Thyrotropin Research Articles

The relation between circulating free thyroxine (FT4) and thyroid stimulating hormone (TSH) levels is very different in people taking levothyroxine vs those who are on no thyroid hormone replacement

The relation between circulating free thyroxine (FT4) and thyroid stimulating hormone (TSH) levels is very different in people taking levothyroxine vs those who are on no thyroid hormone replacement

A confusing situation in the clinic: isolated maternal hypothyroxinemia

Isolated maternal hypothyroxinemia (IMH) is a common problem in the clinic. There is a normal maternal thyroid stimulating hormone (TSH) level with a low maternal free thyroxine (FT4) level. The aim of this review is to explain IMD in the light of current literature and to contribute to clinicians in the management of IMH. Iodine deficiency is the most important factor in etiology. The effects of IMH on the pregnant woman and the fetus are not clear. However, it is a serious concern among serious clinicians, especially considering the importance of the effect of thyroid hormones on fetal brain development. As for the treatment of IMH, the number of studies conducted is not sufficient and there is no consensus and evidence on levothyroxine treatment. However, there is a consensus on iodine supplementation and it is recommended to take 250 mg of iodine daily. As a result, IMH is a problem that should be taken seriously during pregnancy and care should be taken regarding its diagnosis and treatment. Additionally, more research is needed on the effects and treatment of IMH on pregnant and fetal health

No Correlation between PD-L1 and NIS Expression in Lymph Node Metastatic Papillary Thyroid Carcinoma.

Approximately 90% of thyroid cancers are differentiated thyroid cancers (DTCs), originating from follicular epithelial cells. Out of these, 90% are papillary thyroid cancer (PTC), and 10% are follicular thyroid cancer (FTC). The standard care procedure for PTC includes surgery, followed by radioiodine (RAI) ablation and thyroid-stimulating hormone (TSH) suppressive therapy. Globally, treating radioiodine-refractory DTC poses a challenge. During malignant transformation, thyroid epithelial cells often lose their ability to absorb radioiodine due to impaired membrane targeting or lack of NIS (sodium/iodide symporter) expression. Recent reports show an increase in PD-L1 (programmed death ligand 1) expression in thyroid cancer cells during dedifferentiation. However, no research exists wherein NIS and PD-L1 expression are analyzed together in thyroid cancer. Therefore, we aimed to investigate and correlate PD-L1 and NIS expression within primary tumor samples of lymph node metastatic PTC. We analyzed the expression of hNIS (human sodium/iodide symporter) and PD-L1 in primary tumor samples from metastatic PTC patients using immunohistochemistry. Immunohistochemistry analysis of PD-L1 and NIS was conducted in 89 and 86 PTC cases, respectively. Any subcellular NIS localization was counted as a positive result. PD-L1 expression was absent in 25 tumors, while 58 tumors displayed PD-L1 expression in 1-50% of their cells; in 6 tumors, over 50% of the cells tested positive for PD-L1. NIS immunohistochemistry was performed for 86 primary papillary carcinomas, with 51 out of 86 tumors showcasing NIS expression. Only in seven cases was NIS localized in the plasma membrane; in most tumors, NIS was primarily found in the intracytoplasmic membrane compartments. In the case of PD-L1 staining, cells showing linear membrane positivity of any intensity were counted as positive. The evaluation of NIS immunostaining was simpler: cells showing staining of any intensity of cytoplasmic or membranous fashion were counted as positive. The number of NIS positive cells can be further divided into cytoplasmic and membrane positive compartments. There was no observed correlation between PD-L1 and NIS expression. We can speculate that the manipulation of the PD-1/PD-L1 axis using anti-PD-L1 or anti-PD-1 antibodies could reinstate the functional expression of NIS. However, based on our study, the only conclusion that can be drawn is that there is no correlation between the percentage of NIS- or PD-L1-expressing tumor cells in the primary tumor of lymph node metastatic PTC.

