Browse

You are looking at 51 - 60 of 636 items for

Open access

Hrvoje Jakovac, Antun Ferenčić, Christophe Stemberger, Bojana Mohar Vitezić, and Dražen Cuculić

The clinical and laboratory findings of subacute thyroiditis have been repeatedly reported as being associated with acute Sars-Cov-2 infection and post-COVID-19 syndrome. The exact mechanisms and histopathological correlations underlying thyroid involvement remained unresolved, but current insights suggest either direct viral damage, systemic inflammatory reaction, or an autoimmune response as possible noxious effectors. Here we present findings of immunohistochemical/immunofluorescence detection of Sars-Cov-2 viral proteins (spike/S and nucleocapside proteins) in relation to histoarchitectonic changes of autoptic thyroid tissue obtained from patient who deceased from COVID-19.

Open access

Kristine Z Swan, Johnson Thomas, Viveque E Nielsen, Marie Louise Jespersen, and Steen J Bonnema

Background

Artificial intelligence algorithms could be used to risk-stratify thyroid nodules and may reduce the subjectivity of ultrasonography. One such algorithm is AIBx which has shown good performance. However, external validation is crucial prior to clinical implementation.

Materials and methods

Patients harboring thyroid nodules 1–4 cm in size, undergoing thyroid surgery from 2014 to 2016 in a single institution, were included. A histological diagnosis was obtained in all cases. Medullary thyroid cancer, metastasis from other cancers, thyroid lymphomas, and purely cystic nodules were excluded. Retrospectively, transverse ultrasound images of the nodules were analyzed by AIBx, and the results were compared with histopathology and Thyroid Imaging Reporting and Data System (TIRADS), calculated by experienced physicians.

Results

Out of 329 patients, 257 nodules from 209 individuals met the eligibility criteria. Fifty-one nodules (20%) were malignant. AIBx had a negative predictive value (NPV) of 89.2%. Sensitivity, specificity, and positive predictive values (PPV) were 78.4, 44.2, and 25.8%, respectively. Considering both TIRADS 4 and TIRADS 5 nodules as malignant lesions resulted in an NPV of 93.0%, while PPV and specificity were only 22.4 and 19.4%, respectively. By combining AIBx with TIRADS, no malignant nodules were overlooked.

Conclusion

When applied to ultrasound images obtained in a different setting than used for training, AIBx had comparable NPVs to TIRADS. AIBx performed even better when combined with TIRADS, thus reducing false negative assessments. These data support the concept of AIBx for thyroid nodules, and this tool may help less experienced operators by reducing the subjectivity inherent to thyroid ultrasound interpretation.

Open access

Yingxin Fang, Pingping Dang, Yue Liang, Defa Zhao, Ranran Wang, Yue Xi, Dan Zhang, Wei Wang, Zhongyan Shan, Weiping Teng, and Xiaochun Teng

Background

Proper thyroid hormone signaling via the TRα1 nuclear receptor is required for normal neurodevelopmental processes. The specific downstream mechanisms mediated by TRα1 that impact brain development remain to be investigated.

Methods

In this study, the structure, function and transcriptome of hippocampal tissue in a mouse model expressing the first RTHα mutation discovered in a patient, THRA E403X, were analyzed. RNAscope was used to visualize the spatial and temporal expression of Thra1 mRNA in the hippocampus of WT mice, which is corresponding to THRA1 mRNA in humans. The morphological structure was analyzed by Nissl staining, and the synaptic transmission was analyzed on the basis of long-term potentiation. The Morris water maze test and the zero maze test were used to evaluate the behavior. RNA-seq and quantitative real-time PCR were used to analyze the differentially expressed genes (DEGs) of the hippocampal tissues in the mouse model expressing the Thra E403X mutation.

Results

The juvenile mutant Thra E403X mice presented with delayed neuronal migration, disordered neuronal distribution, and decreased synaptic plasticity. A total of 754 DEGs, including 361 upregulated genes and 393 downregulated genes, were identified by RNA-seq. DEG-enriched Gene Ontology (GO) and KEGG pathways were associated with PI3K-Akt signaling, ECM−receptor interaction, neuroactive ligand−receptor interaction, and a range of immune-related pathways. 25 DEGs were validated by qPCR.

