Thyroid Hormone Levels Research Articles

Trace element contaminants and endocrine status of European brown bears assessed using blood as a matrix.

Bioaccumulation of trace element contaminants with endocrine disruptive (ED) potential has been noted in European brown bears, though evidence of their effects is lacking. Generalized linear models were employed to assess circulating levels of reproductive, stress, and thyroid hormones in relation to arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb) and thallium (Tl) in 53 free-ranging brown bears (Ursus arctos) from two European populations (Carpathian and Dinara-Pindos). Other potential drivers of hormone variation, such as essential elements, ecological factors, physiological variables, and capture methods, were included as predictors. The models demonstrated a positive association between cortisol and Cd, and a negative association with Tl. In addition, Tl and Pb were identified as key factors in explaining variation in thyroid hormones (free triiodothyronine, fT3 and free thyroxine, fT4). Trap type was significant in explaining variation in fT3 concentrations, while sex was an important predictor of progesterone levels. The essential elements, cobalt (Co) and copper (Cu) accounted for 41% of testosterone variation, while Cu and selenium (Se) were negatively associated with fT4. Other notable predictors of investigated hormone variation included body condition index (important for cortisol), age (for fT4), year (for fT3), capture day (for fT4 and fT4:fT3 ratio) and population (fT4:fT3 ratio). This study evidenced trace elements as important factors to consider when studying hormonal variation in terrestrial wildlife (Tl for cortisol and fT3, Cd for cortisol, Cu for testosterone and fT4, Co for testosterone, Pb and Se for fT4). To gain a more definitive understanding of the effects of exposure to element contaminants on endocrine status, it is recommended to include more sensitive and specific endocrine disruption-related endpoints in a larger sample size. Doing so will further enhance our understanding of the potential adverse endocrine effects of environmental pollutants on these bear populations and other large mammalian wildlife species.

Potential link between vaping and hypothyroidism: A case report

Background: Vaping has gained popularity as an alternative to traditional smoking, but its potential health effects, particularly on endocrine function, remain under-explored. This case report highlights a possible association between vaping and the development of subclinical hypothyroidism in a young adult female. Case Presentation: A 25-year-old female with a history of vaping for 30 minutes daily over the course of one year presented with symptoms of fatigue, weight gain, and dry skin. Initial thyroid function tests showed elevated TSH (5.08 uIU/mL), reduced T3 (64 ng/dL), and T4 (4.8 ug/dL), consistent with subclinical hypothyroidism. After discontinuing or reducing vaping, repeat thyroid function tests revealed an improvement in thyroid hormone levels (TSH: 4.69 uIU/mL, T3: 136.4 ng/dL, T4: 5.77 ug/dL) and symptom relief. The use of a vaping device with a lithium-ion battery raised concerns about possible lithium exposure, a known factor in thyroid dysfunction. Conclusion: This case suggests a potential reversible association between vaping and subclinical hypothyroidism, possibly exacerbated by lithium toxicity from battery leakage. Further research is necessary to understand the mechanisms behind vaping-related thyroid dysfunction and the potential role of lithium in this process.

Resting metabolic rate and energy efficiency in response to an intensive 84-day combat-swimmer training in the German Armed Forces

Abstract Purpose According to the ‘constrained model’, there are compensations in resting metabolic rate (RMR) at high levels of physical activity (PA). Here, we have used a standardized combat-swimmer training protocol (CST) to investigate whether changes in RMR (i) confirm the ‘constraint model’, and (ii) differ between successful participants and dropouts. Methods Controlled 84d CST in 44 male soldiers with 13 finally successful. Fat mass (FM) and fat-free mass (FFM) were measured using Quantitative Magnetic Resonance. RMR was assessed by indirect calorimetry, VO2max, and work efficiency by treadmill spiroergometry. Plasma levels of thyroid hormones, testosterone, and cortisol were analysed by standard laboratory methods. Results CST increased VO2max (+ 6.9%) and exercise efficiency at low workloads of 10 and 12 km/h (+ 8.7 and + 6.5%; both p < 0.05). As energy balance was moderately negative (−356 ± 383 kcal/d), FFM and FM decreased (−2 and −16%; both p < 0.05). There was a considerable inter-individual variance but no change in in the mean values of RMR and RMRadjFFM. RMRadjFFM before CST had a negative association with its decrease with CST (p < 0.005). Concomitantly, plasma hormone levels were unchanged. When compared with dropouts, successful participants had a higher VO2max at baseline (5.2 ± 0.6 vs. 4.9 ± 04 l/min; p < 0.05) that increased with CST (+ 4.4 vs. −0.4%; p < 0.05) at similar changes in body composition and energy balance. Conclusion While CST increased VO2max and exercise efficiency as a compensation, there was an inter-individual variance in exercise-related compensation of RMR with no differences between ‘completers’ and ‘non-completers’. Trial registration DRKS00018850, November 27, 2019.

