Thyroid Hormone Research Articles

Thyroid hormone regulates both melanin and non-melanin pigmentation in Sinibrama taeniatus via three types of chromophores

Thyroid hormone regulates both melanin and non-melanin pigmentation in Sinibrama taeniatus via three types of chromophores

Lower Free Thyroxine Levels Are Associated with Diabetic Kidney Disease in Males with Type 2 Diabetes Mellitus: An Observational Cross-Sectional Study.

Objectives: We aimed to explore the correlation between thyroid function and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 7516 T2DM patients were enrolled and grouped according to DKD status. Clinical parameters, including blood glucose parameters, thyroid function, and indicators of renal impairment, were collected and compared between the DKD and Non-DKD groups. Correlation analysis and univariate/multivariate logistic regression analyses were performed. Results: Age, T2DM duration, the use of insulin and lipid-lowering drugs, systolic and diastolic blood pressure, body mass index, and fasting blood glucose levels were greater in the DKD group than in the Non-DKD group (p < 0.001). Notably, compared with those in the Non-DKD group, patients in the DKD group had lower triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), and free thyroxine (FT4) levels and higher thyrotropin levels (p < 0.001). Univariate logistic regression analysis revealed that T3, T4, FT3, and FT4 levels were negatively correlated with the risk of DKD. Spearman correlation analysis confirmed that T3, T4, FT3, and FT4 levels were negatively correlated with blood urea nitrogen levels, blood creatinine levels, and the urinary albumin-to-creatinine ratio (p < 0.05). Multivariate logistic regression analysis revealed that a greater FT4 level was a protective factor against DKD in T2DM patients, especially in males, with a cut-off value of 13.35 pmol/L (area under the curve = 0.604). Conclusions: Thyroid hormone levels, especially FT4 levels, were significantly negatively correlated with DKD in T2DM patients.

Brain-Region-Specific Differences in Protein Citrullination/Deimination in a Pre-Motor Parkinson's Disease Rat Model.

The detection of early molecular mechanisms and potential biomarkers in Parkinson's disease (PD) remains a challenge. Recent research has pointed to novel roles for post-translational citrullination/deimination caused by peptidylarginine deiminases (PADs), a family of calcium-activated enzymes, in the early stages of the disease. The current study assessed brain-region-specific citrullinated protein targets and their associated protein-protein interaction networks alongside PAD isozymes in the 6-hydroxydopamine (6-OHDA) induced rat model of pre-motor PD. Six brain regions (cortex, hippocampus, striatum, midbrain, cerebellum and olfactory bulb) were compared between controls/shams and the pre-motor PD model. For all brain regions, there was a significant difference in citrullinated protein IDs between the PD model and the controls. Citrullinated protein hits were most abundant in cortex and hippocampus, followed by cerebellum, midbrain, olfactory bulb and striatum. Citrullinome-associated pathway enrichment analysis showed correspondingly considerable differences between the six brain regions; some were overlapping for controls and PD, some were identified for the PD model only, and some were identified in control brains only. The KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways identified in PD brains only were associated with neurological, metabolic, immune and hormonal functions and included the following: "Axon guidance"; "Spinocerebellar ataxia"; "Hippo signalling pathway"; "NOD-like receptor signalling pathway"; "Phosphatidylinositol signalling system"; "Rap1 signalling pathway"; "Platelet activation"; "Yersinia infection"; "Fc gamma R-mediated phagocytosis"; "Human cytomegalovirus infection"; "Inositol phosphate metabolism"; "Thyroid hormone signalling pathway"; "Progesterone-mediated oocyte maturation"; "Oocyte meiosis"; and "Choline metabolism in cancer". Some brain-region-specific differences were furthermore observed for the five PAD isozymes (PADs 1, 2, 3, 4 and 6), with most changes in PAD 2, 3 and 4 when comparing control and PD brain regions. Our findings indicate that PAD-mediated protein citrullination plays roles in metabolic, immune, cell signalling and neurodegenerative disease-related pathways across brain regions in early pre-motor stages of PD, highlighting PADs as targets for future therapeutic avenues.

Preparation and Characterization of Biopolymeric Hybrid Microbeads for Controlled Drug Delivery of Levothyroxine Sodium

Preparation and Characterization of Biopolymeric Hybrid Microbeads for Controlled Drug Delivery of Levothyroxine Sodium

Roles of thyroid and leptin hormones and their crosstalk in male reproductive functions: an updated review.

