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Yanling Cai Department of Nuclear Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China

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Yan Yang Department of Nuclear Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China

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Xiao Pang Department of Nuclear Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China

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Suping Li Department of Nuclear Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China

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Purpose

The aim was to investigate the effect of radioactive iodine (RAI) treatment for differentiated thyroid cancer (DTC) on male gonadal function.

Methods

PubMed, Embase, Web of Science, OVID, Scopus, and Wanfang databases were searched up to June 10, 2022, to identify published studies related to RAI and male gonadal function. ReviewManager version 5.4.1 software was used to calculate mean differences (MDs) with 95% CIs.

Results

Initially, 1958 articles were retrieved from the databases, and 6 articles were included in the quantitative analysis. The meta-analysis results showed that follicle-stimulating hormone (FSH) increased when the follow-up duration was ≥12 months after RAI, but the difference was not statistically significant (MD = −2.64, 95% CI = (−5.61, 0.33), P = 0.08). But the results of the subgroup analysis showed that when the follow-up time was ≤6 months, FSH levels were significantly higher after RAI (MD = −7.65, 95% CI = (−13.95, −1.34), P = 0.02). The level of inhibin B was significantly lower at ≥12 months and ≤6 months after RAI (MD = 66.38, 95% CI = (8.39, 124.37), P = 0.02) and (MD = 116.27, 95% CI = (43.56, 188.98), P = 0.002). Additionally, luteinizing hormone (LH) and testosterone have similar results – that is, LH and testosterone levels were higher after RAI, but the difference was not statistically significant (MD = –0.87, 95% CI = (−2.04, 0.30), P = 0.15) and (MD = −1.69, 95% CI (−7.29, 3.90), P = 0.55).

Conclusions

Male gonadal function may be temporarily impaired within 6 months after RAI but may return to normal levels afterward.

Open access
G Amiyangoda Department of Pharmacology, Faculty of Medicine, University of Peradeniya, Sri Lanka
Diabetes and Endocrine Unit, National Hospital, Kandy, Sri Lanka

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C N Antonypillai Diabetes and Endocrine Unit, National Hospital, Kandy, Sri Lanka

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S S C Gunatilake Diabetes and Endocrine Unit, National Hospital, Kandy, Sri Lanka

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T T Weerathunge Department of Community Medicine, Faculty of Medicine, University of Colombo, Sri Lanka

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D Ediriweera Health Data Science Unit, Faculty of Medicine, University of Kelaniya, Sri Lanka

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S G P D Kosgallana Diabetes and Endocrine Unit, National Hospital, Kandy, Sri Lanka

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R D P Jayawardana Department of Biochemistry, National Hospital, Kandy, Sri Lanka

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H A N D Thissera Department of Biochemistry, National Hospital, Kandy, Sri Lanka

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W J Emalka Faculty of medicine, University of Peradeniya, Sri Lanka

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H U Daraniyagala Faculty of medicine, University of Peradeniya, Sri Lanka

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Refractory hypothyroidism is associated with high morbidity and increased healthcare expenditure. In general, the use of the levothyroxine absorption test looks promising in evaluating refractory hypothyroidism but has shown significant variability in protocols in multiple settings. We intended to assess the usefulness of the levothyroxine absorption test in a low-resource setting and to assess the factors associated with refractory hypothyroidism. A cross-sectional study among age-matched 25 cases of refractory hypothyroidism and 24 treatment-responsive hypothyroid controls was conducted. A supervised levothyroxine absorption test was performed with levothyroxine 1000 μg tablets after a 10-h fast, and serum free tetraiodothyronine (FT4) levels were measured at 0, 1, 2, 3, 4, and 5 h. Descriptive statistics, chi-square test, Student’s t-test, and logistic regression were used in the analysis. Results showed no significant difference in age, body weight, etiology of hypothyroidism, interfering medications, thyroxine storage, and ingestion technique in cases and controls. Cases had a longer duration of hypothyroidism and males had a higher peak FT4 concentration. During pooled analysis, serum FT4 peaked at 3 h with an increment of 149.4% (128.4–170.5%) from baseline and plateaued thereafter. The absolute value of FT4 at 3 h was 41.59 (s.d. 14.14) pmol/L (3.23 ng/dL). We concluded that there was no significant difference in the pattern of levothyroxine absorption in both groups. The most common cause of refractory disease was pseudo-malabsorption. Rapid supervised levothyroxine absorption test with two blood samples for FT4 at baseline and at the peak of absorption (3 h) is simple, convenient, and cost-effective, particularly in low-resource settings.