Impact of Vitiligo on Fasting Blood Sugar and Thyroid Hormone Profile on Libyan Patients

Vitiligo is a common acquired skin disease characterized by the development of circumscribed white patches of skin. It affects 1-2% of the general population. Autoimmunity plays a significant role in the pathophysiology of vitiligo. This study was intended to assess the prevalence and association of fasting blood sugar and thyroid function abnormalities among Vitiligo patients and healthy controls. A case-control study was carried out among thirty patients with a confirmed diagnosis of vitiligo (53.3% female and 46.7% male) who attended Tripoli Central Hospital (TCH) and Tajoura Hospital for follow-up, and a matched number of control subjects were recruited randomly. All blood samples were collected to assay for the FBS test, triiodothyronine (T3), thyroxin (T4), and thyroid-stimulating hormone (TSH). According to the recent data, the mean age of patients who were involved in this study was 34.4±16.51 years, while the mean age of onset was 20.13 ±14.19. Additionally, the data revealed that there were significant differences in FBS between vitiligo patients and healthy control groups (p-value = <0.001). Moreover, there were statistically significant differences between vitiligo patients and non-vitiligo subjects in T4 (p-value = 0.042). Furthermore, there was no significant correlation between the vitiligo phenotypes and thyroid hormone levels. P-value = 0.911 Chi-Square = 0.186. According to the results of the present study, it appears that vitiligo affects both sexes, especially women. It has also been noted that generalized vitiligo was more common, and there was no correlation between patterns of vitiligo and thyroid state.

The impact of prenatal exposure to fine particulate matter and its components on maternal and neonatal thyroid function and birth weight: a prospective cohort study.

Maternal and child health has garnered considerable attention recently. The effects of prenatal exposure to PM2.5 and its components on thyroid function in both mothers and fetuses, as well as on offspring birth weight, remain unexplored. This study involved 446 mother-infant pairs from a cohort study in Ma'anshan, China, during 2021-2022. Air pollution data were obtained from the Tracking Air Pollution (TAP) project. Thyroid hormone levels (FT3, FT4, and TSH) were measured in maternal blood samples taken at various pregnancy stages and in cord blood. We employed multiple analytical methods to evaluate the effects of PM2.5 and its components on maternal thyroid function and birth weight z-score (BWz). The GLR analysis reveals that the effect of PM2.5 and its components on BWz differs according to the pregnancy stage and the specific pollutant involved. During the late pregnancy, increased exposure to PM2.5 and specific components (for instance, and ) was correlated with elevated maternal FT4 levels (p < 0.05) and reduced BWz (p < 0.05). QgC results illustrated a notable negative correlation between heightened PM2.5 exposure and BWz in late pregnancy. BKMR analysis confirmed that overall exposure to PM2.5 and its components negatively impacted BWz during the third trimester. Mediation analysis showed that changes in maternal FT4 levels accounted for approximately 8.52%, 8.05%, and 8.13% of the negative effects on BWz from exposure to , and , respectively (p < 0.05). In healthy pregnancies, exposure to PM2.5 and its components during the late pregnancy is linked to alterations in maternal thyroid hormone levels, potentially leading to reduced birth weight. Maternal FT4 levels may mediate the connection between PM2.5 components exposure and reduced the weight of offspring.

