Role Of Thyroid-stimulating Hormone Research Articles

Role of thyroid stimulating hormone in the maintenance and functioning of the human corpus luteum.

To evaluate the impact of high thyroid stimulating hormone (TSH) levels on human granulosa-luteal (hGL) cells. hGL cells were isolated from follicular aspirates derived from patients undergoing IVF treatment without any thyroid disorder (serum TSH 0.5-2mU/L). Cells were cultured at 37°C in DMEM, supplemented with 5% FBS. The cells were treated with 1nM LH and increasing concentrations of TSH. At the end of culture, conditioned medium and cells were collected to analyze progesterone production, cell viability, and mRNA levels of genes involved in the steroidogenesis process. Human ovarian tissues were analyzed for TSH receptor (TSHR) expression by IHC. The expression of TSHR was detected in human corpus luteum by IHC and in hGL by RT-PCR. In hGL cells, TSH treatment did not modulate progesterone production nor the expression of steroidogenic genes, such as p450scc and HSD3b 1/2. However, TSH induced a dose-dependent increase in cell death. Finally, TSH did not affect LH-induced p450scc and HSD3b1/2 expression while LH partially reverted TSH negative effect on cell death in hGL. Elevated TSH levels in hypothyroid women may be associated with impaired CL functioning and maintenance. These findings open a new line of research for the importance of the treatment of women with thyroid dysfunction that could contribute to the onset of infertility.

The Relationship between Thyrotropin Serum Concentrations and Thyroid Carcinoma.

Thyroid Stimulating Hormone (TSH) is a hormone secreted by the pituitary gland and plays a role in regulating the production and secretion of thyroid hormones by the thyroid gland. This precise feedback loop is essential for maintaining a harmonious balance of thyroid hormones in the body, which are vital for numerous physiological processes. Consequently, TSH serves as a significant marker in assessing thyroid function, and deviations from normal TSH levels may indicate the presence of a thyroid disorder. Thyroid cancer (TC) is the malignant tumor within the endocrine system. In recent years, numerous experts have dedicated their efforts to discovering efficacious biomarkers for TC. These biomarkers aim to improve the accurate identification of tumors with a poor prognosis, as well as facilitate active monitoring of tumors with a more favorable prognosis. The role of TSH in the thyroid gland underscores its potential influence on the occurrence and progression of TC, which has garnered attention in the scientific community. However, due to the limited scope of clinical research and the dearth of high-quality foundational studies, the precise impact of TSH on TC remains unclear. Consequently, we present a comprehensive review of this subject, aiming to offer a valuable reference for future research endeavors.

High First Trimester Levels of TSH as an Independent Risk Factor for Gestational Diabetes Mellitus: A Retrospective Cohort Study.

Although numerous articles have found an association between alterations in thyroid function and the risk of gestational diabetes mellitus (GDM), other studies have failed to demonstrate this association. This may be due to the different cut-off points used to define subclinical hypothyroidism. We aim to clarify the role of thyroid stimulating hormone (TSH) level in GDM within pregnant women with normal free thyroxine (fT4) levels. This retrospective cohort study was performed in 6775 pregnant women. The association between TSH and GDM was assessed by bivariate and multivariate logistic regression. Pregnant women with subclinical hypothyroidism are at significantly greater risk for GDM when compared with euthyroid pregnant women (OR = 1.85; 95% CI = 1.36–2.52). We have also observed that TSH levels increase the risk of GDM within euthyroid pregnant women, since the TSH levels between 2.5 and 4.71 showed a higher risk of GDM than those whose TSH levels are between 0.31 and 2.49 (OR = 1.54; 95% CI = 1.28–1.84). In addition, pregnant women with positive thyroid antibodies have almost 2.5 times the risk of developing GDM (OR = 2.47; 95% CI = 1.57–3.89). Our results support that in pregnant women with normal fT4 levels, higher first trimester TSH level implies a higher risk of GDM.

P-659 Does Preconception thyroid-stimulating hormone (TSH) levels affect the clinical outcomes of Infertile Women Undergoing Fresh Embryo Transfer Cycle?