Conclusions

The Thra E403X mutation results in histological and functional abnormalities, as well as transcriptomic alterations in the juvenile mouse hippocampus. This study of the Thra E403X mutant offers new insights into the biological cause of RTHα-associated neurological diseases.

Open access

Xian Qiu, Lin Cheng, Ri Sa, Hao Fu, Yuchen Jin, and Libo Chen

Objective

Sorafenib and lenvatinib have been recommended as standard tyrosine kinase inhibitors (TKIs) for progressive radioiodine-refractory differentiated thyroid carcinoma (RR-DTC). However, their efficacy remains limited with unresolved drug resistance. Therefore, we conceived this open-label study based on real-world evidence to investigate the efficacy and safety of apatinib in patients with progressive RR-DTC.

Methods

Off-label use of apatinib as either initial treatment or salvage treatment for sorafenib resistance was investigated. The primary endpoint was progression-free survival (PFS) and the secondary endpoints included objective response rate (ORR), overall survival (OS), and safety.

Results

For all 28 enrolled patients, the median PFS was 15.1 months, with an ORR of 69.6%. The median OS was not reached at the data cut-off. In detail, the median PFS of 17.3 months and the ORR of 75% were determined in patients with TKI-naive RR-DTC (initial treatment group, n  = 14). And, in patients with first-line sorafenib-resistant RR-DTC (salvage treatment group, n  = 14), a median PFS of 12.0 months was reached, with an ORR of 45.5%. In the salvage treatment group, the median OS from the start of apatinib administration was 20.6 months, reaching 89.1 months from sorafenib treatment initiation. Adverse events at grade 3 or higher occurred in 64.3% of all subjects treated with apatinib.

Conclusions

This study demonstrated that apatinib shows promise against RR-DTC with tolerable toxicity, representing a novel initial treatment for progressive RR-DTC and effective salvage treatment for RR-DTC resistant to sorafenib.

Open access

Junyu Tong, Maomei Ruan, Yuchen Jin, Hao Fu, Lin Cheng, Qiong Luo, Zhiyan Liu, Zhongwei Lv, and Libo Chen

Poorly differentiated thyroid carcinoma (PDTC) is a rare thyroid carcinoma originating from follicular epithelial cells. No explicit consensus can be achieved to date due to sparse clinical data, potentially compromising the outcomes of patients. In this comprehensive review from a clinician’s perspective, the epidemiology and prognosis are described, diagnosis based on manifestations, pathology, and medical imaging are discussed, and both traditional and emerging therapeutics are addressed as well. Turin consensus remains the mainstay diagnostic criteria for PDTC, and individualized assessments are decisive for treatment option. The prognosis is optimal if complete resection is performed at early stage but dismal in nearly half of patients with locally advanced and/or distant metastatic diseases, in which adjuvant therapies such as 131I therapy, external beam radiation therapy, and chemotherapy should be incorporated. Emerging therapeutics including molecular targeted therapy, differentiation therapy, and immunotherapy deserve further investigations to improve the prognosis of PDTC patients with advanced disease.

Open access

Julia Ramalho Amalio da Silva Breder, Paulo Alonso Garcia Alves, Mario Lucio Araújo, Barbara Pires, Priscila Valverde, Daniel Alves Bulzico, Fernanda Andrade Accioly, Rossana Corbo, Mario Vaisman, and Fernanda Vaisman

Objective

A sharp increase in pediatric thyroid cancer incidence is observed during adolescence, driven mainly by girls. Differences in disease presentation across sexual maturity stages raise the question of whether sex steroids have a role in the heterogeneity. The aims of this study were to analyze the influence of puberty and sex on clinical presentation and prognosis and to evaluate the correlation between the expression of sex hormone receptors.

Design and methods

Clinical records and immunohistochemical of specimens from 79 patients were analyzed. Puberty was analyzed by two criteria: end of puberty and beginning, in which the age of 10 was the cutoff.