Thyroid hormone levels in patients with bipolar disorder: a systematic review and meta-analysis

PurposeTo investigate the difference in blood (serum/plasma) thyroid hormone (TH) levels, including thyroid-stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3), free thyroxine (FT4), and free triiodothyronine (FT3), in bipolar disorder (BD) during different mood episodes (depression and mania) compared with healthy control (HC) and between manic episodes (BD-M) and depressive episodes (BD-D).MethodsAs of September 1, 2024, the electronic databases PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, China Science and Technology Journal Database, Wanfang Database, and Clinical Trials. Gov were systematically searched with no language limitations. Standardized mean differences (SMD) with 95% confidence interval (CI) were summarized using a random effects model. The chi-squared-based Q test and the I2 test assessed the size of heterogeneity.ResultsThe 21 studies included a total of 3696 participants, Of the 2942 BD patients, 1583 were in depressive episodes 1359 were in manic episodes. The status of measuring blood TH levels included 2 studies in plasma and 19 in serum. Combined with the results of the sensitivity analyses, we obtained the following relatively reliable results: serum T3 (SMD: -0.63, 95%CI: -1.09 to -0.17) and FT3 (SMD: -0.42, 95%CI: -0.83 to -0.00) levels decreased significantly in BD-D compared to HC; serum T3 (SMD: -0.91, 95%CI: -1.49 to -0.32) levels decreased significantly and serum FT4 (SMD: 0.37, 95%CI: 0.14 to 0.60) levels increased significantly in BD-M than in HC; serum T3 (SMD: 0.87, 95%CI: 0.24 to 1.49) and FT3 (SMD: 0.27, 95%CI: 0.13 to 0.42) levels demonstrated a significant elevation in BD-M compared to BD-D. In the group of euthyroidism, apart from serum FT4 (SMD: 0.21, 95%CI: -0.15 to 0.58) levels showed no significant difference between BD-M and HC, other results above remained consistent.ConclusionSerum T3 and FT3 levels decreased significantly in BD-D compared to HC. Serum T3 levels decreased significantly and serum FT4 levels increased significantly in BD-M compared to HC. Serum T3 and FT3 levels increased significantly in BD-M than in BD-D. The temporality of changes in TH levels and BD progression demands further longitudinal studies to illustrate.Trial registrationNumber and date of registration for prospectively registered trials No. CRD42022378530.

Maternal Thyroid Hormones as Mediators between Phthalate Exposure and Neonatal Birth Weight: A Cross-Sectional Study from the Zunyi Birth Cohort.

Studies have shown that exposure to phthalates can affect neonatal birth weight. However, epidemiological evidence on the mediating role of maternal thyroid hormones is limited. Therefore, this study, based on the Compliance Birth Cohort, aimed to reveal the potential mediating function of maternal thyroid hormones during pregnancy between phthalic acid ester (PAE) exposure and neonatal birth weight. The study included 1274 mother-infant pairs. Linear regression analysis revealed a negative association between MIBP and neonatal birth weight (β = -62.236; 95% CI: -118.842, -5.631). Bayesian kernel-machine regression (BKMR) indicated a nonlinear negative association between PAE metabolites (PAEs) and birth weight. Linear regression analysis revealed a positive association between neonatal birth weight and FT3 (β = 41.605; 95% CI: 2.631, 80.380). The BKMR model also found a positive association between thyroid hormones and birth weight but in a nonlinear manner. Additionally, linear regression analyses showed that TSH, TT3, TT4, FT3, and FT4 were associated with PAEs. The BKMR model revealed an inverted U-shaped association of PAEs with TT3 and FT3 and a nonlinear association with TSH, TT4, and FT4. Structural equation modeling revealed that MMP, MIBP, MBP, MEHP, MOP, MBZP, and MEOHP contributed to a net reduction in neonatal birth weight of 32 g through the TT3, FT3, TT4, and FT4 pathways. The findings suggest that exposure to PAEs during pregnancy leads to a reduction in neonatal birth weight, possibly due to the involvement of maternal thyroid hormones as mediators. Controlling maternal thyroid hormone levels during pregnancy may be a viable method to reduce the harmful effects of phthalate exposure on the developing fetus.

Ontogeny of Thyroid Hormone Signaling in the Retina of Zebrafish: Effects of Thyroidal Status on Retinal Morphology, Cell Survival, and Color Preference.

