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Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
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Mayfair Radiology, Calgary, Alberta, Canada
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Departments of Medicine, Oncology, Pathology and Laboratory Medicine, Biochemistry and Molecular Biology, and Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
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Objective
The aim of this study was to prospectively evaluate the quality of postoperative neck ultrasound (POU) for thyroid cancer patients after implementing European Thyroid Association (ETA) guideline-based POU assessment.
Methods
Our analysis involved 672 differentiated thyroid cancer patients. POU report quality was compared between the implementation radiology group (IRG), which implemented ETA guideline-based assessment in 2018, and all non-implementation radiology groups (NIRG). Differences in POU quality were evaluated before and after the implementation of guideline-based assessment. Additionally, we evaluated the ability of serum thyroglobulin (Tg) level <0.2 ng/mL or between 0.21 and 0.99 ng/mL and normal POU lesion status at 1-year follow-up to predict the absence of persistent disease or relapse at 3-year follow-up.
Results
IRG had significantly higher mean utility scores for POU reports of abnormal thyroid bed nodules compared to NIRG (P < 0.001). IRG's POU reports for suspicious nodules and lymph nodes were considered sufficient in 94% and 85% of cases, respectively, compared to 45% and 68% for NIRG. For patients with normal US lesion status and Tg <0.2 ng/mL or Tg 0.21–0.99 ng/mL at 1-year follow-up, the negative predictive values were 96% for both.
Conclusions
Implementation of 2013 ETA POU-reporting guidelines allowed for the provision of high-quality POU reports, which may lead to increased accuracy in assessing the response to treatment and in estimating the risk of recurrence of thyroid cancer and likely reduce unnecessary repeat POU or FNA.
Institute for Health Science Research Germans Trias i Pujol (IGTP), Badalona, Spain
Department of Medicine, Autonomous University of Barcelona, Badalona, Spain
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Department of Obstetrics & Gynecology, Germans Trias i Pujol University Hospital, Badalona, Spain
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Health Department, Centre d’Estudis Epidemiològics sobre les Infeccions de Transmissió Sexual i Sida de Catalunya (CEEISCAT), Generalitat de Catalunya, Badalona, Spain
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Health Department, Centre d’Estudis Epidemiològics sobre les Infeccions de Transmissió Sexual i Sida de Catalunya (CEEISCAT), Generalitat de Catalunya, Badalona, Spain
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Institute for Health Science Research Germans Trias i Pujol (IGTP), Badalona, Spain
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Institute for Health Science Research Germans Trias i Pujol (IGTP), Badalona, Spain
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Health Department, Centre d’Estudis Epidemiològics sobre les Infeccions de Transmissió Sexual i Sida de Catalunya (CEEISCAT), Generalitat de Catalunya, Badalona, Spain
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Institute for Health Science Research Germans Trias i Pujol (IGTP), Badalona, Spain
Department of Medicine, Autonomous University of Barcelona, Badalona, Spain
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Objective
Longitudinal evaluation of thyroid function throughout pregnancy in the same subject could offer precise information about its dynamics as a physiological mechanism of adaption to the requirements. In this study, we evaluated longitudinal trajectories of maternal thyroid function during pregnancy by a latent class growth analysis and explored their association with maternal–fetal outcomes.
Methods
A prospective observational study was carried out, including 414 healthy pregnant women, from the first trimester to delivery. Thyroid function and autoimmunity were measured in the three trimesters. Clinical data during pregnancy were obtained. Longitudinal mixed model techniques were performed to explore trajectories of gestational thyroid function.
Results
Three different longitudinal trajectories were obtained from maternal thyrotropin (TSH) levels: low-increasing TSH (class 1) in 86% of cases, high-increasing TSH (class 2) in 9.7%, and decreasing TSH (class 3) in 4.3%. No statistical differences in free thyroxine levels were found among the three classes. Differences in maternal age (P = 0.027) and initial maternal weight (P = 0.043) were observed among the groups. In logistic regression analysis, maternal age correlated with longitudinal trajectories. The three longitudinal classes remain when women with thyroid autoimmunity (TAI) are excluded. Multinomial logistic regression showed maternal age correlated with longitudinal trajectories independently of TAI status.
