scholarly journals Congenital hypothyroidism and thyroid cancer

2021 ◽  
Author(s):  
Gustavo Penna ◽  
Ileana G S Rubio ◽  
Ester Saraiva Brust ◽  
Juliana Cazarin ◽  
Fabio Hecht ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Congenital Hypothyroidism ◽  
Molecular Mechanisms ◽  
Gene Mutations ◽  
Nodular Goiter ◽  
Analytical Framework ◽  
Differentiated Thyroid Carcinoma ◽  
Thyroid Stimulating Hormone ◽  
Driver Mutations ◽  
Cellular Mechanisms

Differentiated thyroid carcinoma (DTC) combined whit congenital hypothyroidism (CH) is a rare situation, and there is no well-established causal relationship. CH is a common congenital endocrine, while DTC occurring in childhood represents 0.4% to 3% of all malignancies at this stage of life. The association of CH with DTC could be related to dyshormonogenetic goiter (DHG) or developmental abnormalities. This review will explore the clinical features and the molecular mechanisms potentially associated with the appearance of DTC in CH: sporadic somatic driver mutations, chronic increase of thyroid-stimulating hormone (TSH) levels, higher concentrations hydrogen peroxide (H2O2), Borelain /CDCA8 gene mutations and in others genes associated with CH - either alone or associated with the mechanisms involved in dyshormonogenesis. There are some pitfalls in the diagnosis of thyroid cancer in patients with CH with nodular goiter, as the proper cytological diagnosis of nodules of patients with dyshormonogenesis might be demanding due to the specific architectural and cytological appearance, which may lead to an erroneous interpretation of malignancy. The purpose of this article is to suggest an analytical framework that embraces the fundamental relationships between the various aspects of CH and CDT. In face of this scenario, the entire genetic and epigenetic context, the complex functioning and cross talk of cell signaling may determine cellular mechanisms promoting both the maintenance of the differentiated state of the thyroid follicular cell and the disruption of its homeostasis leading to cancer. Whereas, the exact mechanisms for thyroid cancer development in CH remain to be elucidated.

scholarly journals Modern concepts of the molecular pathogenesis of thyroid cancer

2021 ◽  
Vol 8 (2) ◽  
pp. 8-22
Author(s):  
A. A. Mikhailova ◽  
A. V. Shestakov ◽  
K. A. Chubakova ◽  
E. V. Kolokolova ◽  
V. Yu. Eliseev ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tumor Markers ◽  
Molecular Mechanisms ◽  
Thyroid Nodules ◽  
Gene Mutations ◽  
Endocrine System ◽  
Nodular Goiter ◽  
Micro Rna ◽  
Diagnostic Methods ◽  
Patient Treatment

Thyroid cancer remains the most common malignancy of the endocrine system worldwide. The indicators of its morbidity and mortality rates have been increasing rapidly over the last decades. Most cases of differentiated thyroid cancer (follicular and papillary histotypes) are clinically manifested by nodular goiter frequently combined with uncertain results of cytological diagnosis (categories III and IV according to the Bethesda (Bethesda System for Reporting Thyroid Cytopathology) classification). All of that makes it difficult to choose a proper tactic for patient treatment. It is known that the development, progression, invasion, and metastasis of cancer cells are regulated by a variety of molecular mechanisms. This review describes several molecular aspects of thyroid nodules oncogenesis, as well as its most promising diagnostic tumor markers. Following molecular pathways are described in particular: gene mutations, protein tumor markers, and epigenetic effects of micro-RNA, histones, as well as DNA methylation. The study of the pathogenesis of this disease has a prognostic value and contributes to the search for effective therapeutic and diagnostic methods and their improvement. That is why we also reviewed modern test panels aimed at preoperative differential diagnosis of thyroid nodules. Summarizing the results of world research on this topic allows us not only to expand the understanding of the fundamental processes of oncogenesis, but also to outline promising areas for future experimental research projects. All of that together will contribute to developing new prognostic, diagnostic and therapeutic technologies, and as a result, will improve the quality of medical care for patients with thyroid cancer.

scholarly journals Characteristics of thyroid carcinoma in Graves' disease, chronic lymphocitic thyroiditis and nodular goiter

2003 ◽  
Vol 50 (3) ◽  
pp. 135-139
Author(s):  
Aleksandar Filipovic ◽  
Ivan Paunovic
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Nodular Goiter ◽  
Differentiated Thyroid Carcinoma ◽  
Anaplastic Carcinoma ◽  
Graves Disease ◽  
Associated Diseases ◽  
Clinical Centre ◽  
Well Differentiated

