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Sex-Specific Cardiovascular Risks and Mortality in Patients with Panhypopituitarism: A Nationwide Cohort Study. 泛垂体功能减退症患者心血管风险和死亡率的性别特异性:全国队列研究
IF 3.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-02-11 DOI: 10.3803/EnM.2024.2176
Seung Shin Park, Hyunmook Jeong, Chang Ho Ahn, Min Jeong Park, Yong Hwy Kim, Kwangsoo Kim, Jung Hee Kim

Background: Panhypopituitarism is a condition of combined deficiency of multiple pituitary hormones, which requires lifelong hormone replacement therapy. Hormone deficiency or inadequate hormone replacement may contribute to cardiovascular disease. Here, we aimed to investigate the burden of cardiovascular, cerebrovascular diseases and mortality in patients with panhypopituitarism.

Methods: A total of 5,714 patients with panhypopituitarism were enrolled in the Korean National Health Insurance Service database from 2003 to 2020. Panhypopituitarism was defined according to the International Classification of Diseases, 10th Revision (ICD- 10) codes for hypopituitarism, pituitary adenoma, or craniopharyngioma and the continuous prescription of thyroid hormone and glucocorticoids. The risks of all-cause mortality, coronary artery disease (CAD), heart failure (HF), ischemic stroke, and intracranial hemorrhage were compared between patients with panhypopituitarism and age-, sex-, and index year-matched controls.

Results: The mean age of patients with panhypopituitarism and matched controls was 55.1 years, and men accounted for 51.5%. Patients with panhypopituitarism showed significantly higher all-cause mortality compared to matched controls after adjustment for covariates (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.95 to 2.43 in men and HR, 3.09; 95% CI, 2.78 to 3.44 in women). Additionally, there were higher risks of CAD, HF, ischemic stroke, and intracranial hemorrhage in both sexes, except for CAD in men.

Conclusion: Patients with panhypopituitarism have elevated risks of cardiovascular and cerebrovascular diseases as well as increased mortality. These risks are particularly prominent for all-cause mortality in women. Therefore, proactive monitoring for cardiovascular and cerebrovascular complications is required in patients with panhypopituitarism.

{"title":"Sex-Specific Cardiovascular Risks and Mortality in Patients with Panhypopituitarism: A Nationwide Cohort Study.","authors":"Seung Shin Park, Hyunmook Jeong, Chang Ho Ahn, Min Jeong Park, Yong Hwy Kim, Kwangsoo Kim, Jung Hee Kim","doi":"10.3803/EnM.2024.2176","DOIUrl":"https://doi.org/10.3803/EnM.2024.2176","url":null,"abstract":"<p><strong>Background: </strong>Panhypopituitarism is a condition of combined deficiency of multiple pituitary hormones, which requires lifelong hormone replacement therapy. Hormone deficiency or inadequate hormone replacement may contribute to cardiovascular disease. Here, we aimed to investigate the burden of cardiovascular, cerebrovascular diseases and mortality in patients with panhypopituitarism.</p><p><strong>Methods: </strong>A total of 5,714 patients with panhypopituitarism were enrolled in the Korean National Health Insurance Service database from 2003 to 2020. Panhypopituitarism was defined according to the International Classification of Diseases, 10th Revision (ICD- 10) codes for hypopituitarism, pituitary adenoma, or craniopharyngioma and the continuous prescription of thyroid hormone and glucocorticoids. The risks of all-cause mortality, coronary artery disease (CAD), heart failure (HF), ischemic stroke, and intracranial hemorrhage were compared between patients with panhypopituitarism and age-, sex-, and index year-matched controls.</p><p><strong>Results: </strong>The mean age of patients with panhypopituitarism and matched controls was 55.1 years, and men accounted for 51.5%. Patients with panhypopituitarism showed significantly higher all-cause mortality compared to matched controls after adjustment for covariates (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.95 to 2.43 in men and HR, 3.09; 95% CI, 2.78 to 3.44 in women). Additionally, there were higher risks of CAD, HF, ischemic stroke, and intracranial hemorrhage in both sexes, except for CAD in men.</p><p><strong>Conclusion: </strong>Patients with panhypopituitarism have elevated risks of cardiovascular and cerebrovascular diseases as well as increased mortality. These risks are particularly prominent for all-cause mortality in women. Therefore, proactive monitoring for cardiovascular and cerebrovascular complications is required in patients with panhypopituitarism.</p>","PeriodicalId":11636,"journal":{"name":"Endocrinology and Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparison of the Effectiveness and Hypocalcemia Risk of Antiresorptive Agents in Patients with Hypercalcemia of Malignancy.
IF 3.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-02-04 DOI: 10.3803/EnM.2024.2132
Sung Hye Kong, Seung Shin Park, Jung Hee Kim, Sang Wan Kim, Se Hyun Kim, Jee Hyun Kim, Chan Soo Shin

Background: Hypercalcemia of malignancy (HCM), a major metabolic complication of cancer, is often managed with bisphosphonates (BP) and, increasingly, with denosumab. We aimed to compare the effectiveness and safety of denosumab with that of BP, with or without calcitonin, in treating HCM.

