference: -2.20; 95% CI: -3.03, -1.37), and GHQ-28 scores (MD: -2.89; 95% CI: -3.16, -2.63) compared to T4 monotherapy. Total T3 levels increased significantly in combined therapy (MD: 29.82; 95% CI: 22.40, 37.25). The analyses demonstrated moderate to high heterogeneity. There was no significant difference in heart rate, SHBG, TSH, lipid profile, TSQ-36, or BDI score. DTE significantly increased serum total T3 levels (MD: 50.90; 95% CI: 42.39, 59.42) and significantly decreased serum total T4 (MD: -3.11; 95% CI: -3.64, -2.58) and free T4 levels (MD: -0.50; 95% CI: -0.57, -0.43) compared to T4 monotherapy. Moreover, DTE treatment showed a modest increase in TSH levels (MD: 0.49; 95% CI: 0.17, 0.80). The analyses indicated low heterogeneity. There was no significant difference in heart rate, SHBG, lipid profile, TSQ-36, GHQ-28, or BDI score. Conclusions: Our study revealed that combined therapy and DTE lead to higher T3 and lower T4 levels compared to T4 monotherapy in hypothyroidism. However, no significant effects on heart rate, lipid profile, or quality of life were noted. Given the heterogeneity of results, personalized treatment approaches are recommended. Presentation: 6/1/2024

Investigation of the Relationship between Plasma Nesfatin-1 Levels and Neutering in Dogs.

Neutering of dogs, whether male or female, provides various benefits such as contraception, population control, and the prevention of reproductive disorders and undesirable sexual behaviors. However, it is also associated with an increased risk of obesity, which may be directly linked to post-neutering hormonal changes. Our study aims to determine the effects of neutering on plasma levels of nesfatin-1, serotonin, dopamine, TSH, and T4-hormones implicated in obesity and metabolic regulation. Fourteen dogs (seven males and seven females), aged between 1 and 3 years, were included in this study. Male dogs underwent orchiectomy and females underwent ovariohysterectomy. Blood samples were collected before surgery and on days 7 and 14 post-operatively to measure the plasma levels of these hormones using ELISA. The results showed a significant decrease in nesfatin-1, serotonin, and T4 levels, along with a significant increase in TSH levels in both male and female dogs post-neutering. While these hormonal changes are likely part of the body's adaptive response to neutering, they may represent a potential mechanism that contributes to the long-term tendency toward obesity in neutered dogs.

Study of Hematological Parameters of Children with Chronic Kidney Disease on Hemodialysis and Peritoneal Dialysis in Wasit Governorate

ABSTRACT: The aim of this study was to evaluate some hematological parameters in pediatric patients with chronic kidney disease (CKD) in children who are on hemodialysis (HD) and peritoneal dialysis (PD). It is characterized by its irreversibility. Deterioration of kidney function that gradually progresses to end-stage renal function illness. Over the past two decades, the incidence of CKD in children has increased Steady increase. The major health consequences of CKD include not only progression to kidney failure, but also increased risk of cardiovascular disease. The study was conducted in the dialysis unit of Al-Zahraa Teaching Hospital in Wasit governorate and the Child Protection Teaching Hospital -Medical City in Baghdad. During the period from November 2023 to April 2024. This study aimed to examination of risk factors (height, weight, age, sex, inheritance of the disease in the family, medical history, symptoms of the disease, other diseases, treatment methods) for CKD in general. The biochemical effect was also studied and blood indicators for patients on HD and PD purpose. For the purpose of studying the hematological of patients undergoing dialysis and comparing those results with their values ​​in both HD and PD. This study was done on (80) Iraqi children (30) of them suffering from kidney failure and (50) of them was healthy with age range (1 day -17) years old. HD was performed for 22 children with CKD, and PD was performed for 8 patients with CKD. This study involved dividing patients into three Groups according to the age at which the disease begins, from (1 day-5 years), (6-11) years and (12-17) years, included 15 females and 15 males. Samples were collected based on the incidence of CKD and type of treatment, as well as the diagnosis of all patients according to international standard by the physician. The results of our study with regard to the hematological of patients undergoing PD showed a significant increase in the levels of (WBC) p ≤ 0.05 and also showed a significant decrease in the levels of (RBC, Hb, PCV, ESR) p ≤ 0.05. a non-significant increase in TSH levels p ≥ 0.05. The results of our study with regard to the hematological parameters of patients on HD showed a significant increase in the levels of (ESR) p ≤ 0.05 and a significant decrease in the levels of (WBC, RBC, PCV, Hb) p ≤ 0.05.

