Weight Gain and Body Composition Changes during the Transition of Thyroid Function in Patients with Graves' Disease Undergoing Radioiodine Treatment.

Objective: This study aimed at investigating the dynamic changes in the body weight and body composition in a group of patients with Graves' disease undergoing radioiodine therapy. Methods: Seventeen patients with Graves' disease undergoing 131I treatment and forty-three euthyroid controls were recruited. Body weight, BMI, and body composition via bioelectrical impedance were measured for the participants at baseline, hypothyroid stage, and euthyroid stage. Results: Body weight increased significantly during the transition from hyperthyroidism to euthyroidism. However, there were no significant changes in body fat %, lean mass %, and bone mineral %. The body weight of 9 patients at the euthyroid stage exceeded their premorbid weight, while the remaining 8 patients' weight did not exceed the premorbid weight. In the group with excessive weight gain, both body fat and lean mass increased significantly. However, in the group without excessive weight gain, only lean mass increased significantly. The patients with excessive weight gain had significantly higher body fat %, while lower lean mass % compared to patients without excessive weight gain at baseline and at the euthyroid stage. Moreover, body fat % of patients with excessive weight gain was significantly higher than that of controls, while lean mass % was significantly lower than that of controls. There was no difference of body fat % and lean mass % between patients without excessive weight gain and controls. Conclusion: 131I treatment caused significant weight gain in patients with Graves' disease. An undesirable body composition at presentation may be a risk factor for excessive weight gain after hyperthyroidism treatment.

Effect of thyroid function on pre-ß1 high-density lipoprotein levels in patients with Graves' disease undergoing radioiodine treatment.

CONTEXT: The metabolism of HDL is altered in thyroid dysfunctions. Preß-1 HDL is a very small discoidal precursor HDL and promotes cholesterol efflux via ABCA1. The effects of thyroid dysfunctions on pre-ß1 HDL are unknown. Thyroid hormone regulates ANGPTL3 expression, which may participate in HDL metabolism in thyroid dysfunctions. OBJECTIVE: To determine the variation of HDL subfractions, especially preß-1 HDL in thyroid dysfunctions, and whether ANGPTL3 mediates the effect of thyroid function on HDL metabolism. METHODS: We recruited 26 patients with Graves' disease undergoing radioiodine treatment. They were evaluated at three time points: at baseline, when they were hypothyroid after radioiodine treatment, and when they were on stable levothyroxine replacement and euthyroid. RESULTS: The concentrations of smaller HDL particles Preß-1 HDL and HDL3 were highest at the hyperthyroid state, and lowest at the hypothyroid state. While the larger HDL particles HDL2 and HDL1 changed just the opposite. Preß1-HDL and HDL3 were positively correlated to fT3 and fT4, while were negatively correlated to TSH. In contrast, HDL1 was negatively associated with fT3 and fT4, while was positively associated with TSH. The correlations between thyroid hormones and HDL subfractions remained significant after adjusting for ANGPTL3. CONCLUSIONS: There is a shift form smaller HDL particles pre-ß1 HDL and HDL3 to larger HDL particles HDL2 and HDL1 in hypothyroidism, while the change is just the opposite in hyperthyroidism. In future, cholesterol efflux capacity should be measured to determine if the function of HDL particles also changes with the shifting of HDL subfractions.

TNRC6C Functions as a Tumor Suppressor and Is Frequently Downregulated in Papillary Thyroid Cancer.

Our previous study found that trinucleotide repeat containing adaptor 6C (TNRC6C) may act as a tumor suppressor in papillary thyroid cancer (PTC). In this study, we aimed to confirm the effect of TNRC6C on PTC and investigate the underlying molecular mechanism. The difference of mRNA level of TNRC6C between PTC tissue and noncancerous thyroid tissue and the association of expression level of TNRC6C with clinicopathological features of PTC were analyzed using TCGA data. Immunohistochemical assay was performed to detect the protein expression of TNRC6C in PTC and its adjacent noncancerous tissue. Cell proliferation, migration, invasion, and apoptosis were analyzed after knockdown or overexpression of TNRC6C in BCPAP cells. RNA-sequencing was performed to find the target genes of TNRC6C, and potential targets were validated in BCPAP and TPC1 cells. Our results showed that TNRC6C was downregulated in PTC, and lower expression level of TNRC6C was associated with worse clinicopathological features. Overexpression of TNRC6C significantly inhibited proliferation, migration, and invasion of BCPAP cells and promoted its apoptosis, while knockdown of TNRC6C acted the opposite role. By analyzing RNA-sequencing data and TCGA data, 12 genes (SCD, CRLF1, APCDD1L, CTHRC1, PTPRU, ALDH1A3, VCAN, TNC, ECE1, COL1A1, CAMK2N2, and MMP14) were considered as potential target genes of TNRC6C, and most of them were associated with clinicopathological features of PTC in TCGA. All of them except CAMK2N2 were significantly downregulated after overexpressing TNRC6C. Our study demonstrated that TNRC6C functions as a tumor suppressor in PTC and may serve as a useful therapeutic target and prognostic marker for PTC patients.