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Dongyan Han Department of Pathology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China

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Min Ding Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Rongli Xie Department of General Surgery, RuiJin Hospital Lu Wan Branch, Shanghai Jiaotong University School of Medicine, Shanghai, China

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Zhengshi Wang Thyroid Center, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
Shanghai Center of Thyroid Diseases, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China

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Guohui Xiao Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Xiaohong Wang Shanghai Rigen Biotechnology Co., Ltd. Shanghai, China

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Lei Dong Department of Pathology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Zhiqiang Yin Thyroid Center, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
Shanghai Center of Thyroid Diseases, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China

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Jian Fei Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai, China
Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China

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Thyroid fine needle aspiration biopsy (FNAB) remains indeterminate in 16–24% of the cases. Molecular testing could improve the diagnostic accuracy of FNAB. This study examined the gene mutation profile of patients with thyroid nodules and analyzed the diagnostic ability of molecular testing for thyroid nodules using a self-developed 18-gene test. Between January 2019 and August 2021, 513 samples (414 FNABs and 99 formalin-fixed paraffin-embedded (FFPE) specimens) underwent molecular testing at Ruijin Hospital. Sensitivity (Sen), specificity (Spe), positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. There were 457 mutations in 428 samples. The rates of BRAF, RAS, TERT promoter, RET/PTC, and NTRK3 fusion mutations were 73.3% (n = 335), 9.6% (n = 44), 2.8% (n = 13), 4.8% (n = 22), and 0.4% (n = 2), respectively. The diagnostic ability of cytology and molecular testing were evaluated in Bethesda II and V–VI samples. For cytology alone, Sen, Spe, PPV, NPV, and accuracy were 100%, 25.0%, 97.4%, 100%, and 97.4%; these numbers were 87.5%, 50.0%, 98.0%, 12.5%, and 86.2% when considering positive mutation, and 87.5%, 75.0%, 99.0%, 17.6%, and 87.1% when considering positive cytology or and positive mutation. In Bethesda III–IV nodules, when relying solely on the presence of pathogenic mutations for diagnosis, Sen, Spe, PPV, NPV, and AC were 76.2%, 66.7%, 94.1%, 26.8%, and 75.0%, respectively. It might be necessary to analyze the molecular mechanisms of disease development at the genetic level to predict patients with malignant nodules more accurately in different risk strata and develop rational treatment strategies and definite management plans.

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Irfan Vardarli 5th Medical Department, Division of Endocrinology and Diabetes, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

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Susanne Tan Department of Endocrinology, Diabetes and Metabolism, Clinical Chemistry – Division of Laboratory Research Endocrine Tumor Center at WTZ/Comprehensive Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

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Rainer Görges Department of Nuclear Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

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Bernhard K Krämer 5th Medical Department, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

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Ken Herrmann Department of Nuclear Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

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Christoph Brochhausen Institue of Pathology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

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Objective

The management of thyroid nodules with indeterminate cytology (ITN) is still a challenge. To evaluate the performance of commercial molecular tests for ITN, we performed this comprehensive meta-analysis.

Methods

We performed an electronic search using PubMed/Medline, Embase, and the Cochrane Library. Studies assessing the diagnostic accuracy of Afirma gene expression classifier (GEC), Afirma gene sequencing classifier (GSC), ThyroSeq v2 (TSv2), or ThyroSeq v3 (TSv3) in patients with ITN (only Bethesda category III or IV) were selected; Statistical analyses were performed by using Stata.

Results

Seventy-one samples (GEC, n = 38; GSC, n = 16; TSv2, n = 9; TSv3, n = 8) in 53 studies, involving 6490 fine needle aspirations (FNAs) with ITN cytology with molecular diagnostics (GEC, GSC, TSv2, or TSv3), were included in the study. The meta-analysis showed the following pooled estimates: sensitivity 0.95 (95% CI: 0.94–0.97), specificity 0.35 (0.28–0.43), positive likelihood ratio (LR+) 1.5 (1.3–1.6), and negative likelihood ratio (LR−) 0.13 (0.09–0.19), with the best performance for TSv3 (area under the ROC curve 0.95 (0.93–0.96), followed by TSv2 (0.90 (0.87–0.92)), GSC (0.86 (0.82–0.88)), and GEC (0.82 (0.78–0.85)); the best rule-out property was observed for GSC (LR−, 0.07 (0.02–0.19)), followed by TSv3 (0.11 (0.05–0.24)) and GEC (0.16 (0.10–0.28), and the best rule-in was observed for TSv2 (LR+, 2,9 (1.4–4.6)), followed by GSC (1.9 (1.6–2.4)). A meta-regression analysis revealed that study design, Bethesda category, and type of molecular test were independent factors.