A Correlation Study of Anthropometric Measurements and Body Compositions with Thyroid Hormones in Hypothyroidism Patients

Abstract Introduction: Hypothyroidism is often associated with weight gain. In this study, we assessed the correlation of anthropometric measurements and body compositions such as body mass index (BMI), waist circumference (WC), total fat, visceral fat, and triceps fold with different components of the thyroid profile. Methods: All the cases of clinical and subclinical hypothyroidism were evaluated. The anthropometric measurements were taken using skin calipers and the body composition was assessed using a Dexa scan. The blood samples were collected for the estimation of thyroid hormone levels. A statistical correlation was drawn between the various anthropometric measures and body composition with different components of thyroid profile. Results: The gender-wise comparison study revealed that BMI, total fat %, and visceral fat % were significantly higher in the female gender. Total fat and visceral fat have a direct significant association with BMI (P > 0.005). An increase in age is associated with a rise in the values of triiodothyronine (T3) and thyroxine (T4) (P > 0.05). A positive correlation between thyroid-stimulating hormone (TSH) levels and BMI (r = 0.294), total fat % (0.026), visceral fat % (r = 0.216), and triceps fold measurement (0.004). Conversely, a negative correlation was observed between TSH levels and WC (r = −0.178). There was a negative correlation observed between T4 levels and BMI (r = −0.327), visceral fat percentage (r = −0.152), and triceps fold measurements (r = −0.076). However, a positive correlation was found between T4 levels and WC (r = 0.174) and total fat percentage (r = 0.090). A negative correlation was observed between T3 levels and BMI (r = −0.108), while a positive correlation was observed between T3 levels and all other variables. Conclusion: Age and BMI, but not gender, were found to be significantly associated with thyroid profile. Among anthropometric measurements, the total fat percentage demonstrated a positive correlation with all thyroid hormones, suggesting that the total fat percentage may be a more accurate predictor of thyroid hormone levels than other anthropometric variables alone.

Impact of physical activity and diet in the treatment of hypothyroidism: A systematic review

Introduction and Objective: Thyroid diseases constitute a significant health challenge of the 21st century. Due to the growing awareness of the accompanying symptoms and the impact of the proper functioning of the thyroid gland on the overall condition of the body, patients show increasing interest in therapeutic methods. The main aim of the article is to present the impact of physical activity and proper diet on the management of patients with hypothyroidism. Review and Methods: Review and summary of studies and meta-analysis of studies available in open-source format on Google Scholar, Web of Science and PubMed. Abbreviated Description of the State of Knowledge: Hypothyroidism is a clinical condition characterized by the insufficient production of thyroid hormones by the thyroid gland. This hormonal deficiency leads to a generalized decrease in metabolic processes. Clinically, hypothyroidism is diagnosed based on elevated serum levels of thyroid-stimulating hormone (TSH) and decreased levels of free thyroxine (T4). Prevalent symptoms include fatigue, constipation, weight gain, cold intolerance, depression and dry skin. Effective management typically involves hormone replacement therapy with synthetic thyroxine. Summary: Hypothyroidism is a complex disease influenced by many factors. A multidisciplinary approach is recommended in its treatment, including pharmacological treatment, diet and appropriately selected physical activity. Early diagnosis and treatment are essential to improve the physical and mental condition of patients.

Anti-Müllerian Hormone Level Determinants among Non-Polycystic-Ovary-Syndrome Women Undergoing In Vitro Fertilization: A Retrospective Cross-Sectional Study.

Background and Objectives: The anti-Müllerian hormone (AMH) is a crucial biomarker in regulating ovarian follicle development and female fertility. AMH levels predict ovarian responses in in vitro fertilization (IVF) cycles, helping clinicians tailor treatment strategies. This study aims to determine whether thyroid autoimmunity, age, body mass index (BMI), sexual hormone levels, and 25-hydroxyvitamin D levels influence serum AMH in non-polycystic-ovary-syndrome (PCOS) euthyroid women. Materials and Methods: This retrospective cross-sectional study examined 52 female patients at Zygota Fertility Clinic between 2018 and 2022. Women aged 20-45 years with regular menstrual cycles were included, while conditions such as abnormal thyroid-stimulating hormone (TSH) levels, PCOS, and systemic autoimmune diseases were excluded. A number of parameters were measured in the study, including the subjects' age, BMI, 25-hydroxyvitamin D, serum free thyroxine (fT4), TSH, various antibodies, and a range of reproductive hormones. An analysis of the relationships between AMH and other variables was conducted using Spearman's correlation coefficient, and an assessment of the impact of confounding factors on AMH levels was conducted using a multivariable linear regression model. Results: The results revealed significant negative correlations between AMH levels and age (rho: -0.484, p < 0.001) and follicle-stimulating hormone (FSH) (rho: -0.550, p < 0.001), while positive correlations existed between AMH and estradiol (rho: 0.352, p = 0.011) and total testosterone (rho: 0.542, p < 0.001). No significant correlations were found between AMH levels and BMI, LH, or 25-hydroxyvitamin D. Conclusions: In this study, ovarian reserve was influenced by age, estradiol, and total testosterone in non-PCOS euthyroid women undergoing IVF. Conversely, BMI and vitamin D status did not significantly impact AMH levels. In order to better understand and possibly manage ovarian reserve, a holistic approach is absolutely essential, taking into account age, weight, hormonal balance, nutrition, and thyroid health.