Excess Iodine Consumption Induces Oxidative Stress and Pancreatic Damage Independently of Chemical Form in Male Wistar Rats: Participation of PPAR-γ and C/EBP-β.

Human beings consume different chemical forms of iodine in their diet. These are transported by different mechanisms in the cell. The forms of iodine can be part of thyroid hormones, bind to lipids, be an antioxidant, or be an oxidant, depending on their chemical form. The excessive consumption of iodine has been associated with pancreatic damage and diabetes mellitus type 2, but the association between disease and the chemical form consumed in the diet is unknown. This research analyzes the effect of excessive iodine consumption as Lugol (molecular iodine/potassium iodide solution) and iodate on parameters of pancreatic function, thyroid and lipid profiles, antioxidant and oxidant status, the expression of IR/Akt/P-Akt/GLUT4, and transcription factors PPAR-γ and CEBP-β. Three groups of Wistar rats were treated with 300 μg/L of iodine in drinking water: (1) control, (2) KIO3, and (3) Lugol. Lugol and KIO3 consumption increased total iodine levels. Only KIO3 increased TSH levels. Both induced high serum glucose levels and increased oxidative stress and pancreatic alpha-amylase activity. Insulin levels and antioxidant status decreased significantly. PPAR-γ and C/EBP-β mRNA expression increased. The pancreatic damage, hypertriglyceridemia, and oxidative stress were independent of the chemical form of iodine consumed. These effects depended on PPAR-γ, C/EBP-β, GLUT-4, and IR.

Ultra-Low Anti-Müllerian Hormone Levels in Recurrent Cystic Ovarian Neoplasm: A Case Report

Fertility has been a major issue in the management of cystic ovarian neoplasm. This case report presents an extreme case of ultra-low AMH levels in a young female with recurrent cystic ovarian neoplasm and analyzes the potential causes. A twenty-two-year-old female presented with stomach discomfort. The patient had undergone two surgeries for ovarian neoplasm within the last six years. The patient had another abdominal lump suspected to be a residual tumor mass. After further examination, the patient was diagnosed with cystic ovarian neoplasm. The laboratory findings showed low T4 levels, increased TSH levels, and ultra-low AMH levels (0.023 ng/mL). Management of cystic ovarian neoplasm should concern the effect on fertility. The AMH level can be used for pre-treatment counseling in these patients.

Defining the In Vivo Role of mTORC1 in Thyrocytes by Studying the TSC2 Conditional Knockout Mouse Model.

Background: The thyroid gland is susceptible to abnormal epithelial cell growth, often resulting in thyroid dysfunction. The serine-threonine protein kinase mechanistic target of rapamycin (mTOR) regulates cellular metabolism, proliferation, and growth through two different protein complexes, mTORC1 and mTORC2. The PI3K-Akt-mTORC1 pathway's overactivity is well associated with heightened aggressiveness in thyroid cancer, but recent studies indicate the involvement of mTORC2 as well. Methods: To elucidate mTORC1's role in thyrocytes, we developed a novel mouse model with mTORC1 gain of function in thyrocytes by deleting tuberous sclerosis complex 2 (TSC2), an intracellular inhibitor of mTORC1. Results: The resulting TPO-TSC2KO mice exhibited a 70-80% reduction in TSC2 levels, leading to a sixfold increase in mTORC1 activity. Thyroid glands of both male and female TPO-TSC2KO mice displayed rapid enlargement and continued growth throughout life, with larger follicles and increased colloid and epithelium areas. We observed elevated thyrocyte proliferation as indicated by Ki67 staining and elevated cyclin D3 expression in the TPO-TSC2KO mice. mTORC1 activation resulted in a progressive downregulation of key genes involved in thyroid hormone biosynthesis, including thyroglobulin (Tg), thyroid peroxidase (Tpo), and sodium-iodide symporter (Nis), while Tff1, Pax8, and Mct8 mRNA levels remained unaffected. NIS protein expression was also diminished in TPO-TSC2KO mice. Treatment with the mTORC1 inhibitor rapamycin prevented thyroid mass expansion and restored the gene expression alterations in TPO-TSC2KO mice. Although total thyroxine (T4), total triiodothyronine (T3), and TSH plasma levels were normal at 2 months of age, a slight decrease in T4 and an increase in TSH levels were observed at 6 and 12 months of age while T3 remained similar in TPO-TSC2KO compared with littermate control mice. Conclusions: Our thyrocyte-specific mouse model reveals that mTORC1 activation inhibits thyroid hormone (TH) biosynthesis, suppresses thyrocyte gene expression, and promotes growth and proliferation.