The biology of thyroid cancer represents a spectrum of behavior ranging from well - differentiated lesions with an excellent prognosis to anaplastic carcinoma, wich is almost fatal. For this reason, it is important that clinicians have methods at their disposal to asses the characteristics of patient's thyroid malignancy. In this work we discuss the behavior of differentiated thyroid cancer in associated diseases of thyroid as : Graves? disease, chronic lymphocitic thyroiditis - Hashimoto and nodular goiter. This is retrospectively reviewing of 50 patients treated for differentiated thyroid carcinoma at Department of surgery, Clinical Centre of Montenegro in Podgorica from 1998 until 2003. We evaluated occurrence, as well as the role of this diseases in patients with thyroid cancer.We found a more favorable course of thyroid cancer in the presence of chronic lymphocitic thyroiditis and nodular goiter, a contrary Graves? disease. In associated diseases of thyroid, a significantly greater proportion of patients with thyroid cancer, have modular goiter.

scholarly journals Gene Methylation in Thyroid Tumorigenesis

Endocrinology ◽  
2007 ◽  
Vol 148 (3) ◽  
pp. 948-953 ◽  
Author(s):  
Mingzhao Xing
Keyword(s):  
Thyroid Cancer ◽  
Molecular Mechanisms ◽  
Mapk Pathway ◽  
Thyroid Stimulating Hormone ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Thyroid Tumors ◽  
Sodium Iodide Symporter ◽  
Gene Methylation ◽  
Death Associated Protein Kinase ◽  
Aberrant Gene

Aberrant gene methylation plays an important role in human tumorigenesis, including thyroid tumorigenesis. Many tumor suppressor genes are aberrantly methylated in thyroid cancer, and some even in benign thyroid tumors, suggesting a role of this epigenetic event in early thyroid tumorigenesis. Methylation of some of these genes tends to occur in certain types of thyroid cancer and is related to specific signaling pathways. For example, methylation of PTEN and RASSF1A genes occurs mostly in follicular thyroid cancer, and its tumorigenic role may be related to the phosphatidylinositol 3-kinase/Akt signaling pathway, whereas methylation of genes for tissue inhibitor of metalloproteinase-3, SLC5A8, and death-associated protein kinase occurs in papillary thyroid cancer and is related to the BRAF/MAPK kinase/MAPK pathway. Methylation of thyroid-specific genes, such as those for sodium/iodide symporter and thyroid-stimulating hormone receptor, is also common in thyroid cancer. Although its tumorigenic role is not clear, methylation, and hence silencing, of these thyroid-specific genes is a cause for the failure of clinical radioiodine treatment of thyroid cancer. Unlike gene methylation, histone modifications have been relatively poorly investigated in thyroid tumors. Future studies need to emphasize the mechanistic aspects of these two types of epigenetic alterations to uncover new molecular mechanisms in thyroid tumorigenesis and to provide novel therapeutic targets for thyroid cancer.

scholarly journals Thyroid Cancer: Current Molecular Perspectives

2010 ◽  
Vol 2010 ◽  
pp. 1-17 ◽  
Author(s):  
Francesca Giusti ◽  
Alberto Falchetti ◽  
Francesco Franceschelli ◽  
Francesca Marini ◽  
Annalisa Tanini ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Molecular Genetic ◽  
Gene Mutations ◽  
Differentiated Thyroid Carcinoma ◽  
Genetic Alterations ◽  
Malignant Neoplasms ◽  
Genetic Studies ◽  
Thyroid Microcarcinoma ◽  
Indeterminate Cytology

The thyroid cancer is a rare oncological entity, representing no more than 1% of all human malignant neoplasms. Recently, it has been demonstrated a sharp increase in incidence of differentiated thyroid carcinoma, equally occurring in both sexes. So far, multiple genetic alterations have been identified in differentiated thyroid carcinoma, leading to investigate the clinical utility of genetic studies. In particular, molecular genetic approaches searching for gene mutations in the material collected by fine needle ago-biopsy may have a particular utility in small nodules and in those specimens with an indeterminate cytology. The expansion of knowledge about genetic mutations occurring in different thyroid tumors has characterized recent years, allowing the identification of a correlation between specific mutations and phenotypic characteristics of thyroid cancers, essential for their prognosis. This review will briefly report on the histological features and the new entity represented by thyroid microcarcinoma and will focus on both environmental and genetic aspects associated with the occurrence of thyroid cancer.

scholarly journals Prevalence and Spectrum of DICER1Mutations in Adult-Onset Thyroid Nodules

