High T3 Research Articles

The Clinical Implications of Anti-thyroid Peroxidase Antibodies in Graves' Disease in Basrah.

Background Graves' disease (GD) is an autoimmune disease, with thyrotropin receptor antibodies (TRAbs) being the most important cause in the pathogenesis. The aim of this study is to assess the clinical significance of anti-TPO Abs in GD. Methods A retrospective study was conducted at the Faiha specialized Diabetes, Endocrine, and Metabolism Center (FDEMC) in Basrah during the period between December 2021 and December 2022. A total of 141 patients with GD were involved in this study, and of them, 97 (68.8%) were women. They were divided into two groups: patients with positive and negative anti-TPO Abs groups. Results Positive anti-TPO Abs were seen in 83 patients (58.9%) with GD. Pretreatment-free thyroxine level (ng/dL) was higher in the anti-TPO Abs positive GD patients than in those with negative antibodies (3.7±0.2 versus 3.0±0.2 with a p=0.021). Similarly, higher TRAb titers (IU/ml) at baseline were also seen in patients with positive anti-TPO Abs (9.8±0.7 versus 6.8±0.8) with a p=0.008. Giraffe appearance on thyroid ultrasound was more common in the group with positive anti-TPO Abs as compared to patients with negative anti-TPO Abs: 20 (87.0%) versus 3 (13.0%) with a p=0.005. A higher anti-TPO Abs titer (IU/mL) was associated with a baseline TRAb level of more than 6.4 IU/mL, and giraffe appearance on thyroid ultrasound (206.5±20.0 p-value<0.0001 and 228.0±35.3 p value=0.007, respectively). Conclusion A positive anti-TPO Abs in GD is associated with a high TRAb titer and free T4 level at baseline, as well as a giraffe appearance on thyroid ultrasound.

Delaying Surgery After Neoadjuvant Chemotherapy Affects Survival in Patients with Colorectal Peritoneal Metastases: A BIG-RENAPE Network Multicentric Study.

Multimodal treatment for patients with peritoneal metastases (PM) from colorectal cancer (CRC), including perioperative chemotherapy (CT) plus complete resection, is associated with prolonged survival. The oncologic impact of therapeutic delays is unknown. The aim of this study was to assess the survival impact of delaying surgery and CT. Medical records from the national BIG RENAPE network database of patients with complete cytoreductive (CC0-1) surgery of synchronous PM from CRC who received at least one neoadjuvant CT cycle plus one adjuvant CT cycle were retrospectively reviewed. The optimal interval between the end of neoadjuvant CT to surgery, surgery to adjuvant CT, and total interval without systemic CT were estimated using Contal and O'Quigley's method plus restricted cubic spline methods. From 2007 to 2019, 227 patients were identified. After a median follow-up of 45.7 months, the median overall survival (OS) and progression-free survival (PFS) was 47.6 and 10.9months, respectively. The best cut-off period was 42 days in the preoperative interval, no cut-off period was optimal in the postoperative interval, and the best cut-off period in the total interval without CT was 102 days. In multivariate analysis, age, biologic agent use, high peritoneal cancer index, primary T4 or N2 staging, and delay to surgery of more than 42 days (median OS 63 vs. 32.9months; p=0.032) were significantly associated with worse OS. Preoperative delay of surgery was also significantly associated with PFS, but only in univariate analysis. In selected patients undergoing complete resection plus perioperative CT, a period of more than 6 weeks from completion of neoadjuvant CT to cytoreductive surgery was independently associated with worse OS.

Dietary Supplementation of Chestnut Tannins in Prepartum Dairy Cows Improves Antioxidant Defense Mechanisms Interacting with Thyroid Status.

