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Sandeep Kumar Parvathareddy Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

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Abdul K Siraj Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

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Zeeshan Qadri Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

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Saeeda O Ahmed Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

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Felisa DeVera Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

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Saif Al-Sobhi Department of Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

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Fouad Al-Dayel Department of Pathology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

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Khawla S Al-Kuraya Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

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Objective

Recently, lymph node ratio (LNR) has emerged as an alternative to American Joint Committee on Cancer (AJCC) N stage, with superior prognostic value. The utility of LNR in Middle Eastern papillary thyroid carcinoma (PTC) remains unknown. Therefore, we retrospectively analyzed a large cohort of 1407 PTC patients for clinicopathological associations of LNR.

Methods

Receiver operating characteristics (ROC) curve was used to determine the cut-off for LNR. We also performed multivariate logistic regression analysis to determine whether LNR or AJCC N stage was superior in predicting recurrence in PTC.

Results

Based on ROC curve analysis, a cut-off of 0.15 was chosen for LNR. High LNR was significantly associated with adverse clinicopathological characteristics such as male sex, extrathyroidal extension, lymphovascular invasion, multifocality, bilateral tumors, T4 tumors, lateral lymph node (N1b) involvement, distant metastasis, advanced tumor stage, American Thyroid Association (ATA) high-risk category and tumor recurrence. On multivariate analysis, we found that LNR was a better predictor of tumor recurrence than AJCC N stage (odds ratio: 1.96 vs 1.30; P value: 0.0184 vs 0.3831). We also found that LNR combined with TNM stage and ATA risk category improved the prediction of recurrence-free survival, compared to TNM stage or ATA risk category alone.

Conclusions

The present study suggests LNR is an independent predictor of recurrence in Middle Eastern PTC. Integration of LNR with 8th edition AJCC TNM staging system and ATA risk stratification will improve the accuracy to predict recurrence in Middle Eastern PTC and help in tailoring treatment and surveillance strategies in these patients.

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Josi Vidart Thyroid Section, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
Intensive Care Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil

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Paula Jaskulski Internal Medicine Division, Hospital de Clínicas de Porto Alegre, Internal Medicine Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil

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Ana Laura Kunzler Internal Medicine Division, Hospital de Clínicas de Porto Alegre, Internal Medicine Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil

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Rafael Aguiar Marschner Thyroid Section, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil

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André Ferreira de Azeredo da Silva Internal Medicine Division, Hospital de Clínicas de Porto Alegre, Internal Medicine Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil

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Simone Magagnin Wajner Thyroid Section, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
Internal Medicine Division, Hospital de Clínicas de Porto Alegre, Internal Medicine Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil

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We performed a systematic review and meta-analysis to comprehensively determine the prevalence and the prognostic role of non-thyroidal illness syndrome (NTIS) in critically ill patients. We included studies that assessed thyroid function by measuring the serum thyroid hormone (TH) level and in-hospital mortality in adult septic patients. Reviews, case reports, editorials, letters, animal studies, duplicate studies, and studies with irrelevant populations and inappropriate controls were excluded. A total of 6869 patients from 25 studies were included. The median prevalence rate of NTIS was 58% (IQR 33.2–63.7). In univariate analysis, triiodothyronine (T3) and free T3 (FT3) levels in non-survivors were relatively lower than that of survivors (8 studies for T3; standardized mean difference (SMD) 1.16; 95% CI, 0.41–1.92; I2 = 97%; P < 0.01). Free thyroxine (FT4) levels in non-survivors were also lower than that of survivors (12 studies; SMD 0.54; 95% CI, 0.31–0.78; I2 = 83%; P < 0.01). There were no statistically significant differences in thyrotropin levels between non-survivors and survivors. NTIS was independently associated with increased risk of mortality in critically ill patients (odds ratio (OR) = 2.21, 95% CI, 1.64–2.97, I2 = 65% P  < 0.01). The results favor the concept that decreased thyroid function might be associated with a worse outcome in critically ill patients. Hence, the measurement of TH could provide prognostic information on mortality in adult patients admitted to ICU.

