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Thyroid-Related Diseases: Molecular Pathology, Diagnosis and Treatment

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 44868

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Guest Editor
Division of Anatomic Pathology and Histology, Università degli Studi di Messina, Piazza Pugliatti, 1, 98122 Messina, ME, Italy
Interests: hematopathology; glial and central nervous system cancer; gastrointestinal tumor; lung cancer; thyroid cancer; genitourinary cancer
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Special Issue Information

Dear Colleagues,

Molecular testing is becoming increasingly important in thyroid pathology and is now recommended by the American Thyroid Association (ATA), National Comprehensive Cancer Network, and UpToDate. Molecular tests can help to identify malignant neoplasms within the group of cytologically indeterminate thyroid nodules. They can detect specific mutations for thyroid cancer, such as BRAF and RET/PTC, and can help to reduce the number of unnecessary diagnostic surgeries. Therefore, molecular analyses can guide appropriate treatment for thyroid nodules, providing clinically valuable diagnostic information and aiding physicians in the management of indeterminate thyroid nodules.

In this context, this Special Issue aims to cover all sectors of research based on molecular characterization of thyroid nodules. It will include original research, review articles, and short communications on molecular mechanisms implied in thyroid pathology and their potential therapeutic implications.

Dr. Vincenzo Fiorentino
Dr. Maurizio Martini
Guest Editors

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Keywords

  • thyroid disease
  • thyroid nodules
  • thyroid cancer
  • thyroid carcinoma
  • thyroid radiology
  • thyroid–gut axis
  • autoimmune thyroid disorders
  • thyroid hormone
  • molecular mechanisms
  • molecular tests

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Related Special Issue

Published Papers (13 papers)