Possible link between familial susceptibility to cancer and the level of oxidative stress in thyroid cancer patients

BackgroundHereditary cancer is estimated to account for up to 10% of the worldwide cancer burden; 5% of all thyroid cancers are thought to be genetic. Inheritance of a deleterious mutation in genes associated with a high lifetime risk of developing cancer. Cancer-predisposing genes can promote the initiation and progression of thyroid cancer by enhancing the activation of major signaling pathways through oxidative stress mechanisms.AimIdentification of the possible link between familial susceptibility to cancer and the level of oxidative stress in thyroid cancer patients.MethodsPatients with thyroid cancer (with and without genetic predisposition) were investigated. Study participants were treated in Limited Liability Company (LLC) “Oncology Scientific Research Center” (Tbilisi, Georgia). The study group was collected between 2020 and 2021. In patients’ blood, the thyroid hormones content (free Triiodothyronine (fFT3), free Thyroxine (fFT4), bound Triiodothyronine (FT3), bound Thyroxine (FT4), Thyroid-stimulating hormone (TSH)), and oxidative stress intensity (total activity of non-enzymatic antioxidant system (TAA) and the lipid peroxidation product, malondialdehyde (MDA), content) were investigated.ResultsThe difference in free and bound forms of T3 and T4 levels in the blood serum between patients with thyroid cancer (Group 2 and Group 3) and the control group (Group 1) was not statistically significant (F1,2=0.5, p1,2=0.8, F1,3=2.31, p1,3=0.16). In patients with thyroid cancer the TSH level significantly increased compared to the control group (Group 1) (TSH (mean ± Std error): Group 1– 1.21 ± 0.12, Group 2–2.45 ± 0.11 (F1,2=107, p1,2<0.001), Group 3–2.47 ± 0.17 (F1,3=150, p1,3<0.001)) and the MDA levels increased by 4–5 fold. In patients with thyroid cancer from families with cancer aggregation(Group 2), the level of TAA statistically significantly decreased (F1 − 2=200; p1 − 2<0.001), in patients without genetic predisposition to cancer(Group 3), the level of TAA did not change compared to the control (F1 − 3= 2.13; p1 − 3=0.15),ConclusionsOxidative stress plays a critical role in tumorigenesis, and antioxidant/oxidant imbalance may contribute to the malignant transformation of normal tissue. In patients with familial susceptibility to cancer mutations of several genes, which are involved in the regulation of oxidative metabolism, may contribute to the disruption of the redox balance, increase the level of oxidative stress, and contribute to the development of thyroid cancer.

One Haemolytic Anaemia May Hide Another: Paroxysmal Nocturnal Haemoglobinuria Masquerading As Plasmodium Falciparum Infection.