Supplementation with selenium and coenzyme Q10 in an elderly Swedish population low in selenium — positive effects on thyroid hormones, cardiovascular mortality, and quality of life

BackgroundSelenium-dependent deiodinases play a central role in thyroid hormone regulation and metabolism. In many European countries, insufficient selenium intake may consequently lead to adverse effects on thyroid function. In this randomised placebo-controlled double-blind study, we examined the effect of supplementation with selenium and coenzyme Q10 on thyroid hormonal status, cardiovascular (CV) mortality and health-related quality of life (Hr-QoL).MethodsFree T3, free T4, reverse T3, and TSH were determined in 414 individuals at baseline, and the effect of selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day) supplementation on hormone concentrations, CV mortality and Hr-QoL was evaluated after 48 months using Short Form 36 (SF-36). Pre-intervention plasma selenium was low, mean 67 µg/L, corresponding to an estimated intake of 35 µg/day. Changes in concentrations of thyroid hormones following the intervention were assessed using T-tests, repeated measures of variance, and ANCOVA analyses.ResultsIn the total population, the group with the lowest selenium concentration at baseline presented with significantly higher levels of TSH and lower levels of fT3 as compared to subjects with the highest selenium concentration. Supplementation with selenium and coenzyme Q10 for 4 years significantly increased fT3 and rT3, decreased fT4, and diminished the increase in TSH levels compared with placebo treatment (p = 0.03, all). In the placebo group, TSH and fT4 values above the median were associated with an increase in 10-year CV mortality, as compared with the mortality rate among those with TSH and fT4 below the median (p < 0.04, both), with no difference in mortality rate according to TSH and fT4 levels in the active intervention group. Similarly, TSH > median and fT3 < median were associated with a decline in mental Hr-QoL measures vs. TSH < and fT3 > median in the placebo group during 4 years of follow-up, but this was wiped out in the active group.ConclusionsSupplementation with selenium and coenzyme Q10 had a beneficial effect on thyroid hormones with respect to CV mortality and Hr-QoL outcomes. The initial deficient selenium status was associated with an impaired thyroid function and the changes in thyroid hormone levels can be explained by increased activity of deiodinases. We conclude that a substantial part of the elderly study population might suffer from suboptimal thyroidal function with adverse clinical implications due to selenium deficiency.Trial registrationThis study was registered at ClinicalTrials.gov and has the identifier NCT01443780. Since it was not mandatory to register at the time the study began, the study has been registered retrospectively.

Ameliorative effect of ferulic acid on thyroid dysfunction against propyl-thiouracil induced hypothyroid rats.

