Serum Thyroxine Levels Research Articles

Vitamin D3 attenuates autoimmune thyroiditis by regulating Th17/Treg cell differentiation via YAP/JAK1/STAT1 axis

BackgroundAutoimmune thyroiditis (AITD) is an organ-specific autoimmune disease. Substantial evidence suggests that Vitamin D (VitD) deficiency is closely associated with an increased risk of AITD. However, the effects of VitD3 on immune cells, especially Th17/Treg cell subsets, and the underlying molecular mechanism in AITD have not yet been investigated. MethodsAn experimental autoimmune thyroiditis (EAT) mouse model was established with a high-iodine diet. After 8 weeks, thyroid injury was assessed using hematoxylin and eosin (H&E) staining. ELISA was employed to measure serum levels of thyroxine (T3 and T4), thyroid autoimmune antibodies (Tg-Ab and TPO-Ab), and inflammatory cytokines. Flow cytometry and multiplex fluorescence immunohistochemical (mIHC) assays were used to analyze Th17/Treg cell subsets. The CCK-8 and flow cytometry assays were used to determine cell viability and apoptosis. ResultsAdministration of VitD3 reduced thyroid follicle destruction, decreased lymphocyte infiltration, and lowered T3, T4, Tg-Ab, and TPO-Ab serum levels in EAT mice. VitD3 treatment also reduced the frequency of Th17 cells while promoting the Treg cell subset both in the thyroid tissue and in the splenocytes cultured in vitro. Furthermore, VitD3 administration suppressed the production of inflammatory cytokines in EAT mice. VitD3 was also found to regulate Treg cells' differentiation, viability, and apoptosis. Mechanistically, we discovered that VitD3 treatment upregulated YAP expression and activated the JAK/STAT pathway. Rescue assays confirmed that depletion of YAP counteracted the effects of VitD3 on Treg cell differentiation and function. ConclusionVitamin D3 attenuates AITD by modulating Th17/Treg cell balance via regulating the YAP/JAK1/STAT1 axis.

The frequency of clinical and subclinical hypothyroidism in transfusion dependent thalassemia patients in Slemani city /Iraq

Background and objective: Thyroid disorders caused by blood transfusion in thalassemia patients could affect human health and growth, this study was conducted to determine the frequency of clinical and subclinical hypothyroidism in blood transfusion-dependent thalassemia patients in the city of Slemani, Kurdistan Region, Iraq. Methods: The current study is a retrospective cross-sectional study (comparative analysis) conducted in Slemani center for thalassemia patients and congenital blood, between December 2021 and July 2022. Participants included l07 thalassemia patients with medical records the sampling method was a convenience method. The data was collected through the review of patients' files and blood tests, including( thyroid hormones, hemoglobin level, serum ferritin level), with a questionnaire that was completed through an interview with the patients. Results: The results of thyroid function tests have shown that 21/107 pateints (19.6%) have hypothyroidism, 6 patients have overt hypothyroidism, and 15 patients have subclinical showed that 23/107 patients and 4/107 patients had hight and low levels,respectively, and there was statistically a significant difference in the average Thyroid stimulating hormone and serum thyroxin levels in two groups of hypothyroid and euthyroid patients and mean ferritine serum level between these two groups was 2166.7±2174.8 and 2068.37±1919.97 respictively ,which was not a statistically significant difference . Conclusion: Considering the high prevalence of hypothyroidism in thalassemia patients, measuring Thyroid stimulating hormone and thyroxin can be very important and vital in the initial screenings,effective treatment and follow-up of patients.

Transcriptomic and proteomic investigations identify PI3K-akt pathway targets for hyperthyroidism management in rats via polar iridoids from radix Scrophularia

High-polarity iridoids from Radix Scrophulariae (R. Scrophulariae) offer a range of benefits, including anti-inflammatory, antioxidant, antitumour, antibacterial, antiviral, and antiallergic effects. Although previous studies have indicated the potential of R. Scrophulariae for hyperthyroidism prevention and treatment, the specific active compounds involved and their mechanisms of action are not fully understood. This study explored the effects of high-polarity iridoid glycosides from R. Scrophulariae on hyperthyroidism induced in rats by levothyroxine sodium. The experimental design included a control group, a hyperthyroidism model group, and a group treated with iridoid glycosides. Serum triiodothyronine (T3) and thyroxine (T4) levels were quantified using an enzyme-linked immunosorbent assay (ELISA). Transcriptomic and proteomic analyses were applied to liver samples to identify differentially expressed genes and proteins. These analyses were complemented by trend analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The effectiveness of key factors was further examined through molecular biology techniques. ELISA results indicated a notable increase in T3 and T4 in the hyperthyroid rats, which was significantly mitigated by treatment with iridoid glycosides. Transcriptomic analysis revealed 6 upregulated and 6 downregulated genes in the model group, showing marked improvement following treatment. Proteomic analysis revealed changes in 30 upregulated and 50 downregulated proteins, with improvements observed upon treatment. The PI3K-Akt signalling pathway was investigated through KEGG enrichment analysis. Molecular biology methods verified the upregulation of Spp1, Thbs1, PI3K, and Akt in the model group, which was reversed in the treatment group. This study revealed that highly polar iridoids from R. Scrophulariae can modulate the Spp1 gene and Thbs1 protein via the PI3K-Akt signalling pathway, suggesting a therapeutic benefit for hyperthyroidism and providing a basis for drug development targeting this condition.

