Thyroid Hormone Status Research Articles

ASSESSMENT OF THYROID FUNCTION DISORDERS AMONG THE SUBJECTS ATTENDING CENTRAL LABORATORY OF A TERTIARY CARE HOSPITAL: AN OBSERVATIONAL, CROSS-SECTIONAL STUDY

Objective: Thyroid disorders are the most common endocrine disorders worldwide and India is not an exception. Several factors may determine the prevalence of thyroid dysfunction including age, gender, geographical and ethnic background, and most importantly iodine intake. Therefore, data related to thyroid disorders from one population cannot be extrapolated to another. In this study, we aimed to assess the disorders of thyroid function among the subjects attending the central laboratory of a tertiary care hospital. Methods: This observational, cross-sectional study was conducted in the Department of Pharmacology and the Department of Biochemistry of the same institute over a period of 3 months. All subjects of either sex attending the central laboratory of the institute for estimating thyroid function on their outpatient visit during the study period were included. Subjects who were on any medications known to alter the thyroid hormone status or diagnosed with a thyroid disorder and/or on therapy were excluded. A pre-designed and pre-tested data collection form was used for taking interviews to collect relevant data including sociodemographic characteristics, comorbid conditions, thyroid illness, and investigational reports. Results: A total of 132 subjects were included in the study. The majority of them were female (72.27%) and residents of urban areas (52.27%). The most common comorbid conditions and presenting symptoms were hypertension (25.76%) and fatigue (46.97%), respectively. The majority of the subjects were found to be euthyroid (81.81%). About 18.19% of the study subjects were having thyroid disorders, most commonly subclinical hypothyroidism (SCH) (13.64%), followed by primary hypothyroidism (2.27%), secondary hyperthyroidism (1.52%), and subclinical hyperthyroidism (0.76%). Thyroid disorders were mainly found in females, such as primary hypothyroidism (66.67%), SCH (66.67%), and subclinical hyperthyroidism (100%). The majority of the thyroid disorders were found in the age group of 26–50 years (20.27%), where females were found to have more primary hypothyroidism (3.17%), and SCH (12.70%). Conclusion: The findings of our study call for a review of current practices regarding thyroid disorders to include active screening of thyroid function among the subjects at greater risks and an emphasis on regular monitoring of the thyroid status.

Nanoscale organization of cardiac calcium channels is dependent on thyroid hormone status.

Thyroid hormone dysfunction is frequently observed in patients with chronic illnesses including heart failure which increases risk of adverse events. This study examined effects of thyroid hormones (TH) on cardiac T-tubule (TT) integrity, Ca2+ sparks, and nanoscale organization of ion channels in excitation-contraction (EC)-coupling, including L-type calcium channel (Cav1.2), ryanodine receptor-type 2 (RyR2), and junctophilin-2 (Jph2). TH deficiency was established in adult female rats by propyl-thiouracil (PTU) ingestion for 8 weeks; followed by randomization to continued PTU without or with oral triiodo-L-thyronine (T3; 10 ug/kg/d) for two additional weeks (PTU+T3). Confocal microscopy of isolated cardiomyocytes (CM) showed significant misalignment of TTs, and increased Ca2+ sparks in thyroid-deficient CMs. Density-Based Spatial Clustering of Applications with Noise (DBSCAN) analysis of STochastic Optical Reconstruction Microscopy (STORM) images showed decreased (p<0.0001) RyR2 cluster number per cell area in PTU CMs compared to euthyroid (EU) control myocytes, and this was normalized by T3-treatment. Cav1.2 channels and Jph2 localized within 210 nm radius of the RyR2 clusters were significantly reduced in PTU myocytes, and these values were increased with T3 treatment. A significant percentage of the RyR2 clusters in the PTU myocytes had neither Cav1.2 or Jph2, suggesting fewer functional clusters in EC-coupling. Nearest neighbor distances between RyR2 clusters were greater (p<0.001) in PTU cells compared to EU and T3-treated CMs that corresponds to disarray of TTs at the sarcomere z-discs. These results support a regulatory role of T3 in the nanoscale organization of RyR2 clusters and co-localization of Cav1.2 and Jph2 in optimizing EC-coupling.

Serum CD5L as potential biomarker of thyroid hormone status during pregnancy.

