Endocrine journal最新文献

{"title":"Association between gestational weight gain and pregnancy outcomes, neonatal birth weight, and maternal postpartum glucose tolerance in Japanese gestational diabetes mellitus patients: comparison of old and new gestational weight gain standards.","authors":"Akiho Yamashita, Masayuki Kaku, Takuya Ideguchi, Shuhei Nishida, Hiroyuki Kinoshita, Takeshi Nishikawa","doi":"10.1507/endocrj.EJ24-0486","DOIUrl":"10.1507/endocrj.EJ24-0486","url":null,"abstract":"<p><p>In Japan, the guidelines for gestational weight gain (GWG) were revised in 2021. Under the new guidelines, pregnant women are recommended to increase their GWG. The aim of this study was to compare the incidence of adverse pregnancy outcomes (APOs), large for gestational age (LGA), and postpartum glucose tolerance in gestational diabetes mellitus (GDM) patients before and after the revised GWG standards. This retrospective cohort study enrolled 1,021 GDM patients who underwent prenatal glycemic control and a postpartum 75-g oral glucose tolerance test. The endpoint was the incidence of APOs, LGA, and postpartum impaired glucose tolerance (IGT) and diabetes mellitus (DM). There was no significant difference in the incidence of APOs and postpartum IGT and DM in GDM patients before and after the revised GWG standards. On the other hand, when the new GWG standards were applied to GDM patients, the incidence of LGA increased (adjusted odds ratio [aOR]; 1.764, 95% confidence interval [CI]; 1.180-2.637). In particular, when classified by pre-pregnancy body mass index, the incidence of LGA increased in the obese group (aOR; 5.944, 95% CI; 1.847-19.129). Future prospective cohort studies are needed to verify the efficacy and safety of appropriate GWG in Japanese GDM patients.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":"509-524"},"PeriodicalIF":1.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scutellarin mitigates high glucose-induced pyroptosis in diabetic atherosclerosis: Role of Nrf2-FBXL2-mediated NLRP3 degradation.","authors":"Qingxin Meng, Yongpan Huang, Xian Long, Lijing Liu, Yani Tang, Jingjing He, Yayuan Luo","doi":"10.1507/endocrj.EJ24-0505","DOIUrl":"10.1507/endocrj.EJ24-0505","url":null,"abstract":"<p><p>This study investigated the role of scutellarin (Scu) and Nrf2 in diabetic atherosclerosis, focusing on their effects on FBXL2 and NLRP3 ubiquitination. Human umbilical vein endothelial cells were treated with high glucose (HG) to model diabetic atherosclerosis in vitro. Cell viability, cytotoxicity, pyroptosis, and inflammatory cytokine levels were assessed, and gene interactions were examined by dual-luciferase reporter assays. Ubiquitination and protein levels were analyzed through immunoprecipitation and western blotting. The results revealed that HG treatment decreased Nrf2 and FBXL2 levels and enhanced NLRP3-mediated pyroptosis. However, Scu treatment increased Nrf2 expression, improved cell viability, and inhibited pyroptosis. Nrf2 knockdown downregulated FBXL2 and reversed the protective effects of Scu. Additionally, FBXL2 promoted the ubiquitination-mediated degradation of NLRP3 and suppressed pyroptosis. The activation of NLRP3 reversed the protective effects of Scu on diabetic atherosclerosis. These findings suggest that Scu alleviated diabetic atherosclerosis by increasing Nrf2 and FBXL2 expression, promoting NLRP3 ubiquitination-mediated degradation, and suppressing pyroptosis.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":"495-507"},"PeriodicalIF":1.