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Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Objective
A combination of glucocorticoids with mycophenolate is recommended by current guidelines to boost response to Graves’ orbitopathy (GO) therapy. This study was designed to evaluate the therapeutic effects and safety of methotrexate (MTX) plus reduced (3.0 g) or full-dose (4.5 g) i.v. methylprednisolone (MP) vs full-dose i.v. MP alone.
Design and methods
This was a prospective, randomized, observer-masked, single-center clinical trial conducted in a tertiary clinical center. Ninety-seven patients with active moderate-to-severe GO were screened and 90 patients underwent randomization between April 2018 and Oct 2019. All patients completed 12 weeks of treatment and received clinical assessment. The patients received either MP 4.5 g only, MP 4.5 g plus oral MTX, or MP 3.0 g plus oral MTX. The primary outcome was the CAS response at week 12. Secondary outcomes were adverse events and other individual ophthalmic parameters.
Results
At week 12, 53.3% of MP, 76.7% of reduced MP plus MTX, and 76.7% of MP plus MTX achieved a CAS response, although the difference was not significant (P = 0.1). The overall response rates of the MP group, the reduced MP plus MTX group, and the MP plus MTX group were 43.3%, 53.3%, and 60%, respectively (P = 0.5). Subgroup analysis found that smoking status interacted with marginal significance with treatment effect (P = 0.048). Importantly, adverse event incidence was significantly lower in the reduced MP + MTX group (P = 0.017).
Conclusions
Our study shows that reduced MP plus MTX therapy is effective and safer in treating active and moderate-to-severe GO patients than 4.5 g MP monotherapy.
Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
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Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
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Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
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Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
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Introduction
Maternal thyroid function plays a critical role in the normal labor process. Whether maternal thyroid function affects the duration of the first stage of labor is still unknown.
Methods
Maternal serum levels of free thyroxine (FT4), thyroid-stimulating hormone (TSH) and thyroid peroxidase antibody (TPOAb) were detected in 31,382 pregnant women. A multiple linear regression model was applied to investigate the effect of maternal thyroid function on the duration of the first stage of labor.
Results
FT4 level in the second trimester and in the third trimester was found to be negatively associated with duration of the first stage of labor (β = −1.30 h, 95% CI: −2.28, −0.32, P < 0.01; β = −0.35 h, 95% CI: −0.61, −0.10, P < 0.01). TSH level in the third trimester was found to be positively associated with the duration of the first stage of labor (β = 0.12 h, 95% CI: 0.06, 0.18, P < 0.001). Per unit increase in TPOAb (IU/mL) in the second trimester and in the third trimester was significantly associated with prolonged first stage of labor (β = 0.08 h, 95% CI: 0.01, 0.14, P = 0.02; β = 0.09 h, 95% CI: 0.02, 0.15, P = 0.01). For pregnant women suffering from subclinical hypothyroidism combined without TPOAb, TSH level in the third trimester exhibited a significant positive association with the length of the first stage of labor (β = 2.44 h, 95% CI: 0.03, 4.84, P = 0.04).
Conclusions
These findings suggest that maternal FT4, TSH and TPOAb might be important predictors of the first stage of labor.
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Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, People’s Republic of China
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Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, People’s Republic of China
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Background
Proper thyroid hormone signaling via the TRα1 nuclear receptor is required for normal neurodevelopmental processes. The specific downstream mechanisms mediated by TRα1 that impact brain development remain to be investigated.
Methods
In this study, the structure, function and transcriptome of hippocampal tissue in a mouse model expressing the first RTHα mutation discovered in a patient, THRA E403X, were analyzed. RNAscope was used to visualize the spatial and temporal expression of Thra1 mRNA in the hippocampus of WT mice, which is corresponding to THRA1 mRNA in humans. The morphological structure was analyzed by Nissl staining, and the synaptic transmission was analyzed on the basis of long-term potentiation. The Morris water maze test and the zero maze test were used to evaluate the behavior. RNA-seq and quantitative real-time PCR were used to analyze the differentially expressed genes (DEGs) of the hippocampal tissues in the mouse model expressing the Thra E403X mutation.
Results
The juvenile mutant Thra E403X mice presented with delayed neuronal migration, disordered neuronal distribution, and decreased synaptic plasticity. A total of 754 DEGs, including 361 upregulated genes and 393 downregulated genes, were identified by RNA-seq. DEG-enriched Gene Ontology (GO) and KEGG pathways were associated with PI3K-Akt signaling, ECM−receptor interaction, neuroactive ligand−receptor interaction, and a range of immune-related pathways. 25 DEGs were validated by qPCR.
Conclusions
The Thra E403X mutation results in histological and functional abnormalities, as well as transcriptomic alterations in the juvenile mouse hippocampus. This study of the Thra E403X mutant offers new insights into the biological cause of RTHα-associated neurological diseases.