The thyroid hormone (TH) status is routinely assessed by thyrotropin (TSH) and thyroxine (T4). Both biomarkers are mainly regulated by TH receptor beta, whereas many peripheral organs employ the alpha receptor. Serum cluster of differentiation 5-like molecule (CD5L) is a liver-derived protein under control of both TH receptor isoforms. However, clinical data on its relation to TH status are sparse. An additional biomarker of TH status is needed in particular during pregnancy, where the routine biomarkers become dynamically disturbed. This study aimed to determine possible covariates regulating serum CD5L and to test its potential suitability as additional TH biomarker during pregnancy. A sandwich ELISA for serum CD5L was established using newly raised antibodies. Circadian effects and the impact of liver disease on serum CD5L concentrations were assessed. Serum samples from pregnant women with well-characterized TH and trace element status were analyzed, and CD5L concentrations were correlated with other indicators of TH status including TSH, fT4, fT3, copper, and selenium concentrations. The new quantitative assay for CD5L showed high accuracy. Serum CD5L was stable in dilution and refreezing experiments and did not show strong circadian variance or dependency on liver disease. In serum of pregnant women, CD5L correlated positively to fT3, but not to fT4 or TSH. Significant positive correlations of CD5L were observed with serum levels of the TH-responsive trace elements selenium and copper. The data support the potential suitability of serum CD5L as an additional marker of TH status, with potential value for pregnancy and thyroid disease.

Evaluation of thyroid profile among children aged 1-15 years with nephrotic syndrome: An observation study.

The interaction between the kidney and the thyroid is important for normal function of both organs. In nephrotic syndrome, proteinuria leads to loss of several proteins, which in turn causes hypothyroidism. To assess the thyroid function in children with nephrotic syndrome. This cross-sectional study was conducted in a tertiary center, Bhopal, from February 2020 to January 2021. Consecutive children aged 1-15 years admitted with nephrotic syndrome (first-time diagnosed and all relapse cases) were included in the study. A thyroid profile was sent along with routine investigations, and thyroid hormone status was assessed in nephrotic syndrome children. Of the 70 patients, 39 (55.7%) showed abnormal thyroid profiles; 19 (27.1%) had overt hypothyroidism, and 20 (28.6%) had subclinical hypothyroidism. Overt hypothyroidism was seen in 16.1% of newly diagnosed cases, 40% of second relapses, and 2.7% of frequently relapsed cases (P < 0.001). The mean serum free T3 and free T4 levels in frequent relapses were 2.50 ± 0.39 ng/dL and 0.78 ± 0.12 ng/dL, respectively, which were significantly lower than in newly diagnosed cases (2.77 ± 0.37 ng/dL and 0.91 ± 0.19 ng/dL, respectively). The mean thyroid-stimulating hormone (TSH) level was significantly higher in frequent relapses 5.86 ± 1.56 µIU/mL) and second relapse (5.81 ± 1.78 µIU/mL) than in newly diagnosed cases (4.83 ± 0.76 µIU/mL) and first relapse cases (4.74 ± 1.17 µIU/mL), (P < 0.01). An abnormal thyroid profile was commonly observed in children with nephrotic syndrome, and overt hypothyroidism was more common in frequent relapse cases. Therefore, thyroid screening should be a part of the management of nephrotic syndrome so that hypothyroidism can be detected and managed at an early stage.

