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Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
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Background
Filamin A (FLNA) is a member of the filamin family and has been found to be critical for the progression of several cancers. However, its biological function in papillary thyroid cancer (PTC) remains largely unexplored.
Methods
Data from The Cancer Genome Atlas (TCGA) databases were utilized to analyze the FLNA expression level and its influence on the clinical implications of patients with PTC. Gene Expression Omnibus (GEO) and qRT-PCR was used to verify the expression levels of FLNA in PTC. Kaplan–Meier survival analysis was conducted to evaluate the prognostic value of FLNA in PTC. Transwell assays and wound healing were performed to examine the biological function of FLNA knockdown in PTC cells. Gene set enrichment analysis (GSEA) and Western blotting were conducted to investigate the potential mechanisms underlying the role of FLNA in PTC progression. In addition, the relationship between FLNA expression and the tumor immune microenvironment (TME) in PTC was explored.
Results
FLNA was significantly upregulated in PTC tissues. High expression levels of FLNA was correlated with advanced TNM stage, T stage, and N stage, as well as poor disease-free interval (DFI) and progression-free interval (PFI) time in PTC patients. Moreover, we found that FLNA knockdown inhibited the migration and invasion of PTC cells. Mechanistically, FLNA knockdown inhibited epithelial–mesenchymal transition (EMT) in PTC and affected the activation of the FAK/AKT signaling pathway. In addition, FLNA expression was associated with TME in PTC.
Conclusion
FLNA may be regarded as a new therapeutic target for PTC patients.
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While subclinical or overt hypothyroidism are common in Down syndrome (DS); Graves’ disease (GD) is rare (ranges 0.6–3%). We aimed to evaluate the clinical features, course, and treatment of GD in children with DS and compare them with those without DS. Among 161 children with GD, 13 (8 female, 5 male) had DS (8%). Data were collected retrospectively from patients’ medical records. The mean age at diagnosis was 10.6 ± 4.5 years, with a female-to-male ratio 1.6:1. The main symptoms were weight loss (n = 6), increased irritability (n = 3), and increased sweating (n = 3). None had orbitopathy. Seven of 11 patients with a thyroid ultrasound at diagnosis had a goitre. On admission, all had thyroid-stimulating hormone (TSH) <0.01 mU/L (normal range (NR): 0.51–4.30), free triiodothyronine, free thyroxine (mean ± s.d .), and thyrotrophin receptor antibodies (median, range) were 22.2 ± 10.2 pmol/L (NR: 3.5–8.1), 50.2 ± 18.7 pmol/L (NR 12.6–20.9), and 17.0 (2.89–159.0) U/L (NR <1), respectively. Patients were treated either with methimazole (n = 10) or carbimazole (n = 3), a dose of 0.54 ± 0.36 mg/kg/day. The treatment was ‘block and replace’ in ten patients and ‘dose titration’ in three patients, with a mean duration of 43.4 ± 11.0 months. Of 13 patients, four are still receiving primary treatment, three are in remission, one patient had two medically treated recurrences, three underwent surgery without complications, and two patients were lost to follow-up. Our data show that the clinical course of GD in patients with DS was similar to those without DS and suggest that a prolonged medical therapy should be the preferred option.