Hypothyroidism is an endocrine disorder characterised by decreased T3, T4 and increased TSH levels. This study aims to examine the potential effects of Ferulic acid (FA) on rats with hypothyroidism induced by propylthiouracil through the estimation of biochemical parameters and histopathological studies. Twenty-five female wistar rats were allocated into five groups: Control group [1% CMC, p.o.], Disease group [PTU-50 mg/kg, p.o.], [Levothyroxine (LT4) group - 20 µg/kg, p.o. + PTU-50 mg/kg, p.o.], [FA -25 mg/kg, p.o. + PTU-50 mg/kg, p.o.] and [FA 50 mg/kg, p.o. + PTU-50 mg/kg, p.o.]. On 15th day blood was collected and serum was separated for estimation of biochemical parameters, liver and kidney homogenate was utilised for the estimation of oxidative stress markers and the thyroid gland was dissected to examine histological features. PTU administration for 14 days showed a substantial decline in T3 and T4 and increases in TSH levels. PTU-administered rats significantly increased TC, TG and LDL levels, and decreased HDL levels. AST, ALT, urea, creatinine, and IL-6 were determined and these levels were significantly altered in PTU-induced hypothyroid group. In hypothyroid rats MDA, NO, GSH and SOD levels were significantly altered. However, treatment with FA for 14 days attenuated PTU-induced alterations. Furthermore, FA improves the histological changes of the thyroid gland. In conclusion, FA treatment showed a protective effect against hypothyroidism by stimulating the thyroid hormones through the activation of thyroid peroxidase enzyme and improving thyroid function. In addition, FA diminished the increase in lipids, liver and kidney markers, oxidative stress and inflammation.

Effective substances and molecular mechanisms guided by network pharmacology: An example study of Scrophulariae Radix treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries

Ethnopharmacological relevanceScrophulariae Radix (Xuanshen [XS]) has been used for several years to treat hyperthyroidism. However, its effective substances and pharmacological mechanisms in the treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries have not yet been elucidated. Aim of the studyThis study aimed to explore the pharmacological material basis and potential mechanism of XS therapy for hyperthyroidism and thyroid hormone-induced liver and kidney injuries based on network pharmacology prediction and experimental validation. Materials and methodsBased on 31 in vivo XS compounds identified using ultra-performance liquid chromatography tandem quadruple exactive orbitrap high-resolution accurate-mass spectrometry (UPLC-QE-HRMS), a network pharmacology approach was used for mechanism prediction. Systematic networks were constructed to identify the potential molecular targets, biological processes (BP), and signaling pathways. A component-target-pathway network was established. Mice were administered levothyroxine sodium through gavage for 30 d and then treated with different doses of XS extract with or without propylthiouracil (PTU) for 30 d. Blood, liver, and kidney samples were analyzed using an enzyme-linked immunosorbent assay (ELISA) and western blotting. ResultsA total of 31 prototypes, 60 Phase I metabolites, and 23 Phase II metabolites were tentatively identified in the plasma of rats following the oral administration of XS extract. Ninety-six potential common targets between the 31 in vivo compounds and the diseases were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that Bcl-2, BAD, JNK, p38, and ERK1/2 were the top targets. XS extract with or without PTU had the following effects: inhibition of T3/T4/fT3/fT4 caused by levothyroxine; increase of TSH levels in serum; restoration of thyroid structure; improvement of liver and kidney structure and function by elevating the activities of anti-oxidant enzymes catalase (CAT),superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px); activation anti-apoptotic proteins Bcl-2; inhibition the apoptotic protein p-BAD; downregulation inflammation-related proteins p-ERK1/2, p-JNK, and p-p38; and inhibition of the aggregation of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, as well as immune cells in the liver. ConclusionXS can be used to treat hyperthyroidism and liver and kidney injuries caused by thyroid hormones through its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. In addition, serum pharmacochemical analysis revealed that five active compounds, namely 4-methylcatechol, sugiol, eugenol, acetovanillone, and oleic acid, have diverse metabolic pathways in vivo and exhibit potential as effective therapeutic agents.