CORRELATION BETWEEN THE DISORDER OF THE THYROID GLAND, OBESITY AND OVERWEIGHT IN THE FEMALE GENDER

Introduction: The thyroid gland is the endocrine gland responsible for the production of thyroid hormones, a regulator of growth, development and basal metabolic rate of the organism. It also has a wide range of physiological effects on the organism such as: general thermogenesis, physiological metabolic effects, growth and developmental features and when these parameters move up and down they lead to acute or chronic pathology. Pathologies of the thyroid gland are very frequent diseases in our country, especially in the female gender. As far as diseases are concerned, when we have iodine deficiency, imbalance of thyroid hormone values such as an increase that leads to hyperthyroidism or a decrease in values that leads to hypothyroidism, other diseases such as Hashimoto's, Graves etc. Obesity is a state of metabolic disorders, sometimes considered a disease in which excess body fat is accumulated to such an extent that it can negatively affect human health. Obesity is related to the function of the thyroid gland and this metabolic disorders is a very frequently in reproductive female. Body BMI is measured with a metric formula where body weight (in kg) divided by body height (in m2) set to the square power gives us the body index-BMI (%) measure. Purpose of the study: This paper aims to investigate the correlation of thyroid gland disorders and hormonal imbalance with the phenomenon of body weight as the main causes of this metabolic disease . Material and method: The research will take a total of 80 patients, they will be divided by gender and age groups into three categories. The first group will include patients from: 15 to 20 years, the second group from: 21 to 50 years and the third group from: 51 to 70 years. From the patients included in the research, blood samples will be taken and the hormones will be analyzed: TSH, FT4, FT3 also BMI will be measured. The data will be processed with serum and will be analyzed by means of the modern automatic method enzyme Fluorescent Immunoassay (Biomerie). The BMI of the body will be measured with a metric formula where the weight of the patient (in kg) divided by the height of the patient (in m2) set to the square power will give us the measure of body index-BMI (%). SPSS – Software package version 20.0 Numerical series were analyzed using central tendency measures (average, median, minimum values, maximum values), as well as distribution measures (standard deviation); To determine the regularity of the frequency distribution of the examined variables, the Shapiro-Wilk W Test was used; Non-parametric tests for two independent parameters were used to test the significance and difference between some numerical parameters with irregular frequency distribution (Mann Whitney U test); To determine statistical significance, a two-way analysis was used with a significance level (means) of p&lt;0.05. Research results: Endocrine disorders are more frequent and appear faster in the thyroid gland. Statistics show that there are millions of people affected by these metabolic syndrome problems. The results of the research will give a real insight into the function of the thyroid gland, the state of the level of hormonal status and the impact of metabolic syndrome of BMI, which can lead to hormonal imbalance and metabolic disorder. Conclusion: From the analyzes performed on patients of different age groups and genders, we come to the conclusion that: • Hormonal disorders of the thyroid gland can be the main cause of the BMI factor, • The correlation of thyroid hormone status and metabolic status are in continuous correlation with obesity, overweight, infertility, diabetes and hyperlipidemia. • These changes of the thyroid gland and the BMI can have negative consequences for human health such as in osteoporosis and electrolytes imbalance.

Novel biomarkers reveal mismatch between tissue and serum thyroid hormone status in amiodarone-induced hyperthyroidism.

Serum TSH and thyroid hormone (TH) levels are routine markers of thyroid function. However, their diagnostic performance is limited under special conditions, e.g. in amiodarone-induced hyperthyroidism (AIH). Such cases would require the assessment of tissue TH action, which is currently unfeasible. Development of an approach that determines how well serum parameters are reflected in tissue TH action of patients. TH-responsive marker genes were identified from human hair follicles (HF) with Next Generation Sequencing, validated by qPCR. A classification model was built with these markers to assess tissue TH action and was deployed on amiodarone treated patients. The impact of amiodarone on tissue TH action was also studied in Thyroid Hormone Action Indicator (THAI) mice. The classification model was validated and shown to predict tissue TH status of subjects with good performance. Serum- and HF-based TH statuses were concordant in hypothyroid and euthyroid amiodarone treated patients. In contrast, amiodarone decreased the coincidence of serum-based and HF-based TH statuses in hyperthyroid patients, indicating that AIH is not unequivocally associated with tissue hyperthyroidism. This was confirmed in the THAI model, where amiodarone prevented tissue hyperthyroidism in THAI mice despite high serum fT4. We developed a minimally-invasive approach using HF markers to assess tissue TH economy that could complement routine diagnostics in controversial cases. We observed that a substantial proportion of AIH patients do not develop tissue hyperthyroidism, indicating that amiodarone protects tissues from thyrotoxicosis. Assessing tissue TH action in patients with AIH may be warranted for treatment decisions.

Evidence for thyroid hormone regulation of amygdala-dependent fear-relevant memory and plasticity.