Conclusion

We showed that in patients with ITN, TSv3 has the best molecular diagnostic performance, followed by TSv2, GSC, and GEC. As regards rule-out malignancy, GSC, and rule-in, TSV2 is superior to other tests.

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Sílvia Santos Monteiro Division of Endocrinology, Diabetes and Metabolism. Department of Medicine, Centro Hospitalar Universitário do Porto, Largo Professor Abel Salazar Porto, Portugal

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Tiago Silva Santos Division of Endocrinology, Diabetes and Metabolism. Department of Medicine, Centro Hospitalar Universitário do Porto, Largo Professor Abel Salazar Porto, Portugal

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Ana Martins Lopes Division of Endocrinology, Diabetes and Metabolism. Department of Medicine, Centro Hospitalar Universitário do Porto, Largo Professor Abel Salazar Porto, Portugal

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José Carlos Oliveira Department of Clinical Pathology, Centro Hospitalar Universitário do Porto, Largo Professor Abel Salazar Porto, Portugal

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Cláudia Freitas Division of Endocrinology, Diabetes and Metabolism. Department of Medicine, Centro Hospitalar Universitário do Porto, Largo Professor Abel Salazar Porto, Portugal

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André Couto Carvalho Division of Endocrinology, Diabetes and Metabolism. Department of Medicine, Centro Hospitalar Universitário do Porto, Largo Professor Abel Salazar Porto, Portugal

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Purpose

The levothyroxine absorption test (LT4AT) is an important tool for distinguishing hypothyroidism due to malabsorption from ‘pseudomalabsorption’ conditions. Our aim was to review our institution’s LT4AT results and assess its role in the management of patients with refractory hypothyroidism.

Methods

We performed a retrospective study of all patients evaluated for refractory hypothyroidism who underwent LT4AT in our tertiary center between 2014 and 2020. Its results and the impact on thyroid function management during follow-up were assessed.

Results

Ten female patients were included with a mean age of 40 years (min-max: 26–62). Mean weight was 72 kg (min–max: 43–88) and baseline LT4 dosage ranged from 2.5 to 5.3 µg/kg/day. The most common causes of hypothyroidism were postsurgical in 50% (n  = 5) and autoimmune in 20% (n  = 2). During LT4AT, normal LT4 absorption was found in all but one individual (mean FT4 increase of 231%, min–max: 85–668). The only patient with objective LT4 absorption impairment (maximal increase of 48% by hour 5) presented also Helicobacter pylori gastritis and prior history of ‘intestinal surgery’ during childhood. No adverse events were reported during any of the LT4ATs. During follow-up (median 11.5 months (IQR 23)), three patients obtained euthyroidism and six had improved their hypothyroidism state.

Conclusions

The LT4AT is an effective and safe way to assess refractory hypothyroidism and provides valuable information to distinguish LT4 malabsorption from ‘pseudomalabsorption’. Our data suggest that most patients with suspicious LT4 malabsorption perform normally during LT4AT. This test provides relevant information for better management of patients with refractory hypothyroidism.

Open access
Katica Bajuk Studen Department of Nuclear Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia
Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

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Simona Gaberšček Department of Nuclear Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia
Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

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Edvard Pirnat Department of Nuclear Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia

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Nataša Bedernjak Bajuk Department of Nuclear Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia

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Andreja Vendramin Department of Nuclear Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia

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Vito Majcen Department of Nuclear Medicine, SB Celje, Celje, Slovenia

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Katja Zaletel Department of Nuclear Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia
Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

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Objective

The optimal corticosteroid treatment regimen for subacute thyroiditis has not yet been established. To avoid side effects, tapering of the initial dose of corticosteroid is recommended. With reducing dose, the symptoms can recur.

Design

In a prospective clinical study, a 30-day methylprednisolone (MPSL) treatment protocol with a starting dose of 24 mg/day and tapered by 4 mg every 5 days was assessed for effectiveness and safety regarding possible adrenal insufficiency.