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Research

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12 pages, 2177 KiB  
Article
Computational Analysis Suggests That AsnGTT 3′-tRNA-Derived Fragments Are Potential Biomarkers in Papillary Thyroid Carcinoma
by Annie N. Do, Shruti Magesh, Matthew Uzelac, Tianyi Chen, Wei Tse Li, Michael Bouvet, Kevin T. Brumund, Jessica Wang-Rodriguez and Weg M. Ongkeko
Int. J. Mol. Sci. 2024, 25(19), 10631; https://doi.org/10.3390/ijms251910631 - 2 Oct 2024
Viewed by 936
Abstract
Transfer-RNA-derived fragments (tRFs) are a novel class of small non-coding RNAs that have been implicated in oncogenesis. tRFs may act as post-transcriptional regulators by recruiting AGO proteins and binding to highly complementary regions of mRNA at seed regions, resulting in the knockdown of [...] Read more.
Transfer-RNA-derived fragments (tRFs) are a novel class of small non-coding RNAs that have been implicated in oncogenesis. tRFs may act as post-transcriptional regulators by recruiting AGO proteins and binding to highly complementary regions of mRNA at seed regions, resulting in the knockdown of the transcript. Therefore, tRFs may be critical to tumorigenesis and warrant investigation as potential biomarkers. Meanwhile, the incidence of papillary thyroid carcinoma (PTC) has increased in recent decades and current diagnostic technology stands to benefit from new detection methods. Although small non-coding RNAs have been studied for their role in oncogenesis, there is currently no standard for their use as PTC biomarkers, and tRFs are especially underexplored. Accordingly, we aim to identify dysregulated tRFs in PTC that may serve as biomarker candidates. We identified dysregulated tRFs and driver genes between PTC primary tumor samples (n = 511) and adjacent normal tissue samples (n = 59). Expression data were obtained from MINTbase v2.0 and The Cancer Genome Atlas. Dysregulated tRFs and genes were analyzed in tandem to find pairs with anticorrelated expression. Significantly anticorrelated tRF-gene pairs were then tested for potential binding affinity using RNA22—if a heteroduplex can form via complementary binding, this would support the hypothesized RNA silencing mechanism. Four tRFs were significantly dysregulated in PTC tissue (p < 0.05), with only AsnGTT 3′-tRF being upregulated. Binding affinity analysis revealed that tRF-30-RY73W0K5KKOV (AsnGTT 3′-tRF) exhibits sufficient complementarity to potentially bind to and regulate transcripts of SLC26A4, SLC5A8, DIO2, and TPO, which were all found to be downregulated in PTC tissue. In the present study, we identified dysregulated tRFs in PTC and found that AsnGTT 3′-tRF is a potential post-transcriptional regulator and biomarker. Full article
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13 pages, 1897 KiB  
Article
BRAF-AXL-PD-L1 Signaling Axis as a Possible Biological Marker for RAI Treatment in the Thyroid Cancer ATA Intermediate Risk Category
by Cristina Pizzimenti, Vincenzo Fiorentino, Antonio Ieni, Esther Diana Rossi, Emanuela Germanà, Luca Giovanella, Maria Lentini, Ylenia Alessi, Giovanni Tuccari, Alfredo Campennì, Maurizio Martini and Guido Fadda
Int. J. Mol. Sci. 2023, 24(12), 10024; https://doi.org/10.3390/ijms241210024 - 12 Jun 2023
Cited by 5 | Viewed by 1606
Abstract
The use of radioiodine therapy (RIT) is debated in intermediate-risk differentiated thyroid cancer (DTC) patients. The understanding of the molecular mechanisms involved in the pathogenesis of DTC can be useful to refine patient selection for RIT. We analyzed the mutational status of BRAF, [...] Read more.
The use of radioiodine therapy (RIT) is debated in intermediate-risk differentiated thyroid cancer (DTC) patients. The understanding of the molecular mechanisms involved in the pathogenesis of DTC can be useful to refine patient selection for RIT. We analyzed the mutational status of BRAF, RAS, TERT, PIK3 and RET, and the expression of PD-L1 (as a CPS score), the NIS and AXL genes and the tumor-infiltrating lymphocytes (TIL, as the CD4/CD8 ratio), in the tumor tissue in a cohort of forty-six ATA intermediate-risk patients, homogeneously treated with surgery and RIT. We found a significant correlation between BRAF mutations and a less than excellent (LER, according to 2015 ATA classification) response to RIT treatment (p = 0.001), higher expression of the AXL gene (p = 0.007), lower expression of NIS (p = 0.045) and higher expression of PD-L1 (p = 0.004). Moreover, the LER patient group had a significantly higher level of AXL (p = 0.0003), a lower level of NIS (p = 0.0004) and a higher PD-L1 level (p = 0.0001) in comparison to patients having an excellent response to RIT. We also found a significant direct correlation between the AXL level and PD-L1 expression (p < 0.0001) and a significant inverse correlation between AXL and NIS expression and TILs (p = 0.0009 and p = 0.028, respectively). These data suggest that BRAF mutations and AXL expression are involved in LER among DTC patients and in the higher expression of PD-L1 and CD8, becoming new possible biomarkers to personalize RIT in the ATA intermediate-risk group, as well as the use of higher radioiodine activity or other possible therapies. Full article
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22 pages, 13765 KiB  
Article
Modulation of EZH2 Activity Induces an Antitumoral Effect and Cell Redifferentiation in Anaplastic Thyroid Cancer
by Diego Claro de Mello, Kelly Cristina Saito, Marcella Maringolo Cristovão, Edna Teruko Kimura and Cesar Seigi Fuziwara