The amygdala is an established site for fear memory formation, and clinical studies suggest involvement of hormone signaling cascades in development of trauma-related disorders. While an association of thyroid hormone (TH) status and mood disorders is established, the related brain-based mechanisms and the role of TH in anxiety disorders are unknown. Here we examine the role that TH receptor (TR, a nuclear transcriptional repressor when unbound and a transcriptional activator when bound to TH) may have in mediating the initial formation of fear memories in the amygdala. We identified mRNA levels of TR and other TH pathway regulatory genes, including thyrotropin-releasing hormone (Trh), transthyretin (Ttr), thyrotropin-releasing hormone receptor (Trhr), type 2 iodothyronine deiodinase (Dio2), mediator complex subunit 12 (Med12/Trap230) and retinoid X receptor gamma (Rxrg) to be altered in the amygdala following Pavlovian fear conditioning. Using TH agonist and antagonist infusion into the amygdala, we demonstrated that this pathway is both necessary and sufficient for fear memory consolidation. Inhibition of TH signaling with the TR antagonist 1-850 decreased fear memory consolidation; while activation of TR with T3 (triiodothyronine) resulted in increased memory formation. Using a systemic hypothyroid mouse model, we found that intra-amygdala infusions of T3 were sufficient to rescue deficits in fear memory. Finally, we demonstrated that T3 was sufficient to activate TR-specific gene pathways in the amygdala. These findings on the role of activity-dependent TR modulation support a model in which local TH is a critical regulator of fear memory-related plasticity in the amygdala.

Thyroid hormone status in children with transfusion-dependent thalassemia

Thyroid hormone status in children with transfusion-dependent thalassemia

Indications for Intravenous T3 and T4.

Therapy with thyroid hormones normally is restricted to substitution therapy of patients with primary or secondary hypothyroidism. Typically, thyroid hormones are given orally. There are few indications for intravenous use of thyroid hormones. Indications for parenteral application are insufficient resorption of oral medications due to alterations of the gastrointestinal tract, partial or total loss of consciousness, sedation in the intensive care unit or shock. In almost all cases, levothyroxine is the therapy of choice including congenital hypothyroidism. In preterm infants with an altered thyroid hormone status, studies with thyroid hormones including intravenous liothyronine showed a normalisation of T3 levels and in some cases an amelioration of parameters of ventilation. A benefit for mortality or later morbidity could not be seen. Effects on neurological improvements later in life are under discussion. Decreased thyroid hormone levels are often found after cardiac surgery in infants and adults. Intravenous therapy with thyroid hormones improves the cardiac index, but in all other parameters investigated, no substantial effect on morbidity and mortality could be demonstrated. Oral liothyronine therapy in these situations was equivalent to an intravenous route of application. In myxoedema coma, intravenous levothyroxine is given for 3 to 10 days until the patient can take oral medication and normal resorption in the gastrointestinal tract is achieved by restoring at least peripheral euthyroidism. Intravenous levothyroxine is the standard in treating patients with myxoedema coma. A protective effect on the heart of i.v. levothyroxine in brain-dead organ donors may be possible.

The Perioperative Period of Heart Transplantation Is Affected by Thyroid Hormone Status.

Background: Orthotopic heart transplantation (HTx) is a long-term surgical therapeutic approach for patients with end-stage heart failure. The objective of the present study was to uncover associations between altered thyroid hormone (TH) status and adverse outcomes after HTx. Methods: In this prospective, single-center cohort study, 283 patients underwent HTx between 2013 and 2020 at the Heart and Vascular Center of Semmelweis University in Hungary. We measured serum free triiodothyronine (fT3), free thyroxine (fT4), and thyrotropin (TSH) pre- and postoperatively. TaqMan qPCR was used to measure type 2 deiodinase and type 3 deiodinase mRNA (Dio2 and Dio3, respectively) levels from the diseased heart bioptates. To assess the local TH action of the heart, mRNA levels of Hcn2 and Myh7 were measured in a subgroup of patients receiving extracorporeal membrane oxygenation (ECMO) postoperatively. Groups were compared using nonparametric tests. Cox regression analysis and logistic regression test were used to investigate the outcomes. The connection between serum TH parameters and cardiac gene expressions was assessed using linear regression. Results: Serum TSH (p = 0.009), fT3 (p < 0.001), and fT4 (p < 0.001) levels were lower after HTx than preoperatively. Levothyroxine (LT4) administered to donors was associated with better survival after 30 days (p = 0.049). LT4 replacement given to recipients after HTx was associated with better survival after 30 days (p = 0.018), 1 year (p = 0.002), and 2 years (p = 0.001). Dio3 mRNA level was significantly increased in patients who were treated with ECMO (p = 0.026), left ventricular assist device (LVAD) (p = 0.008), and biventricular assist device (BiVAD) (p = 0.013) preoperatively, and ECMO (p = 0.042) postoperatively, compared with those who did not require any type of mechanical circulatory support (MCS). We found no significant difference in the expression of the Hcn2 and Myh7 marker genes between patients on postoperative ECMO and those without MCS, and neither did they correlate with serum hormone levels (p = 0.519 and p = 0.056, respectively). Conclusions: We conclude that TH status plays an important role in HTx patients, and monitoring of TH status in the perioperative period may contribute to improved treatment outcomes. Our findings require independent confirmation in a randomized controlled clinical trial.