Department of Diabetes & Endocrinology, Skåne University Hospital, Malmö, Sweden
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Department of Diabetes & Endocrinology, Skåne University Hospital, Malmö, Sweden
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Department of Ophthalmology, Skåne University Hospital, Malmö, Sweden
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Department of Diabetes & Endocrinology, Skåne University Hospital, Malmö, Sweden
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Graves’ disease (GD) and Graves’ ophthalmopathy (GO) are complex autoimmune diseases. This study delved into the impact of cigarette smoke extract (CSE), simvastatin, and/or diclofenac on peripheral blood mononuclear cells (PBMCs). Specifically, we explored alterations in IL-1B, IL-6, PTGS2 expression, B- and T-lymphocyte proliferation, and Immunoglobulin G (IgG) production. We also assessed IGF1’s influence on B- and T-lymphocyte proliferation. PBMCs from Graves’ patients were exposed to CSE with/without simvastatin and/or diclofenac. Gene and protein expression was compared with untreated PBMCs. B- and T-lymphocyte proliferation was assessed following IGF1 treatment. PBMCs exposed to CSE exhibited increased expression of IL-1B (6-fold), IL-6 (10-fold), and PTGS2 (5.6-fold), and protein levels of IL-1B (4-fold), IL-6 (16-fold) and PGE2 (3.7-fold) compared with untreated PBMCs. Simvastatin and/or diclofenac downregulated the expression of PTGS2 (0.5-fold), IL-6 (0.4-fold), and IL-1B (0.6-fold), and the protein levels of IL-1B (0.6-fold), IL-6 (0.6-fold), and PGE2 (0.6-fold) compared with untreated PBMCs. CSE exposure in PBMCs increased the proliferation of B and T lymphocytes by 1.3-fold and 1.4-fold, respectively, compared with untreated. CSE exposure increased IgG (1.5-fold) in supernatant from PBMCs isolated from Graves’ patients. IGF1 treatment increased the proliferation of B and T lymphocytes by 1.6-fold. Simvastatin downregulated the proliferation of B and T lymphocytes by 0.7-fold. Our study shows that CSE significantly upregulated the expression and release of the inflammatory markers PTGS2, IL-6 and IL-1B,the IgG levels, and the proliferation of B and T lymphocytes. Additionally, IGF1 increased the proliferation of B and T lymphocytes. Finally, these effects were decreased by diclofenac and/or simvastatin treatment.
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Papillary thyroid carcinoma (PTC) with marked cystic formation (CPTC) is not a subtype of PTC, and its clinical characteristics have not been fully investigated. This study aimed to clarify the clinical and pathological characteristics of CPTC and propose important indicators for its clinical management. Thirty-three CPTC nodules with cystic areas occupying >50% of their volume were examined. Two matched controls (MCs) were prepared, one with tumor diameter matched for whole tumor diameter (WTD) of CPTCs and the other with tumor diameter matched for solid area diameter (SAD) of CPTCs. The mean age of patients with CPTC was 55.2 years significantly older than that in SAD-MCs. Of the CPTCs, 69.7% were classified as highly suspicious by ultrasonography, and the prevalence was lower than that in WTD-MCs (88.9%) and SAD-MCs (91.5%). Total thyroidectomy was performed in 69.7% of CPTC cases, which was significantly less frequent than that in WDT-MCs (91.7%) and similar to that in SAD-MCs (76.1%). Histologically, CPTCs exhibited two characteristic findings: invasion from the solid area into the surrounding normal thyroid tissue and granulation tissue around the cystic wall. The frequencies of the cases with pathological lateral node metastasis, extrathyroidal extension, and Ki-67 labeling index ≥5% in CPTCs were significantly lower than those in WTD-MCs and relatively similar to those in SAD-MCs. In the surgical strategy and prognosis of CPTC, the evaluation of tumor size should be based on SAD rather than on WTD. We advocate measuring not only WTD but also SAD in CPTC.
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Objective
Hashimoto’s thyroiditis is an inflammatory disease, and research suggests that a low-carbohydrate diet may have potential anti-inflammatory effects. This study aims to utilize Dixon-T2-weighted imaging (WI) sequence for a semi-quantitative assessment of the impact of a low-carbohydrate diet on the degree of thyroid inflammation in patients with Hashimoto’s thyroiditis.
Methods
Forty patients with Hashimoto’s thyroiditis were recruited for this study and randomly divided into two groups: one with a normal diet and the other with a low-carbohydrate diet. Antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) were measured for all participants. Additionally, thyroid water content was semi-quantitatively measured using Dixon-T2WI. The same tests and measurements were repeated for all participants after 6 months.
Results
After 6 months of a low-carbohydrate diet, patients with Hashimoto’s thyroiditis showed a significant reduction in thyroid water content (94.84 ± 1.57% vs 93.07 ± 2.05%, P < 0.05). Concurrently, a decrease was observed in levels of TPOAb and TgAb (TPOAb: 211.30 (92.63–614.62) vs 89.45 (15.9–215.67); TgAb: 17.05 (1.47–81.64) vs 4.1 (0.51–19.42), P < 0.05). In contrast, there were no significant differences in thyroid water content or TPOAb and TgAb levels for patients with Hashimoto’s thyroiditis following a normal diet after 6 months (P < 0.05).