Int. J. Mol. Sci. 2023, 24(9), 7872; https://doi.org/10.3390/ijms24097872 - 26 Apr 2023
Cited by 6 | Viewed by 2079
Abstract
Anaplastic thyroid cancer (ATC) is a rare and lethal form of thyroid cancer that requires urgent investigation of new molecular targets involved in its aggressive biology. In this context, the overactivation of Polycomb Repressive Complex 2/EZH2, which induces chromatin compaction, is frequently observed [...] Read more.
Anaplastic thyroid cancer (ATC) is a rare and lethal form of thyroid cancer that requires urgent investigation of new molecular targets involved in its aggressive biology. In this context, the overactivation of Polycomb Repressive Complex 2/EZH2, which induces chromatin compaction, is frequently observed in aggressive solid tumors, making the EZH2 methyltransferase a potential target for treatment. However, the deregulation of chromatin accessibility is yet not fully investigated in thyroid cancer. In this study, EZH2 expression was modulated by CRISPR/Cas9-mediated gene editing and pharmacologically inhibited with EZH2 inhibitor EPZ6438 alone or in combination with the MAPK inhibitor U0126. The results showed that CRISPR/Cas9-induced EZH2 gene editing reduced cell growth, migration and invasion in vitro and resulted in a 90% reduction in tumor growth when EZH2-edited cells were injected into an immunocompromised mouse model. Immunohistochemistry analysis of the tumors revealed reduced tumor cell proliferation and less recruitment of cancer-associated fibroblasts in the EZH2-edited tumors compared to the control tumors. Moreover, EZH2 inhibition induced thyroid-differentiation genes’ expression and mesenchymal-to-epithelial transition (MET) in ATC cells. Thus, this study shows that targeting EZH2 could be a promising neoadjuvant treatment for ATC, as it promotes antitumoral effects in vitro and in vivo and induces cell differentiation. Full article
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29 pages, 2029 KiB  
Article
Identification of Novel Candidate Genes for Familial Thyroid Cancer by Whole Exome Sequencing
by Cristina Tous, Carmen Muñoz-Redondo, Nereida Bravo-Gil, Angela Gavilan, Raquel María Fernández, Juan Antiñolo, Elena Navarro-González, Guillermo Antiñolo and Salud Borrego
Int. J. Mol. Sci. 2023, 24(9), 7843; https://doi.org/10.3390/ijms24097843 - 25 Apr 2023
Cited by 1 | Viewed by 2620
Abstract
Thyroid carcinoma (TC) can be classified as medullary (MTC) and non-medullary (NMTC). While most TCs are sporadic, familial forms of MTC and NMTC also exist (less than 1% and 3–9% of all TC cases, respectively). Germline mutations in RET are found in more [...] Read more.
Thyroid carcinoma (TC) can be classified as medullary (MTC) and non-medullary (NMTC). While most TCs are sporadic, familial forms of MTC and NMTC also exist (less than 1% and 3–9% of all TC cases, respectively). Germline mutations in RET are found in more than 95% of familial MTC, whereas familial NMTC shows a high degree of genetic heterogeneity. Herein, we aimed to identify susceptibility genes for familial NMTC and non-RET MTC by whole exome sequencing in 58 individuals belonging to 18 Spanish families with these carcinomas. After data analysis, 53 rare candidate segregating variants were identified in 12 of the families, 7 of them located in previously TC-associated genes. Although no common mutated genes were detected, biological processes regulating functions such as cell proliferation, differentiation, survival and adhesion were enriched. The reported functions of the identified genes together with pathogenicity and structural predictions, reinforced the candidacy of 36 of them, suggesting new loci related to TC and novel genotype–phenotype correlations. Therefore, our strategy provides clues to possible molecular mechanisms underlying familial forms of MTC and NMTC. These new molecular findings and clinical data of patients may be helpful for the early detection, development of tailored therapies and optimizing patient management. Full article
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12 pages, 8186 KiB  
Article
Prostaglandin F2α Regulates Adipogenesis by Modulating Extracellular Signal-Regulated Kinase Signaling in Graves’ Ophthalmopathy
by Ru Zhu, Xing-Hua Wang, Bo-Wen Wang, Xuan Ouyang, Ya-Yan You, Hua-Tao Xie, Ming-Chang Zhang and Fa-Gang Jiang
Int. J. Mol. Sci. 2023, 24(8), 7012; https://doi.org/10.3390/ijms24087012 - 10 Apr 2023
Viewed by 1916
Abstract
Prostaglandin F2α (PGF2α), the first-line anti-glaucoma medication, can cause the deepening of the upper eyelid sulcus due to orbital lipoatrophy. However, the pathogenesis of Graves’ ophthalmopathy (GO) involves the excessive adipogenesis of the orbital tissues. The present study aimed to determine the therapeutic [...] Read more.