The retina is crucial for converting light into neuronal signals for visual perception. Understanding the retina's structure, function, and development is essential for vision research. It is known that the thyroid hormone (TH) receptor type beta 2 (TRβ2) is a key element in the regulation of cone differentiation in the retina, but other elements of TH signaling, such as transporters and enzyme deiodinases, have also been implicated in retinal cell development and survival. In the present study, we investigated the expression profile of genes involved in TH signaling and analyzed the impact of thyroidal status on retinal morphology, opsin expression, cell death/proliferation profile, as well as color preference behavior during the early retina development of zebrafish larvae. mRNA expression analysis on dissected whole eyes revealed that TH signaling elements gradually increase during eye development, with dio3b being the component that shows the most dramatic change. Mutations generated by CRISPR/CAS9 in the dio3b gene, but not in the thrb gene, modifies the structure of the retina. Disruption in TH level reduces the cell number of the ganglion cell layer, increases cell death, and modifies color preference, emphasizing the critical importance of precise TH regulation by its signaling elements for optimal retinal development and function.

Maintaining the physiological stability during artificial spawning of Liza ramada in captivity

In captivity, the physiological condition of mature brood fish has a vital role for a successful artificial spawning. Therefore, the current study aimed to minimize endocrine and metabolic disruptions during routine handling, transportation, and acclimatization during artificial spawning in L. ramada. Here, we determined the impacts of transportation and handling, as well as the acclimation to different salinities on the levels of total thyroxine (T4), triiodothyronine (T3), cortisol, and glucose in the mature L. ramada females. The transportation procedures of cultured mature females of L. ramada without anesthesia induced physiological stress as reflected with a rapid elevation in serum cortisol and glucose concomitant with a decrease in T4 within 3 h. However, the anesthesia protocol and the gradual acclimatization to seawater (24 h) were successful in maintaining baseline concentrations of the measured hormones in mature L. ramada females. The recorded levels of thyroid hormones (T4 and T3) and cortisol proved that 40 mg l−1 of clove oil was superior to anesthetic tricaine methane sulfonate (MS-222). In parallel, clove oil as an anesthetic has a rapid induction time and longer recovery time compared to MS-222 in L. ramada anesthesia. So, the slow acclimation and clove oil anesthesia were crucial during the induction of spawning in L. ramada. Indeed, all injected females were physiologically stable and spawned within the appropriate time consistent with the histological observation of both ovary and liver. Together, these findings recommend that maintaining the physiological stability of broodstock is critical for the successful artificial spawning of mullet.

EGFR Evalutation among the Hypothyroid Patients Attending at a Tertiary Center of Chattogram

Background: Hypothyroidism is a prevalent endocrine illness that affects people all over the world. The modulation of renal hemodynamics and basal metabolic rate is disrupted in hypothyroidism. The kidney is generally involved in thyroid hormone metabolism, breakdown and excretion. Chronic renal hypoperfusion affects the hypothalamic pituitary-thyroid axis, resulting in low circulating thyroid hormone levels, changed peripheral hormone metabolism, decreased tissue thyroid hormone content and altered thyroid iodine storage. Recent research has linked an increased risk of hypothyroidism to a decreased estimated Glomerular Filtration Rate (eGFR). The purpose of the study is to determine the association between eGFR with hypothyroidism in a tertiary care hospital of Chattogram. Materials and methods: A cross-sectional study was done during July 2022 to June 2023 including 100 diagnosed hypothyroidism cases attending in Chittagong Medical College Hospital. Serum Thyroid Stimulating Hormone (TSH) serum free thyroxine (FT4) serum creatinine, and blood urea were measured. The estimated glomerular filtration rate (eGFR) were determined. The result were analysed using SPSS version 25. Results: The mean age was 42.76±10.18 years with 93% female. Most of the patients (92%) were in a subclinical hypothyroid state and 8% were in an overt hypothyroid state. The mean ±SD serum creatinine levels and urea levels were 0.8±0.2mg/dl and 25.4±6.5 mg/dl, respectively. The mean eGFR was 75.36±7.54 ml/min/1.73 m2. There was a significant decrease in mean eGFR in the &lt; 60 ml/min/1.73m2 group among the study population. There was a significant association between decreased eGFR and hypothyroidism. Serum TSH had significantly shown a negative correlation with eGFR. Serum TSH level had a significant positive correlation with serum creatinine (r=0.56, p&lt;0.05) and serum urea (r=0.25, p&lt;0.05). There was a significant eGFR difference between subclinical hypothyroidism and overt hypothyroidism. Conclusion: It can be concluded from this study that the hypothyroidism was significantly correlated with decreased eGFR. IAHS Medical Journal Vol 7(1), June 2024; 86-90