Methods

Fifty-nine patients with subacute thyroiditis were included. At visit 1, after establishing the diagnosis, a short stimulation adrenocorticotrophic hormone (ACTH) test was performed and methylprednisolone treatment was prescribed. At visit 2 (40 ± 5 days after visit 1), clinical, laboratory (including short stimulation ACTH test), and ultrasound evaluation were repeated.

Results

Forty-eight patients (81.4%) were cured by the prescribed protocol, having significantly lower cortisol levels after stimulation at visit 1 than patients who were not cured (mean, 674.9 nmol/L and 764.0 nmol/L, respectively, P = 0.012). Seven patients (12.3%) developed adrenal insufficiency; this group had significantly lower cortisol levels after stimulation at visit 1 than patients without adrenal insufficiency development (mean, 561.5 nmol/L and 704.7 nmol/L, respectively, P = 0.005). Using stimulated cortisol level at visit 1 as the explanatory variable, logistic models were optimized to determine treatment efficacy (AUC = 0.745, optimal threshold 729 nmol/L, specificity 71%, sensitivity 73%) and adrenal function (AUC = 0.861, optimal threshold 629 nmol/L, specificity 73%, sensitivity 100%).

Conclusions

The described protocol was efficient for more than 80% of patients. Using this protocol, the corticosteroid treatment interval is shorter than proposed in current guidelines.

Significance statement

A short but effective protocol for treatment of subacute thyroiditis with methylprednisolone is presented in this article. Using this protocol, the treatment interval is shorter than proposed in current guidelines. Its safety regarding possible adrenal insufficiency is assessed.

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Hyunjae Lee Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea

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Tae-Shin Kim Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Republic of Korea

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Ja-Yoon Gu Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea

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Mi Ran Yu Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea

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Seung-Eun Lee Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea

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Eun Sook Kim Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea

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Hyun Kyung Kim Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea

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Objective

The inflammatory microenvironment has been implicated in differentiated thyroid cancer (DTC). Inflammatory stimuli induce the release of components of neutrophils into extracellular space, leading to formation of neutrophil extracellular trap (NET), which can stimulate growth and progression of cancer. Generation of activated factor XII and thrombin is also involved in cancer progression. This study attempted to determine whether the level of circulating markers of NET, activated factor XII, and endogenous thrombin potential may be useful for detecting the recurrence of DTC.

Methods

A total of 122 patients with DTC were recruited during the postoperative follow-up period. Measurement of the levels of circulating markers of NET (neutrophil elastase, histone–DNA complex, cell-free dsDNA), activated factor XII, and endogenous thrombin potential was performed.

Results

A significantly elevated level of neutrophil elastase was detected in patients with recurrence (n = 12) compared to those without recurrence (n = 110), while significant elevation of the levels of other markers was not observed. The value for area under the curve (0.717, P = 0.018) of neutrophil elastase for detecting recurrence of DTC was superior to that (0.661, P = 0.051) of serum thyroglobulin. An elevated level of neutrophil elastase was significantly associated with recurrence of DTC independent of serum thyroglobulin.

Conclusions

Because an elevated level of neutrophil elastase was detected in patients with recurrence of DTC and showed a significant association with recurrence of DTC, it can be proposed as a novel biomarker for use in detecting recurrence of DTC along with other tests.

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Lian Duan Department of Nuclear Medicine, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, China

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Han-Yu Zhang Changzhi Medical College, Changzhi, Shanxi, China

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Min Lv Department of Nuclear Medicine, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, China

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Han Zhang Changzhi Medical College, Changzhi, Shanxi, China

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Yao Chen Changzhi Medical College, Changzhi, Shanxi, China

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Ting Wang Department of Nuclear Medicine, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, China

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Yan Li Department of Nuclear Medicine, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, China

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Yan Wu Department of Clinical Laboratory, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China

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Junfeng Li Department of Radiology, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, China

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Kefeng Li School of Medicine, University of California, San Diego, California, USA

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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.

Open access
Zherui Fu Department of Emergency, The First People’s Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou, Zhejiang, China

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Yi Lai Department of Emergency, The First People’s Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou, Zhejiang, China

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Qianfei Wang Department of Emergency, The First People’s Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou, Zhejiang, China

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Feng Lin Department of Orthopedics, The First People's Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou, Zhejiang, China

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Jiaping Fang Department of Emergency, The First People’s Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou, Zhejiang, China

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Background

The diagnostic and prognostic value of the leucine-rich alpha-2-glycoprotein 1 (LRG1) gene in thyroid cancer remains unclear. Using the Cancer Genome Atlas (TCGA) database, we conducted a bioinformatics analysis to determine the role of LRG1 in thyroid cancer.