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, genetic and acquired haematologic disease that causes complement-mediated intravascular haemolytic anaemia, thrombosis and bone marrow failure. A 27-year-old migrant patient attended the emergency department in a context of fever and chills over the previous few days as well as chronic fatigue, dyspnoea and chest pain. His medical history included chronic anaemia and erectile dysfunction. Initial biology showed a haemoglobin of 6.3 g/dl, platelets of 25,000/μl, total leucocytes of 3,500/μl with 1,500 neutrophils. B12 vitamin, folic acid, ferritin and thyroid stimulating hormone were normal. Lactate dehydrogenase levels were high and haptoglobin was non-measurable. C-reactive protein was 46.1 mg/l. A thick blood smear revealed Plasmodium falciparum infection with 0.1% parasitaemia. The patient was treated with an oral combination of artemether and lumefantrine. Three weeks later, the patient consulted the infectious disease department given the lack of clinical improvement. The cytopenias worsened, and lactate dehydrogenase (LDH) and reticulocytes increased. Tests for schistocytes, a thick blood smear for malaria and a direct Coombs test were negative; a myelogram was reassuring. An abdominal, pelvic and thoracic CT scan showed a mild hepatomegaly with no focal lesion and no splenomegaly or adenomegaly. A 12-colour flow cytometry unveiled a PNH clone on 90.9545% of neutrophils and 80.7371% of monocytes. PNH patients can be vulnerable to parasites infection (such as P. falciparum) as it may trigger breakthrough haemolysis through uncontrolled resurgence of activity of the complement system. In our patient, P. falciparum infection was a confounding factor, as it commonly causes haemolytic anaemia and thrombocytopenia, and patients living in malaria-endemic regions can carry low parasitaemia while being slightly symptomatic or asymptomatic. Plasmodium falciparum infection can cause breakthrough haemolysis in patients with paroxysmal nocturnal haemoglobinuria.Low P. falciparum parasitemia in patients living in malaria-endemic regions is not always significant as these patients often carry acquired immunity.Patients from malaria-endemic regions presenting with severe sickness and low P. falciparum parasitemia must be assessed for other diseases, as it cannot explain heavy illness.Patients presenting with haemolytic anaemia, no schistocytes, a negative direct Coombs test and other unexplained cytopenia such as thrombocytopenia/neutropenia and other unexplained clinical manifestations such as dyspnoea, chest pain or erectile dysfunction should be assessed for paroxysmal nocturnal haemoglobinuria.

Correlation between thyroid hormone sensitivity and diabetic peripheral neuropathy in euthyroid patients with type 2 diabetes mellitus

Previous studies have revealed that thyroid hormone (TH) levels are associated with the risk of diabetic peripheral neuropathy (DPN) in euthyroid patients with type 2 diabetes mellitus (T2DM). However, the relationship between TH sensitivity, a complementary method for assessing thyroid function, and DPN remains unclear. This study aimed to investigate the correlation between DPN and TH sensitivity in euthyroid patients with T2DM. Exactly 708 euthyroid adults with T2DM were retrospectively enrolled. The FT3/FT4 ratio was used to estimate peripheral TH sensitivity. Central TH sensitivity was assessed using the Thyrotroph T4 Resistance Index (TT4RI), Thyroid-Stimulating Hormone Index (TSHI), Thyroid Feedback Quantile-based Index (TFQI), and Parametric TFQI (PTFQI). DPN was assessed using neurologic symptoms, signs, and nerve conduction velocity tests. The relationship between DPN and TH sensitivity was examined using logistic regression analysis. We observed that an elevated FT3/FT4 ratio was associated with DPN (OR = 1.36, 95%CI: 1.13–1.63, p = 0.0012). For each standard deviation (SD) increase in the TT4RI, TSHI, TFQI, and PTFQI, the OR of DPN was 0.80 (95%CI: 0.68–0.94, p = 0.0078), 0.72 (95%CI: 0.60–0.86, p = 0.0002), 0.69 (95%CI: 0.58–0.83, p < 0.0001), and 0.69 (95%CI: 0.58–0.82, p < 0.0001), respectively. These results suggested that reduced central and peripheral TH sensitivity is associated with a decreased risk of developing DPN.

Medium-Chain Chlorinated Paraffins Trigger Thyroid Hormone Synthesis and Interfere with Mitochondrial Function in the Thyroid Gland.