Abstract Study question Does Preconception TSH levels affect the clinical outcomes of Infertile Women Undergoing Fresh Embryo Transfer Cycle? Summary answer Among euthyroid patients, preconceptional TSH values in the high-normal range (between 2.5 and 4.0 mIU/L) are associated with adverse clinical outcomes. What is known already Serum thyroid-stimulating hormone (TSH) levels are routinely screened in women with infertility given the negative impact of thyroid disease on ovarian function and pregnancy is associated with poor outcomes.In fact, an underlying thyroid abnormality was found in 46% for women experiencing IVF failure and TSH levels were inversely proportional to the fertilization rate at IVF. While it is clear that pregnancies complicated by subclinical hypothyroidism in the fertile population have poor outcomes, the relevance of preconception subclinical hypothyroidism in infertile patients undergoing ART has not been thoroughly examined. Study design, size, duration Outcomes of all fresh IVF patients with an embryo transfer from from January 2019 to August 2021 within 1 yr of TSH screening at a our center were studied. IVF cycles using donor oocyte, TESE sperm, PGT, or those lacking follow-up were excluded. For patients with more than one Preconception TSH measurement prior IVF, the most recent measurement before the IVF cycle was used. Participants/materials, setting, methods Cycles were categorized into two groups based on preconceptional TSH values: Euthyroid (0.4–2.5 μIU/mL), subclinical hypothyroidism (>2.5-4.0 μIU/mL). All women underwent standard IVF protocols following usual individualized practice in our IVF clinic. Chi-square test was used to evaluate the differences between the patient cohorts. Main results and the role of chance A total of 2,669 fresh-ET cycles were reviewed retrospectively by dividing them into a euthyroid group (0.4-2.5 uIU/mL, n = 2397) and subclinical hypothyroidism group (2.5-4.0 uIU/mL, n=272). The overall biochemical pregnancy rate and clinical pregnancy rate was significantly lower in women with subclinical hypothyroidism (50.0% vs 43.4%, 40.0% vs 30.9%, p < 0.05). However, biochemical preganacy loss rate and the miscarriage rate was higher in women with subclinical hypothyroidism. (19.6% vs. 28.8%, 17.3% vs. 25.0%, p = 0.079) Limitations, reasons for caution This is a retrospective study and results must be confirmed on a well-designed randomized controlled study. Correlations must be considered with caution since the role of TSH is under study, especially when considering LBR outcome. Wider implications of the findings Among euthyroid patients, preconceptional TSH values in the high-normal range (between 2.5 and 4.0 mIU/L) are associated with adverse clinical outcomes. Our findings suggest that subclinical hypothyroidism may affect clinical outcomes. Trial registration number not applicable

Mendelian randomization to investigate the link between TSH and thyroid cancer

Evidence from observational studies suggests a positive association between serum thyroid-stimulating hormone (TSH) levels and differentiated thyroid carcinoma. However, the cause-effect relationship is poorly understood, and these studies are susceptible to bias and confounding. Using Mendelian randomization (MR) methodology, this study aimed to investigate the causal role of TSH in both benign thyroid nodules and thyroid cancer in up to 451,025 participants in the UK Biobank. Hospital Episode Statistics and Cancer Registry databases were used to identify 462 patients with differentiated thyroid carcinoma and 2031 patients with benign nodular thyroid disease. MR methods using genetic variants associated with serum TSH were used to test causal relationships between TSH and the two disease outcomes. We observed evidence of an inverse association between TSH levels and both thyroid cancer and benign nodular thyroid disease. Two-sample MR suggested that one standard deviation higher genetically instrumented TSH (approximately 0.8 mlU/L) resulted in an 80% reduction of risk of benign nodular disease (OR 0.20; 95% CI 0.10–0.41) and a 50% reduction of risk of thyroid cancer (OR 0.50; 95% CI 0.27–0.92). In keeping with other recently published studies, our results refute a causal role for TSH in both benign nodular thyroid disease and thyroid cancer, with increasing genetically instrumented TSH resulting in a lower risk of both diseases.