Methods

Data from 512 patients with thyroid cancer and 59 normal individuals were collected from TCGA database. The Kruskal–Wallis test and logistic analysis were used to examine the relationship between LRG1 expression and clinicopathologic characteristics. Cox regression and Kaplan–Meier analysis were used to determine the predictive value of LRG1 on clinical outcomes. Single-sample gene set enrichment analysis (ssGSEA) was used to reveal associations between LRG1 expression and immune infiltration levels in thyroid cancer.

Results

LRG1 was highly expressed in thyroid cancer (P < 0.001) and could effectively distinguish tumor tissue (area under the curve = 0.875) from normal tissue. Moreover, LRG1 was significantly correlated with pathological N stage (odds ratio (OR) = 2.411 (1.659–3.505), P < 0.001). Kaplan–Meier survival analysis revealed that patients with high LRG1 expression had better overall survival (hazard ratio (HR) = 0.30, P = 0.038). Cox regression analysis indicated that pathological M stage was a risk factor for progression-free interval (HR = 5.964 (2.010–17.694), P < 0.001). Using ssGSEA, we found that LRG1 expression was positively correlated with the number of T helper 1 cells (R = 0.435, P < 0.001), dendritic cells (R = 0.442, P < 0.001), and macrophages (R = 0.459, P < 0.001).

Conclusion

LRG1 may be an important biomarker for predicting the prognosis of thyroid cancer and represent a suitable target for immunotherapy associated with immune infiltration.

Open access
Bjarke R Medici Department of Medicine, Herlev Hospital, University of Copenhagen, Herlev, Denmark
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

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Birte Nygaard Department of Medicine, Herlev Hospital, University of Copenhagen, Herlev, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Jeppe L la Cour Department of Medicine, Herlev Hospital, University of Copenhagen, Herlev, Denmark

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Martin Krakauer Department of Clinical Physiology and Nuclear Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
Department of Clinical Physiology and Nuclear Medicine, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark

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Andreas Brønden Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
Department of Clinical Pharmacology, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark

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Mette P Sonne Department of Medicine, Herlev Hospital, University of Copenhagen, Herlev, Denmark

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Jens J Holst Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Jens F Rehfeld Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Tina Vilsbøll Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Steno Diabetes Center Copenhagen, Herlev, Denmark

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Jens Faber Department of Medicine, Herlev Hospital, University of Copenhagen, Herlev, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Filip K Knop Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Steno Diabetes Center Copenhagen, Herlev, Denmark

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Context

In individuals with hypothyroidism and overweight, levothyroxine substitution therapy is often expected to cause weight loss due to its effect on resting energy expenditure. However, despite levothyroxine-induced enhancement of resting energy expenditure, fat mass loss is rarely seen after levothyroxine substitution therapy. The mechanism behind this conundrum is unknown.

Aim

The aim of the study was to assess the effect of levothyroxine therapy on hunger sensations and ad libitum food intake in individuals with hypothyroidism.

Design and setting

Prospective cohort study of 18 newly diagnosed hypothyroid women (thyroid-stimulating hormone (TSH) >10 mU/L). Participants were investigated at diagnosis, after normalization of TSH (<4.0 mU/L), and after 6 months of successful treatment. Eighteen age and body mass index-matched healthy controls were also included.

Intervention

Hypothyroid individuals were treated with levothyroxine according to European Thyroid Association guidelines.

Main outcomes

Changes in hunger sensation were assessed using visual analog scales (cm) before and during a standardized mixed meal test, and food intake was measured during a subsequent ad libitum meal (g).

Results

After 6 months of levothyroxine therapy, mean resting energy expenditure was increased by 144 kcal/day (10%) (P < 0.001). Weight loss was comprised of 0.8 kg fat-free mass while fat mass remained unchanged. Fasting hunger sensation increased from a mean of 4.5 (s.d. 2.2) cm to 5.5 (s.d. 2.2) cm (P = 0.047). The numerical increase in ad libitum meal intake did not reach statistical significance.

Conclusion

Our data suggest that levothyroxine-induced hunger may be a culprit in the lack of fat mass loss from levothyroxine therapy.

Open access