Medium-chain chlorinated paraffins (MCCPs, C14-C17) are frequently detected in diverse environmental media. It has been proposed to be listed in Annex A of the Convention on Persistent Organic Pollutants in 2023. Although MCCPs are a crucial health concern, their toxicity remains unclear. This study investigated the toxic effects of MCCPs (0.1-50 mg/kg body weight/day) on the thyroid gland of female Sprague-Dawley rats and characterized the potential toxic pathways via transcriptomics and metabolomics approaches. MCCPs exposure caused histopathological changes to the endoplasmic reticula and mitochondria in thyroid follicular cells at a dose of 50 mg/kg bw/d and increased serum thyrotropin-releasing hormone, thyroid-stimulating hormones, and thyroxine when exposed to a higher dose of MCCPs. Transcriptomic analysis indicated the excessive expression of key genes related to thyroid hormone synthesis induced by MCCPs. Integrating the dual-omics analysis revealed mitochondrial dysfunction of the thyroid by mediating fatty acid oxidation, Kreb's cycle, and oxidative phosphorylation. Significant metabolic toxicity on the thyroid might be linked to the characteristics of the chlorine content of MCCPs. This study revealed the toxicity of MCCPs to the thyroid gland via triggering thyroid hormone synthesis and interfering with mitochondrial function, which can provide new insights into the modes of action and mechanism-based risk assessment of MCCPs.

Prediction of Gestational Diabetes Mellitus Risk in Early Pregnancy Using Antenatal Screening Biomarkers

Aim: In this study, we aimed to compare their success in predicting the risk of Gestational Diabetes Mellitus (GDM) using demographic (age, gravidity, parity), body mass index (BMI), first-trimester fasting blood glucose (FBG), thyroid-stimulating hormone (TSH), and antenatal screening biomarkers (dual and quadruple tests). Materials and Methods: In this study, 800 pregnant women who underwent a one-step 75 g Oral Glucose Tolerance Test (OGTT) and antenatal screening tests at a tertiary hospital between January 2017 and June 2020 were retrospectively investigated. After patients were divided into two groups based on their GDM screening test results, the examined parameters were compared between the GDM-Positive and GDM-Negative groups. Once the parameters significantly associated with GDM were determined, their clinical utility in the early diagnosis of GDM was investigated. Results: GDM was diagnosed in 159 (19.8%) of 800 patients. The GDM-Positive group had a higher age, gravidity, parity, BMI, and first-trimester serum FBG levels, as well as lower serum PAPP-A MoM levels than the GDM-Negative group (P

The Association between Vitamin D Status and the Impact of Metformin on Hypothalamic-Pituitary-Thyroid Axis Activity in Women with Subclinical Hypothyroidism.

Metformin inhibits enhanced secretion of anterior pituitary hormones. Its impact on prolactin and gonadotropin concentrations is absent in individuals with hypovitaminosis D. The aim of this prospective cohort study was to investigate whether vitamin D status determines the effect of metformin on hypothalamic-pituitary-thyroid axis activity in levothyroxine-naïve women. The study included three groups of women of reproductive age with subclinical non-autoimmune hypothyroidism, which were matched for age, thyroid-stimulating hormone (TSH) concentration, and insulin sensitivity: untreated women with vitamin D deficiency/insufficiency (group A), women effectively supplemented with exogenous calciferol (group B), and untreated women with normal 25-hydroxyvitamin D concentrations (25OHD) (group C). Owing to concomitant type 2 diabetes or prediabetes, all subjects were treated with metformin. Concentrations of 25OHD, TSH, total and free thyroid hormones, glucose, insulin, glycated hemoglobin (HbA1c), prolactin, and peripheral markers of thyroid hormone action were assayed before metformin treatment and six months later. Based on hormone concentration, structure parameters of thyroid homeostasis were calculated. Except for 25OHD concentrations, there were no between-group differences in baseline values of the measured variables. Metformin reduced glucose, the homeostatic model assessment 1 of insulin resistance ratio (HOMA1-IR), and HbA1c in all study group, but these effects were less pronounced in group A than in the remaining groups. The reduction in TSH and Jostel's index was observed only in groups B and C, and its degree correlated with baseline TSH concentrations, baseline 25OHD concentrations, and the degree of improvement in HOMA1-IR. The drug did not affect circulating levels of 25OHD, free and total thyroid hormones, prolactin, other structure parameters of thyroid homeostasis, and markers of thyroid hormone action. The obtained results allow us to conclude that low vitamin D status in young women mitigates the impact of metformin on thyrotroph secretory function.

Analysis of Inflammatory and Thyroid Hormone Levels Based on Hepatitis A and B Virus Immunity Status: Age and Sex Stratification.