Capsiate ameliorates secondary hyperparathyroidism by improving insulin sensitivity and inhibiting angiogenesis.

Secondary hyperparathyroidism has a significant impact on the overall well-being of the body. Capsiates, known for their antioxidant and metabolic properties, have emerged as a promising alternative treatment for secondary hyperparathyroidism. This study aims to evaluate the effects and mechanisms of capsiates in the treatment of secondary hyperparathyroidism. To achieve our research objectives, we conducted a study on patients' serum and examined changes in metabolic markers using serum metabolomics. We induced secondary hyperparathyroidism in rat through dietary intervention and divided them into four groups. The first group, referred to as the Parathyroid Hormone (PTH) group, received a low-calcium and high-phosphate diet (0.2% calcium, 1.2% phosphorus). The second group served as the control group, receiving a standard phosphate and calcium diet (0.6% calcium, 0.6% phosphorus). The third group, called the capsiates group, consisted of rat from the control group treated with capsiates (intraperitoneal injection of 2 mg/kg capsiates for 2 weeks after 2 weeks of dietary intervention). The fourth group was the capsiates-treated PTH group. Subsequently, we conducted ribose nucleic acid (RNA) sequencing on parathyroid gland cells and evaluated serum thyroxine levels, oxidative stress, expression of proteins associated with vascular neogenesis, measurement of SOD, GSH and 3-nitrotyrosine, micro-CT and histological staining. The serum metabolomic data revealed a significant decrease in capsiate levels in the secondary hyperparathyroidism group. Administration of capsiates to PTH rat resulted in increased calcium levels compared to the PTH group. Additionally, the PTH + Capsiates group showed significantly lower levels of PTH and phosphate compared to the PTH group. The PTH group exhibited a notable increase in the quantity and size of mitochondria compared to the control group. Following capsiates administration to the PTH group, there was a significant reduction in the number of mitochondria and length of microvilli, but an increase in the size of mitochondria compared to the PTH group. Sequencing analysis revealed that vascular endothelial growth factor (VEGF) and Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) play crucial roles in this process. Vascular-related variables and downstream signalling were significantly elevated in hyperthyroidism and were alleviated with capsaicin treatment. Finally, combining capsiates with the PTH group improved bone mineral density, Tb.N, BV.TV, Cs.Th, Tt.Ar, OPG, Ob.TV and Oc.TV, as well as the mineral apposition rate, but significantly decreased Tb.Sp and Receptor Activator for Nuclear Factor-κ B Ligand (RANKL) compared to the PTH group. The findings suggest that capsiates can improve secondary hyperparathyroidism and ameliorated osteoporosis outcomes by inhibiting angiogenesis and reducing oxidative stress.

Thyroid Hormone Homeostasis in Levothyroxine-treated Patients: Findings From ELSA-Brasil.

The effectiveness of levothyroxine (LT4) in restoring thyroid hormone (TH) homeostasis, particularly serum thyroxine (T4) and triiodothyronine (T3) levels, remains debatable. This work aimed to assess TH homeostasis in LT4-treated individuals using data from the Longitudinal Study of Adult Health in Brazil (ELSA-Brasil) study. The ELSA-Brasil study follows 15 105 adult Brazilians (aged 35-74 years) over 8.2 years (2008-2019) with 3 observation points assessing health parameters including serum thyrotropin (TSH), free T4 (FT4), and free T3 (FT3) levels. We analyzed 186 participants that initiated treatment with LT4 during the study, and 243 individuals continuously treated with LT4 therapy. Initiation of therapy with LT4 resulted in an 11% to 19% decrease in TSH, an approximately 19% increase in FT4, and a 7% reduction in FT3 serum levels (FT3 dropped >10% in ∼40% of the LT4-treated patients). This was associated with an increase in triglyceride levels and utilization of hypolipidemic and antidiabetic medications. Participants continuously treated with LT4 exhibited a stable elevation in serum FT4 and a reduction in serum FT3 and TSH levels. While 115 participants (47.3%) had at least 1 serum FT4 levels above the control reference range (>1.52 ng/dL), 38 participants (15.6%) had at least 1 serum FT3 below the reference range (<0.23 ng/dL). The present results challenge the dogma that treatment with LT4 for hypothyroidism restores TH homeostasis in all patients. A substantial number of LT4-treated patients exhibit repeated FT4 and FT3 levels outside the normal reference range, despite normal TSH levels. Further studies are needed to define the clinical implications of these findings.