This review aims to provide updated information regarding the role of thyroid and leptin hormones and their crosstalk in affecting the male reproductive function in hypothyroid and obesity conditions. A wide literature search was made using online search engines on published articles using keywords including thyroid hormone, hypothyroidism, leptin hormone, hyperleptinemia, obesity, the relationship between thyroid and leptin hormones and male reproduction, and hypothyroidism, obesity, and male reproduction. All information pertaining thyroid and leptin hormone effects on male reproduction, hypothyroidism, hyperleptinemia, and obesity effect on male fertility as well as the related molecular mechanisms are obtained. Thyroid and leptin hormones individually play a significant role in male reproduction. Alterations of these hormones' levels could adversely affect the male reproductive functions. PI3K/AKT signaling was found to be the major signaling pathway involved in mediating the effect of both hormones on male reproduction. Impaired crosstalk between the two hormones may occur in hypothyroidism with obesity which would contribute towards male reproductive dysfunction.

Increased thyroid hormone sensitivity is correlated with visceral obesity in patients with type 2 diabetes

ObjectiveThe study aimed to assess whether thyroid hormone (TH) sensitivity is related to visceral fat area (VFA) and visceral obesity in euthyroid subjects with type 2 diabetes (T2D).Methods750 euthyroid patients with T2D were enrolled. A VFA of 80 cm2 or more was considered visceral obesity. Central TH sensitivity was conducted using thyrotrophic thyroxine resistance index (TT4RI), thyrotropin index (TSHI), and thyroid feedback quantile-based index (TFQI). Free triiodothyronine to free thyroxine (FT3/FT4) was utilized for assessing peripheral TH sensitivity.ResultsThe subjects had a mean age of 51.5 ± 11.1 years, and 540 (72.0%) of them were men. In multivariable regression analyses, there was a positive correlation of FT3/FT4 tertile with visceral obesity, after full adjustment for confounding variables (P < 0.05). The middle and highest FT3/FT4 tertiles were correlated with a 134% [95% CI (1.24, 4.44)] and 98% [95% CI (1.04, 3.78)] higher prevalence of visceral obesity than the lowest tertile, respectively. Conversely, elevated TFQI levels were linked to a decreased prevalence of visceral obesity. Stratified analysis revealed that these associations were particularly pronounced in participants who are neither overweight nor obese and those aged less than 60 years (all P < 0.05).ConclusionsHigher TH sensitivity is correlated with visceral obesity and elevated VFA in euthyroid patients with T2D, particularly among those younger than 60 years and individuals who are neither overweight nor obese.

A-9-Years-Old Female with Diabetes Mellitus Type 1 with Hyperthyroidism

Diabetes Mellitus Type 1 (DMT1) and thyroid disease can occur together, which is defined as a variant of autoimmune polyglandular syndrome type 3. It is known that the action of insulin and thyroid hormones affect cellular metabolism, thyroid hormones contribute to carbohydrate metabolism and pancreatic function. Since the thyroid gland plays a central role in the regulation of metabolism, abnormal thyroid function can have a major impact on the control of diabetes and poor glycemic control can cause alterations in thyroid hormone. A female, 9 years old, with decreased consciousness. Previous medical history, polyuria, increased appetite, and drastic weight loss. She also complained of sweating even in a cold room and was often emotional. On physical examination, there was fever, shortness of breath, tachycardia, and a soft and diffused slightly enlarged thyroid gland, with no bruit on auscultation. Laboratory tests showed blood glucose levels at 739 mg/dL, HbA1c 9.2%, C-peptide 0.2 ng/mL, TSH levels 0.01 µIU/mL, FT4 levels 2.77 ng/dL, the presence of metabolic acidosis, proteinuria, glucosuria, and ketonuria. Thyroid dysfunction will have a negative effect on DM control while poor glucose control will harm the work of thyroid hormones. Improvement in glycemic control and routine insulin injection with the right dose will reduce the risk of diabetic vascular and metabolic complications onset and progression.

