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Open access

Qing Zhu, Jianbin Su, Xueqin Wang, Mengjie Tang, Yingying Gao, and Dongmei Zhang

Graves’ disease (GD), an organ-specific autoimmune disease, is the most common cause of hyperthyroidism. Tumour necrosis factor-alpha (TNF-α) exhibits immunological and metabolic activities involved in the induction and maintenance of immune responses. We attempted to evaluate the relationship between GD and serum TNF-α and its soluble receptors (sTNFRs), soluble TNF receptor 1 and 2 (sTNF-R1 and sTNF-R2). A total of 72 GD patients and 72 matched healthy individuals were recruited for this study. Serum TNF-α and sTNFRs were measured by sandwich ELISA. In our study, no significant difference was observed in TNF-α, but sTNFRs were found to be significantly elevated in GD patients compared to healthy individuals. Serum sTNFR levels were positively correlated with free triiodothyronine (FT3) and free thyroxine (FT4), and TNF-α was negatively correlated with thyroid-stimulating hormone (TSH) in the GD group. It was also shown that thyrotropin receptor antibody (TRAb) was positively correlated with TNF-α and sTNFRs. Spearman’s correlation analysis showed that only sTNF-R1 was positively correlated with complement C3. Multiple linear regression analysis suggests that serum levels of sTNF-R1 and FT4 may play an important role in the serum level of FT3. According to the median value of FT3 level, GD patients were further divided into a high FT3 group and a low FT3 group. The serum levels of sTNF-R1 in the high FT3 GD group were significantly higher than those in the low FT3 GD group. In conclusion, sTNFRs may play an important role in anti-inflammatory and immune response in GD.

Open access

Jiayang Lin, Peizhen Zhang, Yan Huang, Xueyun Wei, Dan Guo, Jianfang Liu, Deying Liu, Yajuan Deng, Bingyan Xu, Chensihan Huang, Xiaoyu Yang, Yan Lu, Lijing Jia, and Huijie Zhang

Background:

Glycoprotein non-metastatic protein B (Gpnmb) has been identified as a new cytokine secreted by hepatocyte that plays an important role in balancing lipid homeostasis and development of obesity and metabolic disorders. However, information is not available regarding the association between circulating Gpnmb and hyperthyroid in humans.

Methods:

We measured serum Gpnmb in 180 hyperthyroid patients and 82 healthy subjects that were recruited from the clinic. Of them, 46 hyperthyroid patients received thionamide treatment for 3 months.

Results:

Hyperthyroid subjects had higher levels of circulating Gpnmb than healthy controls (47.8 ± 10.1 ng/mL vs 31.0 ± 4.9 ng/mL, P < 0.001). Subjects with higher levels of serum free triiodothyronine (T3) and free thyroxine (T4) had higher levels of circulating Gpnmb. After thionamide treatment, levels of circulating Gpnmb in hyperthyroid subjects remarkably declined with significant improvement of thyroid function (P < 0.001). Furthermore, the change of circulating Gpnmb levels was significantly associated with basal metabolic rate (BMR) and thyroid hormones, including free T3 and free T4, adjusting for age, gender, smoking and BMI before thionamide treatment. In multivariable logistic regression analyses, circulating Gpnmb was significantly associated with risks of hyperthyroidism (OR (95% CI): 1.44 (1.20–1.74), P < 0.001), adjusted for age, gender, BMI, fasting glucose, HOMA-IR, LDL-cholesterol, ALT and AST.

Conclusions:

These findings indicate that circulating Gpnmb concentrations are independently associated with hyperthyroid, suggesting that circulating Gpnmb may be a predictor of risk for hyperthyroidism and can be used for therapeutic monitoring.

