Thyroid Research最新文献

Aim: Studies have shown that renal hypertrophy seen in experimental hyperthyroidism induced by thyroxine (T4) is due to angiotensin (Ang) II. However, other renal effects of Ang II in experimental hyperthyroidism have not been investigated. In addition, Ang 1-7 is believed to be protective against renal injury, but its possible role in thyroxine-induced renal injury is not known. The aim of this study is to elaborate the role of Ang II in thyroxine-induced renal injury and the possible protective role of Ang 1-7. We hypothesize that Ang 1-7 will be as protective against thyroxine-induced renal injury as the use of an ACE inhibitor or an Ang II receptor blocker.

Methods: Adult Sprague Dawley rats were used in this study and were divided into 5 groups: (1) Control (treated with vehicle), (2) Treated with thyroxine (T4, 100 µg/kg), (3) Treated with T4 and Ang 1-7 (500 µg/kg), (4) Treated with T4 and captopril (20 mg/kg), and (5) Treated with T4 and losartan (10 mg/kg). Parameters tested after fourteen days of treatment were creatinine clearance, protein excretion rate, glomerular volume, renal ACE1 and ACE2 protein expression. Data were compared using One-way-ANOVA followed by Tukey's HSD post hoc test.

Results: Thyroxine caused glomerular hypertrophy and proteinuria but had no effect on glomerular filtration rate (GFR). Glomerular hypertrophy was prevented by losartan and captopril, but not by Ang 1-7. Captopril and losartan had no effect on GFR; however, Ang 1-7 caused an increase in GFR in T4-treated rats. The increase in protein excretion rate was prevented by losartan but not by captopril or Ang 1-7. Renal expression of ACE1 protein was not altered in any of the treatment groups except in captopril treated rats were ACE1 expression was increased. Renal ACE2 protein expression was only increased in T4-losartan-treated rats and not affected by any of the other treatments.

Conclusion: We conclude that losartan was more protective than captopril against thyroxine-induced renal changes while Ang 1-7 offered no protection.

Background: Differentiated thyroid cancer (DTC) requires long-term follow-up due to the risk of delayed recurrence. Follow-up surveillance involves serial neck ultrasound (US) and thyroglobulin (Tg); however, the optimal frequency and diagnostic performance of neck US outside of specialized thyroid cancer centres in higher risk patients is not well defined. We sought to evaluate the diagnostic performance of US and serial Tg in advanced stage DTC.

Methods: We retrospectively reviewed our thyroid cancer database for patients with stage III and IV DTC from 2006 to 2018, total thyroidectomy, and at least 2 years follow-up to assess recurrence rates. Those with hemi-thyroidectomy or anti-Tg antibodies were excluded. Diagnostic performance of US and Tg were assessed using a composite reference standard of follow-up imaging and pathology. All relevant US were reviewed by a blinded expert radiologist for uniformity.

Results: Of 136 included patients (91 females, mean age 58.9), 26 (19%) had recurrence of DTC over median follow-up of 6.6 years (IQR 5.3-9.3). The sensitivity and specificity of US in diagnosing cervical recurrence were 73.3% (95% CI 0.51-0.96) and 68.3% (95% CI 0.60-0.77) based on historical reports, respectively, and 80% (95% CI 0.60-1.00) and 87.8% (95% CI 0.82-0.93) based on blinded expert review, respectively. Tg had a sensitivity of 95.5% (95% CI 0.89-1.0) and specificity of 96.2% (95% CI 0.92-0.99) in detecting cervical recurrence or distant metastases. False positive US findings on historical US and subsequent review occurred in 38 (28%) and 15 (11%) patients, respectively, while 5 (3.6%) had false positive Tg results.

Conclusion: Serial Tg has better sensitivity and specificity than US for detecting recurrence of advanced stage DTC. Furthermore, re-interpretation of abnormal findings using structured US reporting with a subspecialized reader may improve diagnostic performance of US and improve its utility in clinical care.

Objective: To investigate the sonographic characteristics of thyroid nodules with a halo, explore the value of contrast-enhanced ultrasound (CEUS) combined with fine needle aspiration (FNA) in identifying nodules with a halo, and predict the risk of metastasis by analyzing the pathological features of the halo.