Cows in the peripartal period undergo changes in thyroid hormones and are susceptible to lipomobilization and/or oxidative stress. The addition of chestnut tannins as polyphenolic compounds in the diet may improve feed efficiency and prevent oxidative stress-related health disorders in transition cows. However, the relationship between chestnut tannin supplementation and thyroid function, which plays an important role in metabolic regulation, has not been investigated in dairy cows. This study was conducted to investigate the effects of chestnut tannin supplementation during the close-up period on thyroid status and to evaluate the interaction between thyroid hormones and oxidative stress biomarkers in prepartum dairy cows. Forty multiparous Holstein cows were fed either a diet containing chestnut tannins (CNTs, n = 20, 1.96 g chestnut tannins/kg feed, dry matter) or a non-supplemented diet (CON, n = 20) during the last 25 ± 2 days of gestation. Blood samples were collected on the first day of study (before chestnut tannin supplementation) and d 5 before parturition to measure hormonal and oxidative stress indices. Serum concentrations of T3 (p = 0.04) and T4 (p = 0.05) were higher in CNT cows than in the CON group on day 5 before parturition. Thyroid status of CNT cows was associated with higher serum total antioxidant capacity (T-AOC, p < 0.01), activities of superoxide dismutase (SOD, p = 0.03) and glutathione peroxidase (GPx, p = 0.01), and reduced glutathione concentration (GSH, p = 0.05). Serum thiobarbituric acid reactive substances (TBARS) were lower (p = 0.04) which was associated with lower aspartate aminotransferase (AST, p = 0.02), and lactate dehydrogenase (LDH, p = 0.01) activities in the CNT than in the CON group. Estradiol and progesterone did not differ between CNT and CON cows. Chestnut tannin supplementation improves antioxidant protection, prevents oxidation-reduction processes, reduces the degree of liver cell membrane damage, and protects thyroid tissue from damage, allowing higher T3 and T4 synthesis. Considering the importance of the thyroid hormone status before parturition, mechanisms of thyroid hormone regulation in CNT-supplemented dairy cows require more detailed investigations.

High Free T3 Levels in the Second Trimester are Correlated with the Control of Gestational Diabetes Mellitus

Gestational Diabetes Mellitus (GDM) and abnormal thyroid function are two common endocrine disorders occurring during pregnancy. In this study, we evaluated the correlation between the levels of different thyroid hormones and blood glucose control in pregnant women with diet-controlled GDM. Mid-pregnancy serum samples were obtained from 439 participants with GDM controlled by diet for analyses of thyroid function. A 2-h 75-g oral glucose tolerance test was used to evaluate the effect of blood glucose controlled by diet. According to blood glucose levels before and 2h after a meal, mothers were grouped into GDM-A1 (≤5.3mmol/L, ≤6.7mmol/L, respectively) and GDM-A2 (&gt;5.3 mmol, &gt;6.7mmol/L, respectively) and these groups were compared to the associated thyroid levels using multivariate logistic regression analysis. Our results show that fT3 was positively associated with GDM-A2. The adjusted odds ratio (95% confidence interval) comparing the highest and lowest fT3 quartile was 3.12 (1.66, 15.87) at the second trimester. Neither TSH nor fT4 was significantly associated with GDM-A2. Higher FT3 levels during the second trimester of pregnancy are a risk for GDM-A2 incidence. This provides new ideas for the control of GDM.

Endocrine Abnormalities in Children With Traumatic Brain Injury at a Tertiary Care Center.

