This study investigated whether high-normal thyrotropin(TSH) levels are associated with metabolic syndrome in euthyroid Chinese people≥40 years old.Clinical and metabolic factors were assessed in 2,356 subjects(40...This study investigated whether high-normal thyrotropin(TSH) levels are associated with metabolic syndrome in euthyroid Chinese people≥40 years old.Clinical and metabolic factors were assessed in 2,356 subjects(40-77 years old) with TSH levels in the normal range(0.35-5.00 mU/L).Using 2.50 mU/L as the cut-off point of TSH level within the normal range,we divided subjects into the high-TSH(2.50-5.00 mU/L;n= 1,064) and low-TSH(0.35-2.50mU/L;n= 1,292) group.The results showed that the mean levels of body mass index(BMI),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),and fasting plasma glucose(FPG) were higher in the high-TSH group and TSH levels were significantly positively con-elated with BMI,LDL-C,TC,and FPG.The prevalence of central obesity,hypertriglyceridemia,low high density lipoprotein cholesterol(HDL-C),and high FPG(〉5.60 mmol/L) was significantly higher in females and subjects with high-TSH levels.Metabolic syndrome was also more prevalent in the high-TSH group.People over the age of 40 years with high-normal TSH levels had a 1.2-fold increased risk of metabolic syndrome,compared with those with low-normal TSII levels,after adjusting for age and gender.In conclusion,high normal TSH is a risk factor for metabolic syndrome in people ≥40 years old.展开更多
The HIV-1 LTR controls the expression of HIV-1 viral genes and thus is critical for viral propagation and pathology. Numerous host factors have been shown to participate in the regulation of the LTR promoter. Among th...The HIV-1 LTR controls the expression of HIV-1 viral genes and thus is critical for viral propagation and pathology. Numerous host factors have been shown to participate in the regulation of the LTR promoter. Among them is the thyroid hormone (T3) receptor (TR). TR has been shown to bind to the critical region of the promoter that contain the NFbB and Sp1 binding sites. Interestingly, earlier transient transfection studies in tissue culture cells have yielded contradicting conclusions on the role of TR in LTR regulation, likely due to the use of different cell types and/or lack of proper chromatin organization. Here, using the frog oocyte as a model system that allows replication-coupled chromatin assembly, mimicking that in somatic cells, we demonstrate that unliganded heterodimers of TR and RXR (9-cis retinoic acid receptor) repress LTR while the addition of T3 relieves the repression and further activates the promoter. More importantly, we show that chromatin and unliganded TR/RXR synergize to repress the promoter in a histone deacetylase-dependent manner.展开更多
Resistance to Thyroid Hormone (RTH) is a rare form of hormone resistance secondary to changes in the genes encoding thyroid hormone receptors. The two subtypes, Pituitary RTH (PRTH) and Generalized RTH (GRTH), cause c...Resistance to Thyroid Hormone (RTH) is a rare form of hormone resistance secondary to changes in the genes encoding thyroid hormone receptors. The two subtypes, Pituitary RTH (PRTH) and Generalized RTH (GRTH), cause clinically distinguishable patient presentations. In PRTH, typically only the pituitary gland is resistant to thyroid hormone (TH) while the rest of the body maintains sensitivity. Selective pituitary resistance to thyroid hormone results in dysregulation of thyroid hormone homeostasis with clinical presentation as either euthyroid or hyperthyroidism. PRTH is characterized by elevated thyroid hormone levels with an elevated or inappropriately normal TSH concentration. Herein we describe a case report of a 70-year-old woman who complained of weight loss of over 35 lbs., palpitations, jitters, hair loss, diarrhea, fatigue, muscle weakness, etc. over 6 months, thus, indicating the presence of iatrogenic hyperthyroidism while receiving levothyroxine 175 ug daily prescribed by her primary care provider because of a reported history of “Graves disease” treated by radioactive iodine ablation of the thyroid several years ago. The daily dose of levothyroxine had been increased gradually at an interval of 3 months over a year because of persistent elevation of serum TSH level. Laboratory tests revealed markedly elevated Free T4, Free T3 and TSH levels, along with low concentrations of all lipid fractions, serum creatinine and urea nitrogen levels, indicating TSH induced hyperthyroidism or PRTH. Further testing documented a mutation of thyroid hormone receptor beta gene 2 confirming presence of PRTH. We believe that the initial diagnosis of Graves Disease was erroneous and I-131 ablation further confounded and missed the diagnosis of PRTH. Thus, the purpose of this report is to report a patient with PRTH and describe potential pitfalls in diagnosis and management of this rare disorder.展开更多