Relationships between depression level and serum inflammatory factors and thyroxine levels in patients with malignant bone tumors associated with depression.

To elucidate the relationships between depression level and serum inflammatory factors and thyroxine levels in patients with malignant bone tumors associated with depression. The depression (n = 28) and non-depression groups (n = 35) were established. Another 35 healthy subjects were selected as the control group. The severity of depression was assessed, and the depression group received the selective serotonin reuptake inhibitor antidepressant sertraline for 4 weeks. Serum levels of inflammatory factors and thyroxine, and the correlation between inflammatory factors, thyroxine, and HAMD-17 score were analyzed. The IL-1β, IL-6, and IL-21 levels were lower and TGF-β1, IL-10, and IL-27 were higher in the depression group after treatment than before treatment. After treatment, T3 levels were higher and T4 levels were lower in the depression group. T4 levels were higher in patients with major depression than those with mild depression. IL-1β and IL-21 levels were elevated in moderately depressed patients [(11.13 ± 1.49) ng/L、(9.71 ± 1.26) ng/L], and IL-1β levels were elevated in severely depressed patients [(11.26 ± 1.95) ng/L], compared to mildly depressed patients [(9.36 ± 1.25) ng/L, (7.95 ± 1.31) ng/L] (all p < 0.05). Serum IL-1β, IL-6, and IL-21 were positively correlated with the total HAMD-17 score, and TGF-β1 and IL-10 were negatively correlated with the total HAMD-17 score. Depression degree in patients with malignant bone tumors correlates with serum inflammatory factors and thyroxine levels. Measurement of serum inflammatory factors and thyroxine levels can assess the progression and prognosis of depressed patients.

Гормональные, биохимические показатели и уровни микроэлементов крови у молодых женщин с субклиническим гипотиреозом в сочетании с носительством антител к тиреопероксидазе

Many studies have been devoted to investigating the relationship between subclinical hypothyroidism (SH), thyroid gland (TG) autoimmunity, and blood trace elements; however, the data presented in these studies are often contradictory. Aim of study. To identify the factors associated with SH in combination with the presence of Anti-thyroid peroxidase antibody (TPO-Ab). Design. Single-center, observational, single-cohort, cross-sectional, and uncontrolled study. Materials and Methods. This study analyzed 859 women aged 18–45 with SH and without TG dysfunction. Based on thyroid function and TPO-Ab status (presence (+) or absence (–)), four study groups were formed: Group 1 — Euthyroidism and TPO-Ab(–) (n = 503); Group 2 — Euthyroidism and TPO-Ab(+) (n = 164); Group 3 — SH and TPO-Ab(–) (n = 128); Group 4 — SH and TPO-Ab(+) (n = 64). Determination of thyroid-stimulating hormone (TSH), free thyroxine (FT4), and TPO-Ab levels in serum was provided by enzyme immunoassay on the Evolis Robotized System using the test systems "Thyroid-ELISA-TSH, 0.23–3.4 µIU/ml", "Thyroid-ELISA FT4, 10–23.2 pmol/l", and "Thyroid ELISA-TPO-Ab &lt; 30 U/ml". The reference values were taken from the instructions of the manufacturer Alkor Bio Group (Russia). Measurement of element concentrations was conducted on the atomic absorption spectrometer "МГА-915МД" from Lumex (Russia). Logistic regression analysis with a series of univariate and multivariate models was performed to determine independent predictors of the likelihood of SH and TPO-Ab positive status (relative to euthyroid and TPO-Ab negative individuals). Results. In young women, a decrease in FT4 is associated with increasing age, elevated levels of TSH, TPO-Ab, mercury, decreased heart rate, and reduced levels of thyroglobulin, alkaline phosphatase (ALP), manganese, nickel, selenium, lead, and the triglyceride/glucose index. An increase in TSH is associated with lower levels of ALP, manganese, and nickel, and higher mercury levels. The likelihood of having SH combined with the presence of TPO-Ab, compared to the group without thyroid dysfunction and elevated antibodies, increases with reduced concentrations of iodine (odds ratio (OR) = 0.739; 95% confidence interval (CI): 0.618–0.884, p = 0.001), selenium (OR = 0.987; 95% CI: 0.976–0.998, p = 0.018), and zinc (OR = 0.998; 95% CI: 0.997–0.999, p = 0.023), and with elevated lead levels (OR = 1.106; 95% CI: 1.006–1.217, p = 0.038). In a multivariate regression model, the probability also increases with decreased iodine and cadmium levels, and elevated lead levels. Conclusion. Reduced concentrations of iodine, selenium, and zinc, along with elevated blood lead levels, are factors associated with the activation of thyroid autoimmunity and the presence of SH in combination with elevated TPO-Ab levels. Keywords: thyroid gland, thyroid function hormones, microelements, thyroid peroxidase antibodies, young age, women.