In silico models for the screening of human transthyretin disruptors

The use of New Approach Methodologies (NAMs), such as Quantitative Structure-Activity Relationship (QSAR) models, is highly recommended by international regulations to speed up hazard and risk assessment of Endocrine Disruptors, which are known to be linked to a wide spectrum of severe diseases on humans and wildlife. A very sensitive target for these chemicals is the thyroid hormone system, which plays a key role in regulating metabolic and cognitive functions. Several chemicals have been demonstrated to compete with the thyroid hormone thyroxine (T4) for binding to human thyroid hormone distributor protein transthyretin (hTTR). In this work, we generated three new datasets composed by T4-hTTR competing potencies of more than 200 heterogeneous chemicals measured by three different in vitro assays. These datasets were used for the development of new regression QSAR models. The best models were thoroughly validated by internal and external validation procedures. The mechanistic interpretation of the selected molecular descriptors provided information on structural features which are relevant to characterise hTTR binders, such as the presence of hydroxylated and halogenated aromatic rings. PCA analysis was used to rank the studied chemicals according to their increasing T4-hTTR competing potency. Hydroxylated and halogenated bicyclic aromatic compounds are ranked as the strongest hTTR binders. The new QSARs are useful to screen potential Thyroid Hormone System-Disrupting Chemicals (THSDCs), and to support the identification of sustainable alternatives to hazardous chemicals.

Impact of thyroid hormones on predicting the occurrence of persistent inflammation, immunosuppression, and catabolism syndrome in patients with sepsis.

The prevalence of persistent inflammation, immunosuppression, and catabolism syndrome (PICS) has an upward trend in sepsis patients and can be associated with poor outcomes. Thyroid hormones are expected to be correlated with inflammation, immunity, and metabolism. Thus, the purpose of this study was to evaluate the effect of thyroid hormones on the occurrence of PICS and then further explore the optimal level of them in sepsis. This retrospective observational study used the online database Medical Information Mart for Intensive Care (MIMIC)-IV. Univariate and multivariate logistic regression analyses were employed to determine correlations between thyroid hormone levels and PICS. A combination of independent PICS development factors was established with accuracy assessed using the area under the receiver operating characteristic curve (AUC-ROC). Patients were divided into PICS (n=205) and non-PICS (n=671) groups. The third quartiles of triiodothyronine (T3) (60-80ng/dl) and thyroxine (T4) (5.5-6.8ug/dl) had the lowest PICS incidence and the adjusted odds ratio (OR) was 0.33 (T3, p=0.009) and 0.39 (T4, p=0.006), respectively, compared with the first quartiles of T3 and T4. For patients with a pre-existing T3 deficiency, severe deficiency (T3 <60ng/dl) and a high Sequential Organ Failure Assessment (SOFA) score were significantly related to PICS incidence. The AUC for these combined parameters in predicting PICS occurrence was 0.748 (all patients) and 0.861 (patients without thyroid disease). A mild T3 deficiency (60-80ng/dl) was significantly associated with the lowest risk-adjusted PICS occurrence in patients with sepsis. A severe T3 deficiency (<60ng/dl) and a high SOFA score were independent risk factors for PICS occurrence.

Successful management of megaoesophagus associated with hypothyroidism in a dog: A case report

A seven-year-old male Dachshund was presented with a history of chronic regurgitation and weight loss for two months. On clinical examination, dry and rough hair coat with alopecia on nose bridge and rat tail appearance were observed. Elevated rectal temperature and increased respiratory rate were noticed. Auscultation of lung field revealed mild crackles. Leucocytosis and mild anaemia were evident on complete blood count. Hypercholesterolaemia, hypertriglyceridaemia and elevation of Lactate dehydrogenase (LDH) and Alkaline phosphatase (ALP) were observed in serum biochemistry. The total T4 (TT4) value was low and canine-specific thyroid stimulating hormone (cTSH) was elevated. Megaoesophagus was confirmed by plain radiography. Barium contrast radiograph revealed generalised dilatation with pooling of barium in the oesophagus. The animal was treated with levothyroxine sodium at 0.02 mg/kg BW PO BID and bethanechol at 10 mg PO TID. Supportive therapy included antibiotics, antacids and antiemetics. Elevated feeding was advised. The animal had no episodes of regurgitation even after one month Keywords: Megaoesophagus, hypothyroidism, bethanechol, elevated feeding

Effects of repetitive transcranial magnetic stimulation on cognitive function and hormone levels in early stroke patients with low thyroid hormone levels.