Impact of Hypothyroidism on Echocardiographic Characteristics of Patients With Heart Valve Disease: A Single-Center Propensity Score-Based Study.

Background: Hypothyroidism is known to be correlated with multiple heart diseases. However, the influence of hypothyroidism on the patients with heart valve disease (HVD) is still unclear. The purpose of our study was to investigate the impact of hypothyroidism on echocardiographic characteristics of patients with heart valve disease. Methods: We conducted a retrospective cohort study which included 2,128 patients with HVD, and they were divided into euthyroid, subclinical hypothyroidism (SCHypoT), and overt hypothyroidism (OHypoT) group. Echocardiographic characteristics before and after valve surgery between groups were compared by using propensity score (PS) analysis. Kaplan-Meier analysis was used to compare the percent of recovery of left atrial (LA) enlargement between groups. Results: Overall, 463 patients had hypothyroidism (404 SCHypoT patients and 59 OHypoT patients), and 1,665 patients were euthyroid. At baseline, hypothyroidism was associated with significantly higher left atrial diameter (LAD), interventricular septum thickness, left ventricular posterior wall thickness, pulmonary artery systolic pressure, and lower left ventricular ejection fraction. After valve surgery, only LAD remained significantly higher in the patients with hypothyroidism. Additionally, patients with hypothyroidism had a significantly lower recovery rate of LA enlargement after valve surgery compared with euthyroid patients. Conclusion: Hypothyroidism was associated with a larger LAD in patients with HVD before and after surgery, which may suggest that hypothyroidism is a risk factor of LA enlargement of HVD. Besides, hypothyroidism was associated with a significantly lower recovery rate of LA enlargement after valve surgery.

Lipoprotein(a) concentration is associated with risk of type 2 diabetes and cardiovascular events in a Chinese population with very high cardiovascular risk.

PURPOSE: Evidences have shown that elevated lipoprotein(a) [Lp(a)] levels were associated with a lower risk of type 2 diabetes, but a higher risk of cardiovascular events in general populations. We aim to demonstrate the effect of Lp(a) concentrations on type 2 diabetes and cardiovascular events in a Chinese population with very high cardiovascular risk. METHODS: Seven hundred ninety-eight participants who underwent coronary angiography between March and November 2013 with normal glucose metabolism were followed up from July to December 2018. RESULTS: Five hundred thirty-five participants completed follow-up, and 395 of them had blood glucose data. Among 395 participants with blood glucose data, a total of 28 incident type 2 diabetes were identified during a median follow-up period of 4.42 years. Compared with the patients in the lowest tertile of Lp(a), the multifactorial adjusted HR for type 2 diabetes was 0.29 in the highest tertile (95% confidence intervals (CI) 0.10-0.89; P for trend = 0.03). Among 535 patients who completed follow-up, a total of 80 cases of major adverse cardiovascular events (MACE) were identified during a median follow-up period of 5.08 years. Compared with the patients in the lowest tertile of Lp(a), the multifactorial adjusted HR for MACE was 1.95 in the highest tertile (95% CI 1.05-3.65; P for trend = 0.03). CONCLUSIONS: Elevated Lp(a) levels were associated with a lower risk of type 2 diabetes, but a higher risk of cardiovascular events in a Chinese population with very high cardiovascular risk.

Identification of gene co-expression modules and hub genes associated with lymph node metastasis of papillary thyroid cancer.

Papillary thyroid cancer (PTC) is the most prevalent histological type among thyroid cancers, and some patients are at a high risk for recurrent disease or even death. Identification for the potential biomarkers of PTC may contribute to early discovery of recurrence and treatment. In The Cancer Genome Atlas (TCGA) database, we obtained the information of RNA sequence data and clinical characteristics of PTC. Weighted gene co-expression network analysis (WGCNA) was performed to construct gene co-expression networks and investigate the relationship between modules and clinical traits. Finally, we constructed 16 co-expression modules in 10,428 genes, and three key modules (darkturquoise, lightyellow, and red) associated with tumor N grade were identified. The results of functional annotation indicated that the darkturquoise module was primarily enriched in the regulation of the extracellular matrix (ECM), collagen metabolism, and cell adhesion, the lightyellow module was primarily enriched in the mitochondrial function regulation and energy synthesis, and the red module was primarily enriched in the process of cell junction, apoptosis, and inflammatory response, suggesting their significant role in the progression of PTC. In addition, the hub genes in the three modules were identified and screened for differentially expressed genes (DEGs). Relapse-free survival analyses found that 11 genes (KCNQ3, MET, FN1, ITGA3, RUNX1, ITGA2, PERP, GCSH, FAAH, NGFRAP1, and HSPA5) may play a pivotal role in PTC relapse. In general, our research revealed the key co-expression modules and identified several prognostic biomarkers, which provides some new insights into the lymph node metastasis of PTC.