Objective Accidental traumatic brain injury (TBI) can lead to severe complications such as endocrine abnormalities and long-term morbidities and can negatively impact patient lives. These conditions are also associated with a high cost of treatment over a lifetime, a significant concern in low-to-middle-income countries (LMICs). In Pakistan, the prevalence of children with endocrine abnormalities secondary to TBI remains largely unexplored. We conducted a retrospective cross-sectional study to estimate the burden of endocrine abnormalities due to TBI among children in our population. Methods Twenty patients previously admitted with head injury between September and October 2019 were retrospectively reviewed with tests for baseline serum sodium, plasma osmolality, cortisol, adrenocorticotropin (ACTH), free thyroxine (fT4), growth hormone (GH), insulin growth factor-1 (IGF-1), follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), prolactin, estradiol, and testosterone. Data were collated from the electronic Health and Information Management System (HIMS) and analyzed using SPSS v25. Chi-square and t-tests were used to identify associations between variable groups. Outcomes of interest included correlations between hormonal levels and demographic factors, interventions and hormonal levels, and complication rates and hormonal levels. Results Our study reports three (15% of the total cohort) patients with pituitary hormone deficits (two with low IGF-1 and one with low TSH). High serum IGF-1 and ACTH levels were also observed in three (15%) children. High IGF-1 was associated with female gender (p=0.007), mechanical ventilation (p=0.038), and falls (p=0.028). IGF-1 (p=0.035) and GH (p=0.049) levels were associated with improvement in Extended Glasgow Outcome Scale (GOS-E) score. Testosterone was positively correlated with a high percentile for height (p=0.005) and GOS-E scores on follow-up (p=0.030). High testosterone levels (592.12 ± 102.28 ng/dl) were associated with good functional outcomes in post-pubescent patients (p<0.05). Serum fT4 was linked with a high GOS-E score at discharge in prepubescent patients (p=0.034). Neurosurgical decompression was the only risk factor for hormone deficiency, comprising 67% of the group with hormone deficiencies (p=0.028). The learning difficulties were observed exclusively in children with hormonal deficiencies (7 patients, p=0.000). Conclusion Hormonal dysfunction due to TBI in children can lead to poor outcomes. High serum IGF-1, testosterone, and free T4 levels were associated with improved functional outcomes in children with TBI. Limited follow-up and resources in LMICs are significant barriers to addressing the morbidity associated with these conditions and need to be addressed at a health policy level.

Independent and combined effects of exposure to organophosphate esters on thyroid hormones in children and adolescents.

Toxicological studies suggest that organophosphate esters (OPEs) may impair thyroid function. Epidemiological evidence, related to children and adolescents, has not been reported, and little is known about the combined effects of exposure to OPE mixtures. In this study, we collected information of 1156 children and adolescents (aged 6-18years, 48.4% males) from a cross-sectional study in Liuzhou, China, and measured the levels of 15 urinary OPE metabolites and 5 serum thyroid hormones. Multivariate linear regression and quantile g-computation (QGC) approach were used to examine the associations which adjusted for demographic and lifestyle characteristics. Few participants had levels of triiodothyronine (T3) and free thyroxine (FT4) outside age-specific pediatric ranges. QGC analyses showed that individuals in the second, third, and fourth quartiles (Q2-Q4) of exposure had 3.93% (2.14%, 5.75%), 8.01% (4.32%, 11.8%), and 12.3% (6.54%, 18.3%) higher T3 than those in the first quartile (Q1), with similar pattern for free triiodothyronine (FT3). Individuals in Q2 and Q3 had higher thyroid-stimulating hormone (TSH) than those in Q1, but no differences were observed in TSH between Q1-Q4. In contrast, compared to the lowest quartile, FT4 was lower for those in Q2 (- 1.54%; 95% CI: - 3.02%, -0.04%), Q3 (-3.07%; 95% CI: -5.95%, -0.09%), and Q4 (-4.56%; 95% CI: - 8.80%, - 0.13%). These associations were consistent with the results from multivariate linear regression. When stratified by sex, OPE exposure (individual or mixtures) was associated with increased T3 and FT3 in males and decreased FT4 in females. This study provides the first evidence to characterize the thyroid-disrupting effects of OPE exposure in children and adolescents.