Efficacy of a levothyroxine dosage regimen based on serum thyrotropin level, for primary hypothyroidism. An open label dose finding study.

There are no guidelines on individualized initial levothyroxine dosage in primary hypothyroidism. This prospective observational study was done to assess whether a predetermined dose of levothyroxine based on Thyroid Stimulating Hormone (TSH) levels would be able to make the patient euthyroid during a period of six weeks and to find other factors which influence the levothyroxine requirement. Newly diagnosed patients with primary hypothyroidism or those patients who were not on levothyroxine therapy were divided into TSH-based groups-Group 1, 5-9.99, Group 2, 10-29.99, Group 3, 30-99.99 and Group 4, >100 μIU/ml and treated with an initial levothyroxine dose of 25,50,75 and100 μg/day for next six weeks. Factors correlating with levothyroxine requirement were determined. Of the 171 patients who were included 142 completed the study, 34,46,28 and 34 patients were included in groups 1 to 4, respectively. Normalization of TSH with the above criteria was achieved in 111 (78.7%) out of 141 patients, and 91%, 67%, 75%, and 82% respectively in the 4 groups. Among adequately replaced patients pre-treatment TSH level (r = 0.81), T4 level (r = 0.61), and body weight (r = 0.19) correlated with the levothyroxine requirement. Based on these factors predicted initial dose (μg/day) was found to be 0.54 (Body Weight [Kg]) +0.47 (TSH [μIU/m]) - 1.4 (Total T4 [μg/dl]) +17.79 or 0.27 (Body Weight) +0.553 (TSH) +21. Serum thyrotropin-based categorization for initial levothyroxine dose leads to euthyroidism in nearly four of five patients with primary hypothyroidism. The dose required for adequate replacement of levothyroxine has correlation with pre-treatment serum TSH levels serum thyroxine levels and body weight.

Benefits of watermelon juice and ascorbic acid supplementation on Institut de Sélection Animale brown layers managed under hot climate

Loss of homeostasis and poor egg production are common in laying hens during hot season. These negative effects of extreme ambient temperature have resulted in great economic losses to poultry farmers in the tropical regions. This study investigated benefits of supplementing watermelon juice (WJ) and ascorbic acid (AA) to ISA Brown (IB) hens managed under hot climate on productive performance and some hormonal responses. Ninety-six IB pullets aged 34 weeks were randomly allotted to four groups (C, T1, T2, and T3), each containing 24 in triplicates. The control group (C) was given water with neither WJ nor AA. Water given to groups T1, T2 was supplemented with 20% and 40% WJ, respectively, while T3 was supplemented with 200mg AA/litre of water. The results show a significant (P≤0.05) increase in water intake in T3 compared to other groups. Total egg production, daily egg production and hen-day egg production were significantly (P≤0.05) improved by the supplements, as total egg weights improved in T1:(272.2 ± 35.16g) and T2:(272.1 ± 35.06g) compared to C:(212.2 ± 25.06g) and T3:(238.5 ± 19.23g). The supplements caused 24.46%, 22.70% and 9.43% rise in percentage egg production in groups T1, T2, and T3 respectively. Serum corticosterone (C:10.88 ± 1.12; T1:10.20 ± 1.06; T2:9.61 ± 0.792; T3:7.23 ± 2.36ng/mL) and thyroxine levels (C:1.45 ± 0.562; T1:0.41 ± 0.109; T2:0.39 ± 0.367; T3:0.60 ± 0.489μg/dL) decreased significantly (P≤0.05) in supplemented layers, while serum prolactin and triiodothyronine differed non-statistically. In conclusion, WJ and AA supplementation ameliorated heat stress in IB layers managed under hot climate as it significantly lowered corticosterone and improved egg production. Therefore, supplementing 20%, 40%WJ or 200mg AA/litre in water is recommended for managing heat stress in IB layer chickens

Assessment of Serum Cortisol Levels in Hypothyroidism Patients: A Cross-Sectional Study.