EXTH-50. THYROID HORMONE-INDUCED DIFFERENTIATION: A PROMISING THERAPEUTIC STRATEGY FOR MEDULLOBLASTOMA

Abstract Medulloblastoma (MB) is the most common malignant brain tumor in children, consisting of four major subgroups (WNT, SHH, Group 3, and Group 4) that differ in genetic/epigenetic profiles and prognoses. Despite current therapy, a significant proportion of patients still succumb to MB. Moreover, survivors often suffer severe side effects from aggressive treatments. Therefore, improved strategies to treat MB are urgently needed. MB tumor cells retain the capacity for differentiation and can undergo terminal differentiation, after which they lose their proliferative and tumorigenic capacity. This suggests that MB can potentially be treated by inducing tumor cell differentiation. However, the mechanisms underlying MB tumor cell differentiation remain unclear. Our recent studies reveal that thyroid hormone (TH) plays a critical role in promoting tumor cell differentiation in MB. Reduced TH levels free the TH receptor, TRα1, to bind to EZH2 and repress the expression of NeuroD1, a transcription factor that drives tumor cell differentiation. Increased TH levels reverse the EZH2-mediated repression of NeuroD1 by disrupting the binding between EZH2 and TRα1, thereby stimulating tumor cell differentiation and reducing MB growth. Importantly, triiodothyronine (T3, active form of TH) inhibits the growth of both SHH- and Group 3 tumors, suggesting that the tumor-inhibitory effect of T3 is not restricted by MB subgroups. Additionally, this effect is significantly enhanced by concurrent chemotherapy. These findings establish an unprecedented association between TH signaling and MB pathogenicity, providing solid evidence for TH as a promising therapeutic modality for MB treatment.

A Review Article: Effects of Oral Contraceptive Pills on Menstrual Cycle, Pregnancy, and Thyroid Gland

Oral contraceptive pills (OCPs) are often used for both birth control and hormone modulation. They have a substantial impact on the menstrual cycle, pregnancy prevention, and general endocrine function, including the thyroid gland. This review examines how OCPs affect menstrual control, pregnancy prevention, and thyroid hormone levels. Understanding these interactions is critical for doctors managing patients on OCPs and women making informed reproductive health decisions.

Neurological and psycho-emotional manifestations of hyperthyroidism during pregnancy

Background. Hyperthyroidism is a state of thyroid hormone excess, which increases the metabolic rate and causes symptoms including anxiety and tremor. Graves’ disease is the most common etiology in developed countries. Excessive levels of thyroid hormones can impact mood, energy levels, and overall well-being. It is crucial to differentiate between symptoms related to thyroid function and clinical depression. The purpose of the study was to investigate the neurological and psycho-emotional manifestations of hyperthyroidism during pregnancy. Materials and methods. An examination of 50 pregnant women with subclinical and overt hyperthyroidism and 20 healthy women (control group) in the second trimester of pregnancy using the method of standardized multivariate personality study was carried out. Results. Based on the results of the study, it can be argued that pregnant women with thyrotoxicosis have changes in the psycho-emotional sphere: psychological maladaptation to the disease, an increase in the level of anxiety with hypochondriac tendencies, neuroticism, a decrease in intellectual performance and activity, a pronounced feeling of depression, anxiety, low mood. The identified criteria allow us to attribute these changes to the personality pattern or to the manifestations of a pathological neurotic state in conditions of mal­adaptation. The specific condition and behavior of pregnant women with thyrotoxicosis requires timely diagnosis and appropriate correction, which will contribute to the normalization and improvement of the psychological state, prevent the development of chronic stress and the occurrence of perinatal complications. Conclusions. Pregnant women with thyrotoxicosis have changes in the psycho-emotional sphere: psychological maladaptation to the disease, an increase in the level of anxiety with hypochondriac tendencies, neuroticism, a decrease in intellectual performance and activity, a pronounced feeling of depression and anxiety.