Open access

Brenda Anguiano, Carlos Montes de Oca, Evangelina Delgado-González, and Carmen Aceves

Thyroid hormones are involved in the development and function of the male reproductive system, but their effects on the prostate have been poorly studied. This work reviews studies related to the interrelationship between the thyroid and prostate. The information presented here is based upon bibliographic searches in PubMed using the following search terms: prostate combined with thyroid hormone or triiodothyronine (T3), thyroxine (T4), hypothyroidism, hyperthyroidism, or deiodinase. We identified and searched 49 articles directly related to the issue, and discarded studies related to endocrine disruptors. The number of publications has grown in the last 20 years, considering that one of the first studies was published in 1965. This review provides information based on in vitro studies, murine models, and clinical protocols in patients with thyroid disorders. Studies indicate that thyroid hormones regulate different aspects of growth, metabolism, and prostate pathology, whose global effect depends on total and/or free concentrations of thyroid hormones in serum, local bioavailability and the endocrine androgen/thyronine context.

Open access

Chun-feng Lu, Wang-shu Liu, Xiao-qin Ge, Feng Xu, Jian-bin Su, Xue-qin Wang, and Yan Wang

Background

Adenosine deaminase (ADA) is essential for the differentiation and maturation of lymphocytes, while lymphocytes infiltration in thyroid tissue is a vital pathological feature of Graves’ disease (GD). The aim of the present study was to compare the concentration of ADA between healthy controls (HC) and patients with GD, and evaluate the association between ADA and GD.

Methods

A total of 112 GD patients and 77 matched HC were enrolled in this study. Each participant was examined for thyroid hormones and autoantibodies, ADA concentration, and thyroid ultrasonography.

Results

Serum ADA levels in GD patients were significantly higher than that in HC subgroup (P < 0.001). In GD patients, serum ADA levels were positively associated with serum-free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), thyroid-stimulating hormone receptor antibody (TRAb) levels, and total thyroid gland volume (thyroid VolT) and negatively associated with serum thyroid-stimulating hormone receptor (TSH) levels (all P < 0.05). There were no similar correlations in the HC subgroup. Multiple linear regression analysis suggested that serum TSH, FT3, and ADA levels played an important role in serum TRAb levels.

Conclusions

Our results demonstrated that serum ADA levels were closely associated with GD.

Open access

Josi Vidart, Paula Jaskulski, Ana Laura Kunzler, Rafael Aguiar Marschner, André Ferreira de Azeredo da Silva, and Simone Magagnin Wajner

We performed a systematic review and meta-analysis to comprehensively determine the prevalence and the prognostic role of nonthyroidal illness syndrome (NTIS) in critically ill patients. We included studies that assessed thyroid function by measuring the serum thyroid hormone level and in-hospital mortality in adult septic patients. Reviews, case reports, editorials, letters, animal studies, duplicate studies, and studies with irrelevant populations and inappropriate controls were excluded. A total of 6869 patients in 25 studies were included. The median prevalence rate of NTIS was 58% (IQR 33.2-63.7). In univariate analysis, triiodothyronine (T3) and free T3 (FT3) levels in non-survivors were relatively lower than that of survivors (8 studies for T3; standardized mean difference (SMD) 1.16; 95% confidence interval (CI), 0.41–1.92; I2 = 97%; P < 0.01). Free thyroxine (FT4) levels in non-survivors were also lower than that of survivors (12 studies; SMD 0.54; 95% CI, 0.31–0.78; I2 = 83%; P < 0.01). There were no statistically significant differences in TSH levels between non-survivors and survivors. NTIS was independently associated with increased risk of mortality in critically ill patients (OR = 2.21, 95% CI 1.64.- 2.97, I2 = 65% p < 0.01) The results favor the concept that decreased thyroid function might be associated with a worse outcome in critically ill patients. Hence, the measurement of TH could provide prognostic information on mortality in adult patients admitted to ICU.

Open access

Flavia Letícia Martins Peçanha, Reinaldo Sousa dos Santos, and Wagner Seixas da-Silva