Conclusions
Three differentiated TSH trajectories were found in healthy pregnant women living in Catalonia, as previously described. No association with obstetric outcomes was observed in these different chronological thyroid pathways, but maternal age might condition the longitudinal mechanism of thyroid function regulation throughout pregnancy.
Amsterdam Gastroenterology, Endocrinology & Metabolism (AGEM) Research Institute, Amsterdam UMC, Amsterdam, the Netherlands
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Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
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Department of Endocrinology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
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Department of Endocrinology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
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Amsterdam Gastroenterology, Endocrinology & Metabolism (AGEM) Research Institute, Amsterdam UMC, Amsterdam, the Netherlands
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Transducin β-like 1 X-linked receptor 1 (TBL1XR1) is a WD40 repeat-containing protein and part of the corepressor complex SMRT/NCoR that binds to the thyroid hormone receptor (TR). We recently described a mutation in TBL1XR1 in patients with Pierpont syndrome. A mouse model bearing this Tbl1xr1 mutation (Tbl1xr1Y446C/Y446C ) displays several aspects of the Pierpont phenotype. Although serum thyroid hormone (TH) concentrations were unremarkable in these mice, tissue TH action might be affected due to the role of TBL1XR1 in the SMRT/NCoR corepressor complex. The aim of the present study was to evaluate tissue TH metabolism and action in a variety of tissues of Tbl1xr1Y446C/Y446C mice. We studied the expression of genes involved in TH metabolism and action in tissues of naïve Tbl1xr1Y446C/Y446C mice and wild type (WT) mice. In addition, we measured deiodinase activity in liver (Dio1 and Dio3), kidney (Dio1 and Dio3) and BAT (Dio2). No striking differences were observed in the liver, hypothalamus, muscle and BAT between Tbl1xr1Y446C/Y446C and WT mice. Pituitary TRα1 mRNA expression was lower in Tbl1xr1Y446C/Y446C mice compared to WT, while the mRNA expression of Tshβ and the positively T3-regulated gene Nmb were significantly increased in mutant mice. Interestingly, Mct8 expression was markedly higher in WAT and kidney of mutants, resulting in (subtle) changes in T3-regulated gene expression in both WAT and kidney. In conclusion, mice harboring a mutation in TBL1XR1 display minor changes in cellular TH metabolism and action. TH transport via MCT8 might be affected as the expression is increased in WAT and kidney. The mechanisms involved need to be clarified.
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Department of Internal Medicine and Therapeutics, University of Pavia, Italy
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Background
Most thyroid cancers of follicular origin have a favorable outcome. Only a small percentage of patients will develop metastatic disease, some of which will become radioiodine refractory (RAI-R). Important challenges to ensure the best therapeutic outcomes include proper, timely, and appropriate diagnosis; decisions on local, systemic treatments; management of side effects of therapies; and a good relationship between the specialist, patients, and caregivers.
Methods
With the aim of providing suggestions that can be useful in everyday practice, a multidisciplinary group of experts organized the following document, based on their shared clinical experience with patients with RAI-R differentiated thyroid cancer (DTC) undergoing treatment with lenvatinib. The main areas covered are patient selection, initiation of therapy, follow-up, and management of adverse events.
Conclusions
It is essential to provide guidance for the management of RAI-R DTC patients with systemic therapies, and especially lenvatinib, since compliance and adherence to treatment are fundamental to achieve the best outcomes. While the therapeutic landscape in RAI-R DTC is evolving, with new targeted therapies, immunotherapy, etc., lenvatinib is expected to remain a first-line treatment and mainstay of therapy for several years in the vast majority of patients and settings. The guidance herein covers baseline work-up and initiation of systemic therapy, relevance of symptoms, multidisciplinary assessment, and patient education. Practical information based on expert experience is also given for the starting dose of lenvatinib, follow-up and monitoring, as well as the management of adverse events and discontinuation and reinitiating of therapy. The importance of patient engagement is also stressed.