BACKGROUND: Although non-thyroidal illness syndrome(NTIS) is considered a negative prognostic factor, the alterations in free triiodothyronine(f T3) levels in trauma patients requiring massive transfusion have not bee...BACKGROUND: Although non-thyroidal illness syndrome(NTIS) is considered a negative prognostic factor, the alterations in free triiodothyronine(f T3) levels in trauma patients requiring massive transfusion have not been reported.METHODS: A prospective observational study comparing 2 groups of trauma patients was conducted. Group M comprised trauma patients requiring massive transfusions(>10 units of packed red blood cells) within 24 hours of emergency admission. Group C comprised patients with an injury severity score >9 but not requiring massive transfusions. Levels of f T3, free thyroxine(f T4), and thyroidstimulating hormone(TSH) were evaluated on admission and on days 1, 2, and 7 after admission. The clinical backgrounds and variables measured including total transfusion amounts were compared and the inter-group prognosis was evaluated. Results are presented as mean±standard deviation.RESULTS: Nineteen patients were enrolled in each group. In both groups, 32 were men, and the mean age was 50±24 years. In group C one patient died from respiratory failure. The initial f T3 levels in group M(1.95±0.37 pg/m L) were signifi cantly lower than those in group C(2.49±0.72 pg/m L; P<0.01) and remained low until 1 week after admission. Initial inter-group f T4 and TSH levels were not significantly different. TSH levels at 1 week(1.99±1.64 μIU/m L) were higher than at admission(1.48±0.5 μIU/m L) in group C(P<0.05).CONCLUSION: Typical NTIS was observed in trauma patients requiring massive transfusions. When initial resuscitation achieved circulatory stabilization, prognosis was not strongly associated with NTIS.展开更多
Background Resistance to thyroid hormone (RTH) is a dominant inherited syndrome of reduced tissue responsiveness to thyroid hormone. It is usually due to mutations located at the ligand-binding domain and adjacent h...Background Resistance to thyroid hormone (RTH) is a dominant inherited syndrome of reduced tissue responsiveness to thyroid hormone. It is usually due to mutations located at the ligand-binding domain and adjacent hinge region of the thyroid hormone receptor β(TRβ). We report the clinical and laboratory characteristics and the genetic analysis of a patient with this rare disorder and his family members. Methods The clinical presentations and changes of thyroid function tests (TFTs) including magnetic resonance imaging (MRI) of pituitary and other laboratory tests were analysed. TFTs of his family's members were detected as well. Direct DNA sequencing of the TRβ gene was done for those with abnormal TFTs. Results The RTH child had goiter, irritability, aggressiveness, and sudoresis. His TFTs showed high levels of circulating free thyroid hormones (FT4 and FT3) and normal thyroid-stimulating hormone (TSH) concentrations. He felt worse when treated as hyperthyroidism (Grave disease) with thiamazole and his clinical presentations got improved obviously when treated as RTH with bromocriptine without obvious advert effect. We identified a novel missense mutation, A317D, located in exon 9 of the gene of this boy and his mother. His mother had not any clinical presentation, but having abnormal TFTs results. Conclusions This patient reported here was concordant with the criteria of RTH. The feature is dysfunction of hypothalamus-pituitary-thyroid axis. A novel mutation was found in the TRβ, A317D, of this family. This research verified the phenomena that there is a clinical heterogeneity within the same mutation of different RTH patients.展开更多