Prostaglandin F2α (PGF2α), the first-line anti-glaucoma medication, can cause the deepening of the upper eyelid sulcus due to orbital lipoatrophy. However, the pathogenesis of Graves’ ophthalmopathy (GO) involves the excessive adipogenesis of the orbital tissues. The present study aimed to determine the therapeutic effects and underlying mechanisms of PGF2α on adipocyte differentiation. In this study primary cultures of orbital fibroblasts (OFs) from six patients with GO were established. Immunohistochemistry, immunofluorescence, and Western blotting (WB) were used to evaluated the expression of the F-prostanoid receptor (FPR) in the orbital adipose tissues and the OFs of GO patients. The OFs were induced to differentiate into adipocytes and treated with different incubation times and concentrations of PGF2α. The results of Oil red O staining showed that the number and size of the lipid droplets decreased with increasing concentrations of PGF2α and the reverse transcription-polymerase chain reaction (RT-PCR) and WB of the peroxisome proliferator-activated receptor γ (PPARγ) and fatty-acid-binding protein 4 (FABP4), both adipogenic markers, were significantly downregulated via PGF2α treatment. Additionally, we found the adipogenesis induction of OFs promoted ERK phosphorylation, whereas PGF2α further induced ERK phosphorylation. We used Ebopiprant (FPR antagonist) to interfere with PGF2α binding to the FPR and U0126, an Extracellular Signal-Regulated Kinase (ERK) inhibitor, to inhibit ERK phosphorylation. The results of Oil red O staining and expression of adipogenic markers showed that blocking the receptor binding or decreasing the phosphorylation state of the ERK both alleviate the inhibitory effect of PGF2a on the OFs adipogenesis. Overall, PGF2α mediated the inhibitory effect of the OFs adipogenesis through the hyperactivation of ERK phosphorylation via coupling with the FPR. Our study provides a further theoretical reference for the potential application of PGF2α in patients with GO. Full article
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18 pages, 4647 KiB  
Article
Transcriptomic Analysis Reveals Dysregulation of the Mycobiome and Archaeome and Distinct Oncogenic Characteristics according to Subtype and Gender in Papillary Thyroid Carcinoma
by Daniel John, Rishabh Yalamarty, Armon Barakchi, Tianyi Chen, Jaideep Chakladar, Wei Tse Li and Weg M. Ongkeko
Int. J. Mol. Sci. 2023, 24(4), 3148; https://doi.org/10.3390/ijms24043148 - 5 Feb 2023
Cited by 5 | Viewed by 2569
Abstract
Papillary Thyroid Carcinoma (PTC) is characterized by unique tumor morphology, treatment response, and patient outcomes according to subtype and gender. While previous studies have implicated the intratumor bacterial microbiome in the incidence and progression of PTC, few studies have investigated the potential role [...] Read more.
Papillary Thyroid Carcinoma (PTC) is characterized by unique tumor morphology, treatment response, and patient outcomes according to subtype and gender. While previous studies have implicated the intratumor bacterial microbiome in the incidence and progression of PTC, few studies have investigated the potential role of fungal and archaeal species in oncogenesis. In this study, we aimed to characterize the intratumor mycobiome and archaeometry in PTC with respect to its three primary subtypes: Classical (CPTC), Follicular Variant (FVPTC), and Tall Cell (TCPTC), and also with respect to gender. RNA-sequencing data were downloaded from The Cancer Genome Atlas (TCGA), including 453 primary tumor tissue samples and 54 adjacent solid tissue normal samples. The PathoScope 2.0 framework was used to extract fungal and archaeal microbial read counts from raw RNA-sequencing data. Overall, we found that the intratumor mycobiome and archaeometry share significant similarities in CPTC, FVPTC, and TCPTC, although most dysregulated species in CPTC are underabundant compared to normal. Furthermore, differences between the mycobiome and archaeometry were more significant between males and females, with a disproportionate number of fungal species overabundant in female tumor samples. Additionally, the expression of oncogenic PTC pathways was distinct across CPTC, FVPTC, and TCPTC, indicating that these microbes may uniquely contribute to PTC pathogenesis in each subtype. Furthermore, differences in the expression of these pathways were observed between males and females. Finally, we found a specific panel of fungi to be dysregulated in BRAF V600E-positive tumors. This study demonstrates the potential importance of microbial species to PTC incidence and oncogenesis. Full article
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16 pages, 3178 KiB  
Article
Prevalence of Transient Hypothyroidism in Children Diagnosed with Congenital Hypothyroidism between 2000 and 2016
by Sabrina Gmür, Daniel Konrad and Ralph Fingerhut
Int. J. Mol. Sci. 2023, 24(3), 2817; https://doi.org/10.3390/ijms24032817 - 1 Feb 2023
Cited by 5 | Viewed by 2052
Abstract
Newborn screening (NBS) for congenital hypothyroidism (CH) was introduced in Switzerland in 1977, which allowed for the preclinical, biochemical diagnosis. The aim of this study was to evaluate the prevalence of transient CH (tCH) in the canton of Zurich. In this analytical cohort [...] Read more.
Newborn screening (NBS) for congenital hypothyroidism (CH) was introduced in Switzerland in 1977, which allowed for the preclinical, biochemical diagnosis. The aim of this study was to evaluate the prevalence of transient CH (tCH) in the canton of Zurich. In this analytical cohort study, all newborns born in the canton of Zurich, between the 1st of January 2000 and the 30st of June 2016, with a TSH value above 15 mU/L (whole blood) were included. There were 115 cases out of 247,918 babies born during the study period. However, 23 cases had to be excluded due to missing data. The definite diagnosis was made after a thyroxine withdrawal at 2 years of age. The total prevalence of confirmed CH and the female to male ratio (f/m) were 1:2695 and 2.17:1; for permanent CH (pCH), 1:3443 and 2.8:1; and for tCH, 1:12,396 and 1:1, respectively. The TSH value was significantly higher in pCH compared to tCH, at 130.3 (62.9–171.9) and 36.4 (26.5–53.3) (median and interquartile range), respectively (p < 0.001). The prevalences found for congenital hypothyroidism and its transient form are comparable to previous studies. TSH concentration at birth was predictive for the further course of the disease. Low birth weight correlated with a tCH, whereas low gestational age did not. The dominance of the female sex in congenital hypothyroidism is supported by a gender ratio of 2.17:1. Full article