The role of thyroid stimulating hormone in the timing of thyroxin supplement after thyroid operations

Thyroid Stimulating Hormone (TSH) levels can be measured accurately down to a very low serum concentration with an immunoassay. When the serum TSH level is in the normal range, measuring the T3 and T4 levels is redundant. The objective of this study is to study the relation of TSH levels postoperatively in thyroid surgeries with the timing for thyroxin treatment as a supplemental and suppressive therapy. A prospective cohort study was done on 84 patients underwent thyroid operations in Al-Yarmouk Teaching Hospital from March 2010 through November 2012. Patients underwent different thyroid operations (lobectomy, subtotal thyroidectomy and total thyroidectomy) for different thyroid pathology. Later, they were followed up by TSH assay in periods of 2, 4, 6 and 12 months postoperatively. Variables were compared by using the analysis of variance, ANOVA test. P – values equal or less than 0.05 and 0.01 were considered to be statistically significant and highly significant, respectively. The mean age of patients was 43.30 ± 10.19 years. The females made the vast majority of study sample (85.7%). Patients were divided into six groups: simple colloid goiters (17 patients), multinodular goiters (32 patients), solitary thyroid nodules (11 patients), Hashimoto’s thyroiditis (8 patients), Graves’ disease (8 patients) and papillary and follicular carcinomas (8 patients). The study revealed that all patients with malignant thyroid nodules (i.e. those with total thyroidectomies) and the vast majority of patients with Hashimoto’s thyroiditis were in definite need for thyroxin treatment post-operatively. Other patients were variable in their need and timing of treatment according to the histopathological results and the type of operations. In conclusion; measurement of TSH level postoperatively is a good indicator for need of thyroxin treatment and for dose adjustment with the help of pathological results and the type of surgery.

Predictive value of thyroid stimulating hormone as a biomarker in intrauterine growth restriction

Normal maternal thyroid function is essential for fetal growth and neurocognitive development. Intra uterine growth restriction (IUGR) is a complex condition arising from maternal, placental, or fetal mechanisms and any imbalance in thyroid function may lead to undesirable results for both mother and fetus.The aim of this study was to co-relate the level of thyroid stimulating hormone (TSH) in clinically diagnosed cases of intra uterine growth restriction.A prospective study was conducted in a tertiary care hospital for a period of one year in which one hundred and twenty consecutive clinically suspected cases of singleton IUGR pregnancies at 34-40 weeks of gestation were enrolled. The reference level of TSH during the third trimester was taken as 0.3 to 3.0 mIU/ L. The TSH levels were recorded and a descriptive analysis of the data was performed.Among the 120 clinically diagnosed cases of IUGR only three antenatal mothers from rural background had TSH levels below 0.3 mIU/L. All three were vegetarians. In these, hypothyroid antenatal mothers, the delivery outcomes were; one was born dead while the other two babies were born alive and required caesarean section. However, the two born alive had a very low birth weight; less than 1.5 kgs and both needed admission to neonatal intensive care unit.Since the causation of IUGR is multifactorial, the role of TSH alone may not be accurate to be used as biomarker for prediction of IUGR.

Thyroid-stimulating hormone decreases the risk of osteoporosis by regulating osteoblast proliferation and differentiation

BackgroundAs the incidence of secretory osteoporosis has increased, bone loss, osteoporosis and their relationships with thyroid-stimulating hormone (TSH) have received increased attention. In this study, the role of TSH in bone metabolism and its possible underlying mechanisms were investigated.MethodsWe analyzed the serum levels of free triiodothyronine (FT3), free thyroxine (FT4), and TSH and the bone mineral density (BMD) levels of 114 men with normal thyroid function. In addition, osteoblasts from rat calvarial samples were treated with different doses of TSH for different lengths of time. The related gene and protein expression levels were investigated.ResultsA comparison of the BMD between the high-level and low-level serum TSH groups showed that the TSH serum concentration was positively correlated with BMD. TSH at concentrations of 10 mU/mL and 100 mU/mL significantly increased the mRNA levels of ALP, COI1 and Runx2 compared with those of the control (P < 0.05, P < 0.01). Bone morphogenetic protein (BMP)2 activity was enhanced with both increased TSH concentration and increased time. The protein levels of Runx2 and osterix were increased in a dose-dependent manner.ConclusionsThe circulating concentrations of TSH and BMD were positively correlated with normal thyroid function in males. TSH promoted osteoblast proliferation and differentiation in rat primary osteoblasts.