Background:Diagnosis of polycystic ovary syndrome(PCOS)depends on 2003 Rotterdam Criteria.According to these criteria there are four possible combinations resulting in various phenotypes.We aimed(i)to confirm that the...Background:Diagnosis of polycystic ovary syndrome(PCOS)depends on 2003 Rotterdam Criteria.According to these criteria there are four possible combinations resulting in various phenotypes.We aimed(i)to confirm that the levels of body mass index(BMI),anti-müllerian hormone(AMH)levels and insulin resistance(IR)are higher in PCOS patients and higher in phenotype-A among PCOS patients,and(ii)to determine cut-off values for the diagnosis of PCOS and phenotype-A.Materials and methods:This study was conducted in an IVF Center,between November 2019 and January 2021.Data of infertile women participating in the study was evaluated retrospectively.Parameters such as menstruation pattern,clinical hyperandrogenism,age,BMI,follicle stimulating hormone(FSH),luteinizing hormone(LH),estradiol,thyroid stimulating hormone(TSH),prolactin,AMH,dehydroepiandrosterone sulphate(DHEA-S),fasting blood glucose,fasting insulin levels,antral follicle counts(AFC)and ovarian volumes were recorded for each patient.Women were grouped as PCOS and non-PCOS,and PCOS group was further divided into 4 subgroups according to their phenotypes.Data of infertile patients with PCOS patients were compared with infertile non-PCOS patients and PCOS phenotypes were compared among each other.Results:Data of 244 infertile patients was included in the study.BMI,AMH,AFC,and HOMA-IR were statistically higher in PCOS patients,compared to non-PCOS patients.We found the AMH level of>3.105 ng/ml to be having 90.8%sensitivity and 90%specificity to diagnose a patient as PCOS.Among different phenotypes,also BMI,AMH,and insulin resistance index(HOMA-IR)levels were significantly higher in infertile PCOS phenotype-A when compared to other three phenotypes(p:0.003,p:0.000,and p:0.000,respectively).The AMH cut-off value to estimate phenotype-A was found as 6.095 ng/ml with 69.2%sensitivity and 86.7%specificity.We did not found threshold levels of BMI and HOMA-IR with high sensitivity to identify phenotype-A.Conclusion:Properly diagnosing PCOS and determining the phenotype are crucial due to the long-term health conditions.Therefore,we suggest that serum AMH level could be included in PCOS diagnosis criteria,and the value of 3.105 ng/ml would have a 90.8%sensitivity and 90%specificity.Also,to identify phenotype-A,AMH level could be used.Therefore,we speculate that AMH may serve to identify PCOS and PCOS phenotype-A in places where ultrasound imaging is not straightforward to perform or not easily accessible.展开更多
Objective: To investigate the alternations of thyroid hormone in traumatic patients with severe inflammatory response syndrome (SIRS). Methods: Fifty traumatic patients with severe SIRS were enrolled and divided ...Objective: To investigate the alternations of thyroid hormone in traumatic patients with severe inflammatory response syndrome (SIRS). Methods: Fifty traumatic patients with severe SIRS were enrolled and divided into two groups according to whether they presented multiorgan dysfunction syndrome (MODS). Thyroid hormone measurements were taken, including total triiodothyronine ( TT3 ), total thyroxine (TT4), free triiodothyronine (FT3), free thyroxine ( FT4 ) and thyroid stimulating hormone (TSH). The acute physiology and chronic health evaluation II ( APACHE II ) score was calculated according to clinical data. The outcomes of recovery or deterioration were recorded, as well as the length of time from the onset of SIRS to the time thyroid hormones were measured. Results: Euthyroid sick syndrome (ESS) was presented in 45 cases. TT3 level was negatively correlated with APACHE II score (r = -0.330, P 〈0. 05), and TT3/TI'4 value was negatively correlated with the duration of SIRS( r = -0.316, P〈0.05). TT3, TT4 and levels in MODS patients were significantly lower than those without MODS ( P 〈 0.05 ). MODS patients got low TT4 or FT4 level more frequently than those without MODS ( P 〈 0.05 ). Compared with the patients in normal TSH group, the patients with decreased TSH had lower T3, T4, recovery rate and higher APACHE II scores, MODS incidence, but there was no difference between two groups (P〉0.05). Conclusions: Trauma patients with severe SIRS have high possibility to get ESS, which occurs more frequently and severely in MODS patients. It shows the influences of SIRS on the thyroid axes. With the persistence and aggravation of SIRS, there is a progressive reduction of thyroid hormone.展开更多