Umbilical cord blood thyroid hormones are inversely related to telomere length and mitochondrial DNA copy number

Hypothyroidism has been linked to reduced mortality rate and increased lifespan and health span. Telomere shortening, enhanced oxidative stress, and reduced cellular mitochondrial content are important hallmarks of aging shown to be related to age-associated diseases. It was proposed that the status of these markers in early life can be predictive of lifespan and the predisposition to certain age-associated disease in adulthood. Animal studies indicated that prenatal injection of thyroid hormones affects postnatal telomere length. Here, we sought to determine whether thyroid hormones TSH and fT4 are related to the telomere length, mitochondrial DNA copy number (mtDNAcn), and oxidative stress resistance marker GPX in the cord blood of newborns. In this study, we analyzed 70 mothers (18–42 years) and neonate dyads born in 2022 at the Nik Nafs maternity Hospital in Rafsanjan. The relative telomere length (RTL) and mtDNAcn were measured in the genomic DNA of cord blood leukocytes using real-time PCR. GPX enzyme activity was measured in the serum using colorimetric assays. In this study the correlation between these markers and the cord blood TSH and fT4 hormones were assessed using regression models. We found a reverse relationship between TSH levels and RTL in the cord blood of neonates. Additionally, our results displayed increased TSH levels associated with enhanced GPX activity. Regarding the mitochondrial DNA copy number, we found an indirect relationship between fT4 level and mtDNAcn only in male newborns. Future analyses of various oxidative stress markers, mitochondrial biogenesis status, telomerase activity, and the level of DNA damage are warranted to demonstrate the underlying mechanism of our observations.

Serum FT3/FT4, but not TSH is associated with handgrip strength in euthyroid U.S. population: evidence from NHANES.

Although several studies have examined the relationship between thyroid function and muscle strength, their population primarily derived from Asian areas, and their results were controversial. Thus, this study aimed to explore the association between thyroid function and handgrip strength (HGS) in the U.S. population. A total of 1,067 participants from NHANES were categorized into three different age groups including young (<45 years), middle (45~64 years), and old (≥65 years) age groups. Thyroid function was measured by the competitive binding immune-enzymatic assays, while HGS was examined by a trained evaluator using a dynamometer. The weighted multiple linear regression models were used to examine the association between thyroid function and handgrip strength. The restricted cubic splines were employed to explore the non-linear relationship between these two variables. All statistical analyses were performed using the SPSS version 20.0 and R software. After adjustment for potential covariates, FT3/FT4, but not TSH was positively associated with HGS in middle age group (β=0.091, t=2.428, P=0.016). The subgroup analysis by sex revealed that the positive association between FT3/FT4 and HGS was observed in the middle age group for both male and female participants (β=0.163, t=2.121, P=0.035; β=0.157, t=2.180, P=0.031). The RCS analysis showed a statistically significant non-linear association between FT3/FT4 and HGS in overall population (P for non-linear=0.026). After adjustment for covariates, men with low HGS had a significant lower FT3/FT4 than those without low HGS in old age group (P=0.013). There was a significant increase in TSH level for female participants with low HGS in old age group compared to those with normal HGS (P=0.048). This study demonstrated FT3/FT4, but not TSH, was positively associated with HGS in middle age group, and the different association was observed in men in middle age group when participants were stratified by sex. Future longitudinal cohort study should be conducted to reveal the causal relationship between thyroid function and muscle strength.

The effect of sleeve gastrectomy on physiological functions and some vital indicators in obese patients in Najaf