Serum TSH level as predictor of Graves' disease recurrence following antithyroid drug withdrawal: A systematic review.

Graves’ disease (GD) has a high recurrence rate despite various and adequate treatment. Numerous studies have been performed to identify the predictor of disease recurrence. This report aims to investigate the role of thyroid stimulating hormone (TSH) level as a thyrotropin in predicting the recurrence of Graves’ disease within 1 to 2 years following antithyroid drug (ATD) withdrawal. Literature searching was conducted on PubMed, Scopus, Cochrane, Proquest, EBSCO in August 2019 and Google Scholar in October 2020. The study criteria include the study that evaluates TSH level 4 weeks following ATD withdrawal, with subjects ≥18 years old who are retrospectively or prospectively followed up after 1 to 2 years following ATD withdrawal. Four eligible studies were selected based on inclusion/exclusion criteria, all of which measured TSH level at 4 weeks following ATD withdrawal. All studies had 1 to 2 years follow up. One study was an RCT, two studies were done in prospective cohort and another in retrospective cohort. All studies had comparable validity and applicability. Three out of four studies suggested that low TSH level measured 4 weeks following treatment withdrawal was associated with higher risk of disease recurrence. In conclusion, low TSH level obtained 4 weeks after ATD withdrawal was associated with higher rate of recurrence rate in GD.

The role of thyroid-stimulating hormone and thyroglobulin antibody in abnormally invasive placenta

Purpose Thyroid hormones and antibodies are known to participate in angiogenesis and invasion and also thyroid hormone receptors are expressed in the placenta. We aimed to evaluate the relationship of serum levels of thyroid-stimulating hormone (TSH), thyroid hormones (TH), and anti-thyroid antibodies with abnormally invasive placenta (AIP). We also aimed to investigate whether they are related with cesarean hysterectomy and massive blood transfusion need in AIP cases. Methods A total of 88 pregnant patients were enrolled in this prospective case-control study (30 with AIP, 28 with non-adherent placenta previa totalis (PPT) and 30 controls). Serum TSH, thyroid hormone [T3 (triiodothyronine) and T4 (thyroxine)] and thyroid antibodies against thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) levels were studied in maternal serum at initial admission to our Perinatology Unit (at early third trimester). The factors associated with increased risk of AIP, cesarean hysterectomy, massive blood transfusion, and adverse perinatal outcomes were evaluated with multiple logistic regression analysis. Adjusted odds ratios and 95% confidence intervals were also calculated. Results Serum TSH and TgAb levels were significantly lower in the AIP group than both PPT and control groups (p = .01, p < .001 and p < .001, p < .001 respectively). Decreased serum levels of TSH (<2.16 mIU/L) and TgAb (<2.70 mIU/L) levels and high previous cesarean section rates were found to be independently associated with AIP in pregnant women with PPT (OR: 0.4, 95% CI: 0.1–0.9; p = .04, OR: 0.7, 95%CI: 0.4–1.3, p = .02 and OR: 0.1, 95% CI: 0.1–0.5, p = .01). Decreased serum TSH and TgAb levels were found to be independently associated with an increased rate of cesarean hysterectomy and massive blood transfusion in AIP cases (OR: 3.7, 95% CI: 1.4–9.8; p = .01, OR: 1.8, 95% CI: 1.1–3.1; p = .03 and OR: 2.6, 95% CI: 1.0–6.5; p = .05, OR: 2.2, 95% CI: 1.1–4.1 p = .02). Decreased TSH and TgAb serum levels were also found to be independently associated with adverse perinatal outcomes in AIP cases (OR: 3.4, 95% CI: 1.3–11.0; p = .01 and OR: 1.978, 95% CI: 2–3.6; p = .03). Conclusion Decreased serum TSH and TgAb levels, and previous history of cesarean section were all found to be significantly associated with AIP in cases with PPT. We suggest that maternal serum TSH and TgAb levels can provide additional contribution to obstetric Doppler ultrasound in the diagnosis of AIP and thus can reduce the risks of unplanned cesarean hysterectomy in cases with PPT.