基金supported by the grants from the Chinese Society of Endocrinology and National Clinical Research Center for Metabolic Diseases(81170726)
文摘This study investigated whether high-normal thyrotropin(TSH) levels are associated with metabolic syndrome in euthyroid Chinese people≥40 years old.Clinical and metabolic factors were assessed in 2,356 subjects(40-77 years old) with TSH levels in the normal range(0.35-5.00 mU/L).Using 2.50 mU/L as the cut-off point of TSH level within the normal range,we divided subjects into the high-TSH(2.50-5.00 mU/L;n= 1,064) and low-TSH(0.35-2.50mU/L;n= 1,292) group.The results showed that the mean levels of body mass index(BMI),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),and fasting plasma glucose(FPG) were higher in the high-TSH group and TSH levels were significantly positively con-elated with BMI,LDL-C,TC,and FPG.The prevalence of central obesity,hypertriglyceridemia,low high density lipoprotein cholesterol(HDL-C),and high FPG(〉5.60 mmol/L) was significantly higher in females and subjects with high-TSH levels.Metabolic syndrome was also more prevalent in the high-TSH group.People over the age of 40 years with high-normal TSH levels had a 1.2-fold increased risk of metabolic syndrome,compared with those with low-normal TSII levels,after adjusting for age and gender.In conclusion,high normal TSH is a risk factor for metabolic syndrome in people ≥40 years old.
文摘The HIV-1 LTR controls the expression of HIV-1 viral genes and thus is critical for viral propagation and pathology. Numerous host factors have been shown to participate in the regulation of the LTR promoter. Among them is the thyroid hormone (T3) receptor (TR). TR has been shown to bind to the critical region of the promoter that contain the NFbB and Sp1 binding sites. Interestingly, earlier transient transfection studies in tissue culture cells have yielded contradicting conclusions on the role of TR in LTR regulation, likely due to the use of different cell types and/or lack of proper chromatin organization. Here, using the frog oocyte as a model system that allows replication-coupled chromatin assembly, mimicking that in somatic cells, we demonstrate that unliganded heterodimers of TR and RXR (9-cis retinoic acid receptor) repress LTR while the addition of T3 relieves the repression and further activates the promoter. More importantly, we show that chromatin and unliganded TR/RXR synergize to repress the promoter in a histone deacetylase-dependent manner.
文摘Resistance to Thyroid Hormone (RTH) is a rare form of hormone resistance secondary to changes in the genes encoding thyroid hormone receptors. The two subtypes, Pituitary RTH (PRTH) and Generalized RTH (GRTH), cause clinically distinguishable patient presentations. In PRTH, typically only the pituitary gland is resistant to thyroid hormone (TH) while the rest of the body maintains sensitivity. Selective pituitary resistance to thyroid hormone results in dysregulation of thyroid hormone homeostasis with clinical presentation as either euthyroid or hyperthyroidism. PRTH is characterized by elevated thyroid hormone levels with an elevated or inappropriately normal TSH concentration. Herein we describe a case report of a 70-year-old woman who complained of weight loss of over 35 lbs., palpitations, jitters, hair loss, diarrhea, fatigue, muscle weakness, etc. over 6 months, thus, indicating the presence of iatrogenic hyperthyroidism while receiving levothyroxine 175 ug daily prescribed by her primary care provider because of a reported history of “Graves disease” treated by radioactive iodine ablation of the thyroid several years ago. The daily dose of levothyroxine had been increased gradually at an interval of 3 months over a year because of persistent elevation of serum TSH level. Laboratory tests revealed markedly elevated Free T4, Free T3 and TSH levels, along with low concentrations of all lipid fractions, serum creatinine and urea nitrogen levels, indicating TSH induced hyperthyroidism or PRTH. Further testing documented a mutation of thyroid hormone receptor beta gene 2 confirming presence of PRTH. We believe that the initial diagnosis of Graves Disease was erroneous and I-131 ablation further confounded and missed the diagnosis of PRTH. Thus, the purpose of this report is to report a patient with PRTH and describe potential pitfalls in diagnosis and management of this rare disorder.