Conclusion
Dixon-T2WI can quantitatively assess the degree of thyroid inflammation in patients with Hashimoto’s thyroiditis. Following a low-carbohydrate diet intervention, there is a significant reduction in thyroid water content and a decrease in levels of TPOAb and TgAb. These results suggest that a low-carbohydrate diet may help alleviate inflammation in patients with Hashimoto’s thyroiditis.
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Background
The most important part of the follow-up of differentiated thyroid carcinoma (DTC) is the measurement of serum thyroglobulin (Tg). An increase of Tg levels indicates likely tumor recurrence. According to the guidelines of the European Society of Medical Oncology (ESMO), the follow-up should consist of serum Tg assays and a neck ultrasound, while the American Thyroid Association (ATA) recommends serum Tg assays, neck ultrasounds, and a diagnostic radioiodine whole-body scan (WBS) if non-stimulated Tg is greater than 10 ng/mL or if Tg is rising. This study questions the necessity of a diagnostic WBS in patients with low stimulated Tg levels during the initial follow-up.
Design
This study is a retrospective data analysis.
Methods
The data of 185 patients, who were in regular treatment and aftercare between 2015 and 2018 at the Department of Nuclear Medicine in Vienna, as well as the data of 185 patients who were treated in Tbilisi between 2015 and 2019, were analyzed.
Results
There was a highly significant relationship between low stimulated Tg levels (<0.5 ng/mL) and the outcome of the diagnostic WBS at the first follow-up (χ 2 = 14.7, P < 0.001). In total, 31 out of 370 patients (8.4%) had positive findings in the diagnostic WBS. Seventy-five of 370 patients (19.74%) had stimulated Tg levels >0.5 ng/mL.
Conclusion
Our data suggest that the first follow-up, 4–12 months after the initial therapy of DTC, including the measurement of basal and stimulated Tg levels and Tg antibody levels, does not mandate a diagnostic WBS on all patients.
Significance statement
In this study, we examined the still commonly used routine diagnostic radioiodine whole-body scan in the first follow-up of patients with differentiated thyroid carcinoma. We questioned the necessity of the scan in patients with low stimulated thyroglobulin levels. Therefore, we combined retrospective data from the University Hospital in Vienna and in Tbilisi to analyze 370 patients. We were able to demostrate a highly significant relationship between low stimulated thyroglobulin levels (<0.5 ng/mL) and the outcome of the diagnostic scan at the first follow-up (χ = 14.7, P < 0.001).
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Purpose
The coexistence of growth hormone-secreting pituitary adenoma (GHPA) and Graves' disease (GD) is rare. This study aimed to investigate the relationship between growth hormone (GH)/insulin-like growth factor 1 (IGF-1) levels and thyroid function in patients with GHPA combined with GD and to explore the underlying mechanisms.
Methods
Eleven patients with GHPA combined with GD during 2015-2022 were collected by searching the medical record system of Beijing Tiantan Hospital, Capital Medical University. Changes in GH/IGF-1 levels and thyroid function were compared before and after the application of antithyroid drugs (ATD) and before and after transsphenoidal surgery (TSS) or somatostatin analog (SSA) treatment, respectively.
Results
After the application of ATD, with the decrease of thyroid hormone levels, GH/IGF-1 levels also decreased gradually. In patients without ATD application, after surgery or SSA treatment, thyroid hormone levels decreased as GH/IGF-1 decreased.
Conclusion
Hyperthyroidism due to GD promotes the secretion of GH/IGF-1, and when thyroid hormone levels were decreased by the use of ATD, GH and IGF-1 levels were also decreased, suggesting that thyroid hormones may influence the synthesis and secretion of GH/IGF-1. The use of ATD to control thyrotoxicosis before TSS is not only beneficial in reducing the risk of anesthesia but may help to promote biochemical control of GHPA. On the other hand, high levels of GH/IGF-1 in patients with GHPA also exacerbate GD hyperthyroidism, which is ameliorated by a decrease in GH/IGF-1 levels by TSS or SSA treatment, suggesting that the GH–IGF-1 axis promotes growth, thyroid function, and thyroid hormone metabolism.
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Objective
The aim was to investigate the ability of superb microvascular imaging (SMI) to improve the differential diagnosis of mummified thyroid nodules (MTNs) and papillary thyroid carcinomas (PTCs) using the 2017 American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS).