RETRACTION: Mendelian randomization supports a causative effect of TSH on thyroid carcinoma.

Evidence from observational studies suggests a positive association between serum thyroid stimulating hormone (TSH) levels and differentiated thyroid carcinoma. However, the cause-effect relationship is poorly understood and these studies are susceptible to bias and confounding. This study aimed to investigate the causal role of TSH in both benign thyroid nodules and thyroid cancer in up to 451,025 UK Biobank participants, using a genetic technique, known as Mendelian randomization (MR). Hospital Episode Statistics and Cancer Registry databases were used to identify 462 patients with differentiated thyroid carcinoma and 2031 patients with benign nodular thyroid disease. MR methods using genetic variants associated with serum TSH were used to test causal relationships between TSH and the two disease outcomes. Mendelian randomization provided evidence of a causal link between TSH and both thyroid cancer and benign nodular thyroid disease. 2-sample MR suggested that a one standard deviation higher genetically instrumented TSH (approximately 0.8 mlU/L) resulted in 4.96-fold higher odds of benign nodular disease (95% CI 2.46 - 9.99) and 2.00-fold higher odds of thyroid cancer (95% CI 1.09 - 3.70). Our results thus support a causal role for TSH in both benign nodular thyroid disease and thyroid cancer.

Thyroid Stimulating Hormone Triggers Hepatic Mitochondrial Stress through Cyclophilin D Acetylation.

Background & Aims Oxidative stress-related liver diseases were shown to be associated with elevated serum thyroid stimulating hormone (TSH) levels. Mitochondria are the main source of cellular reactive oxygen species. However, the relationship between TSH and hepatic mitochondrial stress/dysfunction and the underlying mechanisms are largely unknown. Here, we focused on exploring the effects and mechanism of TSH on hepatic mitochondrial stress. Methods As the function of TSH is mediated through the TSH receptor (TSHR), Tshr−/− mice and liver-specific Tshr knockout (LKO) mice were used in our study. The thyroid-specific Tshr knockout mouse model injected with TSH (TKO+TSH) was used as a mimic for subclinical hypothyroidism (SCH) patients. Hepatic mitochondrial stress and function were analyzed in these mouse models, and the expression of key genes involved in mitochondrial stress was measured. Results A relatively lower degree of mitochondrial stress was observed in the livers of Tshr−/− mice and LKO mice than those of their littermate counterparts. TSH caused concentration- and time-dependent effects on mitochondrial stress and cyclophilin D (CypD) acetylation in hepatocytes in vitro. Microarray and RT-PCR analyses showed that Tshr−/− mice had much higher lncRNA-AK044604 expression than their littermate counterparts. The use of the AK044604 overexpression plasmid and SIRT1 agonist proved that TSH aggravates CypD acetylation and mitochondrial stress via lncRNA-AK044604 and SIRT1. An inhibitor of CypD acetylation, cyclosporine A, suppressed TSH-induced hepatic mitochondrial stress and dysfunction. Conclusions TSH stimulates hepatic CypD acetylation through the lncRNA-AK044604/SIRT1/SIRT3 signaling pathway, indicating an essential role for TSH in mitochondrial stress in the liver.