Challenges in Thyroid Function Testing: Interferences and Clinical Implications

In recent decades, significant advancements have been made in the methodologies used for evaluating thyroid dysfunctions. These advancements include the development of radioimmunoassays, immunometric assays, and liquid chromatography coupled with mass spectrometry. The main thyroid function tests include thyroid-stimulating hormone (TSH) and the measurement of triiodothyronine (T3) and thyroxine (T4), including their total and free fractions. Over time, different generations of TSH tests have been developed, starting from radioimmunoassays to immunometric assays, and more recently, tests utilizing fluorophores and chemiluminescent molecules. The third-generation tests are currently the most widely used due to their high sensitivity and specificity. Thyroid-stimulating hormone is preferred as the initial test for evaluating thyroid function since it has a log-linear relationship with free T4 levels, enabling the identification of subclinical hypothyroidism and subclinical hyperthyroidism. The reference range for normal TSH levels is typically between 0.45 and 4.5 mIU/L. However, there can be variations in TSH levels based on factors such as sex, age, and ethnicity. Specific reference values may be required for certain populations, such as the elderly, pregnancy, and neonates. In the elderly, an increase in TSH levels is expected. In the neonatal period, TSH levels are high after birth and take a few weeks to normalize. During pregnancy, various physiological changes occur, leading to alterations in thyroid hormones to meet fetal demands. Laboratory interferences in thyroid hormone assays must be considered to ensure accurate results. Biotin interference can lead to falsely low TSH and falsely high free T3 and T4 levels. Macro-thyrotropin can cause elevated TSH levels with normal thyroid hormone levels. Heterophilic antibodies can also cause false results. Additionally, the evaluation of autoantibodies and markers used in thyroid cancer follow-up needs special attention. Patients experiencing conditions like trauma, particularly in severe cases, may undergo changes in thyroid hormone levels, even without having a specific thyroid disease, which is called low triiodothyronine syndrome. In conclusion, it is essential to be aware of potential laboratory interferences and consider individual variations to ensure accurate interpretation and appropriate management of patients.

A case of syndromic congenital hypothyroidism with a 15.2 Mb interstitial deletion on 2q12.3q14.2 involving &lt;i&gt;PAX8&lt;/i&gt;

Paired box 8 (PAX8) mutations are an established genetic cause of congenital hypothyroidism (CH). The majority of these mutations are found in the protein-coding exons of the gene. The proband, a 3-yr-old girl, had tetralogy of Fallot and polydactyly soon after birth. She was diagnosed with CH in the newborn screening for CH. She had a high serum TSH level (239 mU/L) and low free T4 level (0.7 ng/dL). Ultrasonography revealed thyroid hypoplasia. We performed array comparative genomic hybridization because the patient exhibited a variety of symptoms across multiple organ systems. The analysis revealed a novel heterozygous deletion that spanned a 15.2 Mb region in 2q12.3q14.3 (GRCh37; chr2:109,568,260-124,779,449). There were 71 protein-coding genes in this region, including two genes (PAX8 and GLI2) associated with congenital endocrine disorders. The common clinical features of the two previously reported patients with a total PAX8 deletion and our case were CH, short stature and intellectual disability, but the severity of hypothyroidism and other clinical features were variable. In conclusion, we describe a syndromic CH patient with a novel 2q12.3q14.3 deletion involving PAX8. Patients with CH, whose unifying diagnosis is not obvious, could have a genomic deletion involving PAX8.

A Case of NMO Presenting with Hyperthyroidism

Neuromyelitis optica (NMO) is an autoimmune disease of central nervous system with extensive clinical presentations but based on the international consensus diagnostic criteria 2015. The horizon has broadened to a larger entity called NMOSD or NMO spectrum disorders. Nonneurological systemic autoimmune diseases especially thyroid disorders are commonly associated with NMOSD, among which Hashimoto’s thyroiditis is common, whereas not much literature is available regarding the association of Graves’ disease with NMOSD. A 38-year-old male presented with acute onset upper motor neuron quadriparesis along with features of hyperthyroidism with a prior history of sudden onset bilateral decreased vision of both eyes 3 years back. Magnetic resonance imaging (MRI) showed T2 hyperintensity involving cervicodorsal cord from C4 to D6 indicating a longitudinally extensive transverse myelitis (LETM) but brain MRI was normal. Serum antiaquaporin 4 antibody in the cell-based assay was positive. Serum thyroid stimulating hormone was very low with high free T4 and positive thyroid stimulating hormone receptor antibody and anti-thyroid peroxidase Ab. With optic neuritis, transverse myelitis (LETM), and positive antiaquaporin 4 antibody, he was diagnosed with NMO with Graves’ disease. Autoimmune thyroid diseases are associated with NMO in many studies but precise clinical and serological quantification of thyroid disorders especially Graves’ disease is still lacking. We are presenting a case of NMO with Graves’ disease who presented with symptoms of hyperthyroidism before myelitis. Our patient developed myelitis almost 3 years after having optic neuritis, but before myelitis, he was having symptoms of hyperthyroidism. Hence, patients of suspected NMO must be monitored for other nonneurological autoimmune diseases both clinically and serologically even in early stage when they are not fulfilling the diagnostic criteria.