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arterial stiffness, high fasting glucose, and fatty liver as risk factors for visceral obesity in middle-aged Chinese individuals: a cross-sectional study.","authors":"Hajime Nawata, Li Ou, Xu Zhang, Qinglan Song, Jing Huang, Jin Hu, Kazue Ito, Shinichi Obo, Takeharu Fukushima, Kaori Iwami, Shizuka Iguchi, Ai Igarashi, Xiaoyang He, Jing Zhang, Yu Xia, Ken Takasaki","doi":"10.1507/endocrj.EJ24-0554","DOIUrl":"10.1507/endocrj.EJ24-0554","url":null,"abstract":"<p><p>The prevalence of obesity is increasing rapidly worldwide, particularly in Asia. Visceral obesity, characterized by intra-abdominal fat accumulation, is a precursor to metabolic syndrome, encompassing hyperglycemia, dyslipidemia, and hypertension, which elevate the risk of atherosclerosis and cardiovascular disease. A visceral fat area (VFA) of ≥100 cm² is a recognized threshold for diagnosing obesity-related metabolic syndrome. This study aimed to identify independent risk factors for VFA ≥100 cm² in middle-aged Chinese individuals from the general population. We analyzed data from 148 participants (mean age: 49.3 ± 10.8 years; 54% male) who underwent health check-ups. VFA and subcutaneous fat area were assessed using computed tomography, while arterial stiffness and fatty liver were evaluated via brachial-ankle pulse wave velocity (baPWV) and abdominal ultrasonography, respectively. Between-group comparisons (VFA ≥100 cm² vs. VFA <100 cm²) were conducted using unpaired t-tests and Mann-Whitney U tests, and logistic regression analysis identified risk factors. Multivariable regression analysis revealed that baPWV ≥1,400 cm/s (odds ratio [OR] = 5.71, p = 0.011), waist circumference ≥85 cm (OR = 5.46, p = 0.026), fasting blood glucose (FBG) ≥100 mg/dL (OR = 5.69, p = 0.030), male sex (OR = 12.79, p = 0.029), and fatty liver (OR = 3.99, p = 0.042) were significant independent risk factors for VFA ≥100 cm². Among these, baPWV ≥1,400 cm/s was the most significant, showing a positive correlation with VFA (r = 0.365, p < 0.001). Visceral obesity (VFA ≥100 cm²) is a critical target for interventions addressing metabolic syndrome, metabolic dysfunction-associated fatty liver disease (MAFLD), and cardiovascular disease, particularly in males.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":"525-533"},"PeriodicalIF":1.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the potential of high-mobility group AT-hook 2 immunohistochemical staining as a prognostic marker of metastatic recurrence in follicular thyroid cancer: a retrospective cohort study.","authors":"Yuka Ito, Junko Sakumoto, Hideki Hirabayashi, Shinichi Haruna, Wataru Konno, Itsuo Nakajima, Kazuyuki Ishida, Yasuo Haruyama, Toshimi Sairenchi, Eijun Nishihara, Shuji Fukata, Akira Hishinuma, Takahiko Kogai","doi":"10.1507/endocrj.EJ24-0557","DOIUrl":"10.1507/endocrj.EJ24-0557","url":null,"abstract":"<p><p>High-mobility group AT-hook 2 (HMGA2) is a nuclear protein involved in the differentiation and proliferation of epithelial-derived tumors and also considered to be involved in the growth and differentiation of various malignant tumors, including thyroid cancer. Immunohistochemistry (IHC) for HMGA2 has been reported to show diffuse positivity in several follicular thyroid carcinoma (FTC) cases. This study aimed to investigate whether positive immunohistochemical staining for HMGA2 in primary tumors can be used to predict the prognosis and detect prognostic factors in malignant thyroid tumors associated with metastatic recurrence in FTC. Formalin-fixed, paraffin-embedded (FFPE) resected specimens used for the IHC for HMGA2. The association of positive HMGA2 staining with metastasis and recurrence, along with the potential of HMGA2 as a prognostic marker of metastatic recurrence, was statistically determined. HMGA2 staining was positive in most malignant tissues, whereas benign tissues were unstained. HMGA2 staining of the marginal and invasive regions was observed in FTC tissues. The association of HMGA2 staining with metastasis and recurrence was significant (p = 0.018). Kaplan-Meier curves showed an association of negative HMGA2 staining with metastasis and disease-free survival (p = 0.090). Tumor size (>4 cm) and wide invasion were also significant factors (p = 0.043, p < 0.001). The risk ratio without HMGA2 was significantly reduced by 30% compared to that with HMGA2. In primary tumors, positive HMGA2 staining can be used to predict prognosis in malignant thyroid tumors associated with metastatic recurrence in FTC and negative HMGA2 staining may indicate longer disease-free survival after surgery.