This study aimed to observe the effects of repetitive transcranial magnetic stimulation (rTMS) on cognitive function and thyroid hormone levels in early older stroke patients with low thyroid hormone levels, and to investigate the correlation between the changes in thyroid hormone levels and the improvements in cognitive function after stroke. Forty older stroke patients who met the inclusion criteria were recruited and randomized into a magnetic-stimulation group (rTMS group) and a sham-stimulation group (Sham group). The rTMS group received low-frequency true stimulation and the Sham group received low-frequency sham stimulation. Patients' cognitive scores, activity of daily living(ADL) scores, and their levels of triiodothyronine (T3), free triiodothyronine (FT3), thyroxin (T4), free thyroxine (FT4), and thyroid stimulating hormone (TSH) were assessed before the intervention, after the 4-week intervention, and after an additional 4 weeks of follow-up; Repeated measurement analysis of variance was used to compare the changes of each index in the two groups at different times and the correlations between patiens' cognitive function scores and their changing hormone levels were subsequently investigated. Thirty-one patients were included in this study: 16 patients in rTMS group and 15 patients in the Sham group. Repeated-measures ANOVA showed that patients' T3,FT3 and TSH levels tended to increase at 4-week intervention and at the follow up (p < 0.05), and that the rTMS group had a better effect on improving T3 than the Sham group (Fgroup = 5.319, p = 0.028); The cognitive scale at different time points in both groups showed an upward trend (p < 0.05), and the MoCA, DSF, DSB scores in the rTMS group were statistically higher than those in the Sham group at the end of the 4-week intervention and at the follow-up (p < 0.05); The changes in the levels of T3 before and after 4-week intervention were positively correlated with the changes in the MoCA scores (r = 0.638, p < 0.05). And the difference in T3 level change was positively correlated with the difference in delayed recall, attention and naming score change (r = 0.562, p < 0.05; r = 0.562, p < 0.05; r = 0.531, p < 0.05); and the difference in FT3 level change was positively correlated with the visuospatial and executive function (r = 0.514, p < 0.05). Repetitive transcranial magnetic stimulation improved cognitive function and elevated T3 levels in older patients with post-stroke cognitive dysfunction who had low thyroid hormone levels. Within the normal range, increases in T3 levels are positively correlated with changes in cognitive function.

TRIP13 is Critical for the Survival of B-cell Lymphomas and Myeloid Leukemias In Vitro

Hematologic malignancies represent a diverse group of blood tumors accounting for approximately 10% of all cancer cases in the US. Based on the site of manifestation, presumed cell of origin, genetic abnormalities, and clinical features, we recognize more than 100 clinically important subtypes of hematologic malignancies broadly categorized into three main groups: leukemia, lymphoma, and multiple myeloma. While the prognosis for patients with specific subtypes of hematologic malignancies, such as Hodgkin lymphomas or chronic lymphocytic leukemia has significantly improved over the last several years, other subtypes such as acute myeloid leukemia or non-Hodgkin lymphomas still present with significant treatment challenges. A better understanding of molecular drivers of tumor maintenance is needed to improve existing therapies. Thyroid hormone receptor interactor 13 (TRIP13) is an AAA + ATPase that plays an important yet poorly understood role in the regulation of the mammalian cell cycle. The TRIP13 gene is highly expressed in various human tumors including colorectal carcinoma and glioblastoma, and it seems to promote tumorigenesis. Recently, we identified TRIP13 as a gene overexpressed in Peripheral T-cell lymphomas where it plays a critical role in tumor maintenance by regulating the G2-M phase of the cell cycle. However, the biological activities of TRIP13 in non-T cell hematologic malignancies have not been investigated to date. Here we used shRNA-mediated knockdown and a small molecule inhibitor to downregulate TRIP13 in B-cell lymphoid and myeloid lineages. We found genetic downregulation inhibited the proliferation of both B-cell lymphomas and acute myeloid leukemia cell lines in vitro. The pharmacologic inhibition of TRIP13 effectively induced the G0/G1 cell cycle arrest and apoptosis of B-cell lymphomas. Altogether these data demonstrate that TRIP13 is critical for the maintenance of hematologic malignancies of B-cell and myeloid malignancies in vitro. Thus, TRIP13 might be a good target in the treatment of various types of hematologic malignancies.