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Brenda Anguiano Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Querétaro, México

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Carlos Montes de Oca Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Querétaro, México

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Evangelina Delgado-González Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Querétaro, México

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Carmen Aceves Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Querétaro, México

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Thyroid hormones (THs) are involved in the development and function of the male reproductive system, but their effects on the prostate have been poorly studied. This work reviews studies related to the interrelationship between the thyroid and the prostate. The information presented here is based upon bibliographic searches in PubMed using the following search terms: prostate combined with thyroid hormone or triiodothyronine, thyroxine, hypothyroidism, hyperthyroidism, or deiodinase. We identified and searched 49 articles directly related to the issue, and discarded studies related to endocrine disruptors. The number of publications has grown in the last 20 years, considering that one of the first studies was published in 1965. This review provides information based on in vitro studies, murine models, and clinical protocols in patients with thyroid disorders. Studies indicate that THs regulate different aspects of growth, metabolism, and prostate pathology, whose global effect depends on total and/or free concentrations of THs in serum, local bioavailability, and the endocrine androgen/thyronine context.

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Huixing Liu Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China

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Daoquan Peng Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China

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Hypothyroidism is often associated with elevated serum levels of total cholesterol, LDL-C and triglycerides. Thyroid hormone (TH) affects the production, clearance and transformation of cholesterol, but current research shows that thyroid-stimulating hormone (TSH) also participates in lipid metabolism independently of TH. Therefore, the mechanism of hypothyroidism-related dyslipidemia is associated with the decrease of TH and the increase of TSH levels. Some newly identified regulatory factors, such as proprotein convertase subtilisin/kexin type 9, angiogenin-like proteins and fibroblast growth factors are the underlying causes of dyslipidemia in hypothyroidism. HDL serum concentration changes were not consistent, and its function was reportedly impaired. The current review focuses on the updated understanding of the mechanism of hypothyroidism-related dyslipidemia.

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Ru-Xuan Zhao Department of Endocrinology, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Ting-Ting Shi Department of Endocrinology, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Sha Luo Department of Nuclear Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Yun-Fu Liu Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Zhong Xin Department of Endocrinology, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Jin-Kui Yang Department of Endocrinology, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Background

Graves’ orbitopathy (GO) is an autoimmune disease with mechanical impairment of orbital muscles and lacrimal gland dysfunction. The frequently used methods of assessing GO activity include Clinical Activity Score (CAS), CT, and MRI. These approaches are mainly associated with orbital muscles; however, there are not many studies that focus on the lacrimal gland inflammation of GO patients.

Objective

The aim of this study is to assess the usefulness of 99mTc-DTPA single-photon emission (SPE) CT/CT in evaluating the lacrimal gland inflammation in GO, as compared with other methods.

Methods

A retrospective analysis of 48 patients with active GO compared with 33 controls was conducted. All subjects underwent clinical–endocrinological analyses, CAS evaluation, CT scans, and SPECT/CT examination. Lacrimal gland dimensions were determined and analyzed.

Results

The lacrimal glands in patients with GO were significantly larger in all measured dimensions (P  < 0.001) on CT scans relative to those in controls. Increased lacrimal gland diethylene triamine pentaacetic acid (DTPA) uptake ratios (P  < 0.001) were displayed in active GO patients compared to controls and were also correlated with thyrotropin receptor antibody levels. The cut-off value for discriminating active and inactive disease was calculated to be 1.735, with specificity of 82.6% and sensitivity of 74.2%. SPECT/CT uptake ratios and CAS values were positively correlated in all GO patients. SPECT/CT uptake ratios were also positively correlated with CT measurements including lacrimal gland volume and coronal width in GO patients.

Conclusions

These data indicated that lacrimal gland SPECT/CT images can serve as a good tool for assessing the inflammation and disease activity of GO.

Open access
Luis Eduardo Barbalho de Mello Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
Postgraduate Program in Health Sciences, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil

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Thaise Nayane Ribeiro Carneiro Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil

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Aline Neves Araujo Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil

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Camila Xavier Alves Postgraduate Program in Health Sciences, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil

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Pedro Alexandre Favoretto Galante Centro de Oncologia Molecular, Hospital Sírio-libanês, São Paulo, São Paulo, Brazil

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Vanessa Candiotti Buzatto Centro de Oncologia Molecular, Hospital Sírio-libanês, São Paulo, São Paulo, Brazil

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Maria das Graças de Almeida Postgraduate Program in Health Sciences, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil
Department of Clinical and Toxicological Analyses, Natal, Rio Grande do Norte, Brazil

