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Background and objective
Radioiodine therapy (RAI) is one of the most common treatment solutions for Graves’ disease (GD). However, many patients will develop hypothyroidism as early as 6 months after RAI. This study aimed to implement machine learning (ML) algorithms for the early prediction of post-RAI hypothyroidism.
Methods
Four hundred and seventy-one GD patients who underwent RAI between January 2016 and June 2019 were retrospectively recruited and randomly split into the training set (310 patients) and the validation set (161 patients). These patients were followed for 6 months after RAI. A set of 138 clinical and lab test features from the electronic medical record (EMR) were extracted, and multiple ML algorithms were conducted to identify the features associated with the occurrence of hypothyroidism 6 months after RAI.
Results
An integrated multivariate model containing patients’ age, thyroid mass, 24-h radioactive iodine uptake, serum concentrations of aspartate aminotransferase, thyrotropin-receptor antibodies, thyroid microsomal antibodies, and blood neutrophil count demonstrated an area under the receiver operating curve (AUROC) of 0.72 (95% CI: 0.61–0.85), an F1 score of 0.74, and an MCC score of 0.63 in the training set. The model also performed well in the validation set with an AUROC of 0.74 (95% CI: 0.65–0.83), an F1 score of 0.74, and a MCC of 0.63. A user-friendly nomogram was then established to facilitate the clinical utility.
Conclusion
The developed multivariate model based on EMR data could be a valuable tool for predicting post-RAI hypothyroidism, allowing them to be treated differently before the therapy. Further study is needed to validate the developed prognostic model at independent sites.
Center for International Health, University of Bergen, Bergen, Norway
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Department of Microbiology, Innlandet Hospital Trust, Lillehammer, Norway
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Department of Clinical Science, University of Bergen, Bergen, Norway
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Department of Research, Innlandet Hospital Trust, Lillehammer, Norway
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Objective
Thyroid disease during pregnancy is associated with adverse pregnancy outcomes and suboptimal fetal development. During the last decades, guidelines for diagnosing thyroid disease during pregnancy have changed considerably and there has been increased awareness. This study aimed to describe the prevalence of thyroid disease treatment over time among pregnant women in Norway.
Design
Nationwide register-based study.
Methods
We combined historical data from the Medical Birth Registry of Norway and the Norwegian Prescription Database, identifying pregnant women using thyroid therapy from 2004 to 2018.
Results
A total of 855,067 pregnancies were included in the analyses. The proportion of women using thyroid hormone replacement therapy during pregnancy increased from 1.46% (n = 800) in 2004 to 3.57% (n = 1940) in 2018. The proportion of women using antithyroid medications also increased from 0.04% (n = 20) in 2004 to 0.10% (n = 56). During these 15 years, the mean maternal age increased by 0.9 years. When adjusting for age, the risk for being on thyroid hormone replacement therapy during pregnancy increased by an average of 5% per year (odds ratio: 1.05, 95% CI: 1.05–1.05).
Conclusion
During the recent 15 years, there has been a substantial increase in the use of thyroid hormone therapy in Norwegian pregnant women. We speculate that this could be due to an increased awareness in combination with overdiagnosis because of inappropriate diagnostic criteria. To truly understand the possible causes and consequences of this development, further research is warranted.
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This study aimed to explore the relationship between thyroid function and autoimmunity and adverse birth outcomes. Serum levels of thyroid function were detected by electrochemiluminescence assay. Urine iodine concentration was detected using the acid digestion method. We used multiple linear regression to assess the correlation between thyroid function indicators and birth weight according to trimester stratification and binary logistic regression to evaluate the correlation between thyroid dysfunction and adverse birth outcomes. Reference ranges for trimester-specific thyroid hormones were established in our 2564 pregnant women cohort with mild iodine deficiency. The higher the maternal thyroid-stimulating hormone in the first trimester (B = 0.09, P = 0.048) and total triiodothyronine (TT3) in the third trimester (B = 0.16, P < 0.001) of TPOAbnegative women, the higher the birth weight Z-score, whereas in the second trimester, free-thyroxine of mothers with TPOAb negative was lower (B = −0.10, P = 0.026) and the birth weight Z-score was higher. Pregnant women with overt and subclinical hyperthyroidism had a higher risk of preterm births than euthyroid women (11.9% vs 4.5%; odds ratio (OR): 2.84; P = 0.009). Women with higher TT3 had a higher risk of preterm (17.0% vs 4.5%; OR: 4.19; P < 0.001) and LGA (34.0% vs 11.1%; OR: 3.70; P < 0.001) births than euthyroid women. In conclusion, thyroid function during pregnancy could affect birth weight and birth outcome.