Hypothyroidism, characterized by insufficient thyroid hormone production, affects a significant global population, particularly women and the elderly. Recent research has emphasized the interaction between hypothyroidism and the hypothalamic-pituitary-adrenal (HPA) axis, highlighting cortisol's crucial role in the disease's physiological manifestations. This study aims to evaluate serum cortisol levels in hypothyroid patients, examining the intricate relationship between these two endocrine systems. By exploring the potential impact of altered cortisol levels on hypothyroidism's clinical presentation and progression, the study seeks to contribute valuable insights to enhance diagnostic approaches and develop more effective treatment strategies. A cross-sectional observational study was conducted at the Indira Gandhi Institute of Medical Sciences, assessing 65 hypothyroid cases and 65 age-matched euthyroid controls. Demographic data, medical history, and blood samples were collected, and serum cortisol, thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) levels were measured. The study adhered to ethical considerations and received institutional approval. The study included 65 hypothyroid cases (56 females, 9 males) and 65 euthyroid controls. Serum cortisol showed a significant correlation with TSH and T4 levels. Linear regression revealed a negative correlation between serum T4 and T3 levels and serum cortisol in hypothyroidism. A positive correlation was observed between TSH and cortisol. These findings align with previous studies, suggesting potential regulatory mechanisms and compensatory responses in hypothyroid patients. The study's results emphasize the complex interaction between cortisol and thyroid function, suggesting a direct relationship between serum cortisol and TSH levels in hypothyroidism. Patients with severe hypothyroidism exhibited elevated cortisol concentrations, indicating a potential compensatory mechanism initiated by the HPA axis. Integrating serum cortisol assessment with conventional thyroid function tests could offer comprehensive insights into hypothyroidism severity and progression, providing a more holistic approach to patient care. This study contributes to understanding the complex relationship between serum cortisol levels and hypothyroidism, emphasizing the need for further research to uncover underlying mechanisms and therapeutic implications. A comprehensive understanding holds the potential for more tailored and effective treatment strategies for individuals with hypothyroidism.

Integrated transcriptomic and metabolomic analyses identify key factors in the vitellogenesis of juvenile Sichuan bream (Sinibrama taeniatus)

Vitellogenesis is the most important stage of ovarian maturation in fish, involving the synthesis and transport of essential yolk substances and their complex mechanisms and coordination process. The liver is the main tissue involved in the vitellogenesis of oviparous animals, but studies of vitellogenesis in fish rarely include the liver and ovary as a whole. The aim of this study was to explore the molecular mechanism and associated regulatory factors behind vitellogenesis in Sichuan bream (Sinibrama taeniatus). The different stages of oogenesis were first identified by successive histological observations. Then, ovary and liver tissues that developed to 115 days (stage II, previtellogenesis stage), 165 days (stage III, vitellogenesis stage) and 185 days (stage IV, late-vitellogenesis stage) were collected for transcriptomic and metabolomic analyses, and serum testosterone (T), 17β-estradiol (E2), vitellogenin (Vtg), triiodothyronine (T3), and thyroxine (T4) levels were measured at the corresponding stages. We found that energy redistribution during vitellogenesis is mainly regulated through glycolysis, fatty acid biosynthesis and the citrate cycle pathway. In the liver, energy metabolism was promoted by activating glucolipid metabolic pathways to provide sufficient ATP, but at the same time, the ovary tends to retain nutrients rather than decompose them to produce energy. In addition, we have identified several key factors involved in the metabolism of neutral lipids, polar lipids, amino acids and vitamins, which are involved in the assembly and transport of important yolk nutrients. The initiation of vitellogenesis was found to be associated with a surge in serum E2 levels, but the sustained increase in Vtg levels in the late stage may be due more to upregulation of the estrogen receptor. These results provide valuable information about the regulation of ovarian development in cultured fish.

THU397 Homeostatic Regulation Of 1,25-dihydroxyvitamin D: Critical Role Of 24-hydroxylation (CYP24A1)