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DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
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Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Germany
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Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
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Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
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Objective
Thyroid hormone (TH) transport represents a critical first step in governing intracellular TH regulation. It is still unknown whether the full repertoire of TH transporters has been identified. Members of the solute carrier (SLC) 22 family have substrates in common with the known TH transporters of the organic anion-transporting peptide family. Therefore, we screened the SLC22 family for TH transporters
Methods
Uptake of 1 nM of iodothyronines or sulfated iodothyronines in COS1 cells expressing SLC22 proteins was performed.
Results
We first tested 25 mouse (m) SLC22 proteins for TH uptake and found that the majority of the organic anion transporter (OAT) clade were capable of 3,3’,5-triiodothyronine and/or thyroxine (T4) transport. Based on phylogenetic tree analysis of the mouse and human (h) SLC22 family, we selected eight hSLC22s that grouped with the newly identified mouse TH transporters. Of these, four tested positive for uptake of one or more substrates, particularly hSLC22A11 showed robust (3-fold over control) uptake of T4. Uptake of sulfated iodothyronines was strongly (up to 17-fold) induced by some SLC22s, most notably SLC22A8, hSLC22A9, mSLC22A27 and mSLC22A29. Finally, the zebrafish orthologues of SLC22A6/8 drOatx and drSlc22a6l also transported almost all (sulfated) iodothyronines tested. The OAT inhibitors lesinurad and probenecid inhibited most SLC22 proteins.
Conclusions
Our results demonstrated that members of the OAT clade of the SLC22 family constitute a novel, evolutionary conserved group of transporters for (sulfated) iodothyronines. Future studies should reveal the relevance of these transporters in TH homeostasis and physiology.
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Progress in the management of thyroid eye disease (TED) has been slow for many decades. The recent introduction of teprotumumab (TEP) in the therapeutic arena for TED has had a major impact in view of its efficacy, particularly with respect to its ability to reduce proptosis. However, the high cost of TEP, limited availability to patients outside the USA, and the lack of data on cost-effectiveness are significant barriers to improving the care of patients with TED globally. Recent guidance from authoritative professional organisations deliver different perspectives on the role of TEP in the routine management of patients with TED, underscoring the complexities of interpreting the evidence. The advance that TEP undoubtedly represents in managing TED effectively has highlighted inequities faced by patients and uncertainties about appropriate metrics of efficacy. Professional organisations have an important role addressing these problems. Future studies need to focus on optimising the measurement of outcomes and on assessing cost-effectiveness.
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Purpose
To determine whether thyroid-stimulating hormone level ≥ 30 mU/L is necessary for radioiodine (131I) remnant ablation (RRA) in patients with differentiated thyroid cancer (DTC), as well as its influencing factors and predictors.
Methods
A total of 487 DTC patients were retrospectively enrolled in this study. They were divided into two groups (TSH < 30 and ≥ 30 mU/L) and further divided into eight subgroups (0–<30, 30–<40, 40–<50, 50–<60, 60–<70, 70–<80, 80–<90, and 90–<100 mU/L). The simultaneous serum lipid level, successful rate of RRA and its influencing factors in different groups were analyzed. The receiver operating characteristic curves derived from pre-ablative thyroglobulin (pre-Tg) and pre-Tg/TSH ratio were compared for RRA success prediction performance.
Results
There was no statistical difference in success rates of RRA between the two groups (P = 0.247) and eight subgroups (P = 0.685). Levels of total cholesterol (P < 0.001), triglyceride (P = 0.006), high-density lipoprotein cholesterol (P = 0.024), low-density lipoprotein cholesterol (P = 0.001), apolipoprotein B (P < 0.001), and apolipoprotein E (P = 0.002) were significantly higher while apoA/apoB ratio (P = 0.024) was significantly lower at TSH ≥ 30 mU/L group. Pre-Tg level, gender, and N stage were influencing factors for RRA. The area under the curve of pre-Tg level and pre-Tg/TSH ratio was 0.7611 (P < 0.0001) and 0.7340 (P < 0.0001) for all enrolled patients and 0.7310 (P = 0.0145) and 0.6524 (P = 0.1068) for TSH < 30 mU/L, respectively.
Conclusion
TSH ≥ 30 mU/L may not be necessary for the success of RRA. Patients with higher serum TSH levels prior to RRA will suffer from severer hyperlipidemia. Pre-Tg level could be used as a predictor for the success of RRA, especially when TSH < 30 mU/L.