High Mean Platelet Volume Is Associated with Cerebral White Matter Hyperintensities in Non-Stroke Individuals

The mean platelet volume (MPV) is regarded as a marker for thrombosis, atherosclerosis, and inflammation in various vascular diseases. However, it still remains unclear whether plasma MPV is associated with cerebral white matter hyperintensities (WMH) and cerebral microvascular pathology in the elderly population. We examined whether MPV level is associated with the presence of cerebral WMH on brain magnetic resonance imaging from 870 non-stroke outpatient subjects. The subjects were divided into three groups according to the consecutive level of MPV (low T1, middle T2, and high T3 MPV tertile groups). To determine the association of MPV levels with the WMH, logistic regression and receiver operating characteristic curve analyses were conducted. Subjects with higher MPV level were older and more likely to have hypertension, diabetes mellitus, and low renal function. Cerebral WMH were more prevalent in subjects with higher MPV level. After adjusting for confounding factors, moderate to severe cerebral WMH were significantly associated with high MPV tertile level. This association remained significant after adjusting for other cerebral vascular pathologies. T2 [odds ratio (OR): 1.49, 95% confidence interval (CI): 1.03-2.15] and T3 MPV tertile groups (OR: 1.51, 95%CI: 1.04-2.20) had more cerebral WMH lesions compared to T1 MPV tertile group. In addition, the subjects with higher Fazekas scores showed higher MPV level (p=0.020). We found that high MPV level is independently associated with cerebral WMH. This result suggests that platelet activation plays a role in the development of cerebral WMH.

Graves’ disease, myxedema and papillary thyroid carcinoma

Graves’ disease (GD) is the leading cause of hyperthyroidism and diffuse toxic goiter in iodine-sufficient geographical areas. GD is associated with classical manifestations such as ophthalmopathy and thyroid dermopathy, in addition to diffuse goiter, which may be the site of carcinomas, as a complication. Case report: A 52-year-old womanpresented with goiter and symptoms compatible with hyperthyroidism, such as heat intolerance, weight loss, fatigue, increased sweat, tachycardia, fine tremors, increased intestinal transit, anxiety, emotional lability, insomnia, exophthalmos, and pretibial myxedema. A complementary investigation confirmed the diagnosis of hyperthyroidism(high free T4 and total T3 levels and low thyroid-stimulating hormone - TSH levels). Ultrasound images showed diffuse enlargement of the thyroid lobes by approximately 10 times and the presence of three thyroid nodules, one of which was larger than 2 cm with heterogeneous echogenicity and vascularization throughout the nodule; ultrasound-guided fine needle aspiration revealed cytology compatible with Bethesda IV; scintigraphy revealed a low uptake area (cold nodule) amid a diffuse high-uptake goiter. A thyroidectomy was performed, and the anatomical specimen diagnosis revealed papillary thyroid carcinoma in the right lobe, with adjacent parenchyma compatible with GD.Histopathological examination of the skin showed the presence of myxedema compatible with Graves’ dermopathy. The patient evolved with the normalization of TSH levels and a reduction of cutaneous manifestations. Conclusion: GD abnormalities may not be restricted to the classic clinical manifestations, and a careful investigation may reveal the coexistence of carcinomas.

Gestational thyroid hormone concentrations and risk of attention-deficit hyperactivity disorder in the Norwegian Mother, Father and Child Cohort Study.