AI Algorithm-Assisted SERS Detection of Levothyroxine Sodium in Urine by an Optoplasmonic Film

AI Algorithm-Assisted SERS Detection of Levothyroxine Sodium in Urine by an Optoplasmonic Film

Effects of Thyroid Hormones on Cellular Development in Human Ovarian Granulosa Tumor Cells (KGN).

Ovarian cancer is a common malignant tumor in the female reproductive system, and Granulosa cell tumor (GCT) of the ovary is a rare type of ovarian cancer, which significantly threatens women's reproductive health. It has been reported that dysregulation of thyroid hormones (THs) may be closely related to the progression and prognosis of ovarian cancer. Moreover, THs regulate phosphorylation of signal transducer and activator of transcription (STAT3) and Octamer-binding transcription factor 4 (OCT4) expression. It has been reported that STAT3 and OCT4 play important roles in cellular development and tumorigenesis. However, the mechanisms by which THs affect the development of GCT are still remained unclear. To evaluate the effect of THs on human ovarian granulosa tumor cells (KGN), cells were treated with 3,5,3' -triiodothyronine (T3). Oct4 small interfering (Oct4 siRNA) or STAT3 inhibitor C188-9 was also co-cultured with cells in some experiments, respectively. The cell viability, proliferation, and proteins content were detected by CCK-8, EdU, and Western Blotting, respectively. The results showed that T3 enhanced cell viability and proliferation. Moreover, T3 also increased the expression of thyroid hormone receptor (TR), p-STAT3, and OCT4 proteins. The effects of T3 on both p-STAT3 and OCT4 expression were blocked by TR antagonist 1-850. Meanwhile, C188-9, an inhibitor of STAT3, decreased T3-induced cellular viability, proliferation, and OCT4 expression, highlighting that p-STAT3 can regulate the expression of OCT4 and affect cellular viability, and proliferation. Furthermore, T3-induced cellular growth was reduced by Oct4 siRNA, which indicates that T3 regulates cellular development through OCT4. These findings suggest that T3 increases cellular development via OCT4, which is mediated by phosphorylation of STAT3, and TR is also involved in these processes.

Thyroid and growth hormone endocrine disruption and mechanisms of homosalate and octisalate using wild-type, thrαa-/-, and dre-miR-499-/- zebrafish embryo/larvae

Homosalate (HS) and octisalate (OS), which are used in sunscreen for the purpose of blocking ultraviolet rays, are frequently detected in water environment. Although effects on estrogens and androgens have been reported, studies on thyroid and growth hormone endocrine disruption are limited. In the present study, larval mortality was compared in wild-type and two knockout fish (thyroid hormone receptor alpha a knockout (thrαa-/-) and dre-miR-499 knockout (dre-miR-499-/-)) after 96 h of exposure to HS and OS (0, 0.003, 0.03, 0.3, 3, 30 and 300 µg/L). To investigate the mechanisms of thyroid and growth hormone endocrine disruption, we measured the levels of triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), growth hormone (GH), and insulin-like growth factor-1 (IGF-1), and the regulation of representative genes related to the hypothalamus-pituitary-thyroid (HPT) and GH/IGF axis in wild-type zebrafish exposed to target chemicals. The significantly lower larval survival rate of thrαa-/- and dre-miR-499-/- fish exposed to 300 μg/L of HS and OS suggest that thyroid hormone receptors and dre-miR-499 play a crucial role in the toxic effects of HS and OS. The finding of a significant increase in T3 and T4 in zebrafish larvae exposed to HS and OS supports a significant decrease in the crh gene. The reduction of GH and IGF-1 in fish exposed to HS and OS is well supported by the regulation of genes involved in the GH/IGF axis. Our observations suggest that exposure to HS and OS affects not only thyroid hormone receptors and their associated miRNAs, but also the feedback routes of HPT and GH/IGF axes, ultimately leading to growth reduction.