Thyroid-stimulating hormone improves insulin sensitivity in skeletal muscle cells via cAMP/PKA/CREB pathway-dependent upregulation of insulin receptor substrate-1 expression

Thyroid-stimulating hormone (TSH) receptor is expressed in extrathyroidal tissues such as hepatocytes, adipocytes, and skeletal muscle, which suggests a possible novel role of TSH in various metabolic processes in extrathyroidal tissues independent of thyroid hormones. We investigated whether TSH has any effects on glucose tolerance and insulin sensitivity in the skeletal muscle using diet-induced obesity (DIO) mouse models and rodent skeletal muscle cells. TSH improved glucose tolerance in DIO mice and this was associated with an improvement of skeletal muscle insulin sensitivity resulting from the increased expression of insulin receptor substrate (IRS)-1 protein and mRNA therein. TSH significantly increased both basal and insulin-stimulated glucose transport in rat L6 myotubes and increased the expression of IRS-1 protein and mRNA in these cells as well. TSH also stimulated Irs1 promoter activation; this stimulation was abolished by protein kinase A (PKA) inhibition using H89 or by mutation of the cAMP-response element site located at −1155 to −875 bp of the Irs1 promoter region, supporting a novel role of TSH activated-cAMP/PKA/CREB signaling in the regulation of Irs1 expression. In conclusion, TSH improves insulin sensitivity in skeletal muscle by increasing Irs1 gene expression. This regulatory effect is mediated by a PKA-CREB-dependent pathway.

Decreased fasting blood glucose is associated with impaired hepatic glucose production in thyroid-stimulating hormone receptor knockout mice

Our previous study reported that thyroid-stimulating hormone (TSH) promotes cholesterol synthesis via the cyclic adenosine monophosphate/protein kinase A/cAMP regulatory element-binding protein (cAMP/PKA/CREB) pathway after binding to TSH receptors (TSHR) in the liver. The hepatic cAMP/PKA/CREB pathway also plays an important role in maintaining fasting glucose homeostasis. These findings implied a possible role for TSH in hepatic glucose metabolism. In this study, we used TSH receptor knockout mice (Tshr-ko mice) to clarify the effect of Tshr deletion on hepatic glucose metabolism, and investigated whether the effects of TSH directly regulate hepatic gluconeogenesis in HepG2 cells. Tshr-ko mice exhibited decreased fasting blood glucose levels, increased insulin sensitivity but normal level of fasting plasma insulin. Tshr deletion impaired hepatic glucose production by down-regulating the expression of glucose-6-phosphatase (G6P) and phosphoenolpyruvate pyruvate carboxylase (PEPCK) mRNA, two rate-limiting enzymes in hepatic gluconeogenesis, and enhancing the abundance of hepatic glucokinase (GK), the first enzyme regulating glycogen synthesis. Moreover, Tshr deletion inhibited the protein expression of hepatic phospho-CREB and increased the protein expression of hepatic phospho-AMP-activated protein kinase (p-AMPK), two up-stream regulators of PEPCK and G6P mRNA. In HepG2 cells, TSH increased the expression of G6P and PEPCK at mRNA level. These results indicated the simulative effects of TSH on hepatic glucose production in vivo and in vitro, suggesting a novel role for TSH in hepatic glucose metabolism.

Role of TSH on Urinary Calcium Excretion In Post Menopausal Women of South Indian Population

Unforeseen aberrations in the hormonal status during the early postmenopausal period are responsible for several complications including osteoporosis. Thyroid Stimulating Hormone (TSH) receptors are isolated from various tissues including the bone. A low serum TSH level is known to stimulate osteoclastic activity in bone and accelerate bone resorption. Urinary calcium/creatinine (UCa/Cr) excretion ratio could be an indirect and an early indicator of loss of Bone Mineral Density (BMD). With this background, this study was planned to explore the association of serum TSH levels with the UCa/Cr excretion ratio. Forty eight women in the postmenopausal age group, with their menopausal age not more than seven years of duration were included in this study. Based on their TSH values, these subjects were divided into two groups A (TSH<0.5 mIU/L) and B (TSH>0.5mIU/L). Urinary calcium, UCa/Cr excretion ratio, serum phosphorous, calcium and calcium phosphorous multiplication products were estimated and compared between the two groups. Twenty two (46%) women were biochemically asymptomatic hyperthyroid cases and Twenty six (54%) were euthyroid. This study documents high UCa/Cr in Group A compared to that of Group B (p<0.05). We also observed significant negative correlation of TSH with UCa/Cr excretion ratio (p=0.041, r = -0.43). Low serum TSH levels were associated with increased UCa/Cr excretion ratio in postmenopausal women of South Indian population.