This study investigated the potential associations between hepatitis virus antibody status and thyroid and inflammatory function. The C-reactive protein (CRP), thyroid-stimulating hormone (TSH), and free thyroxine (FT4) levels were measured in individuals with and without antibodies to the hepatitis A virus (HAV) and hepatitis B virus (HBV). Participants were stratified by age, sex, and HAV/HBV antibody status. Participants with and without antibodies to HAV and HBV had normal CRP, TSH, and FT4 levels. However, notable discrepancies were observed in FT4 levels among participants with HAV antibodies and in CRP and FT4 levels among those with both HAV and HBV antibodies, suggesting potential associations between viral immunity and thyroid function, especially in younger participants. Significant variations in thyroid hormone levels were noted when the sample was stratified by sex and HAV and HBV antibody status, indicating that the association between antibody status and thyroid hormone levels varied by sex. This study underscores the need for further research on the effect of viral immunity on inflammatory parameters and thyroid hormone levels.

The Interplay between Mitochondrial Metabolism and Nasal Mucociliary Function as a Surrogate Method to Diagnose Thyroid Dysfunction: Insights from a Population-Based Study.

Aim and Background. This study aims to explore alternative diagnostic methods to assess thyroid function in patients unable to undergo blood tests for thyroid-stimulating hormones (TSH) and thyroxine (T4), such as individuals with trypanophobia, severe medical conditions, or coagulopathy. Considering the impact of thyroid dysfunction on mitochondrial metabolism and the essential role of proper mitochondrial function in ciliary motility, we postulate that assessing nasal ciliary function could serve as a surrogate diagnostic approach for thyroid dysfunction. Methods. This cross-sectional study was performed on individuals with no history of thyroid diseases. The primary endpoint was the diagnostic value of the nasal mucociliary (NMC) test using Iranica Picris (Asteraceae) aqueous extract in differentiating hypo- or hyperthyroidism cases from euthyroid cases. Results. 232 individuals were recruited (71% females, 86% euthyroid). Receiver operating characteristic (ROC) analysis showed a good diagnostic value for the NMC test in differentiating overt hypothyroidism (area under the ROC curve [AUROC] = 0.82, p = 0.004) and its fair value in diagnosing subclinical hyperthyroidism (AUROC = 0.78, p = 0.01) from the euthyroid condition. The NMC test had a significant positive correlation with TSH (r = 0.47, p < 0.001) and a significant negative correlation with T4 (r = -0.32, p < 0.001). The NMC rate was significantly different in distinct thyroid function groups (p < 0.001). Compared with euthyroid cases, the post-hoc analysis showed that the NMC test is significantly higher in overt hypothyroidism (15.06 vs. 21.07 min, p = 0.003) and significantly lower in subclinical hyperthyroidism (15.05 vs. 10.9 min, p = 0.02). Conclusions. The Iranica Picris-based NMC test might serve as a diagnostic method to distinguish overt hypothyroidism and subclinical hyperthyroidism.

Transcriptome networks and physiology related to cardiac function and motor activity are perturbed in larval zebrafish (Danio rerio) following exposure to the antidepressant citalopram

Citalopram is a selective serotonin reuptake inhibitor (SSRI) used to treat depression and is often detected in aquatic environments. Here, we measured the acute toxicity of citalopram at environmentally relevant concentrations to zebrafish embryos/larvae and utilized RNA-seq to reveal potential mechanisms of toxicity. We also assessed behavioral outcomes in larval zebrafish. Zebrafish embryos were exposed continuously to embryo rearing medium (ERM), or one concentration of 0.1, 1, 10, 100, and 1000 μg/L citalopram for 7 days post-fertilization (dpf). No acute toxicity was noted for citalopram over 7-days in developing zebrafish, nor were there any effects on hatch rates; however, exposure resulted in a dose-dependent decrease in heart rate at 2 dpf. Reactive oxygen species were also increased in 7-day old larvae zebrafish exposed to 100 μg/L citalopram. There were 29 genes differentially expressed in fish exposed to 10 μg/L citalopram [FDR <0.05] and 79 genes differentially expressed in fish exposed to 1000 μg/L citalopram [FDR <0.05]. In the 1000 μg/L citalopram treatment, there were several transcripts downregulated related to muscle function, including myhz2, myhz1, and myom1. Twenty-five gene set pathways were shared between exposure concentrations including ‘IL6 Expression Targets’, ‘Thyroid Stimulating Hormone (TSH) Resistance in Congenital Hypothyroidism’, and ‘GFs/TNF - > Ion Channels.' Enrichment of KEGG pathways revealed that 1000 μg/L citalopram altered processes related to the proteosome and cardiac muscle contractions. Larval zebrafish at 7 dpf showed hypoactivity with exposure to ≥10 μg/L citalopram. This may be related to the downregulation of transcripts involved in muscle function. Overall, our results show that citalopram as a pharmaceutical pollutant may have an adverse influence on aquatic species' ability to survive by reducing their abilities to elude predators (e.g. cardiac output, locomotor activity). This study improves mechanistic understanding of the potential harm citalopram may cause fish and contributes to environmental risk assessments for SSRIs in aquatic species.