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Background
Graves' disease (GD) among children has attracted wide attention. However, data on long-term follow-up are scarce, especially in China. This study aimed to investigate the prognosis after regular treatments of GD and to identify possible influencing factors.
Methods
A total of 204 newly diagnosed GD children in the Children's Hospital of Nanjing Medical University between 2013 and 2019 were included in this study. The cases involved were divided into remission group, relapse group, and continuing treatment group according to therapy outcomes. Relationships between prognosis and possible influencing factors in remission and relapse groups were analyzed.
Results
All 204 cases were treated with methimazole at presentation with GD. Due to severe complications, 4 (2.0%) cases changed medication to propylthiouracil. Of all the GD children included, 79 (38.7%) had remission, and 40 (50.6%) relapsed after remission. For each additional month before free thyroxine fell into the reference range with treatment, the risk of relapse increased 1.510 times (adjusted odds ratio (OR)=2.510, 95%CI: 1.561–4.034) compared to those in the remission group. On the contrary, the risk of relapse was reduced by 0.548 times for each additional hour of sleep duration per day (adjusted OR=0.452, 95%CI: 0.232–0.879).
Conclusion
GD children have a high relapse rate after remission, and most of them occur within 1 year. Thyroid function should be reexamined regularly after drug withdrawal. The response to medication and lifestyle of GD children may affect the prognosis.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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Department of Ultrasound, Fudan University Shanghai Cancer Center, Shanghai, China
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Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
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Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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Objective
The data regarding the mutation landscape in Chinese patients with thyroid cancer are limited. The diagnostic performance of thyroid nodules by fine-needle aspiration (FNA) cytology needs optimization, especially in indeterminate nodules.
Methods
A total of 1039 FNA and surgical resection samples tested using the targeted multigene next-generation sequencing (NGS) panel were retrospectively collected. The features of gene alterations in different thyroid tumors were analyzed, and the diagnostic efficacy was evaluated.
Results
Among 1039 samples, there were 822 FNA and 217 surgical FFPE samples. Among 207 malignant thyroid resections, a total of 181 out of 193 papillary thyroid carcinomas (PTCs) were NGS-positive (93.8%), with a high prevalence of BRAF mutations (81.9%, 158/193) and a low prevalence of RAS (1.0%, 2/193) and TERT promoter mutations (3.6%, 7/193). Gene fusions, involving the RET and NTRK3 genes, were present in 20 PTCs (10.4%) and mutually exclusive with other driver mutations. Two of three follicular thyroid carcinomas harbored multiple mutations. RET gene point mutations were common in medullary thyroid carcinoma (8/11, 72.7%). The combination of cytology and DNA–RNA-based NGS analysis demonstrated superior diagnostic value (98.0%) in FNA samples. For indeterminate thyroid nodules, the diagnostic sensitivity and specificity of NGS testing were 79.2 (38/48) and 80.0% (8/10), respectively. Two mutation-positive benign cases harbored NRAS and TSHR mutations, respectively.
Conclusions
Our study revealed the distinct molecular profile of thyroid tumors in the Chinese population. The combination of NGS testing and FNA cytology could facilitate the accurate diagnosis of thyroid nodules, especially for indeterminate nodules.
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Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei, Taiwan
Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan
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Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
Center of Anti-Aging and Health Consultation, National Taiwan University Hospital, Taipei, Taiwan
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Purpose
Autoimmune polyendocrine syndrome (APS) is a rare immune-endocrinopathy characterized by the failure of at least two endocrine organs. Clinical characteristics have mainly been described in the Western population. This study comprehensively analyzed the demographic and clinical manifestations of APS II and APS III in Taiwan.
Methods
Patients aged ≥20 years with a diagnosis of APS II or APS III in ten hospitals between 2001 and 2021 were enrolled. The clinical and serological characteristics of the patients were retrospectively reviewed.
Results
Among the 187 enrolled patients (45 men and 142 women); only seven (3.7%) had APS II, while the others had APS III. Fifty-five patients developed hyperthyroidism and 44 patients developed hypothyroidism. Men were diagnosed with APS at a younger age than women (16.8 vs 27.8 years old, P = 0.007). Most patients were initially diagnosed with type 1 diabetes mellitus. There was a positive correlation between age at diagnosis and the likelihood of developing thyroid dysfunction. For every year older patients were diagnosed with APS III, the risk of developing hyperthyroidism increased by 3.6% (P = 0.002), and the risk of developing hypothyroidism increased by 3.7% (P = 0.035). Positive anti-parietal cell antibodies (APCA) were associated with a higher risk of anemia in patients with APS III (P < 0.001).
Conclusion
This study provides the most comprehensive analysis of APS II and APS III in Asia. The percentage of patients with APS II was significantly lower than in the Western population. A second autoimmune endocrinopathy may develop several years after the first one. APCA examination is valuable when evaluating anemia in patients with APS.