Thyroid Hormone Status in Children Taking Antiepileptic Drugs (AEDs): An Experience in a Tertiary Care Hospital of Bangladesh.

Introduction: Antiepileptic drugs (AEDs) may alter thyroid hormone homeostasis at the level of biosynthesis, release, transport, metabolism and excretion of thyroid hormones. The purpose of the study was to see the thyroid hormone status in children with epilepsy treating with common antiepileptic drugs. Materials &amp; Method: The cross-sectional study was carried out in department of pediatric neurology, National Institute of Neurosciences and Hospital (NINS), Dhaka. One hundred and sixty epileptic children aged 1 year to 14 years who were on monotherapy or polytherapy with the most commonly used Antiepileptic drugs (AEDs) for at least 6 months or more were enrolled. Serum TSH and FT4 were measured in all selected patients with early morning serum sample. Result: Nearly one third of study subjects had thyroid dysfunction, most of which were Subclinical hypothyroidism (SCH). The frequency of SCH was 29.2% in carbamazepine(CBZ), 50% in oxcabazepine (OXC), 28.6% in phenobarbitone(PHB) and 13% in valproic acid (VPA) treated epileptic children. No child was found to have subclinical hypothyroidism with topiramate and ethosuximide monotherapy. Antiepileptic drugs (AEDs) monotherapy or polytherapy had no significant difference in alteration on thyroid hormone level. Use of CBZ for long duration significantly altered thyroid function. Doses of Antiepileptic drugs (AEDs) didn’t show any significant thyroid dysfunction. Conclusion: Commonly used Antiepileptic drugs (AEDs) in children with epilepsy were associated with alteration of thyroid hormones, most commonly subclinical hypothyroidism. BANGLADESH J CHILD HEALTH 2022; VOL 46 (2) : 58-64

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.

Serum CD5L as potential biomarker of thyroid hormone status during pregnancy

Serum CD5L as potential biomarker of thyroid hormone status during pregnancy

Asymmetric proptosis in thyroid eye disease

PurposePatients with thyroid eye disease (TED) can present with asymmetric disease. The purpose of this study was to evaluate the prevalence of asymmetric TED in an Australian cohort and investigate clinical, biochemical, and radiological associations of asymmetric TED.MethodsThis was a retrospective study of patients with TED who underwent Hertel exophthalmometry and orbital computed tomography (CT) scans. Asymmetry was defined as a difference in the globe protrusion of ≥ 3 mm using Hertel exophthalmometry. Data was collected on patient demographics, clinical disease presentation, thyroid function tests and antibody levels. Muscles volumes were determined by manually segmenting the extraocular muscles on CT scans using a commercially available software.Results172 orbits from 86 patients were included in the study. 28 (33%) patients had asymmetric TED. No significant differences were observed in age, gender, thyroid hormone status, anti-thyroid peroxidase levels, thyroid stimulating hormone receptor antibodies, disease activity status, or dysthyroid optic neuropathy between the asymmetric and non-asymmetric groups. The extraocular muscle volumes were significantly higher in the asymmetric orbit compared to its contralateral orbit.ConclusionAsymmetric TED is a reasonably common occurrence in the course of TED. It is associated with higher extraocular muscle volumes, suggesting muscle enlargement as one of the underlying contributors to asymmetric proptosis. Thyroid eye disease should be considered in the differential of asymmetric orbital inflammatory disease.

Cytological Grading of Lymphocytic Thyroiditis and Its Correlation With Biochemical Parameters: An Experience From a Tertiary Care Center in North India.