Methods: A retrospective analysis was conducted on 185 postoperative cases of thyroid nodules accompanied by halos between January 2019 and December 2022. After describing the ultrasound characteristics of the thyroid nodules and their halos, all patients were divided into three groups, the first group (group I = CEUS only) of patients underwent CEUS, the second group (group II = CEUS + FNA) underwent FNA based on the first group, and the third group (group III = FNA only) underwent FNA directly. The CEUS and FNA results were graded using the Chinese Thyroid Imaging Report and Data System (C-TIRADS) and Bethesda Reporting System for Thyroid Cytopathology, respectively. Those graded below C-TIRADS 4b or Bethesda IV were defined as benign, and the results of FNA were referenced when the two methods were combined. The surgical pathology results were used as the gold standard. We plotted working curves to compare the diagnostic efficacy of CEUS and FNA alone and in combination in the diagnosis of thyroid nodules with halos. The pathological features of the halo were analyzed and the number of patients with cervical lymph node metastases was recorded.

Results: One hundred and sixty patients met the requirements. Benign nodules were mainly characterized by a thin (0.75 ± 0.31 mm) and uniform halo with good integrity, while malignant nodules had a thicker (1.48 ± 0.51 mm) halo with uneven and irregular margins (P < 0.05). The sensitivity and specificity were highest when the cutoff value was 1.09 mm, with 76.08% and 84.29%, respectively. The halos of benign nodules were mostly hyper- or iso-enhanced, whereas the halos of malignant nodules were predominantly hypo-enhanced (P < 0.05). The areas under the curve (AUCs) for CEUS, FNA, and CEUS + FNA were 0.751(95% CI = 0.642-0.841), 0.863(95% CI = 0.767-0.929), and 0.918(95% CI = 0.834-0.967), respectively. Cervical lymph node metastasis occurred in only 13 (11.5%) malignant nodes with halos. The primary pathological components of the halo around malignant nodules were almost reactive hyperplastic fibrous tissue.

Conclusion: The halo surrounding malignant thyroid nodules is thicker, with uneven and irregular margins, and shows hypo-enhancement on CEUS. Combining CEUS with FNA improves the diagnostic efficacy of thyroid nodules with halos. The reactive hyperplastic fibrous halo may be one of the reasons why malignant nodules are less likely to metastasize.

Introduction: Activation of the MAPK pathway by genetic mutations (such as BRAF and RET) initiates and accelerates the growth of papillary thyroid carcinoma (PTC). However, the correlation between genetic mutations and clinical features remains to be established. Therefore, this study aimed to retrospectively analyze major genetic mutations, specifically BRAF mutations and RET rearrangements, and develop a treatment algorithm by comparing background and clinical characteristics.

Method: One hundred thirteen patients with primary PTC were included in this study. BRAF mutations were detected via Sanger sequencing and RET rearrangements were detected via fluorescence in situ hybridization (FISH) analysis, and reverse transcription polymerase chain reaction (RT-PCR). The patients were categorized into two groups based on the presence of BRAF mutations and RET rearrangements and their clinical characteristics (age, sex, TNM, stage, extratumoral extension, tumor size, unifocal/multifocal lesions, vascular invasion, differentiation, chronic thyroiditis, preoperative serum thyroglobulin level, and ¹⁸F-fluorodeoxyglucose (FDG) uptake) were compared subsequently.

Result: After excluding unanalyzable specimens, 80 PTC patients (22 males and 58 females, mean age: 57.2 years) were included in the study. RET rearrangements were positive in 8 cases (10%), and BRAF mutation was positive in 63 (78.6%). The RET rearrangement group was significantly associated with younger age (p = 0.024), multifocal lesion (p = 0.048), distant metastasis (p = 0.025) and decreased ¹⁸F-fluorodeoxyglucose uptake (p < 0.001). The BRAF mutation group was significantly associated with unifocal lesions (p = 0.02) and increased ¹⁸F-FDG uptake (p = 0.004).

Conclusion: In this study, an increase in M classification cases was found in the RET rearrangements group. However, genetic mutations were not associated with the clinical stage, and no factors that could be incorporated into the treatment algorithm were identified.

Background: Our previous study demonstrated that long intergenic noncoding RNA 02454 (LINC02454) may act as an oncogene to promote the proliferation and inhibit the apoptosis of papillary thyroid cancer (PTC) cells. This study was designed to investigate the mechanisms whereby LINC02454 is related to PTC tumorigenesis.