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14 pages, 27772 KiB  
Article
Spatially Resolved Molecular Approaches for the Characterisation of Non-Invasive Follicular Tumours with Papillary-like Features (NIFTPs)
by Isabella Piga, Vincenzo L’Imperio, Lucrezia Principi, Claudio Bellevicine, Nicola Fusco, Fausto Maffini, Konstantinos Venetis, Mariia Ivanova, Davide Seminati, Gabriele Casati, Lisa Pagani, Stefania Galimberti, Giulia Capitoli, Mattia Garancini, Andrea-Valer Gatti, Fulvio Magni and Fabio Pagni
Int. J. Mol. Sci. 2023, 24(3), 2567; https://doi.org/10.3390/ijms24032567 - 29 Jan 2023
Cited by 2 | Viewed by 2826
Abstract
Noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) are low-risk thyroid lesions most often characterised by RAS-type mutations. The histological diagnosis may be challenging, and even immunohistochemistry and molecular approaches have not yet provided conclusive solutions. This study characterises a set of [...] Read more.
Noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) are low-risk thyroid lesions most often characterised by RAS-type mutations. The histological diagnosis may be challenging, and even immunohistochemistry and molecular approaches have not yet provided conclusive solutions. This study characterises a set of NIFTPs by Matrix-Assisted Laser Desorption/Ionisation (MALDI)–Mass Spectrometry Imaging (MSI) to highlight the proteomic signatures capable of overcoming histological challenges. Archived formalin-fixed paraffin-embedded samples from 10 NIFTPs (n = 6 RAS-mutated and n = 4 RAS-wild type) were trypsin-digested and analysed by MALDI–MSI, comparing their profiles to normal tissue and synchronous benign nodules. This allowed the definition of a four-peptide signature able to distinguish RAS-mutant from wild-type cases, the latter showing proteomic similarities to hyperplastic nodules. Moreover, among the differentially expressed signals, Peptidylprolyl Isomerase A (PPIA, 1505.8 m/z), which has already demonstrated a role in the development of cancer, was found overexpressed in NIFTP RAS-mutated nodules compared to wild-type lesions. These results underlined that high-throughput proteomic approaches may add a further level of biological comprehension for NIFTPs. In the future, thanks to the powerful single-cell detail achieved by new instruments, the complementary NGS–MALDI imaging sequence might be the correct methodological approach to confirm that the current NIFTP definition encompasses heterogeneous lesions that must be further characterised. Full article
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12 pages, 4358 KiB  
Article
Annotation-Free Deep Learning-Based Prediction of Thyroid Molecular Cancer Biomarker BRAF (V600E) from Cytological Slides
by Ching-Wei Wang, Hikam Muzakky, Yu-Ching Lee, Yi-Jia Lin and Tai-Kuang Chao
Int. J. Mol. Sci. 2023, 24(3), 2521; https://doi.org/10.3390/ijms24032521 - 28 Jan 2023
Cited by 15 | Viewed by 3805
Abstract
Thyroid cancer is the most common endocrine cancer. Papillary thyroid cancer (PTC) is the most prevalent form of malignancy among all thyroid cancers arising from follicular cells. Fine needle aspiration cytology (FNAC) is a non-invasive method regarded as the most cost-effective and accurate [...] Read more.
Thyroid cancer is the most common endocrine cancer. Papillary thyroid cancer (PTC) is the most prevalent form of malignancy among all thyroid cancers arising from follicular cells. Fine needle aspiration cytology (FNAC) is a non-invasive method regarded as the most cost-effective and accurate diagnostic method of choice in diagnosing PTC. Identification of BRAF (V600E) mutation in thyroid neoplasia may be beneficial because it is specific for malignancy, implies a worse prognosis, and is the target for selective BRAF inhibitors. To the authors’ best knowledge, this is the first automated precision oncology framework effectively predict BRAF (V600E) immunostaining result in thyroidectomy specimen directly from Papanicolaou-stained thyroid fine-needle aspiration cytology and ThinPrep cytological slides, which is helpful for novel targeted therapies and prognosis prediction. The proposed deep learning (DL) framework is evaluated on a dataset of 118 whole slide images. The results show that the proposed DL-based technique achieves an accuracy of 87%, a precision of 94%, a sensitivity of 91%, a specificity of 71% and a mean of sensitivity and specificity at 81% and outperformed three state-of-the-art deep learning approaches. This study demonstrates the feasibility of DL-based prediction of critical molecular features in cytological slides, which not only aid in accurate diagnosis but also provide useful information in guiding clinical decision-making in patients with thyroid cancer. With the accumulation of data and the continuous advancement of technology, the performance of DL systems is expected to be improved in the near future. Therefore, we expect that DL can provide a cost-effective and time-effective alternative tool for patients in the era of precision oncology. Full article
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Review