Maternal thyroid function plays an important role in foetal brain development; however, little consensus exists regarding the relationship between normal variability in thyroid hormones and common neurodevelopmental disorders, such as attention-deficit hyperactivity disorder (ADHD). We sought to examine the association between mid-pregnancy maternal thyroid function and risk of clinically diagnosed ADHD in offspring. We conducted a nested case-control study in the Norwegian Mother, Father and Child Cohort Study. Among children born 2003 or later, we randomly sampled singleton ADHD cases obtained through linkage with the Norwegian Patient Registry (n=298) and 554 controls. Concentrations of maternal triiodothyronine (T3), thyroxine (T4), T3-Uptake, thyroid-stimulating hormone (TSH) and thyroid peroxidase antibody (TPO-Ab) were measured in maternal plasma, collected at approximately 17 weeks' gestation. Indices of free T4 (FT4i) and free T3 (FT3i) were calculated. We used multivariable adjusted logistic regression to calculate odds ratios and accounted for missing covariate data using multiple imputation. We used restricted cubic splines to assess non-linear trends and provide flexible representations. We examined effect measure modification by dietary iodine and selenium intake. In sensitivity analyses, we excluded women with clinically significant thyroid disorders (n=73). High maternal T3 was associated with increased risk of ADHD (5th vs 1st quintile odds ratio 2.27, 95% confidence interval 1.21, 4.26). For FT4i, both the lowest and highest quintiles were associated with an approximate 1.6-fold increase in risk of ADHD, with similar trends found for T4. The FT4i association was modified by dietary iodine intake such that the highest risk strata were confined to the low intake group. Both high and low concentrations of maternal thyroid hormones, although within population reference ranges, increase the risk of ADHD in offspring. Increased susceptibility may be found among women with low dietary intake of iodine and selenium.

Allan-Herndon-Dudley syndrome: Report of a novel pathogenic variant in MCT8 gene

X-linked MCT8 mutations cause Allan-Herndon-Dudley syndrome (AHDS) characterized by severe developmental delay and specific thyroid function abnormality. The report describes a 1 year-old boy with severe developmental delay, truncal hypotonia, quadriparesis (spastic), dystonia, and thyroid function abnormality (high free T3, low reverse T3, low free T4, and normal TSH) suggesting a form of impaired thyroid hormone sensitivity, namely, AHDS. WES analysis yielded novel hemizygous single-base pair duplication in exon 1 of MCT8 gene, validated by Sanger sequencing. MRI revealed generalized demyelination with poor gray and white matter differentiation and loss of brain volume. Indirect markers revealed thyrotoxicosis in some peripheral tissues. Having high index of suspicion for this rare disorder and plausible benefit of inclusion of free T3 assay in initial evaluation of infants and children with idiopathic developmental delay are emphasized. Amelioration of thyrotoxic features with tri-iodothyroacetic acid likely benefits patients at all ages. Neurodevelopmental improvement has been observed in those who received tri-iodoacetic acid early, which is being currently investigated.

RF36 | PSUN101 Liver and Adipose Tissue Effects of Triiodothyronine Treatment in an Animal Model of Metabolic Syndrome

Abstract Introduction Metabolic syndrome (MS) associates to obesity and non-alcoholic fatty liver disease (NAFLD). Besides its high and rising prevalence, the therapeutical options are scarce. Studies show that thyroid hormones (TH) may ameliorate hepatic function and hepatic and extra-hepatic lipid deposition. Aim To evaluate the effects of triiodothyronine (T3) treatment in high and low dose on the liver and adipose tissue of an animal model of metabolic syndrome (ZSF1 rats). Material and methods Four groups of animals were evaluated: 1) ZSF1 lean rats (Ln, used as controls; n=8); 2) untreated ZSF1 obese rats (Ob; animal model of MS; n=10); 3) ZSF1 obese rats treated with high dose T3 (hT3; initially 0.04mg/mL and 0.06mg/mL after 4 weeks; n=5); 4) ZSF1 obese rats treated with low dose T3 (lT3; 0.03mg/mL; n=5). We performed anthropometric and oral glucose tolerance testing (OGTT). Tissues and blood were collected at the 24th week of age for histological evaluation and assessing the levels of thyroid hormones. Results The animals from hT3 and lT3 groups had similar weights and both were significantly heavier (tibial length/weight ratio of 14.7±0.6 and 14.1±0.7g/mm respectively) than Ln (10.7±0.6g/mm, p&amp;lt;0.01). The rats from lT3 group were also significantly lighter than Ob (15.3±1.0g/mm, p=0.042). Fasting glucose of hT3 (118.6±36.0mg/dL) was lower comparing to Ob (228.1±58.6mg/dL, p&amp;lt;0.01) and to lT3 (207.2±69.8mg/dL, p=0.048) and similar to Ln (82.1±9.1mg/dL, p=1.00). The evaluation of the area under the curve (AUC) of OGTT is in agreement with these results. The histological evaluation of the liver showed a ratio between lipids and surrounding tissue significantly lower in the treated groups (hT3 0.35±0.1 and lT3 0.34±0.1) compared to Ob (0.89±0.2, p&amp;lt;0.01) and similar to Ln (0.14±0.1, p=0.106 and p=0.124, respectively). The ratio between glycogen and surrounding tissue was not different between treated animals and either Ob or Ln. Concerning the adipose tissue, adipocyte area was similar between treated animals (hT3 7435±1031mm2 and lT3 6899±554mm2, p=1.00) and was significantly lower compared to Ob (9037±789mm2, p&amp;lt;0.01) and higher compared to Ln (2771±754mm2, p&amp;lt;0.01). The area of fibrosis was similar between hT3 and lT3 (7.7±1.1mm and 6.6±0. 5mm, respectively, p=1. 00), higher when comparing both groups with Ln (2.4±1.3mm, p&amp;lt;0.01) and lower when comparing both groups with Ob (13.5±2.2mm, p&amp;lt;0.01). Conclusion Treatment of obese ZSF1 animals with T3 improved the glycemic profile, and lipid and fibrous deposition in the liver and adipose tissue. The usage of low dose T3 does not seem different from high dose concerning these effects and might be associated with fewer adverse events. TH may, in the future, become an option when treating patients with MS and NAFLD. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:42 p.m. - 12:47 p.m.