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A868-A869
Author(s):  
Anne-Sophie Chong ◽  
Yuri E Nikiforov ◽  
Vincenzo Condello ◽  
Abigail Wald ◽  
Marina Nikiforova ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Nodules ◽  
The United States ◽  
Needle Aspiration ◽  
Differentiated Thyroid Carcinoma ◽  
Pathogenic Variant ◽  
Driver Mutations ◽  
Adult Onset ◽  
Hotspot Mutations ◽  
Dicer1 Syndrome

Abstract Context: DICER1 mutations are found in multinodular goiter and differentiated thyroid carcinoma in children, and can be a manifestation of DICER1 syndrome, but the prevalence of DICER1 mutations and their significance in adult-onset thyroid nodules is unknown. Objective: Determine 1) the prevalence of DICER1 hotspot mutations in thyroid nodules; 2) the frequency of a second DICER1 pathogenic variant in thyroid nodules with DICER1 hotspot mutations; 3) the prevalence of other thyroid cancer driver mutations in thyroid nodules with and without DICER1 hotspot mutations. Design: Population-based study of 14,993 consecutive fine needle aspiration biopsies of thyroid nodules evaluated by ThyroSeq v3. From 214 DICER1 hotspot-positive cases, we selected 61, matched to DICER1 hotspot-negative nodules. We performed full sequencing of all exons and exon-intron boundaries of DICER1. Setting: Commercial and university-based laboratories in the United States and Canada Results: Among 14,993 thyroid nodules, 214 (1.4%) revealed a DICER1 hotspot mutation. A second pathogenic/likely pathogenic variant in DICER1 was found in 45/59 (76%) DICER1 hotspot-positive nodules studied while no other DICER1 variant was identified in the DICER1 hotspot-negative group by full DICER1 sequencing. Other alterations in thyroid-related genes were significantly more frequent in DICER1 hotspot-negative nodules (32/61) than in DICER1 hotspot-positive nodules (4/59) (p<0.0001). Conclusions: DICER1 alterations occur in a proportion of adult thyroid nodules and appear mutually exclusive with alterations in other thyroid cancer-related genes. DICER1 hotspot mutations occur with a second hit in most cases and could suggest occult DICER1 syndrome in adults with thyroid nodules.

scholarly journals Epigenetic modification and BRAF gene mutation in thyroid carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Guo Huang ◽  
Juan Chen ◽  
Jun Zhou ◽  
Shuai Xiao ◽  
Weihong Zeng ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Gene Mutation ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Epigenetic Modification ◽  
Gene Mutations ◽  
Braf Gene ◽  
Braf Mutations ◽  
Rna Regulation

AbstractThyroid cancer remains the most prevailing endocrine malignancy, and a progressively increasing incidence rate has been observed in recent years, with 95% of thyroid cancer represented by differentiated thyroid carcinomas. The genetics and epigenetics of thyroid cancer are gradually increasing, and gene mutations and methylation changes play an important roles in its occurrence and development. Although the role of RAS and BRAF mutations in thyroid cancer have been partially clarified,but the pathogenesis and molecular mechanisms of thyroid cancer remain to be elucidated. Epigenetic modification refer to genetic modification that does not change the DNA sequence of a gene but causes heritable phenotypic changes in its expression. Epigenetic modification mainly includes four aspects: DNA methylation, chromatin remodelling, noncoding RNA regulation, and histone modification. This article reviews the importance of thyroid cancer epigenetic modification and BRAF gene mutation in the treatment of thyroid cancer.

Mendelian randomization to investigate the link between TSH and thyroid cancer

2021 ◽  
Author(s):  
Jonathan M Fussey ◽  
Robin N Beaumont ◽  
Andrew R Wood ◽  
Bijay Vaidya ◽  
Joel Smith ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Thyroid Disease ◽  
Mendelian Randomization ◽  
Positive Association ◽  
Differentiated Thyroid Carcinoma ◽  
Thyroid Stimulating Hormone ◽  
Causal Role ◽  
Inverse Association ◽  
Tsh Levels

Evidence from observational studies suggests a positive association between serum thyroid stimulating hormone (TSH) levels and differentiated thyroid carcinoma. However, the cause-effect relationship is poorly understood and these studies are susceptible to bias and confounding. Using Mendelian randomization (MR) methodology, this study aimed to investigate the causal role of TSH in both benign thyroid nodules and thyroid cancer in up to 451,025 UK Biobank. Hospital Episode Statistics and Cancer Registry databases were used to identify 462 patients with differentiated thyroid carcinoma and 2031 patients with benign nodular thyroid disease. MR methods using genetic variants associated with serum TSH were used to test causal relationships between TSH and the two disease outcomes. We observed evidence of an inverse association between TSH levels and both thyroid cancer and benign nodular thyroid disease. Two-sample MR suggested that a one standard deviation higher genetically instrumented TSH (approximately 0.8 mlU/L) resulted in an 80% reduction of risk of benign nodular disease (OR 0.2; 95% CI 0.10 – 0.41) and a 50% reduction of risk of thyroid cancer (OR 0.50; 95% CI 0.27 – 0.92). In keeping with other recently published studies, our results refute a causal role for TSH in both benign nodular thyroid disease and thyroid cancer, with increasing genetically instrumented TSH resulting in a lower risk of both diseases.