Abstract Background: Obesity usually results from excessive nutrition, which causes a defect in the functions of the immune system as a result of the accumulation of fat, as excess fat in the body is associated with changes in the number of white blood cells, red blood cells, and platelets, and is associated with changes in the function of the thyroid gland, where obesity affects the permeability of vessels It is also related to many metabolic disorders, including iron balance disorders, so many surgical techniques have been developed to treat obesity, including the laparoscopic sleeve gastrectomy, which is one of the common procedures for treating obesity and has gained great popularity due to its great impact on weight. This study aimed to know the complications and some side effects (positive and negative) of one of the surgeries used in the treatment of obesity, represented by sleeve gastrectomy Materials and Methods: Samples were collected from patients with laparoscopic sleeve gastrectomy who underwent the operation at Al-Batool Al-Ahly Hospital and Al-Ghadeer Center in Al-Najaf Governorate from September 2022 to March 2023. (43) Patients who underwent laparoscopic sleeve gastrectomy were selected (18) males and (25) Females aged between (60-18) years and with a body mass index greater than 35 kg / m2, (19) obese people (8) males and (11) females were taken as a control group, matching patients with age Results: The results showed a decrease in Ferritin protein levels and an increase in TSH levels in the patient group compared to the control group without statistical differences. As for blood indicators, the study showed that there were no significant differences (P&gt;0.05) in the following indicators Hgb, HCT , MCV, and MCH, showed an increase in PLTs, MCHC, RBCs, MPV, and a decrease in WBC, Neutro, and Lymph in the patient group compared to the control group. As for the effect of gender on the criteria in the patient group, the results showed a significant decrease in both ferritin and each of Hgb. RBCs, HCT, MCV, MCH and MPV, and a significant increase in the level of TSH in females compared to males, and the results indicated that there were some changes in the studied parameters of sleeve gastrectomy patients divided according to the period after the operation. Conclusion: Although there was no significant difference between ferritin protein levels in the control group and the patients group, the protein levels decreased after gastric sleeve gastrectomy, and its levels were affected by sex and body mass index, and the sleeve gastrectomy was of high quality, clear effects with regard to some blood physiological parameters, especially a decrease in the number of white blood cells, neutrophils, and lymphocytes, which may indicate a decrease in low-grade inflammation resulting from obesity in the sleeved patients.

Arsenic-Induced Thyroid Hormonal Alterations and Their Putative Influence on Ovarian Follicles in Balb/c Mice.

Thyroid issues are common among women in their reproductive years, and women with thyroid dysfunction often encounter challenges with fertility. Arsenic is known for its toxic effects on the thyroid and ovaries, investigated independently. However, there is no known study directly or indirectly addressing the association between arsenic, thyroid function, and ovarian reserve. This study aims to investigate the effect of arsenic on thyroid function and its possible implications on ovarian follicular reserve. Female Balb/c mice were given sodium arsenite (0.2ppm, 2ppm, and 20ppm) via drinking water for 30days. Findings showed that arsenic decreased thyroid hormone levels (fT3 and fT4) while increasing TSH levels, which might have led to elevated levels of FSH and LH. Furthermore, arsenic treatment not only decreased thyroid follicle sizes but also altered the ovarian follicular count. The finding demonstrates that arsenic significantly reduced the expression of LAMP1, a lysosomal marker protein. This reduction leads to increased lysosomal permeability in the thyroid, resulting in a significant release of cathepsin B. These changes led to hypothyroidism, which might indirectly affect the ovaries. Also, the elevated levels of growth differentiation factor-8 in arsenic-treated ovaries indicate impaired folliculogenesis and ovulation. Furthermore, arsenic significantly increased the expressions of pAkt and pFoxo3a, implying that arsenic accelerated the activation of the primordial follicular pools. In conclusion, arsenic disrupts lysosomal stabilization, potentially leading to a decline in circulating fT3 and fT4 levels. This disturbance could, in turn, affect the estrous cycle and may alter the pattern of follicular development.

SAT491 Development of Thyroidal Nodule in Congenital Hypothyroid Girl With Thyroid Peroxidase Gene Mutation