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Background
Numerous studies have found that subclinical hypothyroidism (SCH) may increase adverse pregnancy outcomes; however, the benefit of levothyroxine (LT4) treatment remains controversial. The 2017 guidelines of the American Thyroid Association weakly recommended LT4 therapy for serum antithyroid peroxidase antibody (TPOAb)-negative women with thyroid-stimulating hormone (TSH) concentrations greater than the pregnancy-specific reference range and below 10.0 mU/L. Therefore, the primary goal of this study was to investigate the correlation between thyroid autoantibody-negative SCH with or without LT4 treatment and adverse pregnancy outcomes.
Methods
We prospectively enrolled 1868 consecutive pregnant women. Finally, 1344 women were involved in the study according to the inclusion and exclusion criteria. Assays for TSH, free thyroxine (FT4), TPOAb, anti-thyroglobulin antibody, and laboratory indicators were performed. The participants were divided into the euthyroid (ET) group (n = 1250) and the SCH group(n = 94). The SCH group was further divided into LT4 group (n = 40) and non-LT4 group(n = 54). The laboratory indicators and pregnancy outcomes were evaluated during follow-ups.
Results
Maternal age, BMI, parity, and the history of spontaneous abortion did not differ significantly between the ET group and the different SCH groups. There were no significant differences in lipid profile and homocysteine levels between ET and SCH group in the first and third trimester of pregnancy. After adjusting the confounding factors, the non-LT4 group was a risk factor for spontaneous abortion (odds ratio: 3.141, 95% CI: 1.060–9.302). Survival analysis showed that the time of abortion was different between the ET group and SCH group (log-rank P= 0.042). The spontaneous abortion in SCH, especially in non-LT4, group mainly occurred in the first trimester of pregnancy.
Conclusions
Thyroid autoantibody negative-SCH seems to be associated with increased risk of spontaneous abortions during the first trimester of pregnancy. LT4 therapy in this patient population might be beneficial to reduce adverse pregnancy outcomes.
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Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Université Libre de Bruxelles, Bruxelles, Belgium
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School of Medicine, Zagreb, Croatia
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Department of Clinical Nutrition, Landspitali-National University Hospital, Reykjavik, Iceland
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Goldman School of Medicine, Ben Gurion University of the Negev, Beer Sheva, Israel
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Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
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Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
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Universitat Autònoma de Barcelona, Barcelona, Spain
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Frölunda Specialist Hospital, Västra Frölunda, Sweden
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Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Wallenberg Centre of Molecular and Translational Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
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Objective
Registers of diagnoses and treatments exist in different forms in the European countries and are potential sources to answer important research questions. Prevalence and incidence of thyroid diseases are highly dependent on iodine intake and, thus, iodine deficiency disease prevention programs. We aimed to collect European register data on thyroid outcomes to compare the rates between countries/regions with different iodine status and prevention programs.
Design
Register-based cross-sectional study.
Methods
National register data on thyroid diagnoses and treatments were requested from 23 European countries/regions. The provided data were critically assessed for suitability for comparison between countries/regions. Sex- and age-standardized rates were calculated.
Results
Register data on ≥1 thyroid diagnoses or treatments were available from 22 countries/regions. After critical assessment, data on medication, surgery, and cancer were found suitable for comparison between 9, 10, and 13 countries/regions, respectively. Higher rates of antithyroid medication and thyroid surgery for benign disease and lower rates of thyroid hormone therapy were found for countries with iodine insufficiency before approx. 2001, and no relationship was observed with recent iodine intake or prevention programs.
Conclusions
The collation of register data on thyroid outcomes from European countries is impeded by a high degree of heterogeneity in the availability and quality of data between countries. Nevertheless, a relationship between historic iodine intake and rates of treatments for hyper- and hypothyroid disorders is indicated. This study illustrates both the challenges and the potential for the application of register data of thyroid outcomes across Europe.