Methods: This retrospective cohort study was conducted at a tertiary hospital from 2017 to 2022 and included 317 patients treated for HCM. Participants were divided into three treatment groups: denosumab, intravenous (IV) BP only, and IV BP combined with calcitonin. The primary outcomes measured were changes in calcium levels and the incidence of hypocalcemia. Analysis of covariance was used to adjust for age, sex, body mass index, creatinine level, type of malignancy, and the use of furosemide and steroids.

Results: The mean participant age was 65 years, and 37.5% were female. After adjustment, both denosumab and IV BPs were found to effectively lower calcium levels. Denosumab led to a decrease of 2.0 mg/dL (-15.9%), while IV BP alone resulted in a reduction of 1.8 mg/dL (-13.9%). The largest reduction, of 2.7 mg/dL (-20.9%), occurred with IV BP and calcitonin. Both denosumab and IV BP+calcitonin yielded their lowest calcium levels within 48 hours, whereas the IV BP only group reached a nadir within 72 hours. Despite these differences in treatment effectiveness, hypocalcemia occurred significantly less frequently in the denosumab group compared to the other groups.

Conclusion: Denosumab and IV BP were similarly effective in reducing calcium levels. However, IV BP combined with calcitonin yielded a more rapid and pronounced decrease.

{"title":"Comparison of the Effectiveness and Hypocalcemia Risk of Antiresorptive Agents in Patients with Hypercalcemia of Malignancy.","authors":"Sung Hye Kong, Seung Shin Park, Jung Hee Kim, Sang Wan Kim, Se Hyun Kim, Jee Hyun Kim, Chan Soo Shin","doi":"10.3803/EnM.2024.2132","DOIUrl":"https://doi.org/10.3803/EnM.2024.2132","url":null,"abstract":"<p><strong>Background: </strong>Hypercalcemia of malignancy (HCM), a major metabolic complication of cancer, is often managed with bisphosphonates (BP) and, increasingly, with denosumab. We aimed to compare the effectiveness and safety of denosumab with that of BP, with or without calcitonin, in treating HCM.</p><p><strong>Methods: </strong>This retrospective cohort study was conducted at a tertiary hospital from 2017 to 2022 and included 317 patients treated for HCM. Participants were divided into three treatment groups: denosumab, intravenous (IV) BP only, and IV BP combined with calcitonin. The primary outcomes measured were changes in calcium levels and the incidence of hypocalcemia. Analysis of covariance was used to adjust for age, sex, body mass index, creatinine level, type of malignancy, and the use of furosemide and steroids.</p><p><strong>Results: </strong>The mean participant age was 65 years, and 37.5% were female. After adjustment, both denosumab and IV BPs were found to effectively lower calcium levels. Denosumab led to a decrease of 2.0 mg/dL (-15.9%), while IV BP alone resulted in a reduction of 1.8 mg/dL (-13.9%). The largest reduction, of 2.7 mg/dL (-20.9%), occurred with IV BP and calcitonin. Both denosumab and IV BP+calcitonin yielded their lowest calcium levels within 48 hours, whereas the IV BP only group reached a nadir within 72 hours. Despite these differences in treatment effectiveness, hypocalcemia occurred significantly less frequently in the denosumab group compared to the other groups.</p><p><strong>Conclusion: </strong>Denosumab and IV BP were similarly effective in reducing calcium levels. However, IV BP combined with calcitonin yielded a more rapid and pronounced decrease.</p>","PeriodicalId":11636,"journal":{"name":"Endocrinology and Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Time to Insulin Therapy and Severe Hypoglycemia in Korean Adults Initially Diagnosed with Type 2 Diabetes: A Nationwide Study.
IF 3.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-02-04 DOI: 10.3803/EnM.2024.2082
You-Bin Lee, Kyungdo Han, Bongsung Kim, So Hee Park, Kyu Yeon Hur, Gyuri Kim, Jae Hyeon Kim, Sang-Man Jin

Background: We examined the distribution of time to insulin therapy (TIT) post-diabetes diagnosis and the hazard of severe hypoglycemia (SH) according to TIT in Korean adults initially diagnosed with type 2 diabetes (T2D) and who progressed to insulin therapy.