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17 pages, 356 KiB  
Review
Mouse Models to Examine Differentiated Thyroid Cancer Pathogenesis: Recent Updates
by Hye Ryeon Choi and Kwangsoon Kim
Int. J. Mol. Sci. 2023, 24(13), 11138; https://doi.org/10.3390/ijms241311138 - 6 Jul 2023
Cited by 1 | Viewed by 1761
Abstract
Although the overall prognosis of differentiated thyroid cancer (DTC), the most common endocrine malignancy, is favorable, a subset of patients exhibits aggressive features. Therefore, preclinical models that can be utilized to investigate DTC pathogenesis and novel treatments are necessary. Various mouse models have [...] Read more.
Although the overall prognosis of differentiated thyroid cancer (DTC), the most common endocrine malignancy, is favorable, a subset of patients exhibits aggressive features. Therefore, preclinical models that can be utilized to investigate DTC pathogenesis and novel treatments are necessary. Various mouse models have been developed based on advances in thyroid cancer genetics. This review focuses on recent progress in mouse models that have been developed to elucidate the molecular pathogenesis of DTC. Full article
20 pages, 2162 KiB  
Review
Thyroid Axis and Vestibular Physiopathology: From Animal Model to Pathology
by Guillaume Rastoldo and Brahim Tighilet
Int. J. Mol. Sci. 2023, 24(12), 9826; https://doi.org/10.3390/ijms24129826 - 6 Jun 2023
Cited by 3 | Viewed by 3172
Abstract
A recent work of our group has shown the significant effects of thyroxine treatment on the restoration of postural balance function in a rodent model of acute peripheral vestibulopathy. Based on these findings, we attempt to shed light in this review on the [...] Read more.
A recent work of our group has shown the significant effects of thyroxine treatment on the restoration of postural balance function in a rodent model of acute peripheral vestibulopathy. Based on these findings, we attempt to shed light in this review on the interaction between the hypothalamic–pituitary–thyroid axis and the vestibular system in normal and pathological situations. Pubmed database and relevant websites were searched from inception through to 4 February 2023. All studies relevant to each subsection of this review have been included. After describing the role of thyroid hormones in the development of the inner ear, we investigated the possible link between the thyroid axis and the vestibular system in normal and pathological conditions. The mechanisms and cellular sites of action of thyroid hormones on animal models of vestibulopathy are postulated and therapeutic options are proposed. In view of their pleiotropic action, thyroid hormones represent a target of choice to promote vestibular compensation at different levels. However, very few studies have investigated the relationship between thyroid hormones and the vestibular system. It seems then important to more extensively investigate the link between the endocrine system and the vestibule in order to better understand the vestibular physiopathology and to find new therapeutic leads. Full article
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30 pages, 1990 KiB  
Review
The Thyroid Hormone Axis and Female Reproduction
by Ethan D. L. Brown, Barnabas Obeng-Gyasi, Janet E. Hall and Skand Shekhar
Int. J. Mol. Sci. 2023, 24(12), 9815; https://doi.org/10.3390/ijms24129815 - 6 Jun 2023
Cited by 23 | Viewed by 16028
Abstract
Thyroid function affects multiple sites of the female hypothalamic-pituitary gonadal (HPG) axis. Disruption of thyroid function has been linked to reproductive dysfunction in women and is associated with menstrual irregularity, infertility, poor pregnancy outcomes, and gynecological conditions such as premature ovarian insufficiency and [...] Read more.
Thyroid function affects multiple sites of the female hypothalamic-pituitary gonadal (HPG) axis. Disruption of thyroid function has been linked to reproductive dysfunction in women and is associated with menstrual irregularity, infertility, poor pregnancy outcomes, and gynecological conditions such as premature ovarian insufficiency and polycystic ovarian syndrome. Thus, the complex molecular interplay between hormones involved in thyroid and reproductive functions is further compounded by the association of certain common autoimmune states with disorders of the thyroid and the HPG axes. Furthermore, in prepartum and intrapartum states, even relatively minor disruptions have been shown to adversely impact maternal and fetal outcomes, with some differences of opinion in the management of these conditions. In this review, we provide readers with a foundational understanding of the physiology and pathophysiology of thyroid hormone interactions with the female HPG axis. We also share clinical insights into the management of thyroid dysfunction in reproductive-aged women. Full article
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Other