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":"535-543"},"PeriodicalIF":1.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistence to growth hormone treatment and clinical characteristics of pediatric patients with growth hormone deficiency: A retrospective cohort study of data from the Japan Medical Data Center claims database.","authors":"Sumito Dateki, Yukihito Sato, Satoshi Tsuboi, Jun Mori","doi":"10.1507/endocrj.EJ24-0225","DOIUrl":"10.1507/endocrj.EJ24-0225","url":null,"abstract":"<p><p>Limited real-world data are available on persistence to growth hormone replacement therapy (GHRT) in Japan. Therefore, we used the Japan Medical Data Center claims database to retrospectively investigate persistence with GHRT in patients with pediatric growth hormone deficiency (pGHD). We identified 1,020 patients with pGHD treated with GHRT. The mean age at initial diagnosis was 7.5 ± 3.8 years, and we found a bimodal pattern in age, with peaks at 3 and 12 to 13 years of age; the peaks were more pronounced in male patients. After excluding patients with early withdrawal, 1,016 patients were eligible for persistence analysis. The time to initial treatment discontinuation, i.e., the first prescription-free period of 182 days (6 months) or more, for 50% of the patients was 2,526 days, which was similar to that of treatment completion (2,626 days). Most patients persisted with GHRT until they completed treatment, but 24 out of 1,016 (2.4%) had a treatment discontinuation. The mean proportion of days covered was 89.8%. Being female (hazard ratio [95% CI]: 1.85 [1.36-2.51]) and older age at diagnosis (1.50 [1.41-1.60]) were associated with shorter time to discontinuation. This finding suggests that most patients persist with GHRT until puberty. In conclusion, although most Japanese patients with pGHD appear to persist well with GHRT, some complete GHRT before puberty. Additionally, there are patients diagnosed and starting treatment just before puberty. Therefore, continued efforts towards early referral and diagnosis are important.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":"475-485"},"PeriodicalIF":1.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of Cushing's disease in the initial phase~From detection to surgery~.","authors":"Hidenori Fukuoka","doi":"10.1507/endocrj.EJ24-0309","DOIUrl":"10.1507/endocrj.EJ24-0309","url":null,"abstract":"<p><p>Cushing's disease is a rare endocrine disorder that presents many systemic complications, and its initial phase management can be difficult in atypical and severe cases or at institutes with limited experience. It is a disease in which several complications may have already progressed at the time of diagnosis, and complications may become more severe during the initial management phase, potentially becoming life-threatening. In addition, many patients are young, and depending on this phase management, their quality of life will significantly decline later on. Therefore, this review summarizes the evidence accumulated to date and outlines strategies for disease management, focusing on the initial stages from detection, diagnosis, and referral of patients to surgery.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":"463-473"},"PeriodicalIF":1.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between serum thyroglobulin levels and glycemic control in patients with thyroid cancer after radioiodine therapy.","authors":"Yuji Hataya, Yuko Fujishima, Kanta Fujimoto, Toshio Iwakura, Naoki Matsuoka","doi":"10.1507/endocrj.EJ24-0417","DOIUrl":"10.1507/endocrj.EJ24-0417","url":null,"abstract":"<p><p>Serum thyroglobulin (Tg) levels are highly sensitive and specific tumor markers in patients with thyroid cancer who have undergone total thyroidectomy and radioiodine (RAI) therapy. Recently, we reported a case wherein serum Tg levels fluctuated according to hemoglobin A1c (HbA1c) levels, demonstrating