Gated Ethidium- and Bleomycin-Loading in Phage T4 That Is Subsequently Purified Leak-Free

Chemotherapy-inhibiting tumor cell evolution to drug-resistance is potentially suppressed by using a drug delivery vehicle (DDV) that has gating. Gating would be used to increase tumor-selectivity of delivery of DDV packaged drug. Tumor-selectivity increase would make possible increase in tumor-delivered drug dose, which would suppress opportunities to evolve drug resistance. Currently used DDVs do not have gating but gating is a natural feature of some bacteriophages (phages). Phage T4, which has recently been found highly persistent in murine blood, is a potential gated DDV. Thus, here, we proceed towards a T4-DDV by developing (1) improved procedure for generating high concentrations and amounts of phage T4, (2) elevated temperature-driven gate-opening and ethidium- and bleomycin-loading, and (3) purification of loaded T4 by rate zonal centrifugation. We test for loading by native agarose gel electrophoresis (AGE) with fluorescence detection. We observe loading in both phage T4 and T4 (tail-free) heads. The loaded particles have an openable, closed gate. Stored, mature T4 phages and phage heads do not release ethidium during at least a month at 4 °C and 6 days at 37 and 42 °C. Tumor-specific T4 phage delivery is projected via both the EPR effect and high T4 persistence.

Thyroid Function Abnormalities in Patients with Different Stages of Chronic Kidney Disease

Introduction: Thyroid hormones are crucial for renal development and physiology. Thyroidal hormones affect the cardiovascular system through their influence on renal blood flow as it modulates the glomerular function, the tubular secretory and absorptive capacities as well as the electrolyte pumps and the kidney structure. Objective: To assess the thyroid function abnormalities in patients with different stages of chronic kidney disease. Materials and Methods: The cross sectional observation study was conducted in Department of Medicine, 250 Bed District Hospital, Habiganj, Bangladesh from January to April 2021. Included 54 CKD patients not on dialysis, who are only on conservative management. Results: In our study the age matched graph shows that maximum number of patients in the category of 40-49 years with 8 males and 6 females, 50- 59 years had 8 males and 6 females, whereas between 60 to 69 years there were 6 males and 6 females. The extreme age groups had few patients chronic kidney disease above 70 there were 2 females and 2 males between 18-29 years there were 3 males and 3 females and 30-39 years had 1 male and 3 females. In our study the number of chronic kidney patients having low T3 were 39 which constitutes 72.2%,the patients with normal T3 were 12 constituting 22.2% and those with high T3 were 3, suggesting primary hyperthyroidism, so excluding them 75% of our patients had low T3 syndrome. In our study 39 patients had low T3, 26 had low T4 with 49 patients being normal TSH, only 4 had high high TSH. Excluding patients with primary hypothyroidism. Patients with low T3 low T4 were clustered in more towards end stage renal disease with 60%. Patients also were in moderate number with low T3 and low T4 in stage 4 chronic kidney disease. 20% in stage 3 chronic kidney disease T4 and TSH were almost normal with only 10% patients had low T3 syndrome. In stage 2 chronic kidney disease 10% had low T3, low T4 with rest being normal TSH. In our study patients .....