Advancing thyroid care: An accurate trustworthy diagnostics system with interpretable AI and hybrid machine learning techniques

The worldwide prevalence of thyroid disease is on the rise, representing a chronic condition that significantly impacts global mortality rates. Machine learning (ML) approaches have demonstrated potential superiority in mitigating the occurrence of this disease by facilitating early detection and treatment. However, there is a growing demand among stakeholders and patients for reliable and credible explanations of the generated predictions in sensitive medical domains. Hence, we propose an interpretable thyroid classification model to illustrate outcome explanations and investigate the contribution of predictive features by utilizing explainable AI. Two real-time thyroid datasets underwent various preprocessing approaches, addressing data imbalance issues using the Synthetic Minority Over-sampling Technique with Edited Nearest Neighbors (SMOTE-ENN). Subsequently, two hybrid classifiers, namely RDKVT and RDKST, were introduced to train the processed and selected features from Univariate and Information Gain feature selection techniques. Following the training phase, the Shapley Additive Explanation (SHAP) was applied to identify the influential characteristics and corresponding values contributing to the outcomes. The conducted experiments ultimately concluded that the presented RDKST classifier achieved the highest performance, demonstrating an accuracy of 98.98 % when trained on Information Gain selected features. Notably, the features T3 (triiodothyronine), TT4 (total thyroxine), TSH (thyroid-stimulating hormone), FTI (free thyroxine index), and T3_measured significantly influenced the generated outcomes. By balancing classification accuracy and outcome explanation ability, this study aims to enhance the clinical decision-making process and improve patient care.

Nuclear Receptors and Stress Response Pathways Associated with the Development of Oral Mucositis Induced by Antineoplastic Agents.

Oral mucositis (OM) is one of the common adverse events associated with cancer treatment that decreases the quality of life and affects treatment outcomes. However, the medications used to manage OM are generally only palliative, and our knowledge of the syndrome is limited. The etiology of the syndrome is thought to be complex and multifactorial. We investigated the trends and characteristics of OM and estimated molecular initiating events (MIEs) associated with the development of the syndrome using the FDA Adverse Event Reporting System. The study of trends and characteristics suggested that OM is significantly more likely to occur in females and nonelderly patients and is likely to be induced by protein kinase inhibitors such as afatinib and everolimus. Next, we used Toxicity Predictor, an in-house quantitative structure-activity relationship system, to estimate OM-associated MIEs. The results revealed that the agonist activity of the human pregnane X receptor, thyroid-stimulating hormone-releasing hormone receptor, and androgen receptor may be associated with OM development. Our study findings are expected to help avoid the risk of OM induction during the drug discovery process and clinical use of antineoplastic agents.

A predictive model for L-T4 dose in postoperative DTC after RAI therapy and its clinical validation in two institutions.