Abstract Disclosure: Z. Shahidzadeh Yazdi: None. E.A. Streeten: Grant Recipient; Self; Regeneron Pharmaceuticals. H.B. Whitlatch: Grant Recipient; Self; Regeneron Pharmaceuticals. M.E. Montasser: Grant Recipient; Self; Regeneron Pharmaceuticals. A.L. Beitelshees: None. S.I. Taylor: Consulting Fee; Self; Ionis Pharmaceuticals Inc. The VITAL study raised substantial questions whether current Endocrine Society guidelines provide optimal criteria to identify patients whose bone health would benefit from vitamin D (VitD) supplements. We investigated the impact of VitD supplements on levels of VitD metabolites and other biomarkers in the context of studying interactions between VitD and canagliflozin. 11 healthy Amish participants with 25-hydroxyvitamin-D (25(OH)D) levels ≤20 ng/mL were recruited in the context of our ongoing pharmacogenomic study of canagliflozin. RESULTS: VitD supplements increased mean levels of 25(OH)D from 16.5±1.6 ng/mL to 44.3±5.5 ng/mL (p=0.0006) and 24,25(OH)2D from 1.0±0.1 ng/mL to 4.3±0.6 ng/mL (p=0.0002). Mean levels of 1,25(OH)2D and PTH were unchanged: 43.8±3.6 vs. 44.9±4.1 pg/mL for 1,25(OH)2D and 47.5±4.8 vs. 48.4±5.1 pg/mL for PTH. We applied mathematical modeling, which suggested that regulation of 24-hydroxylation was the principal mechanism responsible for maintaining 1,25(OH)2D levels within a narrow range in our mildly VitD deficient research participants [25(OH)D levels: 10-20 ng/mL]. When 25(OH)D levels were low (&amp;lt;20 ng/mL), 24-hydroxylation was maximally suppressed. Low levels of 24-hydroxylase activity tend to sustain levels of 1,25(OH)2D by decreasing its rate of metabolic clearance. VitD supplementation induced 24-hydroxylase activity by ∼5-fold – reaching a plateau when 25(OH)D levels &amp;gt;60 ng/mL. As suggested in the literature (JCY Tang et al, Sci Rep, 9:6974, 2019), we calculated ratios of 1,25(OH)2D/24,25(OH)2D as an index for the homeostatic response to VitD status. When we plotted the 1,25(OH)2D/24,25(OH)2D ratio as a function of 25(OH)D/1,25(OH)2D, we observed an extremely high degree of correlation (Spearman correlation coefficient of -0.94; p=10-10). DISCUSSION: Clinical assessment of thyroid status provides a highly relevant historical precedent. 50 years ago, thyroid status was assessed by measurement of total serum thyroxine (T4) levels. Diagnostic accuracy was greatly improved when total T4 was replaced by laboratory measurement of either free T4 or TSH (an index of the homeostatic response to thyroid status). Current clinical guidelines recommend assessment of VitD status by measuring total levels of 25(OH)D, which unfortunately are confounded by inter-individual variation in levels of VitD binding proteins (VDBP). We anticipate that diagnostic accuracy would be greatly enhanced if clinicians replaced measurement of total 25(OH)D by laboratory measurements that are not affected by variation in levels of VDBP. By analogy to the approach to clinical assessment of thyroid status, we recommend consideration of VDBP-independent indices of VitD status including 25(OH)D/1,25(OH)2D as an index of VitD stores and 1,25(OH)2D/24,25(OH)2D as an index for the body’s homeostatic response to VitD status. Presentation: Thursday, June 15, 2023

The prevalence of thyroid dysfunction and hyperprolactinemia in women with PCOS.

Ovulatory dysfunction is usually caused by an endocrine disorder, of which polycystic ovary syndrome (PCOS) is the most common cause. PCOS is usually associated with estrogen levels within the normal range and can be characterized by oligo-/anovulation resulting in decreased progesterone levels. It is suggested that decreased progesterone levels may lead to more autoimmune diseases in women with PCOS. In addition, it is often claimed that there is an association between hyperprolactinemia and PCOS. In this large well-phenotyped cohort of women with PCOS, we have studied the prevalence of thyroid dysfunction and hyperprolactinemia compared to controls, and compared this between the four PCOS phenotypes. This retrospective cross-sectional study contains data of 1429 women with PCOS and 299 women without PCOS. Main outcome measures included thyroid stimulating hormone (TSH), Free Thyroxine (FT4), and anti-thyroid peroxidase antibodies (TPOab) levels in serum, the prevalence of thyroid diseases and hyperprolactinemia. The prevalence of thyroid disease in PCOS women was similar to that of controls (1.9% versus 2.7%; P = 0.39 for hypothyroidism and 0.5% versus 0%; P = 0.99 for hyperthyroidism). TSH levels were also similar (1.55 mIU/L versus 1.48 mIU/L; P = 0.54). FT4 levels were slightly elevated in the PCOS group, although within the normal range (18.1 pmol/L versus 17.7 pmol/L; P < 0.05). The prevalence of positive TPOab was similar in both groups (5.7% versus 8.7%; P = 0.12). The prevalence of hyperprolactinemia was similarly not increased in women with PCOS (1.3%% versus 3%; P = 0.05). In a subanalysis of 235 women with PCOS and 235 age- and BMI-matched controls, we found no differences in thyroid dysfunction or hyperprolactinemia. In according to differences between PCOS phenotypes, only the prevalence of subclinical hypothyroidism was significantly higher in phenotype B (6.3%, n = 6) compared to the other phenotypes. Women with PCOS do not suffer from thyroid dysfunction more often than controls. Also, the prevalence of positive TPOab, being a marker for future risk of thyroid pathology, was similar in both groups. Furthermore, the prevalence of hyperprolactinemia was similar in women with PCOS compared to controls.

Hypothyroidism in Adult Women: The Utility of Targeted vs Universal Thyroid Screening.

Hypothyroidism is a common disease that is more prevalent in female populations. The purpose of this paper is to discuss the evidence, risks, and benefits of screening asymptomatic women for hypothyroidism. There is lack of evidence to support clinical management of asymptomatic individuals with an elevated TSH and normal serum thyroxine levels. Patients with subclinical hypothyroidism, especially the elderly, are at risk of overtreatment. Given these considerations, the majority of US and UK professional organizations do not support universal screening. Many do offer caveats for special groups, including pregnant people, who may need screening if there are clinical symptoms or family history of autoimmune disease. In conclusion, targeted screening may be best recommended based on risk factors, symptoms, and clinical suspicion, rather than at a universal level.