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Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
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The clinical consequences of primary hypothyroidism include cardiovascular morbidity, increased mortality, and poor quality of life; therefore guidelines endorsed by several Scientific Societies recommend measuring circulating thyroid-stimulating hormone (TSH) in patients at risk. The assessment of serum TSH levels is also deemed to be the most robust and accurate biomarker during the management of replacement therapy in patients with a previous diagnosis of primary hypothyroidism. In line with a reflex TSH laboratory strategy, free thyroxine is measured only if the TSH falls outside specific cutoffs, in order to streamline investigations and save unjustified costs. This serum TSH-based approach to both diagnosis and monitoring has been widely accepted by several national and local health services; nevertheless, false-negative or -positive testing may occur, leading to inappropriate management or treatment. This review aims to describe several infrequent causes of increased circulating TSH, including analytical interferences, resistance to TSH, consumptive hypothyroidism, and refractoriness to levothyroxine replacement treatment. We propose a clinical flowchart to aid correct recognition of these various conditions, which represent important potential pitfalls in the diagnosis and treatment of primary hypothyroidism.
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Objective
The aim of this multicentre study was to investigate the progression of patient-reported outcomes after thyroid surgery, with emphasis on voice and swallowing difficulties.
Methods
An online platform was used to collect replies to standardised questionnaires (voice handicap index, VHI; voice-related quality of life, VrQoL; EAT-10) preoperatively and at 2–6 weeks and 3–6–12 months after surgery.
Results
A total of 236 patients were recruited from five centres that contributed with median of 11 cases (range 2–186 cases). Average symptoms scores showed voice changes lasting up to 3 months: VHI increased from 41 ± 15 (preop) to 48 ± 21 (6 weeks) and returned to 41 ± 15 at 6 months. Similarly, VrQoL increased from 12 ± 4 to 15 ± 6 and returned to 12 ± 4 (6 months). Severe voice changes (VHI > 60) were reported in 12% of patients preop, 22% at 2 weeks, 18% at 6 weeks, 13% at 3 months and 7% at 12 months. Only five patients with normal preoperative voice had persistent severe voice changes after 6–12 months. Those with severe voice changes at 2 weeks (median VHI 70.5, IQR 65–81) had significant improvement by 6 months (median VHI 54, IQR 39–65) (P < 0.001).
Swallowing assessment showed a median preop score of 0 (IQR 0–3) increasing to a median of 2 (IQR 0–8) at 2 weeks and normal values afterwards.
Conclusion
The ThyVoice online platform allows the assessment of patient-reported outcome measures in thyroid surgery. Voice morbidity appears to be more frequent than commonly reported, and this risk should the quoted during informed consent. Swallowing difficulties are mild but significant in the first 2 weeks.
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Background
Central hyperthyroidism is characterized by elevated free thyroid hormone and unsuppressed thyroid-stimulating hormone (TSH), and this laboratory feature includes TSH-secreting pituitary adenoma (TSHoma) and resistance to thyroid hormone β (RTHβ). Central hyperthyroidism combined with Graves’ disease (GD) has been rarely reported.
Case Report
We describe three patients with TSHoma combined with GD and one patient with GD combined with RTHβ and pituitary adenoma. These three patients with TSHoma combined with GD showed elevated thyroid hormone, while TSH level was normal or elevated, and TSH receptor antibodies were positive. After thyrotoxicosis was controlled, they all underwent transsphenoidal surgery. We also describe a patient with an initial presentation of GD who developed hypothyroidism after anti-hyperthyroidism treatment and TSH was inappropriately significantly increased. His head magnetic resonance imaging revealed a pituitary adenoma. Genetic testing confirmed a heterozygous mutation in the thyroid hormone receptor β gene c.1148G>A (p.R383H). After levothyroxine and desiccated thyroid tablet treatment, the TSH level decreased to normal.
Conclusion
These four cases highlight the need to consider the diagnosis of GD combined with central hyperthyroidism when faced with inconsistent thyroid function test results, illuminating the specific diagnostic and therapeutic challenges of coexisting primary and central hyperthyroidism. Finally, we propose clinical management for central hyperthyroidism combined with GD.