Association between sensitivity to thyroid hormones and non-high-density lipoprotein cholesterol levels in patients with type 2 diabetes mellitus

BACKGROUND Dyslipidemia and type 2 diabetes mellitus (T2DM) are chronic conditions with substantial public health implications. Effective management of lipid metabolism in patients with T2DM is critical. However, there has been insufficient attention given to the relationship between thyroid hormone sensitivity and dyslipidemia in the T2DM population, particularly concerning non-high-density lipoprotein cholesterol (non-HDL-C). AIM To clarify the association between thyroid hormone sensitivity and dyslipidemia in patients with T2DM. METHODS In this cross-sectional study, thyroid hormone sensitivity indices, the thyroid feedback quantile-based index (TFQI), the thyroid-stimulating hormone index (TSHI), the thyrotrophic T4 resistance index (TT4RI), and the free triiodothyronine (FT3)/free thyroxine (FT4) ratio were calculated. Logistic regression analysis was performed to determine the associations between those composite indices and non-HDL-C levels. Random forest variable importance and Shapley Additive Explanations (SHAP) summary plots were used to identify the strength and direction of the association between hyper-non-HDL-C and its major predictor. RESULTS Among the 994 participants, 389 (39.13%) had high non-HDL-C levels. Logistic regression analysis revealed that the risk of hyper-non-HDL-C was positively correlated with the TFQI (OR: 1.584; 95%CI: 1.088-2.304; P = 0.016), TSHI (OR: 1.238; 95%CI: 1.034-1.482; P = 0.02), and TT4RI (OR: 1.075; 95%CI: 1.006-1.149; P = 0.032) but was not significantly correlated with the FT3/FT4 ratio. The relationships between composite indices of the thyroid system and non-HDL-C levels differed according to sex. An increased risk of hyper-non-HDL-C was associated with elevated TSHI levels in men (OR: 1.331; 95%CI: 1.003-1.766; P = 0.048) but elevated TFQI levels in women (OR: 2.337; 95%CI: 1.4-3.901; P = 0.001). Among the analyzed variables, the average SHAP values were highest for TSHI, followed by TT4RI. CONCLUSION Impaired sensitivity to thyroid hormones was associated with high non-HDL-C levels in patients with T2DM.

PFAS-mediated disruptions on thyroid histology

Abstract Introduction/Objective Per-and polyfluroalkyl substances (PFAS), are environmental contaminants of emerging concern due to their abundance in the environment and potential adverse health impacts. PFAS are used in waterproof clothing, makeup, carpets, upholstery, cookware, and fast-food containers. These organic pollutants have been found in the blood of 98% of Americans and have been linked to disruption in thyroid hormones. During fetal life, thyroid hormones are crucial for brain development and alterations in these hormones can induce long-term impacts on intellectual and brain impairments. T3 and T4 are known to be altered by PFAS exposure, but the mechanism by which this is done remains unclear. Methods/Case Report Normal thyroid cells were treated for 72 hours with 1000 nM solution containing either GEnX, PFOA, PFOS, or 1% DMSO control. Immunofluorescence for actin, tubulin, and DAPI was performed using a Nikon spinning disk. In vivo studies where 8-week-old mice are gavaged with 7.5 mg/kg of PFOS, PFOA, and GenX or PBS control for 8 weeks. Results (if a Case Study enter NA) We hypothesized the PFAS treatment alters thyroid cells morphology and histology. Immunofluorescence staining of normal thyroid cells treated with PFAS show a decrease in actin stress fibers compared to control cells. PFAS treated mice show a decrease in follicle size compared to control (average 1017 um2 size, p=0.0483). Conclusion This is the first study to show changes in thyroid histology after 8 weeks of PFAS exposure. As structure and function are closely linked, it is likely that this reduction in follicle size and actin reorganization contribute to alterations in thyroid function. Future studies are needed to illuminate the mechanism by which PFAS alter thyroid function in vivo. Understanding the role of PFAS-mediated thyroid dysregulation will have far reaching implications on environmental regulations and considerations for limiting PFAS in our environment.

Thyroid endocrine disruption effects of OBS in adult zebrafish and offspring after parental exposure at early life stage