Effect of diminazene on cardiac hypertrophy through mitophagy in rat models with hyperthyroidism induced by levothyroxine.

Hyperthyroidism is associated with the alteration in molecular pathways involved in the regulation of mitochondrial mass and apoptosis, which contribute to the development of cardiac hypertrophy. Diminazene (DIZE) is an animal anti-infection drug that has shown promising effects on improving cardiovascular disease. The aim of the present study was to investigate the therapeutic effect of DIZE on cardiac hypertrophy and the signaling pathways involved in this process in the hyperthyroid rat model. Twenty male Wistar rats were equally divided into four groups: control, hyperthyroid, DIZE, and hyperthyroid + DIZE. After 28 days of treatment, serum thyroxine (T4) and thyroid stimulating hormone (TSH) level, cardiac hypertrophy indices, cardiac damage markers, cardiac malondialdehyde (MDA), and superoxide dismutase (SOD) level, the mRNA expression level of mitochondrial and apoptotic genes were evaluated. Hyperthyroidism significantly decreased the cardiac expression level of SIRT1/PGC1α and its downstream involved in the regulation of mitochondrial biogenesis, mitophagy, and antioxidant enzyme activities including TFAM, PINK1/MFN2, Drp1, and Nrf2, respectively, as well as stimulated mitochondrial-dependent apoptosis by reducing Bcl-2 expression and increasing Bax expression. Treatment with DIZE significantly reversed the downregulation of SIRT1, PGC1α, PINK1, MFN2, Drp1, and Nrf2 but did not significantly change the TFAM expression. Moreover, DIZE suppressed apoptosis by normalizing the cardiac expression levels of Bax and Bcl-2. DIZE is effective in attenuating hyperthyroidism-induced cardiac hypertrophy by modulating the mitophagy-related pathway, suppressing apoptosis and oxidative stress.

Hormonal imbalance in patients with chronic kidney disease in the pre-dialysis and dialysis periods (part 2)

In the previous article, we presented the results of literature review showing the changes in hormone concentrations (parathyroid hormone, insulin, growth factor, prolactin) in patients with chronic renal failure (CRF) at the pre-dialysis and dialysis stages, described pathological relationships between renal failure and serum hormones concentrations, as well as changes in their biological effects. In this article, that continues the general topic, we provide the results of literature review that shows changes in serum concentrations of thyroid, adrenal, sex hormones and the features of the functioning of hypothalamus-pituitary-peripheral glands axis in patients with CRF. The presence of close pathogenic interactions of renal functional condition with hormonal activity of the thyroid gland was evaluated, as well as the ability of thyroid gland to influence the CRF progression both during pre-dialysis and dialysis sta­ges of CRF. Most patients with CRF have low serum triiodothyronine and thyroxine levels. It means that CRF is a pathological condition associated with thyroid hypofunction that progressively worsening as glomerular filtration rate decreases. For patients receiving dialysis treatment, hypothyroidism is associated with higher mortality. Secondary adrenal insufficiency is usually progresses in patients on renal replacement therapy. Non-diagnosed chronic adrenal failure may be life-threating that’s why the analysis of adrenal function is especially actual for patients on both pre-­dialysis and dialysis stages of CRF. Secondary adrenal insufficiency caused by long-lasting treatment with corticoids is a diagnostic problem for patients on dialysis treatment, because many nephrological diseases are treated by corticoids, and immunosuppressive therapy protocols used after the kidney transplantation are usually include prednisone. As the endocrine dysfunction progresses in patients with CRF, sexual dysfunction develops due to sex hormone imbalance. Abnormal androgen concentration is a typical fin­ding in CRF. A negative correlation was found between endogenic testosterone concentration and CRF stages I–V that indicated an abnormal profile of male sex hormones. There are gender-specific features of the development and progression of clinical symptoms of hormonal imbalance. The number of experimental studies show that continuous estradiol treatment may prevent the development of glomerulosclerosis. The results of clinical trials concluded that lower CRF progression and the lower incidence of CRF observed in young females compared to males, as well as the absence of gender protection in post-menopausal period, shows the important role of female sex hormones.