The thyroid hormones (THs), triiodothyronine (T3) and thyroxine (T4), are very important in organism metabolism and regulate glucose utilization. Hexokinase (HK) is responsible for the first step of glycolysis, catalyzing the conversion of glucose to glucose 6-phosphate. HK has been found in different cellular compartments, and new functions have been attributed to this enzyme. The effects of hyperthyroidism on subcellular glucose phosphorylation in mouse tissues were examined. Tissues were removed, subcellular fractions were isolated from eu- and hyperthyroid (T3, 0.25 µg/g, i.p. during 21 days) mice and HK activity was assayed. Glucose phosphorylation was increased in the particulate fraction in soleus (312.4% ± 67.1, n = 10), gastrocnemius (369.2% ± 112.4, n = 10) and heart (142.2% ± 13.6, n = 10) muscle in the hyperthyroid group compared to the control group. Hexokinase activity was not affected in brain or liver. No relevant changes were observed in HK activity in the soluble fraction for all tissues investigated. Acute T3 administration (single dose of T3, 1.25 µg/g, i.p.) did not modulate HK activity. Interestingly, HK mRNA levels remained unchanged and HK bound to mitochondria was increased by T3 treatment, suggesting a posttranscriptional mechanism. Analysis of the AKT pathway showed a 2.5-fold increase in AKT and GSK3B phosphorylation in the gastrocnemius muscle in the hyperthyroid group compared to the euthyroid group. Taken together, we show for the first time that THs modulate HK activity specifically in particulate fractions and that this action seems to be under the control of the AKT and GSK3B pathways.

Open access

Till Ittermann, Rehman Mehmood Khattak, Marcello RP Markus, Jens-Peter Kühn, Marie-Luise Kromrey, Giovanni Targher, Antje Steveling, Matthias Nauck, and Henry Volzke

The associations of thyroid function parameters with non-alcoholic fatty liver disease (NAFLD) and hepatic iron overload are not entirely clear. We have cross-sectionally investigated these associations among 2,734 participants of two population-based cross-sectional studies of the Study of Health in Pomerania. Serum levels of thyroid-stimulating hormone (TSH), free tri-iodothyronine (fT3), and free thyroxine (fT4) levels were measured. Liver fat content (by proton-density fat fraction; PDFF) as well as hepatic iron content (by transverse relaxation rate; R2*) were assessed by quantitative magnetic resonance imaging. Thyroid function parameters were associated with hepatic fat and iron contents by median and logistic regression models adjusted for confounding. There were no associations between serum TSH levels and liver fat content, NAFLD or hepatic iron overload. Serum fT4 levels were inversely associated with liver fat content, NAFLD, hepatic iron contents and hepatic iron overload. Serum fT3 levels as well as the fT3 to fT4 ratio were positively associated with hepatic fat, NAFLD, hepatic iron contents, but not with hepatic iron overload. Associations between fT3 levels and liver fat content were strongest in obese individuals, in which we also observed an inverse association between TSH levels and NAFLD. These findings might be the result of a higher conversion of fT4 to the biologically active form fT3. Our results suggest that a subclinical hyperthyroid state may be associated with NAFLD, particularly in obese individuals. Furthermore, thyroid hormone levels seem to be more strongly associated with increased liver fat content compared to hepatic iron content.

Open access

Ling Hu, Ting Li, Xiao-Ling Yin, and Yi Zou

Objective:

The purpose of this study was to explore the prevalence of thyroid nodules (TN) and metabolic syndrome (MS) and to analyze the correlation between TN and the components of MS.

Methods:

A total of 1526 subjects were divided into two groups: a TN group and a non-thyroid nodules (NTN) group. The height, weight, blood pressure, fasting blood glucose level, fasting plasma insulin level, serum lipid profile, uric acid level, serum thyroid-stimulating hormone (TSH) level, free triiodothyronine (FT3) level, and free thyroxine (FT4) level of each patient were measured. Insulin resistance (IR) was estimated by homeostasis model assessment of insulin resistance (HOMA-IR). Fatty liver and TN were detected by color Doppler ultrasonography.

Results:

(i) The overall prevalence of TN was 39.5%; it was significantly higher in women than in men (P < 0.01) and progressively increased with age in both sexes. (ii) The overall prevalence of MS was 25.6%; it was significantly higher in men than in women (P < 0.01) and progressively increased with age in both sexes. (iii) FT3 was significantly lower in the TN group than in the NTN group (P < 0.01). (iv) BMI, triglycerides, and HOMA-IR were higher in the TN group than in the NTN group (P < 0.05). (v) The existence of TN was significantly associated with overweight/obesity (OR = 1.03, 95% CI = 1.024–1.089), and with insulin resistance (IR) (OR = 1.98, 95% CI = 1.645–2.368), after adjusting for age and sex.