Results

Postpubertal were more frequently classified as having low-risk disease and a lower frequency of persistent disease, especially when the completion of puberty was used as the criteria. Male sex was associated with a higher risk of persistent disease at the end of the observation period. Estrogen receptor α positivity was low in the entire sample, while progesterone receptor positivity was positive in 30% of the cases. Female hormone receptor expression was not associated with sex, American Thyroid Association risk score, persistent structural disease, or pubertal status.

Conclusion

Our study showed that the completion of puberty correlated best with the clinical behaviour of pediatric thyroid cancer. It was also shown that postpubertal patients have a less aggressive initial presentation and better outcomes. However, this observation could not be explained by the expression of estrogen and progesterone receptors in the primary tumors.

Open access

Jan Jiskra, Jiří Horáček, Sylvie Špitálníková, Jan Paleček, Zdeňka Límanová, Jan Krátký, Drahomíra Springer, Kristýna Žabková, and Hana Vítková

Objective

Thyroid nodules are a common finding in the general population. The primary aim of the study was to determine the prevalence of thyroid nodules and cancer found by ultrasound (US) in women who underwent screening for thyroid dysfunction during pregnancy.

Design

A double-centric, retrospective, cohort study.

Patients and methods

We searched through medical records, including thyroid ultrasonography, of pregnant women who were positively screened for thyroid disorders (using thyroid-stimulating hormone and thyroid antibodies) from an unselected population (‘universal screening group’, n  = 690) and of women who underwent the testing based on the presence of clinical risk factors defined by American Thyroid Association (’case-finding group’, n  = 249).

Results

Prevalence of benign and malignant thyroid nodules was lower in the ‘universal screening group’ than in the ‘case-finding group’ (9.9% vs 17.7%, P= 0.002, and 0.9% vs 7.2%, P< 0.001, respectively). Consistently, the thyroid cancer rate was lower among the nodules in the ‘universal screening group’ than in the ‘case-finding group’ (8.1% vs 29.0%, P= 0.003). Ultrasound EU-TIRADS (European Thyroid Imaging and Reporting Data System) category ≥4 had a 95.8% sensitivity for thyroid cancer. In palpable nodules, the prevalence of cancer was significantly higher than in the non-palpable ones (44.0% vs 2.2%, P < 0.001). In a multivariate regression analysis, thyroid nodules were associated with a history of infertility and parity.

Conclusions

Compared to the data from cancer registries, universal screening allowed detecting thyroid cancer in pregnancy three to five times more frequently, but the cancer rate among nodules (8.1%) did not differ from the common population. US had very good sensitivity for thyroid cancer in pregnancy.

Open access

Giorgio Radetti, Franco Rigon, Alessandro Salvatoni, Irene Campi, Tiziana De Filippis, Valentina Cirello, Silvia Longhi, Fabiana Guizzardi, Marco Bonomi, and Luca Persani

Introduction

Patients with congenital hypothyroidism (CH) may transiently show a certain degree of pituitary resistance to levothyroxine (LT4) which, however, normalizes subsequently. However, in some individuals, thyroid-stimulating hormone (TSH) fails to normalize despite adequate LT4 treatment.

Methods

Nine patients with CH followed in three Academic Centre who developed over time resistance to thyroid hormones underwent extensive biochemical and genetic analyses. These latter were performed by Sanger sequence or targeted next-generation sequencing technique including a panel of candidate genes involved in thyroid hormone actions and congenital hypothyroidism (CH): THRA, THRB, DIO1, DIO2, SLC16A2, SECISBP2, DUOX2, DUOXA2, FOXE1, GLIS3, IYD, JAG1, NKX2-1, NKX2- 5, PAX8, SLC26A4, SLC5A5, TG, TPO, TSHR.