Methods: Using data from the Korean National Health Insurance Service (2002 to 2018), we selected adult incident insulin users (initially diagnosed as T2D) who underwent health examinations between 2009 and 2012. The hazards of SH, recurrent SH, and problematic hypoglycemia were analyzed according to groups categorized using the TIT and clinical risk factors for SH (TIT ≥5 years with risk factors, TIT ≥5 years without risk factors, 3 ≤TIT <5 years, 1 ≤TIT <3 years, and TIT <1 year).

Results: Among 41,637 individuals, 14,840 (35.64%) and 10,587 (25.43%) initiated insulin therapy within <5 and <3 years postdiabetes diagnosis, respectively. During a median 6.53 years, 3,406 SH events occurred. Compared to individuals with TIT ≥5 years and no risk factor for SH, individuals with TIT <3 years had higher outcome hazards in a graded manner (adjusted hazard ratio [95% confidence intervals] for any SH: 1.117 [0.967 to 1.290] in those with 3 ≤TIT <5 years; 1.459 [1.284 to 1.657] in those with 1 ≤ TIT <3 years; and 1.515 [1.309 to 1.754] in those with TIT <1 year). This relationship was more pronounced in the non-obese subpopulation.

Conclusion: Among adults who progressed to insulin therapy after being diagnosed with T2D, a shorter TIT was not uncommon and may predict an increased risk of SH, particularly in non-obese patients.

{"title":"Time to Insulin Therapy and Severe Hypoglycemia in Korean Adults Initially Diagnosed with Type 2 Diabetes: A Nationwide Study.","authors":"You-Bin Lee, Kyungdo Han, Bongsung Kim, So Hee Park, Kyu Yeon Hur, Gyuri Kim, Jae Hyeon Kim, Sang-Man Jin","doi":"10.3803/EnM.2024.2082","DOIUrl":"https://doi.org/10.3803/EnM.2024.2082","url":null,"abstract":"<p><strong>Background: </strong>We examined the distribution of time to insulin therapy (TIT) post-diabetes diagnosis and the hazard of severe hypoglycemia (SH) according to TIT in Korean adults initially diagnosed with type 2 diabetes (T2D) and who progressed to insulin therapy.</p><p><strong>Methods: </strong>Using data from the Korean National Health Insurance Service (2002 to 2018), we selected adult incident insulin users (initially diagnosed as T2D) who underwent health examinations between 2009 and 2012. The hazards of SH, recurrent SH, and problematic hypoglycemia were analyzed according to groups categorized using the TIT and clinical risk factors for SH (TIT ≥5 years with risk factors, TIT ≥5 years without risk factors, 3 ≤TIT <5 years, 1 ≤TIT <3 years, and TIT <1 year).</p><p><strong>Results: </strong>Among 41,637 individuals, 14,840 (35.64%) and 10,587 (25.43%) initiated insulin therapy within <5 and <3 years postdiabetes diagnosis, respectively. During a median 6.53 years, 3,406 SH events occurred. Compared to individuals with TIT ≥5 years and no risk factor for SH, individuals with TIT <3 years had higher outcome hazards in a graded manner (adjusted hazard ratio [95% confidence intervals] for any SH: 1.117 [0.967 to 1.290] in those with 3 ≤TIT <5 years; 1.459 [1.284 to 1.657] in those with 1 ≤ TIT <3 years; and 1.515 [1.309 to 1.754] in those with TIT <1 year). This relationship was more pronounced in the non-obese subpopulation.</p><p><strong>Conclusion: </strong>Among adults who progressed to insulin therapy after being diagnosed with T2D, a shorter TIT was not uncommon and may predict an increased risk of SH, particularly in non-obese patients.</p>","PeriodicalId":11636,"journal":{"name":"Endocrinology and Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Long-Term Efficacy and Safety of Denosumab: Insights beyond 10 Years of Use. Denosumab的长期疗效和安全性:超过10年使用的见解。
IF 3.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-02-01 Epub Date: 2025-01-13 DOI: 10.3803/EnM.2024.2125
Jeonghoon Ha, Youn-Ju Lee, Jinyoung Kim, Chaiho Jeong, Yejee Lim, Jeongmin Lee, Ki-Hyun Baek