To develop a predictive model using machine learning for levothyroxine (L-T4) dose selection in patients with differentiated thyroid cancer (DTC) after resection and radioactive iodine (RAI) therapy and to prospectively validate the accuracy of the model in two institutions. A total of 266 DTC patients who received RAI therapy after thyroidectomy and achieved target thyroid stimulating hormone (TSH) level were included in this retrospective study. Sixteen clinical and biochemical characteristics that could potentially influence the L-T4 dose were collected; Significant features correlated with L-T4 dose were selected using machine learning random forest method, and a total of eight regression models were established to assess their performance in prediction of L-T4 dose after RAI therapy; The optimal model was validated through a two-center prospective study (n=263). Six significant clinical and biochemical features were selected, including body surface area (BSA), weight, hemoglobin (HB), height, body mass index (BMI), and age. Cross-validation showed that the support vector regression (SVR) model was with the highest accuracy (53.4%) for prediction of L-T4 dose among the established eight models. In the two-center prospective validation study, a total of 263 patients were included. The TSH targeting rate based on constructed SVR model were dramatically higher than that based on empirical administration (Rate 1 (first rate): 52.09% (137/263) vs 10.53% (28/266); Rate 2 (cumulative rate): 85.55% (225/263) vs 53.38% (142/266)). Furthermore, the model significantly shortens the time (days) to achieve target TSH level (62.61 ± 58.78 vs 115.50 ± 71.40). The constructed SVR model can effectively predict the L-T4 dose for postoperative DTC after RAI therapy, thus shortening the time to achieve TSH target level and improving the quality of life for DTC patients.

Bone Mineral Density, Osteoporosis Prevalence and Influential Factors in Osteogenesis in Patients with Beta Thalassemia Major: A Cross-Sectional Study.

Osteoporosis and osteopenia considered as severe problems in Beta thalassemia major (BTM) that can lead to bone fractures. We aimed to investigate bone mineral density status and the laboratory parameters related to bone metabolism in BTM patients and compare the statically differences between the mentioned parameters in the patients with or without bone fractures. The results of laboratory parameters including; Hemoglobin (Hb), Calcium (Ca), Vitamin D (Vit D), Phosphorus (P), Magnesium (Mg), Alkaline Phosphatase (ALP), Ferritin (FER), Serum Iron (SFe), Thyroid Stimulating Hormone (TSH), T3, T4 and Parathyroid Hormone (PTH), and BMD (by using Dual-Energy X-ray Absorptiometry (DEXA) method) were investigated in 143 BTM patients from thalassemia center of Dezful University of Medical Sciences in 2023. Seventy-two women and 71 men with confirmed BTM diagnosis with age range (32.4 ± 9.7) were entered in the study. Laboratory parameters including TSH, T3, T4, ALP, FER 247) and SFe showed a significant difference between fracture and non-fracture groups respectively (P≤0.05). In this study, Z-Score between -1.1 and -2.4 was considered osteopenia, and below -2.5 was osteoporosis. Among the studied patients 36.6%, 39.1% and 24.2% had normal bone density, osteopenia and had osteoporosis respectively. Osteopenia and osteoporosis had a high frequency among the studied patients that can prone them to bone fractures. Continuous examinations of laboratory tests, especially T3, T4, TSH, FER, SFE, can be helpful for faster diagnosis and therapeutic interventions to prevent the occurrence of osteopenia and pathological fractures.

Thyroid Hormone and Diabetes Mellitus Interplay: Making Management of Comorbid Disorders Complicated.

Insulin and thyroid hormones play important roles in our body. Insulin helps regulate the glucose level while the thyroid hormones affect various cells and tissues, metabolizing protein, lipids, and glucose. Hyperthyroidism and thyrotoxicosis are potential hazards for type 2 diabetes mellitus. There is a high prevalence of hypothyroidism being more common compared to hyperthyroidism coexisting with diabetes mellitus. Thyroid hormones affect glucose metabolism through its action on peripheral tissues (gastrointestinal tract, liver, skeletal muscles, adipose tissue, and pancreas). High-level thyroid hormone causes hyperglycemia, upregulation of glucose transport, and reduction in glycogen storage. The reverse is observed during low levels of thyroid hormone along with insulin clearance. The net result of thyroid disorder is insulin resistance. Type 2 diabetes mellitus can downsize the regulation of thyroid stimulating hormones and impair the conversion of thyroxine to triiodothyronine in peripheral tissues. Furthermore, poorly managed type 2 diabetes mellitus may result in insulin resistance and hyperinsulinemia, contributing to the proliferation of thyroid tissue and an increase in nodule formation and goiter size. Although metformin proves advantageous for both type 2 diabetes mellitus and thyroid disorder patients, other antidiabetics like sulfonylureas, pioglitazone, and thiazolidinediones may have adverse effects on thyroid disorders. Moreover, antithyroid drugs such as methimazole can weaken glycemic control in individuals with diabetes. Thus, an interplay between both endocrinopathies is observed and individualized care and management of the disorder needs to be facilitated.