Reproductive and immune effects emerge at similar thresholds of PFHxS in deer mice

Although perfluorohexane sulfonate (PFHxS) is structurally similar to perfluorooctane sulfonate (PFOS) and also widely detected in humans and the environment, comparatively fewer toxicity data exists on this 6-chain perfluoroalkyl sulfonic acid. In this study, repeated oral doses of PFHxS were administered to deer mice (Peromyscus maniculatus) to evaluate subchronic toxicity and potential effects on reproduction and development. Maternal oral exposure to PFHxS caused increased stillbirths, which is relevant for ecological risk assessment, and resulted in a benchmark dose lower limit (BMDL) of 5.72 mg/kg-d PFHxS. Decreased plaque formation, which is relevant for human health risk assessment, occurred in both sexes of adult animals (BMDL = 8.79 mg/kg-d PFHxS). These data are the first to suggest a direct link between PFHxS and decreased functional immunity in an animal model. Additionally, female animals exhibited increased liver:body weight and animals of both sexes exhibited decreased serum thyroxine (T4) levels. Notably, since reproductive effects were used to support 2016 draft health advisories and immune effects were used in 2022 drinking water health advisories released by the United States Environmental Protection Agency for PFOS and perfluorooctanoic acid (PFOA), these novel data can potentially support advisories for PFHxS because relevant points of departure emerge at similar thresholds in a wild mammal and corroborate the general understanding of per- and polyfluoroalkyl substances (PFAS).

Prevalence of Subclinical Hypothyroidism in Obese Adults Population

Objective: Determination of frequency of occurrence of subclinical hypothyroidism (SCH) in a local population of obese adults Study design: A cross-sectional study Place and Duration: This study was conducted at Sindh Government Lyari General Hospital Karachi from March 2022 to March2023 Methodology: The patients aged between 18 years to 55 years. All the participants had a body mass index (BMI)of more than 29 kg/m2. As per the exclusion criteria, those patients having kidney failure, liver failure, or already diagnosed with thyroid dysfunction, were not added to the study. Patients taking cholesterol-lowering drugs were also not considered in the study. A blood sample of all the patients was collected for the measurement of serum thyroxine levels and serum thyroid stimulating hormone (TSH) levels. Results: A total of 150 obese adults were considered in the study. The mean age of the participants was 35.7±8.1 years. Overall69 (46%) patients were male while 81 (54%) patients were females. The mean BMI of the patients was 32.1±2.1 kg/m2. The mean serum thyroxine level in the given population was 1.09±0.24 ng/dl and the mean serum TSH level was 3.12±1.09 mIU/L. A total of 24 (16%) patients were detected with subclinical hypothyroidism. Conclusion: Subclinical hypothyroidism is vastly prevalent in the obese adult population, particularly in adults with a BMI of more than 29 kg/m2. However, there is room for further studies to examine the correlation between obesity and SCH. Keywords: Subclinical Hypothyroidism, Obesity, TSH, Thyroxine, Body mass index

Association of Thyroid Function and Severity of Illness in Liver Cirrhosis as Measured by Child-Pugh Score.

Objective The main aim of this study is to understand the existing knowledge gap between thyroid function tests and the severity of liver cirrhosisas measured by the Child-Pugh score. Materials and methods This is a cross-sectional study conducted on 100 patientsdiagnosed with cirrhosis of liver. Serum triiodothyronine (free T3), thyroxine (free T4), and thyroid stimulating hormone (TSH) levels were measured, and the severity of liver cirrhosis was measured by Child-Pugh score and statistical analysis were done to investigate the association of free T3, free T4 and TSH levels with Child-A, Child-B, and Child-C severity groups. Results The results revealed that there is a statistically significant positive correlation between TSH levels and Child-Pugh score, whereasa statistically significant negative correlation was associated between free T3 (fT3), free T4 (fT4) levels, and Child-Pugh Score.Further, we also observedthat the Child-C group has 7.5-foldrisk of increased TSH levels (odds ratio {OR} = 7.553, 95% CI = 2.869-19.883, p= 0.000), has 5-fold risk of decreased fT3 levels (OR = 5.023, 95% CI = 1.369-18.431, p = 0.009) and has 6.4-fold risk of decreased fT4 levels (OR = 6.402, 95% CI = 2.516-16.290, p = 0.000). Conclusion Our results demonstrated that there is a positive and direct correlation associated between increasing TSH with severity of liver cirrhosis as measured by Child-Pugh score, whereasa negative and inverse correlation was observed between decreasing fT3 and fT4 levels with the severity of liver cirrhosis as measured by Child-Pugh score. This suggests that the Child-Pugh score can be used as a prognostic indicator in cirrhotic patients.

Relation between serum β-endorpin, neuropeptide Y and thyroid hormone in children with anorexia.

The purpose of this study was to investigate whether serum β-endorpin and neuropeptide Y were associated with changes in levels of thyroid hormones in children suffering from anorexia. One hundred and five anorexic children admitted to Xianning City Central Hospital, China, from August 2019 to July 2021, were selected as case group, while 105 normal children were selected as normal control group. Serum β-endorpin and neuropeptide Y levels in the case group were lower than those in the normal control group (both p<0.001), and serum triiodothyronine and thyroxine levels were also lower (both p<0.001). Serum β-endorpin and neuropeptide Y levels in the case group were positively correlated with triiodothyronine and thyroxine. There is a reduced level of serum β-endorpin, neuropeptide Y, and thyroid hormones in anorexic children, and it is possible that they are connected and work together in regulating ingestion.