Osteoporosis management in post-menopausal women focuses on fracture prevention, with denosumab as a key therapeutic option. Despite its proven efficacy in reducing fracture risk and increasing bone mineral density (BMD) over 10 years, its long-term impact remains uncertain. We evaluated the literature on its efficacy and safety beyond the initial decade. Clinical trials and real-world studies confirm denosumab's sustained efficacy, especially in lumbar spine BMD, with hip BMD stabilizing. Concerns about adverse events (AEs) like hypocalcemia and osteonecrosis of the jaw necessitate vigilant monitoring. Risks of atypical femoral fractures and malignancies also require attention, despite unclear links to treatment duration. Clinical guidelines for denosumab beyond 10 years are limited, emphasizing the need for careful monitoring. In certain scenarios, such as advanced chronic kidney disease, prolonged denosumab may be required to balance AE risks with fracture prevention benefits. Denosumab shows potential for long-term efficacy in augmenting BMD; however, monitoring for AEs is crucial to guide clinical decision-making effectively.

绝经后妇女骨质疏松症的管理侧重于骨折预防,denosumab是一个关键的治疗选择。尽管其在降低骨折风险和增加骨密度(BMD)方面的疗效已被证实超过10年,但其长期影响仍不确定。我们评估了最初十年后其有效性和安全性的文献。临床试验和实际研究证实了denosumab的持续疗效,特别是在腰椎骨密度方面,髋部骨密度稳定。关注不良事件(ae),如低钙血症和颌骨骨坏死,需要警惕监测。非典型股骨骨折和恶性肿瘤的风险也需要注意,尽管不清楚与治疗时间的联系。denosumab 10年以上的临床指南是有限的,强调需要仔细监测。在某些情况下,如晚期慢性肾病,可能需要延长denosumab以平衡AE风险和骨折预防益处。Denosumab显示出增加骨密度的长期疗效潜力;然而,监测不良事件对于有效指导临床决策至关重要。
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引用次数: 0
Long-Term Prognosis and Systemic Impact of Acromegaly: Analyses Utilizing Korean National Health Insurance Data.
IF 3.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-02-01 Epub Date: 2025-02-04 DOI: 10.3803/EnM.2024.2285
Sangmo Hong, Kyungdo Han, Cheol-Young Park

Acromegaly is a rare endocrine disorder caused by excessive growth hormone secretion. Its low prevalence poses challenges in studying its long-term prognosis and systemic effects. To address this research gap, we conducted five studies using nationwide cohort data from the Korean National Health Insurance Database (NHID). This review consolidates the findings of these studies, which examined various long-term effects of acromegaly. The results demonstrated significant associations between acromegaly and increased mortality, a higher prevalence of mortality, cardiovascular outcomes, neurodegenerative diseases, depression, end-stage kidney disease, respiratory complications, specifically bronchiectasis, spine & hip fracture, and malignancy. These findings highlight the critical need for early diagnosis, comprehensive care, and long-term monitoring, and underscore the importance of a multidisciplinary approach in managing acromegaly.

{"title":"Long-Term Prognosis and Systemic Impact of Acromegaly: Analyses Utilizing Korean National Health Insurance Data.","authors":"Sangmo Hong, Kyungdo Han, Cheol-Young Park","doi":"10.3803/EnM.2024.2285","DOIUrl":"10.3803/EnM.2024.2285","url":null,"abstract":"<p><p>Acromegaly is a rare endocrine disorder caused by excessive growth hormone secretion. Its low prevalence poses challenges in studying its long-term prognosis and systemic effects. To address this research gap, we conducted five studies using nationwide cohort data from the Korean National Health Insurance Database (NHID). This review consolidates the findings of these studies, which examined various long-term effects of acromegaly. The results demonstrated significant associations between acromegaly and increased mortality, a higher prevalence of mortality, cardiovascular outcomes, neurodegenerative diseases, depression, end-stage kidney disease, respiratory complications, specifically bronchiectasis, spine & hip fracture, and malignancy. These findings highlight the critical need for early diagnosis, comprehensive care, and long-term monitoring, and underscore the importance of a multidisciplinary approach in managing acromegaly.</p>","PeriodicalId":11636,"journal":{"name":"Endocrinology and Metabolism","volume":" ","pages":"1-9"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Elevated Circulating Sclerostin Levels in Frail Older Adults: Implications beyond Bone Health. 体弱老年人体内循环硬骨素水平升高:骨健康之外的影响
IF 3.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-02-01 Epub Date: 2024-10-24 DOI: 10.3803/EnM.2024.2100
Ji Yeon Baek, Seong Hee Ahn, Il-Young Jang, Hee-Won Jung, Eunhye Ji, So Jeong Park, Yunju Jo, Eunju Lee, Dongryeol Ryu, Seongbin Hong, Beom-Jun Kim

Backgruound: Sclerostin, initially recognized for its pivotal role in bone metabolism, has gained attention for its multifaceted impact on overall human health. However, its influence on frailty-a condition that best reflects biological age-has not been thoroughly investigated.