Results

All patients displayed a normal sensitivity to thyroid hormone (TH) in the first years of life but developed variable degrees of resistance to LT4 treatment at later stages. In all cases, TSH normalized only in the presence of high free thyroxine levels. Tri-iodothyronine suppression test followed by thyrotrophin-releasing hormone stimulation was performed in two cases and was compatible with central resistance to THs. This biochemical feature was present independently on the cause of CH, being observed either in patients with an ectopic (n = 2) or eutopic gland (n = 3) or in case of athyreosis (n = 1). None of the patients had genetic variants in genes involved in the regulation of TH actions, while in two cases, we found two double heterozygous missense variants in TSHR and GLIS3 or in DUOX2 and SLC26A4 genes, respectively.

Conclusions

We report CH patients who showed an acquired and unexplainable pituitary refractoriness to TH action.

Open access

Salman Razvi, Avais Jabbar, Arjola Bano, Lorna Ingoe, Peter Carey, Shahid Junejo, Honey Thomas, Caroline Addison, David Austin, John P Greenwood, and Azfar G Zaman

Objectives

To study the relationship between serum-free T3 (FT3), C-reactive protein (CRP) and all-cause mortality in patients with acute myocardial infarction (AMI).

Design

Prospective multicentre longitudinal cohort study.

Methods

Between December 2014 and December 2016, thyroid function and CRP were analysed in AMI (both ST-elevation (STEMI) and non-ST-elevation) patients from the Thyroxine in Acute Myocardial Infarction study. The relationship of FT3 and CRP at baseline with all-cause mortality up to June 2020 was assessed. Mediation analysis was performed to evaluate if CRP mediated the relationship between FT3 and mortality.

Results

In 1919 AMI patients (29.2% women, mean (s.d.) age: 64.2 (12.1) years and 48.7% STEMI) followed over a median (interquartile range) period of 51 (46–58) months, there were 277 (14.4%) deaths. Overall, lower serum FT3 and higher CRP levels were associated with higher risk of mortality. When divided the patients into tertiles based on the levels of FT3 and CRP; the group with the lowest FT3 and highest CRP levels had a 2.5-fold increase in mortality risk (adjusted hazard ratio (95% CI) of 2.48 (1.82–3.16)) compared to the group with the highest FT3 and lowest CRP values. CRP mediated 9.8% (95% CI: 6.1–15.0%) of the relationship between FT3 and mortality.

Conclusions

In AMI patients, lower serum FT3 levels on admission are associated with a higher mortality risk, which is partly mediated by inflammation. Adequately designed trials to explore the potential benefits of T3 in AMI patients are required.

Open access

Stéphane Bardet, Renaud Ciappuccini, Livia Lamartina, and Sophie Leboulleux

Introduction

Serum calcitonin (CT) and carcinoembryonic antigen (CEA) are valuable tumour markers in patients with medullary thyroid carcinoma (MTC). Both markers most often evolve in parallel after treatment. Selpercatinib (LOXO-292) is a highly selective RET kinase inhibitor indicated in advanced RET-mutant MTC patients.

Cases presentation

In this study, we report two observations of RET-mutant progressive metastatic and symptomatic MTC patients who were treated with selpercatinib. Patient 1, a 61-year-old man, presented dyspnoea and diarrhoea at selpercatinib initiation with large neck lymph nodes and lung metastases. Patient 2, a 76-year-old man, had acute discomfort with flush and diarrhoea, with small but diffuse bone and liver disease. Both patients had an objective tumour response with rapid clinical improvement and RECIST 1.1 response (−90%) in patient 1. A rapid dramatic decrease in CT level was observed in both patients (−99% in both patients), while CEA levels gradually and sustainably increased after selpercatinib initiation (+207% at cycle 15 in patient 1 and + 835% at cycle 14 in patient 2). In both patients, 18FDG PET/CT did not show any abnormal uptake that could explain the CEA increase. Colonoscopy and oesogastric fibroscopy showed colonic polyposis with mild oesophagitis and gastritis in patient 1 and were normal in patient 2.

Conclusion

These observations show an unusual and lasting increase in serum CEA in two MTC patients who exhibited an objective tumour response to selpercatinib. The mechanism behind this unexpected rise in CEA level remains unknown. The frequency of this evolving profile will be determined in further phase III studies.