a strong correlation between serum Tg and HbA1c levels. However, whether this association exists broadly in other patients with thyroid cancer remains unclear. Therefore, we retrospectively investigated this association in six patients with thyroid cancer and diabetes who underwent total thyroidectomy and RAI therapy at our institution. Two patients exhibited a significant correlation between serum Tg and HbA1c levels (r = 0.53, p < 0.01 and r = 0.66, p = 0.01). In these patients, a gradual decrease in serum Tg levels was observed, along with improved glycemic control. Two other patients showed a non-significant correlation between serum Tg and HbA1c levels (r = 0.72, p = 0.11 and r = 0.54, p = 0.17). In these patients, a rapid increase in serum Tg levels was observed, with HbA1c levels showing only small fluctuations. In the remaining two patients, no correlation was found; in these patients, the fluctuations in serum Tg levels were only small, despite fluctuations in HbA1c levels. In conclusion, serum Tg levels may be associated with HbA1c levels in some patients with thyroid cancer and diabetes. The correlation between serum Tg and HbA1c levels was more evident in patients with gradual fluctuations in Tg levels. Future studies with larger cohorts are necessary to clarify the underlying mechanism by which glycemic control influences Tg levels and establish appropriate monitoring methods.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":"637-643"},"PeriodicalIF":1.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term outcomes after a radioactive iodine treatment for a single autonomous functioning thyroid nodule in Japan.","authors":"Ai Yoshihara, Jaeduk Yoshimura Noh, Kosuke Inoue, Masakazu Koshibu, Rei Hirose, Masahiro Ichikawa, Nami Suzuki, Masako Matsumoto, Miho Fukushita, Natsuko Watanabe, Kiminori Sugino, Koichi Ito","doi":"10.1507/endocrj.EJ24-0578","DOIUrl":"10.1507/endocrj.EJ24-0578","url":null,"abstract":"<p><p>We investigated the association between a 500 MBq dose of radioactive iodine treatment (RAIT) and both thyroid nodule volume and thyroid function in patients with a single autonomous functioning thyroid nodule (AFTN). We retrospectively studied 201 patients with an AFTN who received RAIT at a dose of 500 MBq and were followed up for more than 2 years. Thyroid function at diagnosis, thyroid antibody positivity, treatment with antithyroid drugs before RAIT, cystic components of the nodule, and ¹³¹I uptake outside the nodule were assessed. Nodule enlargement was observed in 18 patients (9%), persistent hyperthyroidism in 13 patients (6.5%), and hypothyroidism in 45 patients (22.3%). Nodule volume before RAIT was significantly larger in the nodule enlargement group compared to the non-enlargement group. The risk factors for persistent hyperthyroidism were larger nodule volume and absence of a cystic component in multivariate analysis. The cutoff nodule volume before RAIT for predicting nodule enlargement was 15.5 mL, and for predicting persistent hyperthyroidism was 16.6 mL. Nodule volume decreased to 47% in the first year and continued to gradually decrease thereafter. This study provided long-term outcome data regarding nodule volume change and thyroid function in AFTN patients following single fixed-dose RAIT, and it identified risk factors for nodule enlargement and persistent hyperthyroidism after RAIT. Nodule volume before treatment was a good predictor of treatment response.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":"487-494"},"PeriodicalIF":1.