文摘BACKGROUND: Although non-thyroidal illness syndrome(NTIS) is considered a negative prognostic factor, the alterations in free triiodothyronine(f T3) levels in trauma patients requiring massive transfusion have not been reported.METHODS: A prospective observational study comparing 2 groups of trauma patients was conducted. Group M comprised trauma patients requiring massive transfusions(>10 units of packed red blood cells) within 24 hours of emergency admission. Group C comprised patients with an injury severity score >9 but not requiring massive transfusions. Levels of f T3, free thyroxine(f T4), and thyroidstimulating hormone(TSH) were evaluated on admission and on days 1, 2, and 7 after admission. The clinical backgrounds and variables measured including total transfusion amounts were compared and the inter-group prognosis was evaluated. Results are presented as mean±standard deviation.RESULTS: Nineteen patients were enrolled in each group. In both groups, 32 were men, and the mean age was 50±24 years. In group C one patient died from respiratory failure. The initial f T3 levels in group M(1.95±0.37 pg/m L) were signifi cantly lower than those in group C(2.49±0.72 pg/m L; P<0.01) and remained low until 1 week after admission. Initial inter-group f T4 and TSH levels were not significantly different. TSH levels at 1 week(1.99±1.64 μIU/m L) were higher than at admission(1.48±0.5 μIU/m L) in group C(P<0.05).CONCLUSION: Typical NTIS was observed in trauma patients requiring massive transfusions. When initial resuscitation achieved circulatory stabilization, prognosis was not strongly associated with NTIS.
文摘Background Resistance to thyroid hormone (RTH) is a dominant inherited syndrome of reduced tissue responsiveness to thyroid hormone. It is usually due to mutations located at the ligand-binding domain and adjacent hinge region of the thyroid hormone receptor β(TRβ). We report the clinical and laboratory characteristics and the genetic analysis of a patient with this rare disorder and his family members. Methods The clinical presentations and changes of thyroid function tests (TFTs) including magnetic resonance imaging (MRI) of pituitary and other laboratory tests were analysed. TFTs of his family's members were detected as well. Direct DNA sequencing of the TRβ gene was done for those with abnormal TFTs. Results The RTH child had goiter, irritability, aggressiveness, and sudoresis. His TFTs showed high levels of circulating free thyroid hormones (FT4 and FT3) and normal thyroid-stimulating hormone (TSH) concentrations. He felt worse when treated as hyperthyroidism (Grave disease) with thiamazole and his clinical presentations got improved obviously when treated as RTH with bromocriptine without obvious advert effect. We identified a novel missense mutation, A317D, located in exon 9 of the gene of this boy and his mother. His mother had not any clinical presentation, but having abnormal TFTs results. Conclusions This patient reported here was concordant with the criteria of RTH. The feature is dysfunction of hypothalamus-pituitary-thyroid axis. A novel mutation was found in the TRβ, A317D, of this family. This research verified the phenomena that there is a clinical heterogeneity within the same mutation of different RTH patients.