Abstract Disclosure: J. Lee: None. A. Oh: None. H. Han: None. Background: Reduced thyroxine synthesis in dyshormonogenesis induces increased thyrotropin (TSH) secretion through reduced negative feedback of thyroxine. Consequently, the affected patients are born with goiter or develop postnatal goiter, when L-thyroxine (LT4) supplementation is delayed. Cases of thyroid cancer have been reported in congenital hypothyroidism (CH) due to dyshormonogenesis, usually of follicular histology. Clinical Case: A 22-year lady has been taking LT4 since 8-years, under the diagnosis of goitrous CH. Her mother recalled neck swelling at newborn period. However, normal newborn screening test prevented neonatal goiter from further investigation. Initial test at 8-year of age revealed normal thyroid function without thyroid auto-antibodies, diffuse enlarged thyroid gland with increased uptake on 99mTc scan, and diffuse thyroid enlargement with heterogeneous echogenicity on ultrasonography (US). The goiter size waxed and waned according to the drug compliance. The highest TSH level (normal 0.17-4.05 μIU/mL) was 8.68 μIU/mL even without medication for 8 months by her own judgement. At 11.5-years, US found isoechoic solid nodule of 1.8 x 1.7 x 1.6 cm with peripheral halo in the inferior aspect of right thyroid, which was demonstrated to be benign follicular lesion favoring nodular hyperplasia on fine needle aspiration biopsy. With good drug compliance, the nodule size decreased to 1.1 x 0.9 cm at 18-years, and peripheral calcification appeared around the isoechoic solid nodule previously reported without change in size at 22-years. NGS panel for CH reported compound heterozygous variants in TPO gene. One pathogenic variant from asymptomatic father is c.2757del;p.(Met921Trpfs*53), the other likely pathogenic variant from asymptomatic mother is c.1580G&amp;gt;T;p.(Trp527Leu). Conclusion: This case is demonstrating development of thyroid nodule even with mild increased TSH level during LT4 medication in dyshormonogenic CH caused by TPO mutation. Regular follow-up and compliance to LT4 might be important to avoid thyroid tissue stimulation and possibly nodule formation by elevated TSH. Presentation Date: Saturday, June 17, 2023

Effect of Libyan Sidr honey on thyroid gland damage induced by cigarette smoke in male rats.

The toxicity of cigarette smoke (CS) products is through vast production of reactive oxygen species. So, this study aimed to evaluation the effect of Libyan Sidr honey on thyroid gland damage induced cigarette smoke in male rats. 28 adult male rats were divided into four groups; Group 1: Control group (NC); group 2: rats were received the Libyan Sidr honey (LSH) orally (100 mg/kg b.w./d.) for 4 w.; group 3: rats were exposed to 5 lit of the Karelia red cigarette smoke (KRC) (5 times/d.) by a machine smoking for 4 w.; and group 4: (LSH+KRC) rats were received the LSH orally (100 mg/kg b.w./d.) for 2 w., then the rats were exposed to the KRC generated by a machine smoking for 4 w. with the continuation of LSH doses. The result revealed that T4 showed, non-significant decrease in the KRC group compared to the NC group. While, it was significant declining in T3 with a significant increase in TSH levels as compared to NC group. Moreover, the (LSH+KRC) group showed a noticeable improvement in T4 &amp; T3 as compared with the KRC group. Furthermore, the (LSH + KRC) group showed a significantly positive change in TSH as compared with KRC group. The histopathological examination of the thyroid of rats after exposure to KRC alone showed different histopathological changes when compared with control group. Whereas, the (LSH + KRC) group showed, improve thyroid arrangement with normal thyroid follicles when compared with KRC group. Conclusion, results indicate that the Libyan Sidr honey antioxidant activity against thyroid tissues damage induced cigarette smoke in adult male albino rats.

P92 PERIMYOCARDITIS AS FIRST MANIFESTATION OF DYSTHYROIDISM: AN UNUSUAL CASE

Abstract Thyroid and cardiovascular system are inextricably related and cardiovascular complications can occur in both subclinical and overt thyroid dysfunction. We report the case of a 42–year–old woman presenting with chest pain. She had a positive SARS–CoV–2 swab in June and she was hospitalised in suspicion of COVID–related pneumonia and pericarditis in July: treatment with ibuprofen and colchicine was started and patient was discharged. On July 26th, the patient came back to emergency department due to worsening chest pain and myalgias after therapy decalage. She had face edema and hoarse voice. 12–leads EKG was normal; echocardiography showed 8 mm pericardial effusion and normal ejection fraction. Blood testing revealed no inflammatory signs, a mild increase of Troponin (peak value 19.1 ng/L, n.v. 0–14) and a high value of CPK (peak value 2299 U/L, 464 U/L at time of discharge, n.v. 30–150). Moreover, she had a biohumoral profile of Hashimoto thyroiditis: severe hypothyroidism with increase in TSH levels (538 microU/ml peak value, 322 microU/ml at time of discharge, n.v. 0.27–4.2) and positivity to thyroid autoantibodies. The patient underwent a cardiac magnetic resonance imaging that was suggestive for acute perimyocarditis with biventricular diffuse myocardial edema, preserved biventricular function and mild–to–moderate pericardial effusion. Low dose L–T4 therapy was started together with liothyronine that was stopped after few days, once acceptable FT3 concentrations were obtained. At echocardiography control after 8 days, we registered a significant reduction of pericardial effusion (2 mm). Myocarditis is an inflammatory disease of the myocardium and it is predominantly mediated by viral infection. A rare cause of myocarditis is represented by dysthyroidism. In our case, the severe hypothyroidism seems to be the cause of myocardial and pericardial edema. The failure in diagnosis of this endocrinological disorder can determine a delay in specific therapy with possible serious cardiovascular manifestations. So, it would be reasonable to check the thyroid status of all patients presenting with myopericarditis, in the absence of another clearly identifiable aetiology. The role of to the prior SARS–CoV–2 infection in not certain in our case, but the quick recovery after specific endocrinological therapy suggests the low probability of perimyocarditis as SARS–CoV2 related manifestation.