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biased antibodies and beyond: a new era in the diagnosis of PTH-dependent hypercalcemia.","authors":"Noriko Makita, Katsunori Manaka, Maho Taguchi, Hirofumi Horikoshi, Junichiro Sato, Taroh Iiri","doi":"10.1507/endocrj.EJ25-0051","DOIUrl":"https://doi.org/10.1507/endocrj.EJ25-0051","url":null,"abstract":"<p><p>Hypercalcemia, a common electrolyte imbalance, requires accurate differential diagnosis to guide appropriate management. PTH-dependent hypercalcemia, predominantly caused by primary hyperparathyroidism (PHPT) and rarely by familial hypocalciuric hypercalcemia (FHH)-mainly due to heterozygous loss-of-function mutations in the CASR gene encoding the calcium-sensing receptor (CaSR)-now includes acquired hypocalciuric hypercalcemia (AHH) as an emerging disease entity. Initially identified as analogous to FHH, AHH was characterized by blocking antibodies targeting the CaSR. However, our research has identified unique autoantibodies, termed biased antibodies, that paradoxically regulate signaling by enhancing Gq activity while suppressing Gi activity. Investigating their mechanisms has not only provided insights into specific treatments for AHH but also suggested novel activation mechanisms and binding sites of the CaSR, offering a fresh perspective on the regulation of PTH secretion. In clinical practice, recognizing AHH is crucial. A key diagnostic feature is fluctuating serum calcium levels, making a wait-and-see approach viable for mild hypercalcemia. Conversely, hypercalcemic crises necessitate immediate diagnostic and therapeutic interventions. The most important diagnostic clue to differentiate AHH from PHPT is hypermagnesemia. Additionally, AHH is less likely to involve AVP resistance (i.e., nephrogenic diabetes insipidus) and acute kidney injury (AKI), owing to preserved medullary hyperosmolarity and minimal interference with AVP signaling. Finally, a relatively low PTH level serves as another distinguishing feature. Based on these observations, we propose a novel diagnostic guide for PTH-dependent hypercalcemia. We anticipate that this guide will help identify previously undiagnosed AHH cases in routine practice, enabling timely and effective management of this rare condition.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, pharmacokinetics, and potential benefits of TSH-receptor-specific monoclonal autoantibody K1-70^TM in Japanese Graves' disease patients: results of a phase 1 trial.","authors":"Jaeduk Yoshimura Noh, Natsuko Watanabe, Koichi Ito, Mika Tsuiki, Yuki Ishihara, Tetsuya Tagami, Ichiro Yamauchi, Ai Kozaki, Toshu Inoue, Bernard Rees Smith","doi":"10.1507/endocrj.EJ25-0043","DOIUrl":"https://doi.org/10.1507/endocrj.EJ25-0043","url":null,"abstract":"<p><p>This phase 1 dose-escalation study evaluated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of K1-70^TM, a TSH-receptor-specific monoclonal autoantibody that inhibits ligand binding and receptor activation, in Japanese Graves' disease (GD) patients. Twelve patients were enrolled, divided into four dosage cohorts (5 mg, 25 mg, 75 mg, and 150 mg), and monitored for 100 days post-administration. The primary objective was to assess safety and tolerability, and the secondary objectives were evaluation of PK and thyroid function. Exploratory analyses focused on the dynamics of the anti-TSH receptor antibodies and Thyroid eye disease (TED). K1-70^TM demonstrated a favorable safety profile, with no reports of serious adverse events. Mild to moderate treatment-emergent adverse events, such as headache and fatigue, were observed in 83.3% of the participants, but none were deemed severe. PK analysis revealed a dose-dependent increase in half-life, suggesting prolonged systemic exposure at higher doses. Thyroid function remained stable at lower doses, but there were dose-dependent reductions at higher doses that were managed with adjunctive L-thyroxine therapy. Marked reductions in TSAb levels were observed across all cohorts, indicating effective suppression of TSH receptor activity. An improvement in proptosis was noted in 50% of the eyes, suggesting a potential therapeutic benefit against inactive-phase TED. These findings support K1-70^TM as a promising targeted therapy for GD and TED, and they warrant further studies involving larger patient populations and active disease phases to confirm its efficacy and safety (jRCT Registration Number: JRCT2080224902).</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}