文摘Background:Diagnosis of polycystic ovary syndrome(PCOS)depends on 2003 Rotterdam Criteria.According to these criteria there are four possible combinations resulting in various phenotypes.We aimed(i)to confirm that the levels of body mass index(BMI),anti-müllerian hormone(AMH)levels and insulin resistance(IR)are higher in PCOS patients and higher in phenotype-A among PCOS patients,and(ii)to determine cut-off values for the diagnosis of PCOS and phenotype-A.Materials and methods:This study was conducted in an IVF Center,between November 2019 and January 2021.Data of infertile women participating in the study was evaluated retrospectively.Parameters such as menstruation pattern,clinical hyperandrogenism,age,BMI,follicle stimulating hormone(FSH),luteinizing hormone(LH),estradiol,thyroid stimulating hormone(TSH),prolactin,AMH,dehydroepiandrosterone sulphate(DHEA-S),fasting blood glucose,fasting insulin levels,antral follicle counts(AFC)and ovarian volumes were recorded for each patient.Women were grouped as PCOS and non-PCOS,and PCOS group was further divided into 4 subgroups according to their phenotypes.Data of infertile patients with PCOS patients were compared with infertile non-PCOS patients and PCOS phenotypes were compared among each other.Results:Data of 244 infertile patients was included in the study.BMI,AMH,AFC,and HOMA-IR were statistically higher in PCOS patients,compared to non-PCOS patients.We found the AMH level of>3.105 ng/ml to be having 90.8%sensitivity and 90%specificity to diagnose a patient as PCOS.Among different phenotypes,also BMI,AMH,and insulin resistance index(HOMA-IR)levels were significantly higher in infertile PCOS phenotype-A when compared to other three phenotypes(p:0.003,p:0.000,and p:0.000,respectively).The AMH cut-off value to estimate phenotype-A was found as 6.095 ng/ml with 69.2%sensitivity and 86.7%specificity.We did not found threshold levels of BMI and HOMA-IR with high sensitivity to identify phenotype-A.Conclusion:Properly diagnosing PCOS and determining the phenotype are crucial due to the long-term health conditions.Therefore,we suggest that serum AMH level could be included in PCOS diagnosis criteria,and the value of 3.105 ng/ml would have a 90.8%sensitivity and 90%specificity.Also,to identify phenotype-A,AMH level could be used.Therefore,we speculate that AMH may serve to identify PCOS and PCOS phenotype-A in places where ultrasound imaging is not straightforward to perform or not easily accessible.
文摘Objective: To investigate the alternations of thyroid hormone in traumatic patients with severe inflammatory response syndrome (SIRS). Methods: Fifty traumatic patients with severe SIRS were enrolled and divided into two groups according to whether they presented multiorgan dysfunction syndrome (MODS). Thyroid hormone measurements were taken, including total triiodothyronine ( TT3 ), total thyroxine (TT4), free triiodothyronine (FT3), free thyroxine ( FT4 ) and thyroid stimulating hormone (TSH). The acute physiology and chronic health evaluation II ( APACHE II ) score was calculated according to clinical data. The outcomes of recovery or deterioration were recorded, as well as the length of time from the onset of SIRS to the time thyroid hormones were measured. Results: Euthyroid sick syndrome (ESS) was presented in 45 cases. TT3 level was negatively correlated with APACHE II score (r = -0.330, P 〈0. 05), and TT3/TI'4 value was negatively correlated with the duration of SIRS( r = -0.316, P〈0.05). TT3, TT4 and levels in MODS patients were significantly lower than those without MODS ( P 〈 0.05 ). MODS patients got low TT4 or FT4 level more frequently than those without MODS ( P 〈 0.05 ). Compared with the patients in normal TSH group, the patients with decreased TSH had lower T3, T4, recovery rate and higher APACHE II scores, MODS incidence, but there was no difference between two groups (P〉0.05). Conclusions: Trauma patients with severe SIRS have high possibility to get ESS, which occurs more frequently and severely in MODS patients. It shows the influences of SIRS on the thyroid axes. With the persistence and aggravation of SIRS, there is a progressive reduction of thyroid hormone.