Materials and methods
We enrolled 110 cases of MTNs and 110 cases of PTCs confirmed by fine needle aspiration (FNA) or surgery. Conventional ultrasound (US) and the quantity of microvessels detected by SMI were analyzed for all nodules. Thyroid nodules were initially categorized by ACR-TIRADS based on US imaging features and then reclassified based on ACR-TIRADS combined with SMI blood-flow grade (SMI-TIRADS). We compared the diagnostic performances of ACR-TIRADS and SMI-TIRADS by receiver operating characteristic curve, sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV).
Results
US-detected margin, shape, and echogenic foci differed between MTNs and PTCs (P < 0.05). The SMI blood-flow grade was significantly greater in PTCs compared with MTNs (Χ 2 = 158.78, P < 0.05). There was no significant difference in ACR-TIRADS indicators between MTNs and PTCs (Χ 2 = 1.585, P = 0.453); however, reclassification by SMI-TIRADS showed significant differences between the groups (Χ 2 = 129.521, P < 0.001). The area under the curve was significantly lower for ACR-TIRADS compared with SMI-TIRADS (0.517 vs 0.887, P < 0.05). SMI-TIRADS had significantly higher diagnostic value for distinguishing MTNs and PTCs than ACR-TIRADS (sensitivity: 91.82% vs 74.55%, P < 0.05; specificity: 84.55% vs 21.82%, P < 0.05; accuracy: 88.18% vs 48.18%, P < 0.05; PPV: 85.59% vs 48.81%, P < 0.05; and NPV: 91.18% vs 46.15%, P < 0.05).
Conclusion
The detection of microvascular flow and large vessels in thyroid nodules by SMI resulted in high diagnostic specificity and sensitivity. ACR-TIRADS combined with SMI could effectively distinguish between MTNs and PTCs, to avoid unnecessary FNA or surgical excision.
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Hypothyroidism is a relatively common finding during pregnancy. This may be due either to the presence of existing thyroid disease and/or to the increased demands that pregnancy places the thyroid gland to provide thyroid hormones for the mother and the developing fetus. There is no doubt that overt hypothyroidism is associated strongly with adverse pregnancy outcomes, including miscarriage. Meta-analyses show that thyroid hormone replacement with levothyroxine (LT4) reduces the risk of adverse pregnancy outcomes in the setting of overt hypothyroidism. Accordingly, management guidelines in this area are unanimous in recommending intervention with to control the level of thyrotropin (TSH) to below 2.5 μIU/mL. The evidence for an adverse impact of subclinical hypothyroidism (SCH) on pregnancy outcomes is less clear, although meta-analyses suggest that SCH reduces the chance of a successful pregnancy outcome. Guidelines also support intervention for some patients with SCH, particularly where TSH is high (>10 μIU/mL), or where TSH is above its trimester-specific reference range in a woman with thyroid autoimmunity (giving LT4 to euthyroid women with thyroid autoimmunity is not supported). Real-world evidence suggests that hypothyroidism in pregnancy is often overlooked or that LT4 is not given appropriately to gain tight control of TSH. More research is needed to identify the barriers to optimal thyroid care with LT4 at this crucial time.
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The introduction and generalization of next-generation sequencing techniques have significantly increased the identification of mutations in thyroid tumors from multiple patient cohorts. The understanding of the association between specific mutations and clinical outcomes is gradually leading to individualizing the care of patients with thyroid cancer. BRAFV600 is the most common mutation seen in thyroid cancer patients and unequivocally predicts malignancy, but when considered in isolation, it is not recommended to be used as an independent prognostic factor. Mutations in RAS are the second most common alterations in thyroid cancer but can be found in benign and malignant lesions. Rearrangements involving receptor tyrosine kinases, primarily RET, are found in a subset of thyroid tumors without mutations in either BRAF or RAS. The assessment of additional mutations is increasingly employed in thyroid cancer prognostication. The coexistence of BRAF with alterations in genes such as PIK3CA, TERT promoter, or TP53 is associated with less favorable outcomes. Similar studies have also shown that additional oncogenic mutations in RAS-mutant thyroid carcinoma, such as those affecting the EIF1AX gene, likely predict a more aggressive clinicopathologic behavior. Overall, emerging evidence suggests that the co-occurrence of specific alterations in defined genes with BRAF or RAS mutations can become prognostic tools and useful predictors of thyroid tumor aggressiveness.