Conclusions:

The prevalence of thyroid nodules and metabolic syndrome in the Nanchang area increases with age, and overweight/obesity and IR in patients are associated with thyroid nodules.

Open access

Beibei Zhu, Yan Han, Fen Deng, Kun Huang, Shuangqin Yan, Jiahu Hao, Peng Zhu, and Fangbiao Tao

Objectives

Compared with other thyroid markers, fewer studies have explored the associations between triiodothyronine (T3), T3/free thyroxine (fT4) and glucose abnormality during pregnancy. Thus, we aimed to: (i) examine the associations of T3 and T3/fT4 with glucose metabolism indicators and (ii) evaluate, in the first trimester, the performance of the two markers as predictors of gestational diabetes mellitus (GDM) risk.

Methods

Longitudinal data from 2723 individuals, consisting of three repeated measurements of T3 and fT4, from the Man’anshan birth cohort study (MABC), China, were analyzed using a time-specific generalized estimating equation (GEE). The receiver operating characteristic curve (ROC) – area under the curve (AUC) and Hosmer–Lemeshow goodness of fit test was used to assess the discrimination and calibration of prediction models.

Results

T3 and T3/fT4 presented stable associations with the level of fasting glucose, glucose at 1h/2 h during pregnancy. T3 and T3/fT4 in both the first and second trimesters were positively associated with the risk of GDM, with the larger magnitude of association observed in the second trimester (odds ratio (OR) = 2.50, 95% CI = 1.95, 3.21 for T3; OR = 1.09, 95% CI = 1.07, 1.12 for T3/fT4). T3 ((AUC) = 0.726, 95% CI = 0.698, 0.754) and T3/fT4 (AUC = 0.724, 95% CI = 0.696, 0.753) in the first trimester could improve the performance of the prediction model; however, the overall performance is not good.

Conclusion

Significant and stable associations of T3, T3/fT4 and glucose metabolism indicators were documented. Both T3 and T3/fT4 improve the performance of the GDM predictive model.

Open access

Stine Linding Andersen, Louise Knøsgaard, Aase Handberg, Peter Vestergaard, and Stig Andersen

Objective

A high activity of the deiodinase type 2 has been proposed in overweight, obese, and smoking pregnant women as reflected by a high triiodothyronine (T3)/thyroxine (T4) ratio. We speculated how maternal adiposity and smoking would associate with different thyroid function tests in the early pregnancy.

Design

Cross-sectional study within the North Denmark Region Pregnancy Cohort.

Methods

Maternal thyroid-stimulating hormone (TSH), total T4 (TT4), total T3 (TT3), free T4 (fT4), and free T3 (fT3) were measured in stored blood samples (median gestational week 10) by an automatic immunoassay. Results were linked to nationwide registers, and live-birth pregnancies were included. The associations between maternal adiposity (overweight or obese), smoking, and log-transformed TSH, fT3/fT4 ratio, and TT3/TT4 ratio were assessed using multivariate linear regression and reported as adjusted exponentiated β coefficient (aβ) with 95% CI. The adjusted model included maternal age, parity, origin, week of blood sampling, and diabetes.

Results

Altogether 5529 pregnant women were included, and 40% were classified with adiposity, whereas 10% were smoking. Maternal adiposity was associated with higher TSH (aβ 1.13 (95% CI 1.08–1.20)), whereas maternal smoking was associated with lower TSH in the early pregnancy (0.875 (0.806–0.950)). Considering the T3/T4 ratio, both maternal adiposity (fT3/fT4 ratio: 1.06 (1.05–1.07); TT3/TT4 ratio: 1.07 (1.06–1.08)) and smoking (fT3/fT4 ratio: 1.07 (1.06–1.09); TT3/TT4 ratio: 1.10 (1.09–1.12)) were associated with a higher ratio.

Conclusions

In a large cohort of Danish pregnant women, adiposity and smoking showed opposite associations with maternal TSH. On the other hand, both conditions were associated with a higher T3/T4 ratio in early pregnancy, which may reflect altered deiodinase activity.