Subclinical Hypothyroidism in Grown-Up Congenital Heart Disease Patients

Subclinical hypothyroidism usually is asymptomatic, but it can be associated with various adverse cardiologic outcomes. With the objective of gaining insight into the role of thyroid-stimulating hormone (TSH) in congenital heart abnormalities, this study measured serum TSH concentrations in different subtypes of grown-up congenital heart disease (GUCHD) patients. Serum TSH (reference range, 0.34-5.6 mIU/L), creatinine, cholesterol, C-reactive protein (CRP), N-terminal proB-type natriuretic peptide (NT-pro-BNP), and 24-h proteinuria were measured in 249 GUCHD patients. Of 24 GUCHD patients (9.6 %) with a TSH level higher than 5.6 mUI/L, nine were cyanotic (37.5 %) and seven (29.1 %) had Down syndrome. The GUCHD patients with serum TSH exceeding 5.6 mIU/L had a significantly higher level of serum NT-pro-BNP (195.1 [0.28; 5,280.3] vs 57.6 [0.00; 929.8]; p = 0.001) and CRP (0.30 [0.06; 1.87] vs 0.16 [0.00; 1.40]; p = 0.011] than those with a TSH level of 5.6 mIU/L or lower. No significant differences were found in serum creatinine, lipids, or 24-h proteinuria between the two groups. The T4 concentrations in the GUCHD patients with TSH exceeding 5.6 mIU/L were within the normal range (0.89 ± 0.23 ng/dL). In the multivariate analysis, cyanosis (odds ratio [OR], 6,399; 95 % confidence interval [CI] 2,296-17,830; p < 0.001), Down syndrome (OR, 6,208; 95 % CI, 1,963-19,636; p = 0.002), and NT-pro-BNP concentrations (OR, 1,001; 95 % CI, 1,000-1,002; p < 0.026) proved to be risk factors for TSH levels higher than 5.6 mIU/L. Because subclinical hypothyroidism entails a cardiovascular risk, the authors postulate that TSH screening should be included in the routine follow-up evaluation of GUCHD patients with cyanosis or Down syndrome.

The role of TSH in cholesterol synthesis

Thyroid diseases are often accompanied with dyslipidemia.In me past,low level of myroid hormone(TH) was considered a main factor in causing elevated level of blood cholesterol in hypothyroid patients.However,some clinical features can not be explained by this traditional theory. For example,in subclinical hypothyroid cases,both levels of thyroid-stimulating hormone (TSH) and serum total cholesterol (TC) increase,while TH level remains normal.From this phenomenon,we speculate that in case with hypothyroidism,not only there is a relationship between serum TC and TH levels,but also serum TC level change is related to TSH in some way,which has not been noticed.The purpose of this paper is to review the new and most advanced progress in the research of TSH and cholesterol. Key words: TSH; Liver cells; HMG-CoA reductase; Total cholesterol

Role of extrathyroidal TSHR expression in adipocyte differentiation and its association with obesity

BackgroundObesity is known to be associated with higher risks of cardiovascular disease, metabolic syndrome, and diabetes mellitus. Thyroid-stimulating hormone (TSHR) is the receptor for thyroid-stimulating hormone (TSH, or thyrotropin), the key regulator of thyroid functions. The expression of TSHR, once considered to be limited to thyrocytes, has been so far detected in many extrathyroidal tissues including liver and fat. Previous studies have shown that TSHR expression is upregulated when preadipocytes differentiate into mature adipocytes, suggestive of a possible role of TSHR in adipogenesis. However, it remains unclear whether TSHR expression in adipocytes is implicated in the pathogenesis of obesity.MethodsIn the present study, TSHR expression in adipose tissues from both mice and human was analyzed, and its association with obesity was evaluated.ResultsWe here showed that TSHR expression was increased at both mRNA and protein levels when 3T3-L1 preadipocytes were induced to differentiate. Knockdown of TSHR blocked the adipocyte differentiation of 3T3-L1 preadipocytes as evaluated by Oil-red-O staining for lipid accumulation and by RT-PCR analyses of PPAR-γ and ALBP mRNA expression. We generated obesity mice (C57/BL6) by high-fat diet feeding and found that the TSHR protein expression in visceral adipose tissues from obesity mice was significantly higher in comparison with the non-obesity control mice (P < 0.05). Finally, the TSHR expression in adipose tissues was determined in 120 patients. The results showed that TSHR expression in subcutaneous adipose tissue is correlated with BMI (body mass index).ConclusionTaken together, these results suggested that TSHR is an important regulator of adipocyte differentiation. Dysregulated expression of TSHR in adipose tissues is associated with obesity, which may involve a mechanism of excess adipogenesis.