The effects of methimazole combined with propranolol on heart rate, bone metabolism, and thyroid hormone levels in patients with hyperthyroidism: A systematic review and a meta-analysis of case-control studies.

The combination of methimazole and propranolol is considered an effective treatment regimen for hyperthyroidism in clinical practice; however, detrimental effects on the heart rate, bone metabolism and thyroid hormone levels have been reported. Therefore, the present study aimed to systematically review the efficacy and safety differences in patients with hyperthyroidism and the effects of treatment on heart rate, bone metabolism, cortisol, and adrenocorticotropic hormone levels using case-control studies. Clinical case-control trials of methimazole combined with propranolol for the treatment of hyperthyroidism were selected from Chinese and English databases, and data were collected from the establishment of the database until August 2024. Two independent researchers evaluated the quality of the literature using the Newcastle-Ottawa Scale (NOS). Meta-analysis of each effect index was performed using RevMan software (version 5.3), and the quality of the results was evaluated using the GRADE profiler system letter description method. Sixteen clinical case-control trials were included in this study. Of these, 2 trials exhibited NOS scores of 7, 6 trials exhibited NOS scores of 6, and 8 trials exhibited NOS scores of 5. These accounted for 12.5% of the high-quality literatures, and included 772 patients treated with methimazole combined with propranolol (observation group) and 771 patients treated with methimazole alone (control group). The results of the meta-analysis demonstrated that methimazole combined with propranolol improved the cure rate, the total effective rate, and heart rate, compared with the control group (P < .05). In addition, calcification, bone glutamate protein, free triiodothyronine, free tetraiodothyronine, thyroid-stimulating hormone, cortisol, and adrenocorticotropic hormone were significantly different between the 2 groups (P < .05). There were no significant differences in leukemia, headache, dizziness, skin pruritus, bone pain, arthralgia, or in improving parathyroid hormone or reducing gastrointestinal reactions between the 2 groups. The present study demonstrated that methimazole combined with propranolol may significantly improve the heart rate, bone metabolism and associated hormone levels in patients with hyperthyroidism, without significantly increasing the risk of adverse reactions. However, due to the impact of primary literature type, quality or research methods high-quality, multicenter, rigorously designed clinical trials are required for further verification.

Relationship of serum iron and thyroid hormone in obesity and after laparoscopic sleeve gastrectomy

BackgroundIron is an essential element for thyroid function. However, no study focuses on the association between iron and thyroid in individuals with obesity. Our research aimed to investigate the iron status in relation to baseline thyroid hormone levels and after laparoscopic sleeve gastrectomy (LSG).MethodsA total of 216 subjects with obesity were enrolled and divided into low and high iron groups depending on the median value. The association between iron and thyroid hormone was analyzed and compared before and after LSG at the 6-month follow-up in patients who underwent LSG.Results1) In all, Total Triiodothyronine (TT3) was significantly higher in high iron than low iron group (P = 0.008). TT3 and thyroid stimulating hormone (TSH) were significantly higher in high iron than low iron group (1.92 ± 0.61 vs. 1.69 ± 0.28 nmol/l, P = 0.029; 2.93 ± 1.66 vs. 1.88 ± 1.03 mU/l, P = 0.002) in females while not in males (all P > 0.05). 2) Iron was significantly positively associated with free triiodothyronine (FT3), free thyroxine (FT4), TT3 and TSH (all P < 0.05). Adjusted for body mass index (BMI), total cholesterol (TCH), high-density lipoprotein cholesterol (HDL-C), fasting insulin (FINS) and homeostatic model assessment of insulin resistance (HOMA-IR), FT3, FT4 and TSH were still significantly associated with iron (all P < 0.05). 3). Regression analysis showed that iron was significantly associated with FT4 (β = 0.338, P = 0.038). 3) LSG led to decreased FT3, FT3, TT3, total thyroxine (TT4) and TSH at 6 months follow-up (all P < 0.05). Changed FT4 was significantly associated with changed iron (r = 0.520, P = 0.009). Subjects with iron decreased had more significant decreased TT4 than subjects without iron decreased (P = 0.021).ConclusionSerum iron overload is significantly associated with impaired thyroid function in subjects with obesity. LSG led to improved thyroid function which is associated with a change in iron.Trial RegistrationNCT04548232 registration date is on October 9, 2022, registered in https://register.clinicaltrials.gov/.