As an alternative to perfluorooctane sulfonate, sodium p-perfluorous nonenoxybenzene sulfonate (OBS) has been widely used and caused ubiquitous water pollution. However, its toxicity to aquatic organisms is still not well known. Therefore, in this study, parental zebrafish were exposed to OBS at environmentally relevant concentrations from ∼ 2 h post-fertilization to 21 days post-fertilization (dpf) in order to investigate the thyroid disrupting effects in F0 adults and F1 offspring. Histopathological changes, such as hyperplasia of thyroid follicular epithelia and colloidal depletion, were observed in F0 adults at 180 dpf. In F0 females, thyroxine (T4) levels were significantly reduced in 30 and 300 μg/L exposure groups, while triiodothyronine (T3) levels were significantly increased in 3 μg/L exposure group. For F0 males, significant increases of T4 and T3 levels were observed, revealing the sex-specific differences after the OBS exposure. The transcription levels of some key genes related to the hypothalamic-pituitary-thyroid (HPT) axis were significantly disrupted, which induced the thyroid endocrine disruption effects in adult zebrafish even after a prolonged recovery period. For F1 offspring, the thyroid hormone (TH) homeostasis was also altered as T4 and T3 levels in embryos/larvae exhibited similar changes as F0 females. The transcription levels of some key genes related to the HPT axis were also significantly dysregulated, suggesting the transgenerational thyroid disrupting effects of OBS in F1 offspring. In addition, the decreased swirl-escape rate was observed in F1 larvae, which could be caused by disrupting gene expressions related to the central nervous system development and be associated with the TH dyshomeostasis. Therefore, parental OBS exposure at early life stage resulted in thyroid endocrine disruption effects in both F0 adult zebrafish and F1 offspring, and caused the developmental neurotoxicity in F1 larvae.

The influence of calibration on bias in quality control and patient results for TSH on Vitros XT 7600 analyzer.

Thyroid-stimulating hormone (TSH) is a glycoprotein secreted by the anterior pituitary gland and is regulated by negative feedback from the serum free thyroid hormones. In this study we aimed to quantitate the relative bias caused by calibration drifting as seen in our TSH Levey-Jennings quality control (QC) charts and assess the magnitude of bias on patients' samples. In the period from October 2021 to August 2022 we looked at the QC results of ten 28-days' calibration time intervals and calculated relative bias compared to the mean. For each time interval the mean from three QC points before and after calibration was calculated. The average from 10 pre- and post-calibration means was calculated and the relative bias, pre- and post-calibration, was then calculated. We used 5 patient samples with low, normal and high TSH concentrations and calculated relative bias pre- and post-calibration. The allowed relative bias for TSH is ± 6.7%. At both QC levels, with the respective means of 5.14 mIU/L (coefficient of variation, CV% = 3.1%) and 27.80 mIU/L (CV% = 3.2%) had their respective relative bias - 8.2% and - 7.9%. The patient samples with low (0.586 mIU/L), normal (2.89 mIU/L and 5.19 mIU/L) and high (20.5 mIU/L and 39.8 mIU/L) TSH had - 4.1%, - 4.0%, - 3.5%, - 5.1% and - 4.1%, respectively. Even though the relative bias exceeded allowable criteria for the QC samples, this was not manifested on the patients' samples.

Perinatal exposure to environmental chemicals that disrupt thyroid function can perturb testis development

Thyroid hormones (THs) are essential for normal growth and development. Their role in skeletal and brain development is well established, with congenital hypothyroidism causing stunted growth and severe intellectual disability. THs are also important for the development of other tissues and organs, including the testis. Developmental hypothyroidism can manifest as smaller testes in early postnatal life that later develop into macroorchidism in adulthood due to increased proliferation of Sertoli cells. Effects of hypothyroidism on the testes can be modelled in rodents by exposing developing animals to TH-suppressing pharmaceuticals such as propylthiouracil (PTU) and methimazole (MMI). These drugs act by inhibiting the thyroperoxidase (TPO) enzyme in the thyroid gland, inhibiting the synthesis of THs. It is possible that environmental chemicals that inhibit TPO activity can also cause TH-mediated effects on the developing testis, but the extent to which this occurs is not known. Herein, we characterized the effects of perinatal exposure to the herbicide amitrole together with the antithyroid drug MMI. Pregnant Sprague-Dawley rats were exposed by oral gavage to two doses of amitrole (25 or 50 mg/kg body weight/day) or MMI (8 or 16 mg/kg body weight/day) from gestational day 7 until birth. After birth, pup exposure was continued by dosing lactating dams from day of delivery until pup day 16. Both chemicals caused a significant reduction in TH levels on day 16. This perinatal hypothyroidism disrupted both germ and Sertoli cell development, resulting in smaller testes and reduced seminiferous tubule diameter in 16-day old pups. Notably, fetal male blood progesterone levels were increased after exposure to both amitrole and MMI, whereas the amitrole-exposed animals also displayed increased estradiol levels. Our study raises concerns that exposure to environmental chemicals that happen to disrupt TH production may disrupt TH-dependent testis development, with adverse consequences to human reproductive health.