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Department of Zoology, Islamia College Peshawar (CU), Peshawar, Pakistan
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DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, University Medicine, Greifswald, Germany
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The associations of thyroid function parameters with non-alcoholic fatty liver disease (NAFLD) and hepatic iron overload are not entirely clear. We have cross-sectionally investigated these associations among 2734 participants of two population-based cross-sectional studies of the Study of Health in Pomerania. Serum levels of thyroid-stimulating hormone (TSH), free tri-iodothyronine (fT3), and free thyroxine (fT4) levels were measured. Liver fat content (by proton-density fat fraction) as well as hepatic iron content (by transverse relaxation rate; R2*) were assessed by quantitative MRI. Thyroid function parameters were associated with hepatic fat and iron contents by median and logistic regression models adjusted for confounding. There were no associations between serum TSH levels and liver fat content, NAFLD, or hepatic iron overload. Serum fT4 levels were inversely associated with liver fat content, NAFLD, hepatic iron contents, and hepatic iron overload. Serum fT3 levels as well as the fT3 to fT4 ratio were positively associated with hepatic fat, NAFLD, hepatic iron contents, but not with hepatic iron overload. Associations between fT3 levels and liver fat content were strongest in obese individuals, in which we also observed an inverse association between TSH levels and NAFLD. These findings might be the result of a higher conversion of fT4 to the biologically active form fT3. Our results suggest that a subclinical hyperthyroid state may be associated with NAFLD, particularly in obese individuals. Furthermore, thyroid hormone levels seem to be more strongly associated with increased liver fat content compared to hepatic iron content.
Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, China
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Hashimoto’s thyroiditis (HT) is a very common organ-specific autoimmune disease characterized by lymphocyte infiltration and the destruction of thyroid follicular cells (TFCs), in which IFN-γ and chemokines play pivotal roles. Moreover, β-catenin has been implicated in the regulation of T cell infiltration. However, whether β-catenin is involved in Hashimoto’s thyroiditis is unknown. Here, we examined β-catenin expression in thyroid tissues and investigated its role in the pathogenesis of HT. The results showed that β-catenin expression was markedly reduced in the thyroid tissues of HT patients; more importantly, IFN-γ treatment markedly reduced the expression of β-catenin and was accompanied by the secretion of chemokines such as CCL5, CXCL16, GRO-β, and GRO-γ in TFCs in vitro, which was attributed to GSK-3β/β-catenin signaling pathway activation. Collectively, the decreased expression of β-catenin might contribute to IFNγ-induced chemokine secretion and lymphocyte infiltration in the development of HT.
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Background
Cancer-related fatigue is one of the most important issues for patients, but research on this topic is sparse. This study aimed to determine the prevalence of fatigue in postoperative patients with papillary thyroid carcinoma (PTC) and to identify the clinical features associated with fatigue.
Methods
We conducted a cross-sectional study on 292 thyroid cancer survivors. Fatigue and quality of life were the study outcomes, measured using the Cancer Fatigue Scale (CFS) and the SF-36 version 2.0. Furthermore, correlations of demographic characteristics and hormonal data with the CFS scores were assessed by univariable and multivariable analyses.
Results
The prevalence of fatigue was 41.8% (95% CI: 36.1, 47.5). The CFS score was significantly correlated with the free T3 level (Pearson’s r = −0.123, 95% CI: −0.234, −0.008). Multiple regression analysis revealed that the free T3 level and having a job were significant predictors of the CFS score, with unstandardized regression coefficients of −2.52 (95% CI: −4.94, −0.09) and 2.85 (95% CI: 0.49, 5.20), respectively. The median Z-scores were negative for General Health (−0.28) and Vitality (−0.15) subscales of the SF-36. The CFS score was a significant predictor of summary scores of the SF-36. The free T3 level was significantly associated with the physical component summary score with an unstandardized coefficient of 3.20 (95% CI: 0.77, 5.63).
Conclusions
Fatigue was prevalent and associated with poor quality of life among PTC survivors. Thyroid functional status, particularly the level of free T3, may be worth to be considered in alleviating the burden.
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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.
Intensive Care Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
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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.