Chronic lymphocytic thyroiditis is the most common cause of acquired hypothyroidism. The clinical management of thyroid nodules, with or without chronic lymphocytic thyroiditis, mainly depends on clinical data, ultrasonography, and fine-needle aspiration cytology (FNAC), the latter being the gold standard for the pre-surgical diagnosis of thyroidal nodules. The grading of chronic lymphocytic thyroiditis can be divided into three categories. The spectrum of the thyroid profile can be correlated to the cytological diagnosis of chronic lymphocytic thyroiditis. This study aims to study the cytomorphology of various grades of chronic lymphocytic thyroiditis and its correlation with the hormonal profile. In this study, 44 patients with a diagnosis of lymphocytic thyroiditis on FNAC were included. The cases of lymphocytic thyroiditis were graded cytomorphologically, and correlation with the thyroid hormone profile was done. The majority of the patients were between 16 and 30 years age group, with a female predominance. The majority of the patients presented with diffuse enlargement of the thyroid gland. The maximum number of cases was graded in the grade II cytological category (70.46%). A hypothyroid profile was present in 63% of patients, followed by an euthyroid profile. The majority of patients with grade II thyroiditis also had a hypothyroid profile. However, no significant association was found between cytological grading and hormonal status. Cytological grading is a clear, easy-to-use diagnostic tool for confirmation of lymphocytic thyroiditis. However, the cytological grades show no statistically significant correlation with thyroid hormonal status. Lymphocytic thyroiditis should be diagnosed with a multidisciplinary approach, as clinical features and hormonal profile when used alone may result in a missed diagnosis.

Homeostatic status of thyroid hormones and brain water movement as determinant factors in biology of cerebral gliomas: a pilot study using a bioinformatics approach.

The expression and localization of the water channel transporters, aquaporins (AQPs), in the brain are substantially modified in gliomas during tumorigenesis, cell migration, edema formation, and resolution. We hypothesized that the molecular changes associated with AQP1 and AQP4 in the brain may potentially be anticancer therapeutic targets. To test this hypothesis, a bioinformatics analysis of publicly available data from international consortia was performed. We used RNA-seq as an experimental strategy and identified the number of differential AQP1 and AQP4 transcript expressions in glioma tissue compared to normal brain tissue. AQPs genes are overexpressed in patients with glioma. Among the glioma subtypes, AQP1 and AQP4 were overexpressed in astrocytoma (low-grade glioma) and classical (high-grade glioma). Overall survival analysis demonstrated that both AQP genes can be used as prognostic factors for patients with low-grade glioma. Additionally, we observed a correlation between the expression of genes involved in the tyrosine and thyroid hormone pathways and AQPs, namely: PNMT, ALDH1A3, AOC2, HGDATP1B1, ADCY5, PLCB4, ITPR1, ATP1A3, LRP2, HDAC1, MED24, MTOR, and ACTB1 (Spearman's coefficient = geq 0.20 and p-value = ≤ 0.05). Our findings indicate that the thyroid hormone pathways and AQPs 1 and 4 are potential targets for new anti-tumor drugs and therapeutic biomarkers for malignant gliomas.

Evaluation of the Thyroid Hormone Status among Normal New Born Preterm Infants

Introduction: Thyroid dysfunction poses a greater risk in preterm newborns (PN) compared to term newborns (TN), often eluding detection in neonatal screening due to delayed thyrotropin (TSH) elevation in these cases. Objective: To assess thyroid function during the second week of life in PN born before 32 weeks gestation and identify factors associated with its alteration. Methods: A retrospective study examined thyroid function in &lt; 32 weeks gestation neonates, analyzing thyroxine (T4L) and TSH levels in relation to perinatal and neonatal outcomes. The study included 358 patients with a mean gestational age of 29.3 weeks and a mean birth weight of 1127 grams. Results: Linear correlations were observed between T4L and birth weight (BW) (R=0.356; p&lt;0.001) and gestational age (GA) (R=0.442; p&lt;0.001). TSH values were associated with small for gestational age (SGA) (5.3 mU/L [1.5-37] for SGA vs. 2.89 mU/L [0.2-19.5] for non-SGA; p&lt;0.001), inotropic support (3.98 mU/L [0.6-22.9] for Yes vs. 3.16 mU/L [0.2-37] for No; p=0.019), and BW (R=-0.249; p&lt;0.001). Levothyroxine treatment was administered to 2.5% of patients, with six being SGA. Conclusions: Analyzing thyroid function in the second week aids in identifying asymptomatic newborns at risk of thyroid dysfunction, particularly in the case of SGA newborns who exhibit a higher susceptibility to thyroid function alterations.

Cardiac recovery from pressure overload is not altered by thyroid hormone status in old mice.