Methods: We collected blood samples from 244 older adults who underwent comprehensive geriatric assessments. Sclerostin levels were quantified using an enzyme-linked immunosorbent assay. Frailty was assessed using two validated approaches: the phenotypic model by Fried and the deficit accumulation frailty index (FI) by Rockwood.

Results: After controlling for sex, age, and body mass index, we found that serum sclerostin levels were significantly elevated in frail individuals compared to their robust counterparts (P<0.001). There was a positive correlation between serum sclerostin concentrations and the FI (P<0.001). Each standard deviation increase in serum sclerostin was associated with an odds ratio of 1.87 for frailty (P=0.003). Moreover, participants in the highest quartile of sclerostin levels had a significantly higher FI and a 9.91-fold increased odds of frailty compared to those in the lowest quartile (P=0.003 and P=0.039, respectively).

Conclusion: These findings, which for the first time explore the association between circulating sclerostin levels and frailty, have significant clinical implications, positioning sclerostin as one of potential blood-based biomarkers for frailty that captures the comprehensive physical, mental, and social aspects of the elderly, extending beyond its traditional role in bone metabolism.

背景:硬骨蛋白最初被认为在骨代谢中起着关键作用,但因其对人体整体健康的多方面影响而备受关注。然而,它对虚弱--一种最能反映生理年龄的状况--的影响尚未得到深入研究:方法:我们采集了 244 名接受了综合老年评估的老年人的血液样本。方法:我们采集了 244 名接受了综合老年评估的老年人的血液样本,并使用酶联免疫吸附测定法对硬骨蛋白水平进行了量化。采用两种经过验证的方法评估虚弱程度:弗里德的表型模型和洛克伍德的虚弱指数(FI):结果:在控制了性别、年龄和体重指数后,我们发现体弱者的血清硬骨蛋白水平明显高于健壮者(PC结论:这些研究结果是首次发现体弱者的血清硬骨蛋白水平高于健壮者:这些研究结果首次探讨了循环硬骨素水平与虚弱之间的关系,具有重要的临床意义,将硬骨素定位为潜在的基于血液的虚弱生物标志物之一,它能全面捕捉老年人的身体、精神和社会方面,超越了其在骨代谢中的传统作用。
{"title":"Elevated Circulating Sclerostin Levels in Frail Older Adults: Implications beyond Bone Health.","authors":"Ji Yeon Baek, Seong Hee Ahn, Il-Young Jang, Hee-Won Jung, Eunhye Ji, So Jeong Park, Yunju Jo, Eunju Lee, Dongryeol Ryu, Seongbin Hong, Beom-Jun Kim","doi":"10.3803/EnM.2024.2100","DOIUrl":"10.3803/EnM.2024.2100","url":null,"abstract":"<p><strong>Backgruound: </strong>Sclerostin, initially recognized for its pivotal role in bone metabolism, has gained attention for its multifaceted impact on overall human health. However, its influence on frailty-a condition that best reflects biological age-has not been thoroughly investigated.</p><p><strong>Methods: </strong>We collected blood samples from 244 older adults who underwent comprehensive geriatric assessments. Sclerostin levels were quantified using an enzyme-linked immunosorbent assay. Frailty was assessed using two validated approaches: the phenotypic model by Fried and the deficit accumulation frailty index (FI) by Rockwood.</p><p><strong>Results: </strong>After controlling for sex, age, and body mass index, we found that serum sclerostin levels were significantly elevated in frail individuals compared to their robust counterparts (P<0.001). There was a positive correlation between serum sclerostin concentrations and the FI (P<0.001). Each standard deviation increase in serum sclerostin was associated with an odds ratio of 1.87 for frailty (P=0.003). Moreover, participants in the highest quartile of sclerostin levels had a significantly higher FI and a 9.91-fold increased odds of frailty compared to those in the lowest quartile (P=0.003 and P=0.039, respectively).</p><p><strong>Conclusion: </strong>These findings, which for the first time explore the association between circulating sclerostin levels and frailty, have significant clinical implications, positioning sclerostin as one of potential blood-based biomarkers for frailty that captures the comprehensive physical, mental, and social aspects of the elderly, extending beyond its traditional role in bone metabolism.</p>","PeriodicalId":11636,"journal":{"name":"Endocrinology and Metabolism","volume":" ","pages":"73-81"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Development of a Long-Acting Follicle-Stimulating Hormone Using Serum Albumin Fab-Associated Technology for Female Infertility. 利用血清白蛋白fab相关技术开发长效促卵泡激素治疗女性不育症。
IF 3.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-02-01 Epub Date: 2024-12-04 DOI: 10.3803/EnM.2024.2090
Daham Kim, Yoon Hee Cho, Min Jeong Kang, So Jeong Lee, Soohyun Lee, Bo Hyon Yun, Hyunjin Chi, Jeongsuk An, Kyungsun Lee, Jaekyu Han, Susan Chi, Moo Young Song, Sang-Hoon Cha, Eun Jig Lee