Methods: Thyroid cancer RNA sequence data were obtained from The Cancer Genome Atlas (TCGA) database. Weighted gene coexpression network analysis (WGCNA) was applied to identify modules closely associated with PTC. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to identify the key pathways, and the maximal clique centrality (MCC) topological method was used to identify the hub genes. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to compare expression levels of key genes between PTC samples and normal samples and explore the prognostic value of key genes. The key genes were further validated with GEO dataset.

Results: The top 5000 variable genes were investigated, followed by an analysis of 8 modules, and the turquoise module was the most positively correlated with the clinical stage of PTC. KEGG pathway analysis found the top two pathways of the ECM - receptor interaction and MAPK signaling pathway. In addition, five key genes (FN1, LAMB3, ITGA3, SDC4, and IL1RAP) were identified through the MCC algorithm and KEGG analysis. The expression levels of the five key genes were significantly upregulated in thyroid cancer in both TCGA and GEO datasets, and of these five genes, FN1 and ITGA3 were associated with poor disease-free prognosis.

Conclusions: Our study identified five key genes and two key pathways associated with LINC02454, which might shed light on the underlying mechanism of LINC02454 action in PTC.

Background: Hypothyroidism, a common worldwide syndrome caused by insufficient thyroid hormone secretion, affects number of people at different ages. Artemisinin (ART), a well-known effective agent in the treatment of malaria, also has anti-oxidative stress functions in various diseases. The L1 cell adhesion molecule exerts multiple protective roles in diseased systems. The aim of the present study was to evaluate the role of ART in adult male hypothyroid rats and the underlying mechanisms.

Methods: The propylthiouracil (PTU) rat model was treated with or without 5 mg/kg ART and with or without L1 short-interfering RNA (siRNA), followed by the experiments to determine the effect of ART on thyroid function, depression and anxiety, cognition impairments, liver, kidney and heart functions, and oxidative stress.

Results: In the current study, it was shown that ART can ameliorate thyroid function, mitigate depression and anxiety symptoms, attenuate cognition impairments, improve liver, kidney and heart functions, and inhibit oxidative stress; however, the effects exerted by ART could not be observed when L1 was silenced by L1 siRNA.

Conclusion: These results indicated that ART can upregulate the L1 cell adhesion molecule to ameliorate thyroid function and the complications in adult male hypothyroid rats, laying the foundation for ART to be a novel strategy for the treatment of hypothyroidism.

Background: It is believed that loss of p53 function plays a crucial role in the progression of well to poorly differentiated thyroid cancers including anaplastic thyroid carcinoma (ATC). Given the poor prognosis of ATC due to its strong therapeutic resistance, there is a need to establish new therapeutic targets to extend the survival of ATC patients. Activating transcription factor 3 (ATF3) can inhibit the oncogenic activity of mutant p53 and, as a result, contribute to tumor suppression in several TP53-mutated cancers. Herein, we demonstrate that the ectopic overexpression of ATF3 leads to the suppression of oncogenic mutant p53 activity in chemo-resistant 8305 C thyroid cancer cells harboring R273C p53 gene mutation.

Methods: The biological behavior of 8305 C cells was assessed pre- and post-transfection with pCMV6-ATF3 plasmid using MTT assay, fluorescent microscopy, cell cycle, and annexin V/PI flow cytometric analysis. The effect of ectopic ATF3 overexpression on the cellular level of p53 was examined by western blotting assay. The mRNA expression levels of TP53, TAp63, ΔNp63, and SHARP1 were evaluated in ectopic ATF3-expressing cells compared to controls.

Results: The overexpression of ATF3 in 8305 C thyroid cancer cells significantly decreased cell viability and induced apoptosis and cell cycle arrest in vitro. The immunoblotting of p53 protein revealed that ATF3 overexpression significantly increased the level of mutant p53 in 8305C cells compared to mock-transfected control cells. Additionally, elevated mRNA levels of TAp63 and SHARP1 and a decreased mRNA level of ΔNp63 were observed in PCMV6-AC-ATF3-transfected 8305 C cells with significant differences compared to the mock and untreated cells.

Conclusion: In light of our findings, it is evident that therapeutic strategies aimed at increasing ATF3 expression or enhancing the interaction between ATF3 and mutant p53 can be a promising approach for the treatment of p53-mutated metastatic thyroid cancer.