Breast cancer cells utilize T3 to trigger proliferation through cellular Ca2+ modulation

High levels of thyroid hormones are linked to increased risk and advanced stages of breast cancer. Our previous work demonstrated that the biologically active triiodothyronine (T3) facilitates mitochondrial ATP production by upregulating Ca2+ handling proteins, thereby boosting mitochondrial Ca2+ uptake and Krebs cycle activity. In this study, different cell types were utilized to investigate whether T3 activates a Ca2+-induced signaling pathway to boost cancer cell proliferation. Using live-cell imaging, biochemical assays, and molecular profiling, differences in intracellular signaling among MCF7 and MDA-MB-468 breast cancer cells, non-cancerous breast cells hTERT-HME1, and PC3 prostate carcinoma cells, previously found to be insensitive to thyroid hormones in terms of proliferation, were investigated. Our findings revealed that T3 upregulates 1,4,5-trisphosphate receptor 3 via thyroid hormone receptor α. This boosts mitochondrial Ca2+ uptake, reduction equivalent yield, and mitochondrial ATP production, supporting the viability and proliferation of breast cancer cells without affecting non-cancerous hTERT-HME1 or PC3 prostate carcinoma cells. Understanding the interplay between T3 signaling, organellar interaction, and breast cancer metabolism could lead to targeted therapies that exploit cancer cell vulnerabilities. Our findings highlight T3 as a crucial regulator of cancer metabolism, reinforcing its potential as a therapeutic target in breast cancer.Graphical

Meta-analysis of experimental studies of the effect of melatonin monotherapy on the levels of thyroid hormones and glucocorticoids in rats kept under standard condition

Melatonin is known to modulate circadian and seasonal rhythms in metabolism, reproduction, and behavior. However, the effect of exogenous melatonin supplementation on the functioning of the thyroid and adrenal glands in species without a clear seasonality in reproduction is still unclear. Using a meta-analysis of publications, to investigate the effect of melatonin monotherapy on the concentrations of pituitary thyroid-stimulating hormone, thyroid hormones (TG), pituitary adrenocorticotropic hormone and corticosterone (CS) in rats kept under standard laboratory conditions. In our work, using the Review Manager 5.3 program, we conducted a meta-analysis of publications examining the effect of melatonin monotherapy on the functioning of the thyroid gland (22 papers) and adrenal glands (20 papers) in rats kept under standard conditions. According to the results of our meta-analysis, the effects of melatonin on the levels of TG and CS depend on the dose and duration of therapy. A decrease in TG and CS was associated with therapy lasting no more than 4-5 weeks and with high doses of melatonin. An increase in CS and a trend toward increased TG levels were observed with longer therapy. However, a few studies have observed a decrease in TG with very long-term melatonin therapy (≥32 weeks). Among all TGs, total thyroxine (T4) showed maximum sensitivity to exogenous melatonin, which indicates the influence of melatonin on the secretory function of the thyroid gland. In addition, melatonin increased the relative weight of the adrenal glands. There was no convincing evidence that the effects of melatonin were influenced by the route and timing of administration, or the timing of blood sampling. As a result, exogenous melatonin can modulate TG and CS levels, even in species without a clear seasonality in reproductive function.