Backgruound: Recombinant human follicle-stimulating hormone (rhFSH) is commonly used to treat female infertility, but its short half-life necessitates multiple doses. Even corifollitropin alfa, with an extended half-life, requires supplementary injections of rhFSH after 7 days. This study aimed to develop and evaluate a long-acting follicle-stimulating hormone (FSH) formulation using anti-serum albumin Fab-associated (SAFA) technology to avoid additional injections and enhance ovarian function.

Methods: SAFA-FSH was synthesized using a Chinese hamster ovary expression system. Its biological efficacy was confirmed through assays measuring its ability to stimulate cyclic adenosine monophosphate (cAMP) production, estradiol synthesis, and the expression of human cytochrome P450 family 19 subfamily A member 1 (hCYP19α1) and human steroidogenic acute regulatory protein (hSTAR) in human ovarian granulosa (KGN) cells. To evaluate the effects of SAFA-FSH, we compared its impact on serum estradiol levels and ovarian weight increase with that of rhFSH in Sprague-Dawley (SD) rats using the modified Steelman-Pohley test.

Results: The results indicated that SAFA-FSH induces cAMP synthesis in KGN cells and upregulates the expression of hCYP19α1 and hSTAR in a dose-dependent manner. Female SD rats, aged 21 days, receiving daily subcutaneous human chorionic gonadotropin injections for 5 days exhibited a significant increase in serum estradiol levels and ovarian weight when administered SAFA-FSH on the first day or when given nine injections of rhFSH over 5 days. Notably, the group receiving SAFA-FSH on the first and third days demonstrated an even greater rise in serum estradiol levels and ovarian weight.

Conclusion: These findings suggest that SAFA-FSH presents a promising alternative to current rhFSH treatments for female infertility. However, further research is essential to thoroughly assess its safety and efficacy in clinical contexts.

背景:重组人促卵泡激素(rhFSH)常用于治疗女性不孕症,但其半衰期短,需要多次服用。即使是半衰期延长的corifollitropin α,也需要在7天后补充注射rhFSH。本研究旨在开发和评估使用抗血清白蛋白fab相关(SAFA)技术的长效促卵泡激素(FSH)制剂,以避免额外注射并增强卵巢功能。方法:利用中国仓鼠卵巢表达系统合成SAFA-FSH。通过测定其在人卵巢颗粒(KGN)细胞中刺激环磷酸腺苷(cAMP)生成、雌二醇合成以及人细胞色素P450家族19亚家族A成员1 (hCYP19α1)和人类固醇急性调节蛋白(hSTAR)表达的能力,证实了其生物学功效。为了评价SAFA-FSH对SD大鼠血清雌二醇水平和卵巢重量增加的影响,我们采用改良的Steelman-Pohley试验比较了SAFA-FSH与rhFSH对SD大鼠血清雌二醇水平和卵巢重量增加的影响。结果:SAFA-FSH诱导KGN细胞cAMP合成,上调hCYP19α1和hSTAR的表达,并呈剂量依赖性。雌性SD大鼠,21日龄,每天皮下注射人绒毛膜促性腺激素5天,在第一天注射SAFA-FSH或在5天内注射9次rhFSH时,血清雌二醇水平和卵巢重量显著增加。值得注意的是,在第一天和第三天接受SAFA-FSH治疗的组显示出血清雌二醇水平和卵巢重量的更大上升。结论:这些发现表明SAFA-FSH是目前rhFSH治疗女性不孕症的一个有希望的替代方法。然而,进一步的研究是必要的,以彻底评估其在临床环境中的安全性和有效性。
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引用次数: 0
Pituitary Neuroendocrine Tumors in Multiple Endocrine Neoplasia. 多发性内分泌肿瘤中的垂体神经内分泌肿瘤。
IF 3.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-02-01 Epub Date: 2024-08-30 DOI: 10.3803/EnM.2024.2074
Sang Ouk Chin, Constance Chik, Toru Tateno