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Karina Marques Vermeulen-Serpa Postgraduate Program in Health Sciences, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil

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Sancha Helena de Lima Vale Department of Clinical and Toxicological Analyses, Natal, Rio Grande do Norte, Brazil
Department of Nutrition, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil

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Fernando José de Pinto Paiva Postgraduate Program in Health Sciences, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil

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José Brandão-Neto Postgraduate Program in Health Sciences, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil

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Janete Maria Cerutti Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil

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The genetics underlying non-syndromic familial non-medullary thyroid carcinoma (FNMTC) is still poorly understood. To identify susceptibility genes for FNMTC, we performed whole-exome sequencing (WES) in a Brazilian family affected by papillary thyroid carcinoma (PTC) in three consecutive generations. WES was performed in four affected and two unaffected family members. Manual inspection in over 100 previously reported susceptibility genes for FNMTC showed that no variants in known genes co-segregated with disease phenotype in this family. Novel candidate genes were investigated using PhenoDB and filtered using Genome Aggregation (gnomAD) and Online Archive of Brazilian Mutations (ABraOM) population databases. The missense variant p.Ile657Met in the NID1 gene was the only variant that co-segregated with the disease, while absent in unaffected family members and controls. The allele frequency for this variant was <0.0001 in the gnomAD and ABbraOM databases. In silico analysis predicted the variant to be deleterious or likely damaging to the protein function. Somatic mutations in NID1 gene were found in nearly 500 cases of different cancer subtypes in the intOGen platform. Immunohistochemistry analysis showed NID1 expression in PTC cells, while it was absent in normal thyroid tissue. Our findings were corroborated using data from the TCGA cohort. Moreover, higher expression of NID1 was associated with higher likelihood of relapse after treatment and N1b disease in PTCs from the TCGA cohort. Although replication studies are needed to better understand the role of this variant in the FNMTC susceptibility, the NID1 variant (c.1971T>G) identified in this study fulfills several criteria that suggest it as a new FNMTC predisposing gene.

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W J Bom Department of Internal Medicine, Rijnstate Hospital, Arnhem, the Netherlands

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F B M Joosten Department of Radiology, Rijnstate Hospital, Arnhem, the Netherlands

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M M G J van Borren Department of Clinical Chemistry, Rijnstate Hospital, Arnhem, the Netherlands

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E P Bom Department of Radiology, Rijnstate Hospital, Arnhem, the Netherlands

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R R J P van Eekeren Department of Surgery, Rijnstate Hospital, Arnhem, the Netherlands

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H de Boer Department of Internal Medicine, Rijnstate Hospital, Arnhem, the Netherlands

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Objective

Radiofrequency ablation (RFA) is increasingly considered the prime option for treating symptomatic, benign, non-functioning thyroid nodules (NFTN). However, little is known about the degree of operator experience required to achieve optimal results. This study describes the RFA learning curve of a single-center team.

Methods

A retrospective cohort study of the first 103 patients receiving RFA treatment for a single, symptomatic, and benign NFTN, with a follow-up of at least 1 year. The primary outcome measure was technique efficacy, defined as the percentage of patients with a 6-month nodal volume reduction ratio (VRR) >50% after single-session RFA. Optimal treatment efficacy was defined as a 6-month VRR >50% achieved in at least 75% of patients. Secondary outcomes were complications of RFA and indications of secondary interventions.

Results

Median nodal volume at baseline was 12.0 mL (range 2.0–58.0 mL). A 6-month VRR >50% was achieved in 45% of the first 20 patients, 75% of the next 20, and 79% of the following 63 patients. Complications included minor bleeding (N = 4), transient hyperthyroidism (N = 4), and transient loss of voice (N = 1). Poor volume reduction or nodular regrowth led to diagnostic lobectomy in 11 patients and a second RFA in 5. Lobectomy revealed a follicular carcinoma (T2N0M0) in 2 patients. In 1 patient, nodule regrowth was caused by an intranodular solitary B-cell lymphoma.

Conclusion

About 40 procedures are required to achieve a 6-month VRR >50% in the majority of patients. Appropriate follow-up with re-evaluation is recommended for all patients with a VRR <50% and in those with regrowth to exclude underlying malignancy.

Open access