Jump to: Research, Review

5 pages, 881 KiB  
Case Report
Atrial Fibrillation with Heart Failure in a Case with Resistance to Thyroid Hormone Due to a Rare Thyroid Hormone Receptor β Gene Mutation
by Huei-Pin Lai and Mei-Hsiu Chen
Int. J. Mol. Sci. 2022, 23(23), 15241; https://doi.org/10.3390/ijms232315241 - 3 Dec 2022
Viewed by 1666
Abstract
Resistance to thyroid hormone (RTH) is a rare disease typically associated with elevated levels of thyroid hormones and non-suppressed thyroid stimulating hormones. The most common cause of RTH is thyroid hormone receptor β (THRβ) gene mutation. Most individuals with RTH are [...] Read more.
Resistance to thyroid hormone (RTH) is a rare disease typically associated with elevated levels of thyroid hormones and non-suppressed thyroid stimulating hormones. The most common cause of RTH is thyroid hormone receptor β (THRβ) gene mutation. Most individuals with RTH are considered clinical euthyroid. We report a family with a rare heterozygous point mutation, c.959G>T, (p.R320L) of the THRβ gene. The proband developed atrial fibrillation and life-threatening heart failure with pulmonary edema, which was quite different from previously reported THRβ gene mutations. Considering the rareness of RTH and the heterogeneity of its phenotypes, our report allows for a better understanding of the manifestation and management of patients with RTH and THRβ gene mutation. Full article
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