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal-dominant disorder characterized by tumors of the pituitary, parathyroid, and endocrine-gastrointestinal tract. Pituitary neuroendocrine tumors (PitNETs) occur in about 40% of MEN1 cases, with 10% being the first manifestation. Recent studies show a slight female predominance, with microPitNETs (<1 cm) being more common than macroPitNETs (>1 cm). Functional PitNETs (FPitNETs) are more frequent than non-functional ones (36% to 48%), with prolactinomas being the most common FPitNETs. MEN1-associated PitNETs are often plurihormonal, larger, and more invasive compared to sporadic types, though patient age and FPitNET proportions are similar. MEN1 mutation-negative patients tend to have larger, symptomatic PitNETs at diagnosis. Six patients with MEN1 have been reported to have pituitary carcinomas, including a mutation- negative patient. Treatment approach between PitNETs in MEN1 and sporadic types appears to be similar. PitNETs also occur in MEN4, but their epidemiology is less understood. In patients with a MEN1-like phenotype and negative genetic testing, MEN4 should be considered.

多发性内分泌肿瘤 1 型(MEN1)是一种常染色体显性遗传疾病,以垂体、甲状旁腺和内分泌-胃肠道肿瘤为特征。垂体神经内分泌肿瘤(PitNET)约占MEN1病例的40%,其中10%为首发症状。最近的研究显示,女性略占多数,且多为微小的 PitNET(1 厘米)。功能性 PitNET(FPitNET)比非功能性 PitNET 更常见(36% 到 48%),泌乳素瘤是最常见的 FPitNET。与散发性PitNET相比,MEN1相关PitNET通常为多激素性,体积更大,侵袭性更强,但患者年龄和FPitNET的比例相似。MEN1 基因突变阴性的患者在确诊时往往患有较大、无症状的 PitNET。据报道,有六名MEN1患者患有垂体癌,其中包括一名突变阴性患者。MEN1和散发性PitNET的治疗方法似乎相似。MEN4也会发生垂体网状细胞瘤,但对其流行病学的了解较少。对于表型类似 MEN1 但基因检测阴性的患者,应考虑 MEN4。
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引用次数: 0
Unveiling Risk Factors for Treatment Failure in Patients with Graves' Disease: A Nationwide Cohort Study in Korea. 揭示格雷夫斯病患者治疗失败的危险因素:韩国一项全国性队列研究
IF 3.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-02-01 Epub Date: 2025-01-13 DOI: 10.3803/EnM.2024.2093
Jung A Kim, Kyeong Jin Kim, Jimi Choi, Kyoung Jin Kim, Eyun Song, Ji Hee Yu, Nam Hoon Kim, Hye Jin Yoo, Ji A Seo, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Sin Gon Kim

Backgruound: Antithyroid drug (ATD) treatment is the preferred initial treatment for Graves' disease (GD) in South Korea, despite higher treatment failure rates than radioactive iodine (RAI) therapy or thyroidectomy. This study aimed to evaluate the incidence of treatment failure associated with the primary modalities for GD treatment in real-world practice.

Methods: We included 452,001 patients diagnosed with GD between 2004 and 2020 from the Korean National Health Insurance Service-National Health Information Database. Treatment failure was defined as switching from ATD, RAI, or thyroidectomy treatments, and for ATD specifically, inability to discontinue medication for over 2 years.

Results: Mean age was 46.2 years, with females constituting 70.8%. Initial treatments for GD included ATDs (98.0%), thyroidectomy (1.3%), and RAI (0.7%), with a noted increment in ATD application from 96.2% in 2004 to 98.8% in 2020. During a median follow- up of 8.5 years, the treatment failure rates were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Multivariate analysis indicated that the hazard ratio for treatment failure with ATD was 2.81 times higher than RAI. RAI treatments ≥10 mCi had 37% lower failure rates than doses <10 mCi.

Conclusion: ATDs are the most commonly used for GD in South Korea, followed by thyroidectomy and RAI. Although the risk of treatment failure for ATD is higher than that of RAI therapy, initial RAI treatment in South Korea is relatively limited compared to that in Western countries. Further studies are required to evaluate the cause of low initial RAI treatment rates in South Korea.