Thyroid hormones (THs) are known to have various effects on the cardiovascular system. However, the impact of TH levels on preexisting cardiac diseases is still unclear. Pressure overload due to arterial hypertension or aortic stenosis and aging are major risk factors for the development of structural and functional abnormalities and subsequent heart failure. Here, we assessed the sensitivity to altered TH levels in aged mice with maladaptive cardiac hypertrophy and cardiac dysfunction induced by transverse aortic constriction (TAC). Mice at the age of 12 months underwent TAC and received T4 or anti-thyroid medication in drinking water over the course of 4 weeks after induction of left ventricular pressure overload. T4 excess or deprivation in older mice had no or only very little impact on cardiac function (fractional shortening), cardiac remodeling (cardiac wall thickness, heart weight, cardiomyocyte size, apoptosis, and interstitial fibrosis), and mortality. This is surprising because T4 excess or deprivation had significantly changed the outcome after TAC in young 8-week-old mice. Comparing the gene expression of deiodinases (Dio) 2 and 3 and TH receptor alpha (TRα) 1 and the dominant-negative acting isoform TRα2 between young and aged mice revealed that aged mice exhibited a higher expression of TRα2 and Dio3, while expression of Dio2 was reduced compared with young mice. These changes in Dio2 and 3 expressions might lead to reduced TH availability in the hearts of 12-month-old mice accompanied by reduced TRα action due to higher TRα2. In summary, our study shows that low and high TH availability have little impact on cardiac function and remodeling in older mice with preexisting pressure-induced cardiac damage. This observation seems to be the result of an altered expression of deiodinases and TRα isoforms, thus suggesting that even though cardiovascular risk is increasing with age, the response to TH stress may be dampened in certain conditions.

The effects of choline supplementation in mothers with hypothyroidism on the alteration of cognitive-behavioral, long-term potentiation, morphology, and apoptosis in the hippocampus of pre-pubertal offspring rats.

The mother's thyroid hormone status during gestation and the first few months after delivery can play a crucial role in maturation during the brain development of the child. Transient abnormalities in thyroid function at birth indicate developmental and cognitive disorders in adulthood. Choline supplementation during gestation and the perinatal period in rats causes long-lasting memory improvement in the offspring. However, it remains unclear whether choline is able to restore the deficits in rats with maternal hypothyroidism. The aim of this study was to evaluate the effects of choline supplementation on the alteration of cognitive-behavioral function, long-term potentiation (LTP), and morphological changes as well as apoptosis in pre-pubertal offspring rats. To induce hypothyroidism, 6-propyl-2-thiouracil was added to the drinking water from the 6th day of gestation to the 21st postnatal day (PND). Choline treatment was started twice a day on the first day of the gestation until PND 21 via gavage. LTP recording and Morris water maze (MWM) test were conducted at PND 28. Then, the rats were sacrificed to assess their brains. The results revealed that developmental thyroid hormone deficiency impaired spatial learning and memory and reduced LTP (both: P < 0.001). Choline treatment alleviated LTP (P < 0.001), as well as learning and memory deficits (P < 0.01) in both male and female hypothyroid rats. However, no significant changes were observed in the number of caspase-3 stained cells in choline-receiving hypothyroid groups. The results revealed that developmental thyroid hormone deficiency impaired spatial learning and memory and reduced LTP. Choline treatment alleviated LTP, as well as learning and memory deficits in both male and female hypothyroid rats.

Tuning of liver circadian transcriptome rhythms by thyroid hormone state in male mice

Thyroid hormones (THs) are important regulators of systemic energy metabolism. In the liver, they stimulate lipid and cholesterol turnover and increase systemic energy bioavailability. It is still unknown how the TH state interacts with the circadian clock, another important regulator of energy metabolism. We addressed this question using a mouse model of hypothyroidism and performed circadian analyses. Low TH levels decreased locomotor activity, food intake, and body temperature mostly in the active phase. Concurrently, liver transcriptome profiling showed only subtle effects compared to elevated TH conditions. Comparative circadian transcriptome profiling revealed alterations in mesor, amplitude, and phase of transcript levels in the livers of low-TH mice. Genes associated with cholesterol uptake, biosynthesis, and bile acid secretion showed reduced mesor. Increased and decreased cholesterol levels in the serum and liver were identified, respectively. Combining data from low- and high-TH conditions allowed the identification of 516 genes with mesor changes as molecular markers of the liver TH state. We explored these genes and created an expression panel that assesses liver TH state in a time-of-day dependent manner. Our findings suggest that the liver has a low TH action under physiological conditions. Circadian profiling reveals genes as potential markers of liver TH state.