High-refined carbohydrate diet alters different metabolic functions in female rats

A diet containing refined carbohydrate (HCD) caused obesity and white adipose tissue (WAT) abnormalities, but it is unclear if HCD is linked with other metabolic dysfunctions in female models. Thus, we assessed whether HCD results in WAT, pancreas, liver, skeletal muscle (SM) and thyroid (TH) abnormalities in female rats. Female rats were fed with HCD for 15 days and metabolic morphophysiology, inflammation, oxidative stress (OS), and fibrosis markers were assessed. HCD rats presented large adipocytes, hyperleptinemia, and WAT OS. HCD caused irregular glucose metabolism, low insulin levels, and large pancreatic isle. Granulomas, reduced glycogen, and OS were observed in HCD livers. HCD caused hypertrophy and increased in glycogen in SM. HCD caused irregular TH morphophysiology, reduced colloid area and high T3 levels. In all selected tissues, inflammation and fibrosis were observed in HCD rats. Collectively, these data suggest that the HCD impairs metabolic function linked with irregularities in WAT, pancreas, liver, SM and TH in female rats.

A Case of Hypothyroidism Cured by Natrum Muriaticum

A case of hypothyroidism treated by constitutional homoeopathic medicine is presented here with serial thyroid function test reports. It is worthwhile mentioning here that initially she had high T3, T4 and low TSH for which she was given Neomercazole. Later her TSH became raised and was given Thyrocab, Eltroxin etc. She was perturbed due to fluctuation of her condition between hyper and hypothyroidism and stopped all allopathic medicines. Referred by some of her relatives she consulted us for treatment of her ailment.

Rewiring of liver diurnal transcriptome rhythms by triiodothyronine (T3) supplementation.

Diurnal (i.e., 24 hr) physiological rhythms depend on transcriptional programs controlled by a set of circadian clock genes/proteins. Systemic factors like humoral and neuronal signals, oscillations in body temperature, and food intake align physiological circadian rhythms with external time. Thyroid hormones (THs) are major regulators of circadian clock target processes such as energy metabolism, but little is known about how fluctuations in TH levels affect the circadian coordination of tissue physiology. In this study, a high triiodothyronine (T3) state was induced in mice by supplementing T3 in the drinking water, which affected body temperature, and oxygen consumption in a time-of-day-dependent manner. A 24-hr transcriptome profiling of liver tissue identified 37 robustly and time independently T3-associated transcripts as potential TH state markers in the liver. Such genes participated in xenobiotic transport, lipid and xenobiotic metabolism. We also identified 10-15% of the liver transcriptome as rhythmic in control and T3 groups, but only 4% of the liver transcriptome (1033 genes) were rhythmic across both conditions - amongst these, several core clock genes. In-depth rhythm analyses showed that most changes in transcript rhythms were related to mesor (50%), followed by amplitude (10%), and phase (10%). Gene set enrichment analysis revealed TH state-dependent reorganization of metabolic processes such as lipid and glucose metabolism. At high T3 levels, we observed weakening or loss of rhythmicity for transcripts associated with glucose and fatty acid metabolism, suggesting increased hepatic energy turnover. In summary, we provide evidence that tonic changes in T3 levels restructure the diurnal liver metabolic transcriptome independent of local molecular circadian clocks.

Commentary on Questionable High Free T4 Concentrations: When Confirming against an Alternative Method Is Not Enough.

Commentary on Questionable High Free T4 Concentrations: When Confirming against an Alternative Method Is Not Enough.