Prevalence and Spectrum of DICER1 Mutations in Adult-onset Thyroid Nodules with Indeterminate Cytology

2021 ◽  
Author(s):  
Anne-Sophie Chong ◽  
Yuri E Nikiforov ◽  
Vincenzo Condello ◽  
Abigail I Wald ◽  
Marina N Nikiforova ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Nodules ◽  
The United States ◽  
Needle Aspiration ◽  
Differentiated Thyroid Carcinoma ◽  
Pathogenic Variant ◽  
Driver Mutations ◽  
Adult Onset ◽  
Hotspot Mutations ◽  
Dicer1 Syndrome

Abstract Context DICER1 mutations are found in multinodular goiter and differentiated thyroid carcinoma in children, and can be a manifestation of DICER1 syndrome, but the prevalence of DICER1 mutations and their significance in adult-onset thyroid nodules is unknown. Objective Determine (1) the prevalence of DICER1 hotspot mutations in thyroid nodules; (2) the frequency of a second DICER1 pathogenic variant in thyroid nodules with DICER1 hotspot mutations; (3) the prevalence of other thyroid cancer driver mutations in thyroid nodules with and without DICER1 hotspot mutations. Methods Population-based study of 14 993 consecutive fine needle aspiration biopsies of thyroid nodules evaluated by ThyroSeq v3. From 214 DICER1 hotspot–positive cases, we selected 61, matched to DICER1 hotspot–negative nodules. We performed full sequencing of all exons and exon–intron boundaries of DICER1. Setting Commercial and university-based laboratories in the United States and Canada. Results Among 14 993 thyroid nodules, 214 (1.4%) revealed a DICER1 hotspot mutation. A second pathogenic/likely pathogenic variant in DICER1 was found in 45/59 (76%) DICER1 hotspot–positive nodules studied while no other DICER1 variant was identified in the DICER1 hotspot–negative group by full DICER1 sequencing. Other alterations in thyroid-related genes were significantly more frequent in DICER1 hotspot–negative nodules (32/61) than in DICER1 hotspot-–positive nodules (4/59) (P < .0001). Conclusion DICER1 alterations occur in a proportion of adult thyroid nodules and appear mutually exclusive with alterations in other thyroid cancer–related genes. DICER1 hotspot mutations occur with a second hit in most cases and could suggest occult DICER1 syndrome in adults with thyroid nodules.

scholarly journals Mendelian randomization supports a causative effect of TSH on thyroid carcinoma

2020 ◽  
Vol 27 (10) ◽  
pp. 551-559 ◽  
Author(s):  
Jonathan M Fussey ◽  
Robin N Beaumont ◽  
Andrew R Wood ◽  
Bijay Vaidya ◽  
Joel Smith ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Thyroid Disease ◽  
Mendelian Randomization ◽  
Positive Association ◽  
Differentiated Thyroid Carcinoma ◽  
Causal Link ◽  
Thyroid Stimulating Hormone ◽  
Causal Role ◽  
Causative Effect

Evidence from observational studies suggest a positive association between serum thyroid-stimulating hormone (TSH) levels and differentiated thyroid carcinoma. However, the cause–effect relationship is poorly understood and these studies are susceptible to bias and confounding. This study aimed to investigate the causal role of TSH in both benign thyroid nodules and thyroid cancer in up to 451,025 UK Biobank participants, using a genetic technique, known as Mendelian randomization (MR). Hospital Episode Statistics and Cancer Registry databases were used to identify 462 patients with differentiated thyroid carcinoma and 2031 patients with benign nodular thyroid disease. MR methods using genetic variants associated with serum TSH were used to test causal relationships between TSH and the two disease outcomes. Mendelian randomization provided evidence of a causal link between TSH and both thyroid cancer and benign nodular thyroid disease. Two-sample MR suggested that a 1 s.d. higher genetically instrumented TSH (approximately 0.8 mIU/L) resulted in 4.96-fold higher odds of benign nodular disease (95% CI 2.46–9.99) and 2.00-fold higher odds of thyroid cancer (95% CI 1.09–3.70). Our results thus support a causal role for TSH in both benign nodular thyroid disease and thyroid cancer.

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