Preoperative serum thyroid stimulating hormone levels in well-differentiated thyroid carcinoma is a predictive factor for lateral lymph node metastasis as well as extrathyroidal extension in Korean patients: a single-center experience

It has been known that thyroid stimulating hormone (TSH) stimulates the growth or development of thyroid malignancy and higher serum TSH has association with both thyroid cancer incidence and advanced tumor stage. However, the role of TSH in high-risk features of well-differentiated thyroid cancer was not fully evaluated especially in Asian population. The purpose of our study is to evaluate the association of preoperative serum TSH levels with the advance of differentiated thyroid cancer and its high-risk clinicopathological features in Korean patients. We evaluated 554 patients retrospectively who underwent thyroidectomy and diagnosed as differentiated thyroid cancer during a 3-year period at Pusan National University Hospital. The preoperative TSH levels were significantly higher in the patients with extrathyroidal extension (P = 0.002) and those with lateral lymph node metastasis (P = 0.007). As the increase of the serum TSH concentration, there were significant rising trends in the prevalence of extrathyroidal extension (P = 0.009). In the patients with TSH ≥ 2.5 mIU/L, the prevalences of extrathyroidal extension (P = 0.006) and lateral lymph node metastasis (P = 0.024) were also significantly higher. Using multiple logistic regression, preoperative TSH level was a predictive factor for the presence of extrathyroidal extension (P = 0.008) and lateral lymph node metastasis (P = 0.025). Hashimoto's thyroiditis itself was not associated with the status of extrathyroidal extension and lateral lymph node metastasis. In conclusion, preoperative TSH levels were associated with lateral lymph node matastasis, a novel finding, and extrathyroidal extension in well differentiated thyroid cancer and might be useful as a preoperative supplementary marker for determining the optimal extent of differentiated thyroid cancer surgery in Korean patients.

Role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients affected by differentiated thyroid carcinoma, high thyroglobulin level, and negative 131I scan: review of the literature

Differentiated thyroid carcinoma (DTC) is a slow-growing tumor that represents 1% of all malignant tumors and is the most frequent endocrine cancer. ¹⁸F-Fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) imaging is an increasingly important imaging tool in oncology and is still under investigation in numerous studies looking into its efficacy and cost-effectiveness. Despite the fact that ¹⁸F-FDG-PET/CT has been shown to be a powerful and accurate diagnostic tool in patients affected by DTC with high serum thyroglobulin (Tg) levels and negative radioiodine (¹³¹I) total body scan, its definitive role is not completely clear, in particular regarding the role of thyroid stimulating hormone (TSH) and Tg value "cutoff" over which is better to perform the study. In this review, these issues are analyzed to clarify controversial aspects and identify established cornerstones. In particular, the literature analysis suggests that levothyroxine withdrawal is preferable in cases of relatively low Tg levels (<10 ng/ml) and good clinical compliance to hypothyroidism. Moreover, recombinant thyrotropin stimulating hormone (rTSH) could be a preferable alternative in patients clinically unable to tolerate therapy withdrawal. A Tg cutoff level over which to perform the study seems to be 10 ng/ml, a reasonable value maintaining high accuracy in terms of a good compromise between sensitivity and specificity.