Background: Understanding the relationship of thyroid hormones with the development of chronic kidney disease (CKD) has important clinical implications for managing patients with both thyroid and kidney dysfunction. In this review, our purpose was to provide a thorough comprehension of the interplay between thyroid hormones, thyroid dysfunctions, and CKD. While there is evidence linking thyroid hormone levels to renal diseases, the association between thyroid hormones, specifically within the normal range, and the risk of CKD incidence is still a subject of debate. The Google Scholar, PubMed, Scopus, and Web of Science, were searched using the medical subject heading (MeSH) terms for the relevant keywords up to December 2023.

Conclusion: Based on the review, the development of CKD is more consistently associated with higher serum TSH and thereafter lower serum free T3 levels; however, its association with free T4 is more controversial. Furthermore, subclinical and overt hypothyroidisms were considerably associated with incident CKD. Hyperthyroidism and Hashimoto thyroiditis might increase the risk of CKD.

Background: The incidence of hypothyroidism following hemithyroidectomy and risk factors associated with its occurrence are not completely understood. This systematic review investigated the incidence and risk factors for hypothyroidism, thyroxine supplementation following hemithyroidectomy as well as the course of post-operative hypothyroidism, including the time to hypothyroidism and incidence of transient hypothyroidism.

Methods: Searches were conducted in MEDLINE, EMBASE, Scopus, and Cochrane library for studies reporting the incidence of hypothyroidism or thyroxine supplementation following hemithyroidectomy.

Results: Sixty-six studies were eligible for inclusion: 36 reported risk factors, and 27 reported post-operative course of hypothyroidism. Median follow-up was 25.2 months. The pooled incidence of hypothyroidism was 29% (95% CI, 25-34%; P<0.001). Transient hypothyroidism occurred in 34% of patients (95% CI, 21-47%; P<0.001). The pooled incidence of thyroxine supplementation was 23% (95% CI, 19-27%; P<0.001), overt hypothyroidism 4% (95% CI, 2-6%, P<0.001). Risk factors for development of hypothyroidism included pre-operative thyroid stimulating hormone (TSH) (WMD, 0.87; 95% CI, 0.75-0.98; P<0.001), TSH ≥ 2 mIU/L (RR, 2.87; 95% CI, 2.43-3.40; P<0.001), female sex (RR, 1.19; 95% CI, 1.08-1.32; P=0.007), age (WMD, 2.29; 95% CI, 1.20-3.38; P<0.001), right sided hemithyroidectomy (RR, 1.35; 95% CI, 1.10-1.65, P=0.003), the presence of autoantibodies anti-TPO (RR, 1.92; 95% CI, 1.49-2.48; P<0.001), anti-Tg (RR, 1.53; 95% CI, 1.40-1.88; P<0.001), and Hashimoto's thyroiditis (RR, 2.05; 95% CI, 1.57-2.68; P=0.001).

Conclusion: A significant number of patients will develop hypothyroidism or require thyroxine following hemithyroidectomy. An awareness of patient risk factors and postoperative thyroid function course will assist in counselling patients on their risk profile and guiding management.

Background: Despite the presence of evidence that establishes a strong correlation between oxidative stress and thyroid cancer, there exists a scarcity of research that investigates the specific role of glutathione as an important antioxidant in this particular context. The objective of this study was to assess the altered balance of oxidative stress in cases of thyroid cancer, which includes both papillary thyroid carcinoma (PTC) and micro PTC (mPTC), by examining and comparing the total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), reduced glutathione (GSH), oxidized glutathione (GSSG), and GSSG/GSH ratio with those of individuals diagnosed with multinodular goiter (MNG) as well as Healthy subjects.

Materials and methods: Plasma samples were collected from 92 patients (23 mPTC, 23 PTC, 23 MNG, 23 Healthy). The levels of TAC, TOS, GSH, and GSSG were measured using a commercial assay kits, and the OSI and GSSG/GSH ratio were calculated for each sample. Statistical analyses were performed to compare the oxidative stress between the groups.

Results: The plasma levels of TOS were significantly higher in the mPTC, PTC, and MNG groups compared to the Healthy individuals (p < 0.05). The OSI in the mPTC and PTC groups showed a significant increase compared to the Healthy group (p < 0.05). The levels of GSH in mPTC and PTC were markedly lower compared to the Healthy subjects (p < 0.01). Interestingly, the concentration of GSH in mPTC was found to be considerably lower than in PTC and MNG patients (p < 0.01).

Conclusion: These findings indicate that GSH may be a useful biomarker for evaluating oxidative stress and antioxidant system status in patients with PTC, especially mPTC. Low levels of GSH may indicate increased levels of oxidative stress, which may contribute to the development and progression of mPTC to PTC.