Antithyroid Peroxidase and Thyroid Hormones in a Sample of Iraqi Patients with Type 2 Diabetic Mellitus

This study aims to investigate the relationship between thyroid peroxidase antibody (TPO) and thyroid function tests (TSH, T3 and T4) in patients with type 2 diabetes mellitus (T2DM). Ninety women and men, with ages ranging between 35-65 years and weighing 60-80 kgs, were selected for this study. They were classified into three groups: G1 included 15 healthy control group, G2 had15 patients with T2DM and G3 had 60 patients with T2DM and hypothyroidism. Blood samples were collected from each individual via vein puncture to assess thyroid hormone and TPO-Ab. The results showed highly significant (p &lt; 0.01) increase in TSH level in the diabetic group with hypothyroidism when compared to the other groups. There was no significant difference between diabetic and control groups. T4 and T3 levels showed highly significant (p&lt;0.01) decrease in the diabetic group with hypothyroidism when compared to the diabetic and healthy control groups. On the other hand, there was no significant difference between the diabetic and healthy control groups. The results showed highly significant (p &lt; 0.01) increase in the TPO-AB level in diabetic group with hypothyroidism when compared with the diabetic and healthy control groups.

Alpinea galanga (L) Extracts Decreases TSH Levels and Balances tri-iodothyronine (T3), Thyroxine (T4) levels with protective effect on Thyroid Tissue in Wistar Rats with Thyroid Disorder

In India Endocrine disorders, especially thyroid disorders are prevailing. Among different thyroid disorders hypothyroidism precedes and stands as a challenge in our society. There is a strong need to control its prevalence because it majorly contributes to a large number of chronic disorders. Presently the major choice of therapy is intake of Thyroxine hormone. However there are various alternative medicines, specifically herbal treatments, being reported in the literature and now a day’s the authentic investigation of such herbal treatments is gaining popularity. Present study explores the anti- hypothyroid potential of Alpinea Galanga (L) rhizome extracts. The rhizome extracts were prepared and Acute toxicity studies (425) were performed. Hypothyroidism was induced in female albino rats using Propylthiouracil (PTU) at a dose of 60µg/kg bodyweight orally for one month. Hypothyroidism was confirmed by increased TSH levels in blood. Those animals which were exposed to PTU were treated with standard thyroxine at a dose of 10µg/kg bodyweight by oral route and different extracts were given at a dose of 200mg/kg bodyweight by oral route to their respective groups. Treatment was carried for two months. Methanolic extract at dose of 200mg/kg bodyweight was found more effective in restoring the elevated levels of TSH when compared to the other treated groups. The results of extract indicate less damage to the follicles of thyroid tissue which shows minimizing effect of Alpinea Galanga (L) rhizome extracts over PTU induced Hypothyroidism. Histopathological examination shows the restoration of thyroid follicles by Thyroxine hormone and Rhizome extracts as compared to untreated groups. This study depicts the Thyroid protective and enhancing property of Alpinea Galanga (L) rhizome extracts by lowering TSH levels and by reducing damage to thyroid tissues.

Late Breaking Abstracts

Late Breaking Abstracts