背景:在韩国,抗甲状腺药物(ATD)治疗是Graves病(GD)的首选初始治疗,尽管治疗失败率高于放射性碘(RAI)治疗或甲状腺切除术。本研究旨在评估与现实世界中GD治疗的主要方式相关的治疗失败发生率。方法:我们从韩国国民健康保险服务-国家健康信息数据库中纳入了2004年至2020年间诊断为GD的452,001例患者。治疗失败被定义为从ATD、RAI或甲状腺切除术治疗中切换,特别是对于ATD,无法停药超过2年。结果:平均年龄46.2岁,女性占70.8%。GD的初始治疗包括ATD(98.0%)、甲状腺切除术(1.3%)和RAI (0.7%), ATD的应用从2004年的96.2%增加到2020年的98.8%。在中位随访8.5年期间,ATDs的治疗失败率为58.5%,RAI为21.3%,甲状腺切除术为2.1%。多因素分析表明,ATD治疗失败的风险比为RAI的2.81倍。≥10 mCi的RAI治疗失败率比剂量治疗低37%。结论:在韩国,ATDs是GD最常用的治疗方法,其次是甲状腺切除术和RAI。虽然ATD治疗失败的风险高于RAI治疗,但与西方国家相比,韩国的初始RAI治疗相对有限。需要进一步的研究来评估韩国RAI初始治疗率低的原因。
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引用次数: 0
Tirzepatide and Cancer Risk in Individuals with and without Diabetes: A Systematic Review and Meta-Analysis. 替西帕肽与糖尿病患者和非糖尿病患者的癌症风险:一项系统综述和荟萃分析。
IF 3.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-02-01 Epub Date: 2025-01-15 DOI: 10.3803/EnM.2024.2164
A B M Kamrul-Hasan, Muhammad Shah Alam, Deep Dutta, Thanikai Sasikanth, Fatema Tuz Zahura Aalpona, Lakshmi Nagendra

Backgruound: Data on the carcinogenic potential of tirzepatide from randomized controlled trials (RCTs) are limited. Furthermore, no meta-analysis has included all relevant RCTs to assess the cancer risk associated with tirzepatide.

Methods: RCTs involving patients receiving tirzepatide in the intervention arm and either a placebo or any active comparator in the control arm were searched through electronic databases. The primary outcome was the overall risk of any cancer, and secondary outcomes were the risks of specific types of cancer in the tirzepatide versus the control groups.

Results: Thirteen RCTs with 13,761 participants were analyzed. Over 26 to 72 weeks, the tirzepatide and pooled control groups had identical risks of any cancer (risk ratio, 0.78; 95% confidence interval, 0.53 to 1.16; P=0.22). The two groups had comparable cancer risks in patients with and without diabetes. In subgroup analyses, the risks were also similar in the tirzepatide versus placebo, insulin, and glucagon-like peptide-1 receptor agonist groups. The overall cancer risk was also comparable for different doses of tirzepatide compared to the control groups; only a 10-mg tirzepatide dose had a lower risk of any cancer than placebo. Furthermore, compared to the control groups (pooled or separately), tirzepatide did not increase the risk of any specific cancer types. Despite greater increments in serum calcitonin with 10- and 15-mg tirzepatide doses than with placebo, the included RCTs reported no cases of papillary thyroid carcinoma.

Conclusion: Tirzepatide use in RCTs over 26 to 72 weeks did not increase overall or specific cancer risk.

背景:来自随机对照试验(rct)的关于替西帕肽致癌潜力的数据有限。此外,没有荟萃分析纳入所有相关的随机对照试验来评估与替西肽相关的癌症风险。方法:通过电子数据库检索涉及干预组接受替西帕肽治疗的患者和对照组接受安慰剂或任何活性比较物治疗的患者的随机对照试验。主要结果是任何癌症的总体风险,次要结果是替西帕肽组与对照组中特定类型癌症的风险。结果:13项随机对照试验共13761名受试者进行了分析。在26至72周内,替西肽组和合并对照组患任何癌症的风险相同(风险比,0.78;95%置信区间为0.53 ~ 1.16;P = 0.22)。两组糖尿病患者和非糖尿病患者患癌症的风险相当。在亚组分析中,替西帕肽与安慰剂、胰岛素和胰高血糖素样肽-1受体激动剂组的风险也相似。与对照组相比,不同剂量的替西帕肽的总体癌症风险也相当;只有10mg剂量的替西帕肽比安慰剂有更低的癌症风险。此外,与对照组(合并或单独)相比,替西帕肽没有增加任何特定癌症类型的风险。尽管10-和15-mg替西帕肽组的血清降钙素比安慰剂组有更大的增加,但纳入的随机对照试验未报告甲状腺乳头状癌病例。结论:在26 - 72周的随机对照试验中使用替西帕肽不会增加总体或特定的癌症风险。
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