Perinatal exposure to PBDE-47 decreases brain glucose metabolism in male adult rats: Associations with shifts in triiodothyronine and neurobehavior

BackgroundThe brominated flame retardant 2, 2′, 4, 4′-tetrabromodiphenyl ether (PBDE-47) is well known as a developmental neurotoxicant, yet the underlying mechanisms remain elusive. Increasing evidence has demonstrated that brain glucose metabolism perturbation plays a role in neural impairments. Nevertheless, whether this disturbance is involved in PBDE-47-induced neurotoxicity remains unknown. ObjectivesTo explore the impacts of perinatal PBDE-47 exposure on brain glucose metabolism, and its link to thyroid hormones (THs) levels as well as neurobehavioral changes. MethodsFemale Sprague-Dawley rats were orally exposed to PBDE-47 at environmentally relevant levels (0.1, 1.0, and 10.0 mg/kg bw) from pre-pregnancy through weaning of offspring. The male offspring were continued to raise to 88 days after birth for follow-up experiments. Morris water maze and Open field tests were performed to assess the neurobehavioral alterations. The brain glucose metabolism was evaluated using 18F-labeled fluorodeoxyglucose (18F-FDG) positron emission tomography. Serum THs levels were measured via enzyme-linked immunosorbent assay. ResultsPerinatal exposure to PBDE-47 induced neurobehavioral impairments in adult male rats as evidenced by learning and memory impairments, hyperactivity and anxiety-like behavior. Moreover, positron emission tomography showed that the glucose metabolism in the whole and the specific brain regions were markedly declined. Interestingly, variations in brain glucose metabolism were associated with the increased serum triiodothyronine (T3) levels, and both were linked to neurobehavioral disorders. ConclusionExposure to environmentally related levels of PBDE-47 at critical developmental stages lowers glucose metabolism in the whole brain and in various brain regions, which is associated with behavioral and cognitive deficits in adult male rats. Moreover, the association may be influenced by the disturbance of T3 homeostasis.

Gender-Dependent Association Between Thyroid Hormones and Severity of Coronary Artery Disease by SYNTAX Score

Thyroid function has been shown to be associated with cardiovascular diseases. Moreover, sex can influence on the association between thyroid function and other diseases. We aimed to evaluate the relationship between thyroid hormones and the severity of coronary artery disease (CAD) and outcomes. In a prospective study, patients with chest pain undergoing diagnostic coronary angiography were evaluated. Patients were categorized based on the number of involved coronary arteries. Moreover, the severity of CAD was quantitatively calculated using the Syntax score (SS). All patients were also followed up for 3-month duration. The level of TSH in 150 patients was significantly higher in females than males (3.1 [1.7, 5] versus 1.8 [1, 3.3] mU/L; P=0.002). There was significant correlation between THS and the SS among females (ρ=0.477, P&lt;0.001), but not males. Among both sexes, thyroid hormones were comparable between those with or without events during follow-up. The main predictors of high SS values included age (odds ratio [OR] 1.060, 95% confidence interval [CI] 1.018-1.104; P=0.005) and female (OR 2.941, 95% CI 1.198-7.218). The main predictors of multivessel disease were age (OR 1.077, 95% CI 1.026-1.132), female (OR 5.853, 95% CI 1.880-18.222), thyroxin (OR 0.733, 95% CI 0.547-0.981), and thyrotropin (OR 1.333, 95% CI 1.079-1.647). Thyroid hormones are associated with the presence and the severity of CAD, but it might be sex-related. However, thyroid hormone levels could not predict short-term outcomes of patients.

Associations Between Thyroid Hormones Levels and Gray Matter Volume of Frontal Lobe Involved into Violence in Male Schizophrenia Patients.

Thyroid dysfunction and frontal lobe gray matter volume (GMV) alterations are associated with violence in schizophrenia (SCZ); however, little is known about the relationship between thyroid dysfunction and frontal lobe GMV. This study aimed to evaluate whether thyroid hormone levels were associated with frontal lobe GMV in male patients with schizophrenia and violence. Fifty-five male patients with SCZ underwent triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) tests and structural magnetic resonance imaging (sMRI) scans. The sMRI data were processed using the FreeSurfer version 5.0. Multiple linear stepwise regression analysis was used to investigate the relationship between frontal lobe GMV and thyroid hormone levels in all patients. Patients with SCZ and violence exhibited lower GMV of the left frontal pole and higher TSH levels than those without violence. After controlling for potential covariates, the frontal pole GMV was negatively associated with TSH levels in all participants. These findings expand our understanding of the influence of TSH on frontal pole GMV in patients with schizophrenia and violence.